Aciclovir - anti viral, nu-acyclovir

Common use Aciclovir is an antiviral drug, it is a synthetic ingredient with a similar molecular structure to purine nucleoside. Aciclovir is used to treat viral infections such as cold sores, to stop the growth of Herpes simplex virus, Varicella zoster virus (caused by chickenpox and shingles), Epstein Barr Virus (caused by glandular fever), and to a lesser extent Cytomegalovirus (CMV). It is also useful in preventing genital herpes and in preventing viral infections occurring in those with a lowered immune system. This medication may also help reduce the time when pain remains after the sores heal. In addition, in people with a weakened immune system, Aciclovir can decrease the risk of the virus spreading to other parts of the body and causing serious infections.

Dosage and direction

Take this medication by mouth with or without food, usually 2 to 5 times a day as directed by your doctor. Take this medicine by mouth with a glass of water. Take your medicine at regular intervals. Do not take your medicine more often than directed. Take all of your medicine as directed even if you think your are better. If you are using the liquid form of this medication, shake the bottle well before each dose. Carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose. Dosage is based on your medical condition and response to treatment. In children, dosage is also based on weight.

You should talk with your healthcare provider prior to taking Aciclovir if you have kidney disease, including kidney failure (renal failure), any allergies, including allergies to food, dyes, or preservatives. Let your healthcare provider know if you are pregnant or thinking of becoming pregnant, breastfeeding. Make sure to tell your healthcare provider about all medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. The medication passes through breast milk. Therefore, if you are breastfeeding or plan to start, discuss this with your healthcare provider prior to taking the drug.

Aciclovir Injection is contraindicated for patients who develop hypersensitivity to Nu-acyclovir or valaciclovir.

Possible side effects Side effects are potentially serious and you should report to your doctor or health care professional as soon as possible. These include, but are not limited to: allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue, chest pain, confusion, hallucinations, tremor, dark urine, increased sensitivity to the sun, redness, blistering, peeling or loosening of the skin (including inside the mouth), seizures, trouble passing urine or change in the amount of urine, unusual bleeding or bruising, or pinpoint red spots on the skin, unusually weak or tired, yellowing of the eyes or skin. Side effects that usually do not require medical attention: diarrhea, fever, headache, nausea, vomiting stomach upset. In this way report to your doctor or health care professional if they continue or are bothersome.

Drug interactions There are negative interactions that can occur when Aciclovir is combined with any of the drugs listed above. Phenytoin (Fosphenytoin) and Aciclovir: it may decrease the level of phenytoin in your blood, perhaps making it less effective. Your healthcare provider may need to measure the level of phenytoin in your blood (using a blood test) and adjust your dose as necessary. Probenecid can increase the level of Aciclovir in your blood, increasing your risk of acyclovir side effects. Your healthcare provider may need to decrease your acyclovir dosage to prevent this interaction from occurring. Acyclovir can increase the level of Tenofovir in your blood, potentially increasing your risk of side effects. Your healthcare provider may need to lower your tenofovir dosage to prevent drug interactions.

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

Seek emergency medical attention if you think you have used too much of this medicine. Overdose symptoms may include seizure (convulsions), hallucinations, and urinating less than usual or not at all.

Store at controlled room temperature of 15°C to 25°C (59°F to 77°F). Keep this medicine out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Disclaimer We provide only general information about medications which does not cover all directions, possible drug integrations, or precautions. Information on the site cannot be used for self-treatment and self-diagnosis. Any specific instructions for a particular patient should be agreed with your health care adviser or doctor in charge of the case. We disclaim reliability of this information and mistakes it could contain. We are not responsible for any direct, indirect, special or other indirect damage as a result of any use of the information on this site and also for consequences of self-treatment.

Common use Aciclovir is an antiviral drug, it is a synthetic ingredient with a similar molecular structure to purine nucleoside. Aciclovir is used to treat viral infections such as cold sores, to stop the growth of Herpes simplex virus, Varicella zoster virus (caused by chickenpox and shingles), Epstein Barr Virus (caused by glandular fever), and to a lesser extent Cytomegalovirus (CMV). It is also useful in preventing genital herpes and in preventing viral infections occurring in those with a lowered immune system. This medication may also help reduce the time when pain remains after the sores heal. In addition, in people with a weakened immune system, Aciclovir can decrease the risk of the virus spreading to other parts of the body and causing serious infections.

Dosage and direction

Take this medication by mouth with or without food, usually 2 to 5 times a day as directed by your doctor. Take this medicine by mouth with a glass of water. Take your medicine at regular intervals. Do not take your medicine more often than directed. Take all of your medicine as directed even if you think your are better. If you are using the liquid form of this medication, shake the bottle well before each dose. Carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose. Dosage is based on your medical condition and response to treatment. In children, dosage is also based on weight.

You should talk with your healthcare provider prior to taking Aciclovir if you have kidney disease, including kidney failure (renal failure), any allergies, including allergies to food, dyes, or preservatives. Let your healthcare provider know if you are pregnant or thinking of becoming pregnant, breastfeeding. Make sure to tell your healthcare provider about all medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. The medication passes through breast milk. Therefore, if you are breastfeeding or plan to start, discuss this with your healthcare provider prior to taking the drug.

Aciclovir Injection is contraindicated for patients who develop hypersensitivity to aciclovir or valaciclovir.

Possible side effects Side effects are potentially serious and you should report to your doctor or health care professional as soon as possible. These include, but are not limited to: allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue, chest pain, confusion, hallucinations, tremor, dark urine, increased sensitivity to the sun, redness, blistering, peeling or loosening of the skin (including inside the mouth), seizures, trouble passing urine or change in the amount of urine, unusual bleeding or bruising, or pinpoint red spots on the skin, unusually weak or tired, yellowing of the eyes or skin. Side effects that usually do not require medical attention: diarrhea, fever, headache, nausea, vomiting stomach upset. In this way report to your doctor or health care professional if they continue or are bothersome.

Drug interactions There are negative interactions that can occur when Aciclovir is combined with any of the drugs listed above. Phenytoin (Fosphenytoin) and Aciclovir: it may decrease the level of phenytoin in your blood, perhaps making it less effective. Your healthcare provider may need to measure the level of phenytoin in your blood (using a blood test) and adjust your dose as necessary. Probenecid can increase the level of Aciclovir in your blood, increasing your risk of acyclovir side effects. Your healthcare provider may need to decrease your acyclovir dosage to prevent this interaction from occurring. Acyclovir can increase the level of Tenofovir in your blood, potentially increasing your risk of side effects. Your healthcare provider may need to lower your tenofovir dosage to prevent drug interactions.

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

Seek emergency medical attention if you think you have used too much of this medicine. Overdose symptoms may include seizure (convulsions), hallucinations, and urinating less than usual or not at all.

Store at controlled room temperature of 15°C to 25°C (59°F to 77°F). Keep this medicine out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Disclaimer We provide only general information about medications which does not cover all directions, possible drug integrations, or precautions. Information on the site cannot be used for self-treatment and self-diagnosis. Any specific instructions for a particular patient should be agreed with your health care adviser or doctor in charge of the case. We disclaim reliability of this information and mistakes it could contain. We are not responsible for any direct, indirect, special or other indirect damage as a result of any use of the information on this site and also for consequences of self-treatment.

Diltiazem hydrochloride (professional patient advice), diltzac 120mg

Diltiazem Hydrochloride

Trade Names

Cardizem - Tablets 30 mg - Tablets 60 mg - Tablets 90 mg - Tablets 120 mg - Powder for injection 25 mg - Injection 5 mg/mL

Cardizem CD - Capsules, ER 120 mg - Capsules, ER 180 mg - Capsules, ER 240 mg - Capsules, ER 300 mg - Capsules, ER 360 mg

Cardizem LA - Tablets, ER 120 mg - Tablets, ER 180 mg - Tablets, ER 240 mg - Tablets, ER 300 mg - Tablets, ER 360 mg - Tablets, ER 420 mg

Cartia XT - Capsules, ER 120 mg - Capsules, ER 180 mg - Capsules, ER 240 mg - Capsules, ER 300 mg

Dilacor XR - Capsules, ER 120 mg - Capsules, ER 180 mg - Capsules, ER 240 mg

Dilt-XR - Capsules, ER 120 mg - Capsules, ER 180 mg - Capsules, ER 240 mg

Diltia XT - Capsules, ER 180 mg

Diltiazem Hydrochloride Extended Release - Capsules, ER 60 mg - Capsules, ER 90 mg

Diltzac - Capsules, ER 120 mg - Capsules, ER 180 mg - Capsules, ER 240 mg - Capsules, ER 300 mg - Capsules, ER 360 mg

Matzim LA - Tablets, ER 120 mg - Tablets, ER 180 mg - Tablets, ER 240 mg - Tablets, ER 300 mg - Tablets, ER 360 mg - Tablets, ER 420 mg

Taztia XT - Capsules, ER 120 mg - Capsules, ER 180 mg - Capsules, ER 240 mg

Tiazac - Capsules, ER 120 mg - Capsules, ER 180 mg - Capsules, ER 240 mg - Capsules, ER 300 mg - Capsules, ER 360 mg - Capsules, ER 420 mg

Apo-Diltiaz (Canada) Apo-Diltiaz CD (Canada) Apo-Diltiaz Injectable (Canada) Apo-Diltiaz SR (Canada) Gen-Diltiazem (Canada) Gen-Diltiazem CD (Canada) Novo-Diltiazem (Canada) Novo-Diltiazem CD (Canada) Nu-Diltiaz (Canada) Nu-Diltiaz-CD (Canada) ratio-Diltiazem CD (Canada) Sandoz Diltiazem CD (Canada) Tiazac XC (Canada)

Pharmacology

Inhibits movement of calcium ions across the cell membrane in systemic and coronary vascular smooth muscle; slows calcium ion movement across cell membranes in both cardiac muscle and cardiac pacemaker cells, decreasing sinoatrial and atrioventricular (AV) conduction.

Pharmacokinetics

Absorption

T max is 2 to 3 h.

Extended release (ER)

T max is 10 to 14 h.

Immediate release (IR)

T max is 2 to 4 h.

Distribution

Vd approximately 305 L. 70% to 80% protein bound (approximately 40% to alpha l - acid glycoprotein and approximately 30% to albumin). Excreted in breast milk.

Metabolism

Metabolized in the liver (including via CYP-450) to several metabolites; desacetyl diltiazem is 25% to 50% as potent as diltiazem. Undergoes first-pass metabolism after oral administration.

Elimination

The half-life is approximately 3.4 h (IV), 4 to 9 h (ER), and 3 to 4.5 h (IR). 2% to 4% is excreted unchanged in the urine (oral). Systemic Cl is approximately 65 L/h (IV).

Peak

2 to 5 min (IV); 11 to 18 h (ER).

Special Populations

Renal Function Impairment

No difference in the pharmacokinetic profile of diltiazem in patients with severely impaired renal function.

Hepatic Function Impairment

Bioavailability is increased, and half-life is prolonged.

Indications and Usage

Treatment of angina pectoris caused by coronary artery spasm; chronic stable angina (classic effort-associated angina); essential hypertension (ER and sustained-release forms only).

Treatment of atrial fibrillation or flutter; paroxysmal supraventricular tachycardia.

Contraindications

Sick sinus syndrome or second - or third-degree AV block, except with functioning pacemaker; hypotension with systolic pressure less than 90 mm Hg; acute MI; pulmonary congestion; hypersensitivity to the drug; ventricular tachycardia (IV); atrial fibrillation or atrial flutter associated with an accessory bypass tract (IV); IV diltiazem and IV beta-blockers administered together (within a few hours).

Dosage and Administration

Dosage regimens should be individualized.

PO Start with 30 mg 4 times daily before meals and at bedtime. Gradually increase dosage at 1- to 2-day intervals until optimum response (average optimum dose range 180 to 360 mg/day).

Cardizem CD and Cartia XT

PO Start with 120 to 180 mg once daily. Some patients may respond to doses up to 480 mg once daily. When necessary, titrate the dose over 7 to 14 days.

Cardizem LA and Matzim LA

PO Start with 180 mg once daily. Some patients may respond to doses up to 360 mg once daily. Titrate dose over 7 to 14 days.

Dilacor XR and Diltia XT

PO Start with 120 mg once daily. Some patients may respond to doses up to 480 mg once daily. When necessary, titrate the dose over 7 to 14 days.

Diltzac and Tiazac

PO Start with 120 to 180 mg once daily. Some patients may respond to doses up to 540 mg once daily. When necessary, titrate the dose over 7 to 14 days.

Atrial Fibrillation/Flutter/Paroxysmal Supraventricular Tachycardia Adults Direct IV single bolus injection

Parenteral Initial dose is 0.25 mg/kg as a bolus administered over 2 min (reasonable dose is 20 mg for average patient). If response is inadequate after 15 min, administer as a second 0.35 mg/kg over 2 min (reasonable dose is 25 mg for average patient). Individualize subsequent IV doses. Dose low body weight patients on a mg/kg basis. Although the duration of action may be shorter, some patients may respond to an initial dose of 0.15 mg/kg.

Continuous IV infusion

Parenteral For continued reduction of heart rate (up to 24 h) in patients with atrial fibrillation or atrial flutter, IV infusion may be administered. Immediately following administration of a bolus dose of 20 mg (0.25 mg/kg) or 25 mg (0.35 mg/kg) and reduction of heart rate, begin an IV infusion. The recommended initial infusion rate is 10 mg/h; however, some patients may maintain response to an initial rate of 5 mg/h. The infusion rate may be increased in 5 mg/h increments up to 15 mg/h as needed, if further reduction in heart rate is necessary. The infusion may be maintained for up to 24 h (max, 24 h and 15 mg/h).

Hypertension Adults Extended-release capsules

PO Start with 60 to 120 mg twice daily or 180 to 240 mg once daily. Max antihypertensive effect usually occurs by 14 days of chronic therapy (optimum dose range 240 to 360 mg once daily, but some patients respond to lower doses or higher doses up to 480 mg once daily).

Cardizem CD and Cartia XT

PO 180 to 240 mg once daily; however, some patients may respond to lower doses. Maximum effect is usually achieved by 14 days of chronic therapy. Usual range is 240 to 360 mg once daily. Some patients may respond to doses up to 480 mg once daily.

Cardizem LA and Matzim LA

PO Start with 180 to 240 mg once daily; however, some patients may respond to lower doses. Max effect is usually achieved by 14 days of chronic therapy. Dose range studied in clinical trials was 120 to 540 mg once daily (max, 540 mg daily).

Dilacor XR and Diltia XT

PO 180 to 240 mg once daily (usual dose range, 180 to 480 mg once daily). Individual patients, particularly those 60 yr of age and older, may respond to lower doses of 120 mg once daily. Some patients may require doses up to 540 mg once daily.

Diltzac and Tiazac

PO Start with 120 to 240 mg once daily. Max effect is usually achieved by 14 days of chronic therapy. Usual dose range is 120 to 540 mg once daily.

General Advice

May be used alone or in combination with other CV medications for the treatment of hypertension and angina.

Swallow tablets and capsules whole. Do not crush, chew, or break.

Diltzac capsules may be opened and contents sprinkled onto a spoonful of applesauce. Swallow applesauce immediately without chewing, and follow with a glass of cool water.

For administration by IV bolus or infusion only.

For IV infusion, add prescribed dose to prescribed volume of sodium chloride 0.9%, dextrose 5% in water, or dextrose 5% in sodium chloride 0.45% following manufacturer's dilution charts.

Storage/Stability

Store tablets and capsules at controlled room temperature (59° to 86°F). Protect from moisture and avoid excessive humidity. Discard any unused solution. Do not save for future use. Store vials for injection in refrigerator (36° to 46°F). May store vials for injection at room temperature for up to 1 mo, but any unused injection must be destroyed after 1 mo. Store syringes and vials of powder for injection at room temperature (59° to 86°F). Do not freeze. Use reconstituted solution immediately or store for up to 24 h at controlled room temperature.

Drug Interactions

Depression of cardiac contractility, conductivity, and automaticity as well as vascular dilation associated with anesthetics may be potentiated.

Benzodiazepines (eg, midazolam, triazolam), buspirone, carbamazepine, cyclosporine, digitalis, lovastatin, quinidine, simvastatin

Plasma levels of these agents may be elevated by diltiazem, increasing the pharmacologic and toxic effects. The dose of simvastatin should not exceed 10 mg/day.

Beta-blockers (eg, propanolol)

May have additive negative inotropic and chronotropic effects. Use with caution.

Diltiazem levels may be increased.

Other antihypertensive agents

May have additive effects.

Coadministration lowered diltiazem plasma concentrations to undetectable levels. Avoid coadministration.

Incompatibility

Do not mix with furosemide.

Adverse Reactions

Cardiovascular

Bradycardia (4%); first-degree AV block (3%); angina, arrhythmia, AV block (second - or third-degree), bundle branch block, CHF, ECG abnormalities, hypotension, palpitations, syncope, tachycardia, ventricular extrasystoles (less than 2%); peripheral edema, asystole, MI (postmarketing).

CNS

Dizziness (6%); headache, fatigue (5%); asthenia (3%); abnormal dreams, amnesia, asthenia, depression, gait abnormalities, hallucinations, insomnia, nervousness, paresthesia, personality change, somnolence, tremor (less than 2%); extrapyramidal symptoms, lightheadedness, weakness, shakiness (postmarketing).

Dermatologic

Rash (2%); ecchymosis, petechiae, photosensitivity, pruritus (less than 2%); alopecia, erythema multiforme (including Stevens-Johnson syndrome and TEN), exfoliative dermatitis, purpura, generalized rash (postmarketing).

EENT

Sinus congestion (2%); amblyopia, epistaxis, eye irritation, nasal congestion, rhinitis, tinnitus (less than 2%); retinopathy (postmarketing).

GI

Nausea (1%); anorexia, constipation, diarrhea, dry mouth, dysgeusia, thirst, vomiting (less than 2%); abdominal discomfort, cramps, dyspepsia, gingival hyperplasia (postmarketing).

Genitourinary

Albuminuria, crystalluria, hyperuricemia, impotence, nocturia, polyuria, sexual difficulties, gynecomastia (less than 2%).

Hematologic-Lymphatic

Hemolytic anemia, increased bleeding time, leukopenia, thrombocytopenia (postmarketing).

Lab Tests

Mild elevations of ALT, AST, LDH, and alkaline phosphatase, CPK increase (less than 2%).

Metabolic-Nutritional

Hyperglycemia, weight gain (less than 2%).

Musculoskeletal

Muscle cramps, neck rigidity, osteoarticular pain (less than 2%); joint pain.

Respiratory

Cough (2%); dyspnea (less than 2%).

Miscellaneous

Lower limb edema (8%); edema (5%); flushing (1%); allergic reactions, pain (less than 2%); angioedema (postmarketing).

Etodolac - fda prescribing information, side effects and uses, etodolac 300mg

Etodolac

Cardiovascular Thrombotic Events

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use [see Warnings and Precautions ].

Etodolac capsules USP, 200 mg and 300 mg, and Etodolac tablets USP, 400 mg and 500 mg are contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see Contraindications and Warnings ].

Gastrointestinal Risk

NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal (GI) events. (See WARNINGS ).

Etodolac Description

Etodolac capsules and tablets, USP are members of the pyranocarboxylic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). Each tablet and capsule contains Etodolac for oral administration. Etodolac is a racemic mixture of [+]S and [-]R-enantiomers. Etodolac is a white crystalline compound, insoluble in water but soluble in alcohols, chloroform, dimethyl sulfoxide, and aqueous polyethylene glycol.

The chemical name is (±) 1,8-diethyl-1,3,4,9-tetrahydropyrano-[3,4-b]indole-1-acetic acid. The molecular weight of the base is 287.37. It has a pKa of 4.65 and an n-octanol: water partition coefficient of 11.4 at pH 7.4. The molecular formula for Etodolac is C 17 H 21 NO 3. and it has the following structural formula:

Each Capsule, for oral administration, contains 200 or 300 mg of Etodolac. In addition, each capsule contains the following inactive ingredients: Ammonium Hydroxide USP, Black Iron Oxide USP, Colloidal Silicone Dioxide NF, Erythrosine (200 mg only), Ethyl Alcohol USP, Gelatin, Isopropyl Alcohol USP, Lactose Monohydrate NF, Magnesium Stearate NF, Microcrystalline Cellulose NF, N-Butyl Alcohol USP, Povidone USP, Propylene Glycol USP, Purified Water USP, Shellac, Titanium Dioxide.

Each Tablet, for oral administration, contains 400 mg or 500 mg of Etodolac. In addition, each tablet contains the following inactive ingredients: Hydroxypropyl Methylcellulose USP, Lactose Monohydrate NF, Magnesium Stearate, Microcrystalline Cellulose NF, Polyethylene Glycol, Povidone USP, Sodium Starch Glycolate NF and Titanium Dioxide. Also, each 400 mg tablet contains Iron Oxide Red and Iron Oxide Yellow. Each 500 mg tablet contains D&C Yellow #10 Aluminum Lake, FD&C Blue #1 Aluminum Lake, and FD&C Red #40 Aluminum Lake.

Etodolac - Clinical Pharmacology

Pharmacodynamics

Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of Etodolac, like that of other NSAIDs, is not completely understood, but may be related to the prostaglandin synthetase inhibition.

Etodolac is a racemic mixture of [-]R - and [+]S-Etodolac. As with other NSAIDs, it has been demonstrated in animals that the [+]S-form is biologically active. Both enantiomers are stable and there is no [-]R to [+]S conversion in vivo.

Pharmacokinetics

The systemic bioavailability of Etodolac from Etodolac capsules and tablets, USP is 100% as compared to solution and at least 80% as determined from mass balance studies. Etodolac is well absorbed and had a relative bioavailability of 100% when 200 mg capsules were compared with a solution of Etodolac. Based on mass balance studies, the systemic availability of Etodolac from either the tablet or capsule formulation is at least 80%. Etodolac does not undergo significant first-pass metabolism following oral administration. Mean (± 1 SD) peak plasma concentrations (C max ) range from approximately 14 ± 4 to 37 ± 9 μg/mL after 200 to 600 mg single doses and are reached in 80 ± 30 minutes (see Table 1 for summary of pharmacokinetic parameters). The dose-proportionality based on the area under the plasma concentration-time curve (AUC) is linear following doses up to 600 mg every 12 hours. Peak concentrations are dose proportional for both total and free Etodolac following doses up to 400 mg every 12 hours, but following a 600 mg dose, the peak is about 20% higher than predicted on the basis of lower doses. The extent of absorption of Etodolac is not affected when Etodolac tablets or capsules are administered after a meal. Food intake, however, reduces the peak concentration reached by approximately one-half and increases the time to peak concentration by 1.4 to 3.8 hours.

Table 1. Mean (CV%)* Pharmacokinetic Parameters of Etodolac in Normal Healthy Adults and Various Special Populations

Normal Healthy Adults (18-65)†

Healthy Males (18-65)

The mean apparent volume of distribution (Vd/F) of Etodolac is approximately 390 mL/kg. Etodolac is more than 99% bound to plasma proteins, primarily to albumin. The free fraction is less than 1% and is independent of Etodolac total concentration over the dose range studied. It is not known whether Etodolac is excreted in human milk; however, based on its physical-chemical properties, excretion into breast milk is expected. Data from in vitro studies, using peak serum concentrations at reported therapeutic doses in humans, show that the Etodolac free fraction is not significantly altered by acetaminophen, ibuprofen, indomethacin, naproxen, piroxicam, chlorpropamide, glipizide, glyburide, phenytoin, and probenecid.

Etodolac is extensively metabolized in the liver. The role, if any, of a specific cytochrome P450 system in the metabolism of Etodolac is unknown. Several Etodolac metabolites have been identified in human plasma and urine. Other metabolites remain to be identified. The metabolites include 6-, 7-, and 8-hydroxylated-Etodolac and Etodolac glucuronide. After a single dose of 14 C-Etodolac, hydroxylated metabolites accounted for less than 10% of total drug in serum. On chronic dosing, hydroxylated-Etodolac metabolite does not accumulate in the plasma of patients with normal renal function. The extent of accumulation of hydroxylated-Etodolac metabolites in patients with renal dysfunction has not been studied. The hydroxylated-Etodolac metabolites undergo further glucuronidation followed by renal excretion and partial elimination in the feces.

The mean oral clearance of Etodolac following oral dosing is 49 (± 16) mL/h/kg. Approximately 1% of an Etodolac dose is excreted unchanged in the urine with 72% of the dose excreted into urine as parent drug plus metabolite:

-hydroxylated metabolites (6-, 7-, and 8-OH)

-hydroxylated metabolite glucuronides

Although renal elimination is a significant pathway of excretion for Etodolac metabolites, no dosing adjustment in patients with mild to moderate renal dysfunction is generally necessary. The terminal half-life (t ½ ) of Etodolac is 6.4 hours (22% CV). In patients with severe renal dysfunction or undergoing hemodialysis, dosing adjustment is not generally necessary.

Fecal excretion accounted for 16% of the dose.

Geriatric

In Etodolac clinical studies, no overall differences in safety or effectiveness were observed between these patients and younger patients. In pharmacokinetic studies, age was shown not to have any effect on Etodolac half-life or protein binding, and there was no change in expected drug accumulation. Therefore no dosage adjustment is generally necessary in the elderly on the basis of pharmacokinetics (see PRECAUTIONS, Geriatric Use ).

Etodolac is eliminated primarily by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see WARNINGS, Renal Effects ).

Pediatric

Safety and effectiveness in pediatric patients below the age of 18 years have not been established.

Race

Pharmacokinetic differences due to race have not been identified. Clinical studies included patients of many races, all of whom responded in a similar fashion.

Hepatic Insufficiency

Etodolac is predominantly metabolized by the liver. In patients with compensated hepatic cirrhosis, the disposition of total and free Etodolac is not altered. Patients with acute and chronic hepatic diseases do not generally require reduced doses of Etodolac compared to patients with normal hepatic function. However, Etodolac clearance is dependent on liver function and could be reduced in patients with severe hepatic failure. Etodolac plasma protein binding did not change in patients with compensated hepatic cirrhosis given Etodolac.

Renal Insufficiency

Etodolac pharmacokinetics have been investigated in subjects with renal insufficiency. Etodolac renal clearance was unchanged in the presence of mild-to-moderate renal failure (creatinine clearance 37 to 88 mL/min). Furthermore, there were no significant differences in the disposition of total and free Etodolac in these patients. However, Etodolac should be used with caution in such patients because, as with other NSAIDs, it may further decrease renal function in some patients. In patients undergoing hemodialysis, there was a 50% greater apparent clearance of total Etodolac, due to a 50% greater unbound fraction. Free Etodolac clearance was not altered, indicating the importance of protein binding in Etodolac's disposition. Etodolac is not significantly removed from the blood in patients undergoing hemodialysis.

Clinical Trials

Analgesia

Controlled clinical trials in analgesia were single-dose, randomized, double-blind, parallel studies in three pain models, including dental extractions. The analgesic effective dose for Etodolac established in these acute pain models was 200 to 400 mg. The onset of analgesia occurred approximately 30 minutes after oral administration. Etodolac 200 mg provided efficacy comparable to that obtained with aspirin (650 mg). Etodolac 400 mg provided efficacy comparable to that obtained with acetaminophen with codeine (600 mg + 60 mg). The peak analgesic effect was between 1 to 2 hours. Duration of relief averaged 4 to 5 hours for 200 mg of Etodolac and 5 to 6 hours for 400 mg of Etodolac as measured by when approximately half of the patients required remedication.

Osteoarthritis

The use of Etodolac in managing the signs and symptoms of osteoarthritis of the hip or knee was assessed in double-blind, randomized, controlled clinical trials in 341 patients. In patients with osteoarthritis of the knee, Etodolac, in doses of 600 to 1000 mg/day, was better than placebo in two studies. The clinical trials in osteoarthritis used b. i.d. dosage regimens.

Rheumatoid Arthritis

In a 3-month study with 426 patients, Etodolac 300 mg b. i.d. was effective in management of rheumatoid arthritis and comparable in efficacy to piroxicam 20 mg/day. In a long-term study with 1,446 patients in which 60% of patients completed 6 months of therapy and 20% completed 3 years of therapy, Etodolac in a dose of 500 mg b. i.d. provided efficacy comparable to that obtained with ibuprofen 600 mg q. i.d. In clinical trials of rheumatoid arthritis patients, Etodolac has been used in combination with gold, d-penicillamine, chloroquine, corticosteroids, and methotrexate.

Indications and Usage for Etodolac

Carefully consider the potential benefits and risks of Etodolac capsules and tablets, USP, and other treatment options before deciding to use Etodolac capsules and tablets, USP. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ).

Etodolac Capsules and Tablets, USP are indicated:

For acute and long-term use in the management of signs and symptoms of the following:

Osteoarthritis

Rheumatoid arthritis

For the management of acute pain

Contraindications

Etodolac Capsules and Tablets, USP are contraindicated in patients with known hypersensitivity to Etodolac or other ingredients in Etodolac.

Etodolac Capsules and Tablets, USP should not be given to patients who have experienced asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (see WARNINGS, Anaphylactoid Reactions and PRECAUTIONS, Pre-existing Asthma ).

In the setting of coronary artery bypass graft (CABG) surgery [see Warnings ]

Warnings

CARDIOVASCULAR EFFECTS

Cardiovascular Thrombotic Events

Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.

To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.

There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as Etodolac, increases the risk of serious gastrointestinal (GI) events [see Warnings ].

Status Post Coronary Artery Bypass Graft (CABG) Surgery

Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10–14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG [see Contraindications ].

Post-MI Patients

Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up.

Avoid the use of Etodolac capsules and tablets, USP in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If Etodolac capsules and tablets, USP are used in patients with a recent MI, monitor patients for signs of cardiac ischemia.

NSAIDs, including Etodolac capsules and tablets, USP, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including Etodolac capsules and tablets, USP, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.

Heart Failure and Edema

The Coxib and traditional NSAID Trialists' Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.

Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs.

Use of Etodolac may blunt the CV effects of several therapeutic agents used to treat these medical conditions [e. g. diuretics, ACE inhibitors, or angiotensin receptor blockers (ARBs)] [see Drug Interactions ].

Avoid the use of Etodolac capsules and tablets, USP in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If Etodolac capsules and tablets, USP are used in patients with severe heart failure, monitor patients for signs of worsening heart failure.

Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation

NSAIDs, including Etodolac capsules and tablets, USP, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk. Physicians should inform patients about the signs and/or symptoms of serious GI toxicity and what steps to take if they occur.

NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease, and/or gastrointestinal bleeding. and who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients, and therefore, special care should be taken in treating this population.

To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.

Renal Effects

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greater risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.

Renal pelvic transitional epithelial hyperplasia, a spontaneous change occurring with variable frequency, was observed with increased frequency in treated male rats in a 2-year chronic study.

Caution is recommended in patients with pre-existing kidney disease.

Advanced Renal Disease

No information is available from controlled clinical studies regarding the use of Etodolac capsules and tablets, USP, in patients with advanced renal disease. Therefore, treatment with Etodolac capsules and tablets, USP is not recommended in these patients with advanced renal disease. If Etodolac capsules and tablets, USP therapy must be initiated, close monitoring of the patient's renal function is advisable.

Anaphylactoid Reactions

As with other NSAIDs, anaphylactoid reactions may occur in patients without prior exposure to Etodolac capsules and tablets, USP. Etodolac capsules and tablets, USP should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs. Fatal reactions have been reported in such patients (see CONTRAINDICATIONS and PRECAUTIONS, General, Pre-existing Asthma ). Emergency help should be sought in cases where an anaphylactoid reaction occurs.

Skin Reactions

NSAIDs, including Etodolac capsules and tablets, USP, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

Pregnancy

In late pregnancy, the third trimester, as with other NSAIDs, Etodolac capsules and tablets, USP should be avoided because it may cause premature closure of the ductus arteriosus (see PRECAUTIONS, Pregnancy, Nonteratogenic Effects ).

Precautions

General

Etodolac capsules and tablets, USP cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered solely if a decision is made to discontinue corticosteroids.

The pharmacological activity of Etodolac capsules and tablets, USP in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including Etodolac capsules and tablets, USP. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes, have been reported.

A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with Etodolac. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e. g. eosinophilia, rash, etc.), Etodolac capsules and tablets, USP should be discontinued.

Anemia is sometimes seen in patients receiving NSAIDs including Etodolac capsules and tablets, USP. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including Etodolac capsules and tablets, USP, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.

NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving Etodolac capsules and tablets, USP, who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.

Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthmas has been associated with severe bronchospasm which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, Etodolac capsules and tablets, USP should not be administered to patients with this form of aspirin sensitivity and should be used with caution in all patients with pre-existing asthma.

Information for Patients

Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.

Cardiovascular Thrombotic Events Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately [ see Warnings ].

Etodolac capsules and tablets, USP, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up (see WARNINGS, Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation ).

Etodolac capsules and tablets, USP, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms. Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible.

Heart Failure And Edema Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur [ see Warnings ] .

Patients should be informed of the warning signs and symptoms of hepatotoxicity (e. g. nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy.

Patients should be informed of the signs of an anaphylactoid reaction (e. g. difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS ).

In late pregnancy, the third trimester, as with other NSAIDs, Etodolac capsules and tablets, USP should be avoided because they may cause premature closure of the ductus arteriosus.

Laboratory Tests

Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs should have their CBC and a chemistry profile checked periodically for signs or symptoms of anemia. Appropriate measures should be taken in case such signs of anemia occur. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e. g. eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, Etodolac capsules and tablets, USP should be discontinued.

Drug Interactions

Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors (see WARNINGS ).

The concomitant administration of antacids has no apparent effect on the extent of absorption of Etodolac capsules and tablets, USP. However, antacids can decrease the peak concentration reached by 15% to 20% but have no detectable effect on the time-to-peak.

When Etodolac capsules and tablets, USP are administered with aspirin, its protein binding is reduced, although the clearance of free Etodolac is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of Etodolac and aspirin is not generally recommended because of the potential of increased adverse effects.

Cyclosporine, Digoxin, Methotrexate

Etodolac, like other NSAIDs, through effects on renal prostaglandins, may cause changes in the elimination of these drugs leading to elevated serum levels of cyclosporine, digoxin, methotrexate, and increased toxicity. Nephrotoxicity associated with cyclosporine may also be enhanced. Patients receiving these drugs who are given Etodolac, or any other NSAID, and particularly those patients with altered renal function, should be observed for the development of the specific toxicities of these drugs. NSAIDs, such as Etodolac, should not be administered prior to or concomitantly with high doses of methotrexate. NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. In general, caution should be used when NSAIDs are administered concomitantly with methotrexate.

Etodolac has no apparent pharmacokinetic interaction when administered with furosemide or hydrochlorothiazide. Nevertheless, clinical studies, as well as postmarketing observations have shown that Etodolac can reduce the natriuretic effect of furosemide and thiazides in some patients with possible loss of blood pressure control. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal insufficiency or failure (see WARNINGS, Renal Effects ), as well as to assure diuretic efficacy.

Etodolac has no apparent pharmacokinetic interaction when administered with glyburide.

NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. Careful monitoring of lithium levels is advised in the event NSAID dosage adjustments are required.

Phenylbutazone causes increase (by about 80%) in the free fraction of Etodolac. Although in vivo studies have not been done to see if Etodolac clearance is changed by coadministration of phenylbutazone, it is not recommended that they be coadministered.

Etodolac has no apparent pharmacokinetic interaction when administered with phenytoin.

The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than that of users of either drug alone. Short-term pharmacokinetic studies have demonstrated that concomitant administration of warfarin and Etodolac capsules and tablets, USP results in reduced protein binding of warfarin, but there was no change in the clearance of free warfarin. There was no significant difference in the pharmacodynamic effect of warfarin administered alone and warfarin administered with Etodolac capsules and tablets, USP as measured by prothrombin time. Thus, concomitant therapy with warfarin and Etodolac should not require dosage adjustment of either drug. However, caution should be exercised because there have been a few spontaneous reports of prolonged prothrombin times, with or without bleeding, in Etodolac-treated patients receiving concomitant warfarin therapy. Close monitoring of such patients is therefore recommended.

Drug/Laboratory Test Interactions

The urine of patients who take Etodolac can give a false-positive reaction for urinary bilirubin (urobilin) due to the presence of phenolic metabolites of Etodolac. Diagnostic dip-stick methodology, used to detect ketone bodies in urine, has resulted in false-positive findings in some patients treated with Etodolac. Generally, this phenomenon has not been associated with other clinically significant events. No dose relationship has been observed.

Etodolac treatment is associated with a small decrease in serum uric acid levels. In clinical trials, mean decreases of 1 to 2 mg/dL were observed in arthritic patients receiving Etodolac (600 to 1000 mg/day) after 4 weeks of therapy. These levels then remained stable for up to 1 year of therapy.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

No carcinogenic effect of Etodolac was observed in mice or rats receiving oral doses of 15 mg/kg/day (45 to 89 mg/m 2. respectively) or less for periods of 2 years or 18 months, respectively. Etodolac was not mutagenic in in vitro tests performed with S. typhimurium and mouse lymphoma cells as well as in an in vivo mouse micronucleus test. However, data from the in vitro human peripheral lymphocyte test showed an increase in the number of gaps (3.0 to 5.3% unstained regions in the chromatid without dislocation) among the Etodolac-treated cultures (50 to 200 μg/mL) compared to negative controls (2.0%); no other difference was noted between the controls and drug-treated groups. Etodolac showed no impairment of fertility in male and female rats up to oral doses of 16 mg/kg (94 mg/m 2 ). However, reduced implantation of fertilized eggs occurred in the 8 mg/kg group.

Pregnancy

Pregnancy Category C

In teratology studies, isolated occurrences of alterations in limb development were found and included polydactyly, oligodactyly, syndactyly, and unossified phalanges in rats and oligodactyly and synostosis of metatarsals in rabbits. These were observed at dose levels (2 to 14 mg/kg/day) close to human clinical doses. However, the frequency and the dosage group distribution of these findings in initial or repeated studies did not establish a clear drug or dose-response relationship. Animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women. Etodolac capsules and tablets, USP should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Etodolac capsules and tablets, USP should be used during pregnancy only if the potential benefits justify the potential risk to the fetus. Because of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly during the third trimester) should be avoided.

Labor and Delivery

In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. The effects of Etodolac capsules and tablets, USP on labor and delivery in pregnant women are unknown.

Nursing Mothers

Trace amounts of some NSAIDs have been reported in human milk. It is not known whether etodalac is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Etodolac capsules and tablets, USP, a decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 18 have not been established.

Geriatric Use

As with any NSAID, caution should be exercised in treating the elderly (65 years and older) and when increasing the dose (see WARNINGS ).

In Etodolac capsules and tablets, USP clinical studies, no overall differences in safety or effectiveness were observed between these patients and younger patients. In pharmacokinetic studies, age was shown not to have any effect on Etodolac half-life or protein binding, and there was no change in expected drug accumulation. Therefore, no dosage adjustment is generally necessary in the elderly on the basis of pharmacokinetics (see CLINICAL PHARMACOLOGY, Special Populations ).

Elderly patients may be more sensitive to the antiprostaglandin effects of NSAIDs (on the gastrointestinal tract and kidneys) than younger patients (see WARNINGS ). In particular, elderly or debilitated patients who receive NSAID therapy seem to tolerate gastrointestinal ulceration or bleeding less well than other individuals, and most spontaneous reports of fatal GI events are in this population.

Etodolac is eliminated primarily by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see WARNINGS, Renal Effects ).

Adverse Reactions

In patients taking Etodolac capsules and tablets, USP or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1-10% of patients are:

Gastrointestinal experiences including: abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers (gastric/duodenal), vomiting.

Other events including: abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritis, rashes, tinnitus.

Adverse-reaction information for Etodolac was derived from 2,629 arthritic patients treated with Etodolac capsules and tablets in double-blind and open-label clinical trials of 4 to 320 weeks in duration and worldwide postmarketing surveillance studies. In clinical trials, most adverse reactions were mild and transient. The discontinuation rate in controlled clinical trials, because of adverse events, was up to 10% for patients treated with Etodolac.

New patient complaints (with an incidence greater than or equal to 1%) are listed below by body system. The incidences were determined from clinical trials involving 465 patients with osteoarthritis treated with 300 to 500 mg of Etodolac b. i.d. (i. e. 600 to 1000 mg/day).

Incidence Greater Than Or Equal To 1% - Probably Causally Related

Body as a whole - Chills and fever.

Digestive system - Dyspepsia (10%), abdominal pain1. diarrhea1. flatulence1. nausea1. abdominal distension, epigastric pain, abnormal stools, constipation, gastritis, melena, vomiting.

Nervous system - Asthenia/malaise1. dizziness1. depression, nervousness, fatigue.

Skin and appendages - Pruritus, rash.

Special senses - Blurred vision, tinnitus.

Urogenital system - Dysuria, urinary frequency.

1 Drug-related patient complaints occurring in 3 to 9% of patients treated with Etodolac. Drug-related patient complaints occurring in fewer than 3%, but more than 1%, are unmarked.

Incidence Less Than 1% - Probably Causally Related

(Adverse reactions reported only in worldwide postmarketing experience, not seen in clinical trials, are considered rarer and are italicized.)

Body as a whole - Allergic reaction, anaphylactic/anaphylactoid reactions (including shock).

Cardiovascular system - Hypertension, congestive heart failure, flushing, palpitations, syncope, vasculitis (including necrotizing and allergic).

Digestive system - Thirst, dry mouth, ulcerative stomatitis, anorexia, eructation, elevated liver enzymes, cholestatic hepatitis, hepatitis, cholestatic jaundice, duodenitis, jaundice, hepatic failure, liver necrosis, peptic ulcer with or without bleeding and/or perforation, intestinal ulceration, pancreatitis.

Hemic and lymphatic system - Ecchymosis, anemia, thrombocytopenia, bleeding time increased, agranulocytosis, hemolytic anemia, aplastic anemia, leukopenia, neutropenia, pancytopenia.

Metabolic and nutritional - Edema, serum creatinine increase, hyperglycemia in previously controlled diabetic patients.

Nervous system - Insomnia, somnolence.

Respiratory system - Asthma, pulmonary infiltration with eosinophilia .

Skin and appendages - Angioedema, sweating, urticaria, exfoliative dermatitis, vesiculobullous rash, cutaneous vasculitis with purpura, Stevens-Johnson Syndrome, toxic epidermal necrolysis, leukocytoclastic vasculitis, hyperpigmentation. erythema multiforme.

Special senses - Photophobia, transient visual disturbances.

Urogenital system - Elevated BUN, renal failure, renal insufficiency, renal papillary necrosis.

Incidence Less Than 1% - Causal Relationship Unknown

(Medical events occurring under circumstances where causal relationship to Etodolac is uncertain. These reactions are listed as alerting information for physicians.)

Body as a whole - Infection, headache.

Cardiovascular system - Arrhythmias, myocardial infarction, cerebrovascular accident.

Digestive system - Esophagitis with or without stricture or cardiospasm, colitis, GI discomfort, burning sensation, blood in stools, gastralgia, upper abdominal discomfort.

Metabolic and nutritional - Change in weight.

Nervous system - Paresthesia, confusion, irritability.

Respiratory system - Bronchitis, bronchospasm, dyspnea, pharyngitis, rhinitis, sinusitis.

Skin and appendages - Alopecia, maculopapular rash, photosensitivity, skin peeling.

Special senses - Conjunctivitis, deafness, taste perversion, loss of taste.

Urogenital system - Cystitis, hematuria, leukorrhea, renal calculus, interstitial nephritis, uterine bleeding irregularities, renal impairment.

Additional Adverse Reactions Reported with NSAIDs

Body as a whole - Sepsis, death

Cardiovascular system - Tachycardia

Digestive system - Gastric ulcers, gastritis, gastrointestinal bleeding, glossitis, hematemesis

Hemic and lymphatic system - Lymphadenopathy

Nervous system - Anxiety, dream abnormalities, convulsions, coma, hallucinations, meningitis, tremors, vertigo

Respiratory system - Respiratory depression, pneumonia

Urogenital system - Oliguria/polyuria, proteinuria

Overdosage

Symptoms following acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur and coma has occurred following massive ibuprofen or mefenamic-acid overdose. Hypertension, acute renal failure, and respiratory depression may occur but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following overdose. Patients should be managed by symptomatic and supportive care following an NSAID overdose.

There are no specific antidotes. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose (5 to 10 times the usual dose). Forced diuresis, alkalinization of the urine, hemodialysis, or hemoperfusion would probably not be useful due to Etodolac's high protein binding.

Etodolac Dosage and Administration

Carefully consider the potential benefits and risks of Etodolac capsules and tablets, USP and other treatment options before deciding to use Etodolac capsules and tablets, USP. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ).

After observing the response to initial therapy with Etodolac capsules and tablets, USP, the dose and frequency should be adjusted to suit an individual patient's needs.

Dosage adjustment of Etodolac capsules and tablets, USP is generally not required in patients with mild to moderate renal impairment. Etodolac should be used with caution in such patients, because, as with other NSAIDs, it may further decrease renal function in some patients with impaired renal function (see WARNINGS, Renal Effects ).

Analgesia

The recommended total daily dose of Etodolac for acute pain is up to 1000 mg, given as 200-400 mg every 6 to 8 hours. Doses of Etodolac greater than 1000 mg/day have not been adequately evaluated in well-controlled trials.

Osteoarthritis and Rheumatoid Arthritis

The recommended starting dose of Etodolac for the management of the signs and symptoms of osteoarthritis or rheumatoid arthritis is: 300 mg b. i.d. t. i.d. or 400 mg b. i.d. or 500 mg b. i.d. A lower dose of 600 mg/day may suffice for long-term administration. Physicians should be aware that doses above 1000 mg/day have not been adequately evaluated in well-controlled clinical trials.

In chronic conditions, a therapeutic response to therapy with Etodolac is sometimes seen within one week of therapy, but most often is observed by two weeks. After a satisfactory response has been achieved, the patient's dose should be reviewed and adjusted as required.

How is Etodolac Supplied

Etodolac Capsules and Tablets, USP are available as:

Etodolac Capsules, USP

200 mg capsules (dark pink gelatin capsule, with black imprint "ETO 200 MG" on cap and body, white to off-white powder filling)

- in bottles of 100, NDC 51672-4016-1

300 mg capsules (light pink gelatin capsule, with black imprint "ETO 300 MG" on cap and body, white to off-white powder filling)

- in bottles of 100, NDC 51672-4017-1

Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature] protected from moisture .

Etodolac Tablets, USP

400 mg tablets (peach, oval shaped, film coated tablet engraved with "T88" on one side and other side plain)

- in bottles of 100, NDC 51672-4018-1

500 mg tablets (blue, oval shaped, film coated tablet engraved with "TARO" on one side and "89" engraved on the other side)

- in bottles of 100, NDC 51672-4036-1

Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature]. Store tablets in original container until ready to use. Dispense in light-resistant container.

Medication Guide for Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

What is the most important information I should know about medicines called Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?

NSAIDs can cause serious side effects, including:

Increased risk of a heart attack or stroke that can lead to death. This risk may happen early in treatment and may increase:

with increasing doses of NSAIDs

with longer use of NSAIDs

Do not take NSAIDs right before or after a heart surgery called a "coronary artery bypass graft (CABG)." Avoid taking NSAIDs after a recent heart attack, unless your healthcare provider tells you to. You may have an increased risk of another heart attack if you take NSAIDs after a recent heart attack.

Increased risk of bleeding, ulcers, and tears (perforation) of the esophagus (tube leading from the mouth to the stomach), stomach and intestines:

anytime during use

without warning symptoms

that may cause death

The risk of getting an ulcer or bleeding increases with:

past history of stomach ulcers, or stomach or intestinal bleeding with use of NSAIDs

taking medicines called "corticosteroids", "anticoagulants", "SSRIs", or "SNRIs"

increasing doses of NSAIDs

longer use of NSAIDs

smoking

drinking alcohol

older age

poor health

advanced liver disease

bleeding problems

NSAIDs should only be used:

exactly as prescribed

at the lowest dose possible for your treatment

for the shortest time needed

What are NSAIDs?

NSAIDs are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as different types of arthritis, menstrual cramps, and other types of short-term pain.

Who should not take NSAIDs?

Do not take NSAIDs:

if you have had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAIDs.

right before or after heart bypass surgery.

Before taking NSAIDs, tell your healthcare provider about all of your medical conditions, including if you:

have liver or kidney problems

have high blood pressure

have asthma

are pregnant or plan to become pregnant. Talk to your healthcare provider if you are considering taking NSAIDs during pregnancy. You should not take NSAIDs after 29 weeks of pregnancy.

are breastfeeding or plan to breast feed.

Tell your healthcare provider about all of the medicines you take, including prescription or over-the-counter medicines, vitamins or herbal supplements. NSAIDs and some other medicines can interact with each other and cause serious side effects. Do not start taking any new medicine without talking to your healthcare provider first.

What are the possible side effects of NSAIDs?

NSAIDs can cause serious side effects, including:

new or worse high blood pressure

heart failure

liver problems including liver failure

kidney problems including kidney failure

low red blood cells (anemia)

life-threatening skin reactions

life-threatening allergic reactions

Other side effects of NSAIDs include: stomach pain, constipation, diarrhea, gas, heartburn, nausea, vomiting, and dizziness.

Get emergency help right away if you get any of the following symptoms:

shortness of breath or trouble breathing

chest pain

weakness in one part or side of your body

slurred speech

swelling of the face or throat

Stop taking your NSAID and call your healthcare provider right away if you get any of the following symptoms:

nausea

more tired or weaker than usual

diarrhea

itching

your skin or eyes look yellow

indigestion or stomach pain

flu-like symptoms

vomit blood

there is blood in your bowel movement or it is black and sticky like tar

unusual weight gain

skin rash or blisters with fever

swelling of the arms, legs, hands and feet

If you take too much of your NSAID, call your healthcare provider or get medical help right away.

These are not all the possible side effects of NSAIDs. For more information, ask your healthcare provider or pharmacist about NSAIDs.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Other information about NSAIDs

Aspirin is an NSAID but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines.

Some NSAIDs are sold in lower doses without a prescription (over-the-counter). Talk to your healthcare provider before using over-the-counter NSAIDs for more than 10 days.

General information about the safe and effective use of NSAIDs

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide.

Do not use NSAIDs for a condition for which it was not prescribed. Do not give NSAIDs to other people, even if they have the same symptoms that you have. It may harm them.

If you would like more information about NSAIDs, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about NSAIDs that is written for health professionals.

Mfd. by: Taro Pharmaceutical Industries Ltd. Haifa Bay, Israel 2624761 Dist. by: Taro Pharmaceuticals U. S.A. Inc. Hawthorne, NY 10532

This Medication Guide has been approved by the U. S. Food and Drug Administration.

Revised: October 2015 89927-1015-6

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Product Overview

What are Leucine Tablets?

Leucine is an essential amino acid meaning it cannot be synthesised by the human body and therefore, must be consumed through our dietary food intake or in supplement form.

Leucine Tablets Benefits

Leucine is one of the three Branch Chain Amino Acids (BCAA’s). This is commonly found in high amounts in many animal-based foods such as lean meats, poultry and fish in varying amounts.

Who are Leucine Tablets Suitable for?

Leucine Tablets are ideal for anyone taking part in intense physical activity. These can be taken either before or after a workout.

Please note that the labelling on this product is provided in English as a minimum. French, Italian, German, Spanish, Danish, Swedish and Finnish may also be present on a product by product basis.

Nutritional Information

Consume 2 tablets, 1-2 times daily. For optimal results take 45 minutes before your workout and also post workout. One serving should be sufficient on non-training days.

Do not exceed the stated recommended daily dose. This product should not be used as a substitute for a varied, balanced diet. Keep in a cool dry place out of direct sunlight. Not suitable for vegetarians. Store out of the reach of young children.

Ingredients

L Leucine, Bulking Agents (Microcrystalline Cellulose), Anti Caking Agents (Pharmaceutical Talc, Magnesium Stearate).

Made in a facility that handles Milk, Soy, Egg, Gluten and products thereof.

Express Delivery Available

If ordered before 8pm, delivered by courier next working day. Available on orders placed before 8pm (2pm weekends and Bank Holidays) for delivery next business day. Applies to most delivery addresses within mainland UK.

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Please check the stock availability notice on your item when placing your order. This item is: In stock | Usually dispatched within 24 hours

Please remember to add postal time (2-3 working days) to obtain a complete estimate of delivery to your door.

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You will receive an email to confirm when your item has been sent.

You can also check the status of your order and individual items by accessing My Account details and following the prompts.

Please allow 10 working days from dispatch of your order before notifying us of any late deliveries.

It may be advisable to check with your neighbours to see if a parcel has been left with them, check any outhouses you might have where it may be left if it cannot fit through your letterbox and contact your local sorting office to see if the item has been returned to the depot as undelivered and awaiting collection.

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The present invention relates to the use of acetyl-leucine for the preparation of a medicament for the treatment of balance disorders.

Acetyl-leucine in racemate form and the salts of same are known for their effectiveness in the treatment of vertigo of various origins, notably Meniere's vertigo and vertigo of inflammatory (vestibular neuritis) or toxic origin.

Acetyl-leucine is marketed by Pierre Fabre Medicament in racemate form as an anti-vertigo medicament under the name Tanganil®. Clinical results relating to said medicament reported by various authors demonstrate an improvement in vertigo symptomatology in more than 95% of cases, including the disappearance of vertigo attacks.

Acetyl-leucine is also known to accelerate vestibular compensation after unilateral labyrinthectomy in the guinea pig, whereas it has no effect on normal vestibular functioning (P. P. Vidal et al. Eur. J. Neurosci. (2001), 13(4), 735-748).

Recent studies have shown that acetyl-leucine administered by oral route at a dose of 28 mg per kg per day facilitates the recovery of locomotor equilibrium in cats having undergone vestibular neurotomy (Sun Jiurong, Zhongguo Yingyong Shenlixue Zasti Bianjibu (1997), 13(3), 257-260).

Vertigo attacks are related to disequilibrium in the membrane potentials of median vestibular nuclei neurons. This disturbance of the system is expressed by neuronal hyperpolarization or depolarization. One treatment for vertigo attacks thus consists of attenuating the imbalance by returning the membrane potentials of these neurons to their resting potential.

Vestibular neurotomy is a surgical technique for the treatment of vertigo cases that are incapacitating and highly resistant to conservative therapies. The principle involves deafferentation of the peripheral vestibular system by sectioning the vestibular nerve while maintaining the integrity of the cochlear and facial nerves.

Following a unilateral vestibular neurotomy, patients often experience compensation which within a week relieves the postural or oculomotor static deficits observed during the acute stage. On the other hand, dynamic deficits also recover but never fully (C. De Waele, review ref. AN 19824, 33rd Symposium of the International Society of Otoneurology, Geneva, May 14-15, 1999).

However, such compensation is observed only when neurotomy is performed at an early stage of a tumor's development; when the tumor is diagnosed late, the transmission of vestibular information has long stopped by the time neurotomy is performed.

Surprisingly, however, the inventors have shown that acetyl-leucine, which has no effect in a patient population exhibiting no vestibular functioning before neurotomy, accelerates the compensation observed in a population of patients exhibiting residual vestibular functioning.

Consequently, the present invention relates to the use of acetyl-leucine for the preparation of a medicament intended to treat acute deafferentiation syndromes in patients whose vestibular deficit is less than 88%, advantageously less than 75%, to caloric tests.

In one advantageous embodiment of the invention, said syndromes are intermittent acute deafferentiation syndromes resulting from an imbalance in the predominantly unilateral transmission of sensory impulses in the auditory nerve.

In another advantageous embodiment of the invention, the syndromes are intermittent acute deafferentiation syndromes resulting from any event causing a unilateral loss of sensory impulse transmission in the auditory nerve, accompanied by vertigo.

Acute deafferentiation syndromes may result from surgical unilateral neurotomy. Intermittent acute deafferentiation syndromes may result in particular from unilateral neurotomy selected from the group comprising traumatic unilateral neurotomy, unilateral neurotomy related to acute ischemia of the auditory nerve, unilateral neurotomy due to extrinsic compression, unilateral neurotomy due to structural edemas and unilateral neurotomy resulting from endogenous viral attacks.

Vestibular deficit is evaluated by caloric testing which provides information about the vestibular reflex, i. e. the capacity of the vestibule to respond to stimulation (irrigation of the external auditory meatus by warm water followed by cold).

In the sense of the present invention, acetyl-leucine means (DL)-acetyl-leucine, (L)-acetyl-leucine, (D)-acetyl-leucine and pharmaceutically acceptable salts of same.

In the context of the present invention, acetyl-leucine may be administered by oral route at a dose between 500 mg and 10 g per day, advantageously between 1 g and 2 g per day.

The inventive acetyl-leucine may also be administered by intravenous route at a dose between 500 mg and 1 g per day, without interruption.

The inventive acetyl-leucine may be provided in any dosage form suitable for oral administration, notably in the form of granules, powders, hard capsules, soft capsules, gelatin capsules, lyophilized tablets, syrups, emulsions, suspensions or solutions, or in any form suitable for intravenous administration.

The following examples illustrate the invention.

EXAMPLE 1 Effect of Tanganil® on the Ability to Maintain a Standing Position Eight Days Following Neurotomy

1.1.1. Subject Selection and Treatment

Sixty patients with an indication for acoustic neurinoma excision or for vestibular neurotomy were included and randomized. Patients were treated for 60 days either with Tanganil® (six injections of two 500 mg vials by IV route, with an interval of 12 hours between injections, the first taking place one hour after the surgery, followed by an oral treatment at a dose of two 500 mg tablets, one in the morning and one in the evening) or with a placebo.

1.1.2. Measurement of Vestibular Deficit

Vestibular deficit was measured according to the methods described in Vertigo and the practitioner [Les vertiges et le praticien] by P. Tran Ba Huy and C. De Waele (Coll Pathologie Sciences Formation [in French], Ed. John Libbey Eurotext, Paris, 1996) and in Vertigo [Les vertiges] by G. Rancurel, O. Sterkers, E. Vitte, foreword by G. Freyss (Ed. Med. Specia. [in French], 1989).

Vestibular reflex was tested at day zero (D 0 ) before neurotomy by caloric testing to objectivize vestibular hyporeflexia or areflexia. This test consists of successively irrigating with warm water then cold the right external auditory meatus then the left, causing in the semicircular canal an endolymph current which moves the ampullary crest. Caloric response is expressed by the appearance of a nystagmus that beats toward the side of the stimulated ear when warm water is applied and toward the opposite side when cold water is applied. The nystagmic response was recorded by video nystagmography and its frequency calculated, i. e. the number of nystagmic beats occurring between the 60th and 90th seconds following the initiation of stimulation. This number quantifies the vestibular response.

The difference in responses between one ear and the other expresses so-called hypovalence, i. e. the difference between the warm and cold responses on the left side and the warm and cold responses on the right side, divided by the total number of responses. In normal subjects, hypovalence is less than 15%. Hypovalence is the main sign of damage to the peripheral vestibular apparatus.

Results from 56 subjects were analyzed: 25 patients had a vestibular deficit greater than 75% and 31 patients had a vestibular deficit less than or equal to 75%.

1.1.3. Measurement of Standing Position at D 8

The principle criterion was “able to maintain a standing position at D 8 ” (Yes/No)

The principle analysis (of 49 patients with no major deviation regarding evaluation of the principle criterion at D 8 ) showed no statistically significant difference between Tanganil® (13 of 22 patients, or 59.1%, able to maintain a standing position at D 8 ) and the placebo (12 of 27 patients, or 44.4%, able to maintain a standing position at D 8 ).

Similarly, among the 25 patients whose vestibular deficit was greater than 75%, no significant difference between the two treatment groups was demonstrated.

On the other hand, among 31 patients whose vestibular deficit was less than or equal to 75%, a statistically significant difference was observed between the two treatment groups in favor of Tanganil® (? 2 =0.048, less than 5%). In this subgroup, 12 of 16 patients given Tanganil® (75%) were able to maintain a standing position compared to 6 of 15 patients given placebo (40%).

EXAMPLE 2 Effect of Tanganil® on Various Symptoms Evaluated Using Visual Analog Scales (VAS)

Subjective signs (vertigo and vomiting) were rated by patients on a 10 cm VAS from “absent” to “highly incapacitating”.

In the subgroup of patients whose vestibular deficit was less than or equal to 75%, a statistically significant difference at D 8 between the group treated with Tanganil® and the group treated with placebo was observed (Wilcoxon test, p=0.037, less than 5%).

An average decrease of ?23.5 mm on the vertigo VAS among patients treated with Tanganil® was observed compared to an average increase of +4.7 mm for placebo.

On the other hand, no significant difference was observed in the subgroup of patients whose vestibular deficit was greater than 75% (Wilcoxon test, p=0.154, greater than 5%).

2.2.2. Effects on Vomiting

No significant difference was demonstrated in the subgroup of patients whose vestibular deficit was greater than 75%. On the other hand, for the subgroup of patients whose vestibular deficit was less than or equal to 75%, a significant difference between the two groups appeared, namely a reduction in vomiting severity for patients given Tanganil®.

EXAMPLE 3 Effect of Tanganil® on Balance, Evaluated by Static Posturography

Postural tonus is expressed by the human body's overall bearing, setting the various joints in specific positions interdependently, primarily in response to gravitational forces. Vestibular afferents, extrinsic ocular musculature, proprioceptive afferents and visual afferents play a major role in maintaining a standing position. Subjects are never perfectly motionless when standing at rest: they are constantly oscillating.

Static posturography (not performed at D 8 if the subject could not remain standing) was carried out in a standing position under four conditions (eyes open or closed, with or without foam carpeting). With foam carpeting and/or eyes closed, patients are placed under conditions which minimize the role of visual and proprioceptive information.

Shifts in a subject's center of gravity during a given time period are recorded in a statokinesigram. This plot makes it possible to study oscillation amplitudes and surface areas. “Anteroposterior” oscillations can be separated from “right-left” oscillations.

In the subgroup of patients whose vestibular deficit was greater than 75% at D 8 . regardless of which protocol was used (eyes open or closed and/or with or without foam), either no significant difference was observed between Tanganil® and the placebo or a significant difference was observed between the two groups in favor of the placebo.

On the other hand, regardless of experimental conditions a significant difference between treatment groups in favor of Tanganil® was demonstrated only in the subgroup of patients whose vestibular deficit was less than or equal to 75%.

Moreover, regardless of the experimental conditions under which it was demonstrated, a significant reduction between the treatment groups in favor of Tanganil® was demonstrated only on “right-left” postural oscillations.

With regard to right/left posturography, no significant difference was observed between Tanganil® and placebo at D 8 for the “without foam, eyes open” test. On the other hand, at D 8 . in the group of patients whose vestibular deficit was less than or equal to 75%, there was a significant difference (p=0.034) between the two treatments in favor of Tanganil® (+7.9 mm vs. +19.9 mm) in the “with foam, eyes open” test.

In this same group of patients, there was also a significant difference between the two treatments in favor of Tanganil® in the “without foam, eyes closed” test (+2.8 mm vs. +10.9 mm; p=0.028) and in the “with foam, eyes closed” test (+5.4 mm vs. +13.5 mm; p=0.016).

The results thus obtained demonstrate the positive action of Tanganil® on the reduction of vestibular asymmetry among patients with a vestibular deficit less than or equal to 75% and the effectiveness of this product on acute deafferentiation syndrome and compensation among neurotomy patients.

EXAMPLE 4 In Vitro Effect of (D) and (L) Enantiomers of Acetyl-Leucine on Median Vestibular Neurons in the Mouse

An electrophysiological study was conducted on mouse median vestibular neurons (MVN) in which the membrane potential was artificially maintained at various resting values. In this study, the effects of the D and L enantiomers of acetyl-leucine (1 mM) were tested on the membrane properties of neurons in “current clamp” mode at various membrane potential values: normal membrane potential (approximately ?45 mV), potential maintained at a hyperpolarized level of approximately ?70 mV or potential maintained at a depolarized level of approximately ?35 mV.

4.2.1. Effect of D and L Enantiomers of Acetyl-Leucine on Neurons Spontaneously Active at the Resting Potential

Leucine

In Progress

This page on Leucine is currently marked as in-progress . We are still compiling research.

Leucine is one of the three Branched Chain Amino Acids and sometimes referred to as the 'main' amino acid due to the most popular benefit of BCAAs (muscle building) being mostly due to leucine. Leucine is an activator of the protein known as mTOR, which then induces muscle protein synthesis via S6K; the other two BCAAs may also activate mTOR, but are much weaker than leucine in doing so (and as such, 5g of leucine will be more effective than 5g mixed BCAAs). The leucine metabolite, HMB. is also weaker than leucine at inducing muscle protein synthesis despite being more effective at preserving lean mass from breakdown.

Leucine is a tad different from the other two BCAAs Isoleucine and Valine as leucine seems to have a fair bit of testing on the amino acid in isolation rather than in a BCAA mixture, whereas the other two BCAAs are not as well studied.

The studies assessing leucine mostly look at muscle protein synthesis when additional leucine is added to the diet or to a test meal, and it appears that leucine is able to reliably increase muscle protein synthesis after test meals. Whether this results in more lean mass over a period of time is somewhat less reliable though, and leucine appears to be more effective at promoting gains in muscle in people with lower dietary protein intake and in the elderly (who tend to have impaired muscle protein synthesis in response to the diet).

The interactions of leucine on glucose are not clear, to be honest. Leucine possesses both blood sugar reducing properties (can release insulin from the pancreas, can directly stimulate glucose uptake into a cell without insulin) but also the opposite (via stimulating S6K, it can inhibit insulin-stimulated glucose uptake). In a cell culture, leucine stimulates glucose uptake for up to 45 minutes and then hinders itself while in living systems acute doses of leucine do not appear to do anything remarkable (some limited evidence that leucine can be rehabilitative in diabetes, but this is preliminary). Isoleucine is a more potent hypoglycemic agent, but to less inhibition of its own actions.

Confused about supplements?

Things To Know

Also Known As

1 Sources and Structure

1.1. Sources

Leucine (also known as 2-Amino-4-methylpentanoic acid ) is an essential amino acid of the Branched Chain Amino Acids class (alongside Isoleucine and Valine ). Of the three amino acids, leucine stands out for being the most potent activator of a protein known as mTOR (its activation is able to positively influence muscle protein synthesis) and also being an exclusively ketogenic amino acid [1] [2] (producing ketone bodies after catabolism) whereas valine is glucogenic (produced glucose) and isoleucine is both.

Leucine is one of the branched chain amino acids, sometimes referred to as the main BCAA. It is the most potent inducer of muscle protein synthesis on a molecular level, and is ketogenic (produced ketones when metabolized)

1.2. Metabolism

Leucine is reversibly metabolized in the body first by the branched-chain aminotransferase enzyme (BCAT) into the intermediate known as α-Ketoisocaproic acid (KIC). KIC can be metabolized into a few intermediates, either β-hydroxyisovalerate (via the mitochondrial KIC dioxygenase enzyme [3] ), into isovaleryl-CoA (via branched-chain α-keto acid dehydrogenase (BCKDH) [4] ) or into HMB (via the cytosolic KIC dioxygenase enzyme [3] ); the last route of metabolism into HMB is approximately 5% of ingested leucine [5] and the only source of HMB in the body. [5]

The first route that converts α-Ketoisocaproic acid (KIC) into β-hydroxyisovalerate can also convert KIC into the metabolite known as α-hydroxycaproic acid (Leucic Acid or HICA).

Leucine is metabolized into one of several metabolites which may contribute to the effects of leucine. Of these, two of them are standalone supplements (HMB and HICA)

2 Pharmacology

2.1. Mechanism of action

The primary mechanism of action from leucine is activation of Target of Rapamycin (TOR) which is referred to as mTOR in mammals (specifically, leucine activates mTORc1 which is one of two subsets of the complex [6] ).

The first complex (mTORc1) is a complexation of a few proteins; TOR itself alongside the r egulatory a ssociated p rotein of TOR (Raptor), G-protien β-subunit like protein (GβL), and proline-rich PKB/Akt substrate of 40kDa (PRAS40). [7] [8] This complex is activated by leucine supplementation, whereas the other complex (containing another regulatory protein of TOR known as Rictor and its own regulatory protein known as Proctor, GβL again, and a protein known as mSin1) is not activated by leucine.

TOR, or mammalian TOR (mTOR) is a protein complex that serves a pivotal role in regulating cellular signalling. Leucine is able to activate one of the two complexes it makes up, known as mTORc1 (c1 standing for 'complex one'). When mTOR is mentioned in this article, it is shorthand for mTORc1 unless otherwise specified

Although signalling via the insulin receptor is able to stimulate mTOR (via class 1 PI3K and Akt/PKB, which activate Rheb and mTOR [8] ) mTOR from leucine appears to due to a protein officially known as human vacuolar protein sorting 34 (hVPS34) [9] but sometimes colloquiolly referred to as PI3K class 3 [10]

hVPS34 depletion is known to blunt leucine-induced mTOR activation [9] while not hindering insulin-induced Akt activation. [9] Incubation of a cell with leucine actiates mTOR without activating Akt [11] [12] and this effect is very similar to a general increase in intracellular calcium; [13] [14] interestingly, leucine seems to induce mTOR activity via increasing intracellular calcium, as the increase in calcium and the binding of calmodulin (a protein involved in calcium homeostasis) to hVPS34 are vital to leucine-induced mTOR activation. [15] [16]

There is a protein known as SHP-2 (a tyrosine phosphatase) which is critical to muscle protein synthesis [17] and is known to limit muscle growth under periods of nutrient deprivation, [18] and it appears to signal to S6K1 via mobilizing intracellular calcium at a point upstream of upstream of phospholipase C β4 and seems to work via Rheb protein stimulation of mTOR, [16] Rheb proteins are known to be positive modulators of mTOR function inherently. [19]

Leucine and/or its metabolites appear to increase intracellular calcium, similar to muscle contractions, and the increase in calcium will activate proteins such as mTOR which then induce muscle protein synthesis. Unlike muscle contraction, however, leucine likely does this in all cells rather than localized to skeletal muscle

In other words: SHP-2 (currently the furthest far back in the chain) -> calcium mobilization -> hVPS34 binding to calmodulin -> mTORc1 activation (possibly via Rheb) -> S6K1 activation -> muscle protein synthesis

2.2. Hyperaminoacidemia

Hyper(aminoacid)emia is a term used to refer to an excess (hyper-) of amino acids in the blood (-emia), and similar to that hyperleucinemia refers to an excess of leucine in particular.

In older men, leucine has been found to increase muscle protein synthesis independent of hyperaminoacidemia suggesting it itself is an independent predictor of muscle protein synthesis. [20]

3 Longevity

3.1. Sirtuins

Sirtuin proteins (SIRT being an acronym for Silent Information Regulator Transcript ) are NAD + dependent enzymes that are sensitive to a cellular NAD + /NADH ratio and thus energy status of a cell. [21] Of these, SIRT1 is a histone deacetylase that can modify signalling of the nuclear proteins p53, NF-κB and FOXO [22] [23] and can induce the mitochondrial biogenesis factor PGC-1α. [24] Activation of SIRT1 (the molecule most commonly said to do this is Resveratrol ) is thought to be a pro-longevity mechanism.

Leucine is thought to underlie the health benefits of dairy proteins on lifespan [25] [26] which have independently been shown to promote health and reduce the risk of premature death in rats. [27] Serum taken from patients consuming a dairy-rich diet has been shown in vitro to stimulte SIRT1 activity by 13% (adipose) and 43% (muscle tissue), suggesting biological plausibility. [25]

Both leucine metabolites (α-Ketoisocaproic acid and HMB ) are activators of SIRT1 in the range of 30-100%, which is a comparable potency to resveratrol (2-10μM) but requires a higher concentration (0.5mM). [25] Mitochondrial biogenesis has been noted with leucine incubation in both fat and muscle cells, and abolishing SIRT1 attenuates (but does not eliminate) leucine-induced mitochondrial biogenesis. [28]

Leucine metabolites are able to stimulate SIRT1 activity, which is a mechanism thought to underlie mitochondrial biogenesis. It is actually moderately potent at doing so

4 Interactions with Glucose Metabolism

4.1. Glucose Uptake

Leucine has potential to promote insulin-induced activation of Akt, but it requires PI3K to be inhibited or suppressed first (and then leucine preserves insulin-induced Akt activation). [29] Due to leucine also stimulating insulin secretion from the pancreas (insulin then activates PI3K) this is likely not practically relevant.

Otherwise, in conditions where insulin is not present 2mM leucine and (to a lesser degree) its metabolite α-ketoisocaproate appear to promote glucose uptake via PI3K/aPKC (atypical PKC [30] ) and indepedent of mTOR (blocking mTOR does not alter the effects). [31] This study noted stimulation only at 2-2.5mM for 15-45 minutes (resistance developed at 60 minutes) and was comparable in potency to physiological concentrations of basal insulin but underperformed (50% as potent) as 100nM insulin. [31] This mechanism of action is similar to Isoleucine and appears to be of somewhat similar potency.

However, leucine is also able to hinder cellular glucose uptake [32] [33] [34] which is thought to either be related to activation of mTOR signalling which naturally suppresses AMPK signalling [35] (AMPK signalling being one that mediates glucose uptake during periods of low cellular energy and exercise [36] [37] ) in combination with mTOR signalling acting on S6K; signalling via mTOR/S6K will cause degradation of IRS-1 [38] (the first protein that carries the 'signal' of insulin-induced effects) via activating proteasomal degradation of IRS-1 or simply directly binding to IRS-1, [39] this forms a negative feedback control loop of insulin signalling. [40] Inhibiting the negative effects on IRS-1 promotes leucine-induced glucose uptake [41] and this negative feedback explains why glucose is taken up for 45-60 minutes and then suddenly inhibited. [31] Since isoleucine is less potent at activating mTOR and thus this negative feedback pathway, isoleucine but not leucine leads to appreciable glucose uptake in muscle cells.

Leucine appears to initially promote glucose uptake into muscle cells for about 45 minutes, and then cuts itself off which reduces overall effects somewhat. The 'cut off' is a negative feedback that normally occurs after mTOR activation. Isoleucine is better than leucine at promoting glucose uptake due to less activation of mTOR

4.2. Insulin Secretion

Leucine, via its metabolite KIC, is able to induce insulin secretion from the pancreas and this insulin release is suppressed by both other BCAAs and two similar branched amino acids (norvaline and norleucine). [42] The potency at 10mM is approximately 73% that of glucose. [42]

In general, leucine is either additive or synergistic with glucose in inducing insulin secretion (for example, a 170% and 240% increase seen with leucine and glucose respectively is increased to 450% with the combination [43] ). Despite leucine and Yohimbine being of comparable potencies, they are not additive due to having overlapping mechanisms. [43]

Leucine is known to stimulate insulin secretion from the pancreas, and appears to be the most potent BCAA at doing this. On a equimolar basis (same concentration of the molecule within a cell), leucine is approximately as potent as yohimbine but about two-thirds as potent as glucose itself

Leucine is a positive allosteric regulator of glutamate dehydrogenase (GDH), [44] [45] an enzyme that can convert some amino acids into α-ketoglutarate. This conversion increases cellular ATP concentrations (relative to ADP), and the increase in ATP levels causes an increase in insulin secretion by mechanisms that are independent of mTOR activation. [46] [47]

The metabolite KIC is able to both inhibit K ATP channels [48] and trigger calcium oscillations [49] [50] in pancreatic β-cells. The calcium release can further act upon mTOR (standard target of leucine) [15] and activation of mTOR can suppress the expression of α2A receptors. [43] Since α2A receptors are suppressors of insulin release when activated [51] and overexpression induced diabetes, [52] less expression of these receptors causes a relative increase in insulin secretion. This pathway is likely the more important one from a practical standpoint, since the mTOR antagonist rapamycin is able to abolish leucine-induced insulin secretion [43] and suppress insulin secretion by itself. [53] [54]

Leucine works via two pathways to stimulate insulin secretion from pancreatic beta-cells, but the major pathway appears to be due to reducing the influence of a negative regulator (α2A receptors). Reducing a negative regulator's influence causes a refractory increase in activity

5 Skeletal Muscle and Physical Performance

5.1. Protein Synthesis

Leucine's primary mechanism of action is stimulating the activity of mTOR [55] [56] which then stimulates the activity of p70S6K via PDK1 [57] and p70S6K then positively controls muscle protein synthesis. [12] Furthermore, leucine is able to induce activity of the eukaryotic initiation factor (eIF, specifically eIF4E) and suppresses its inhibitory binding protein (4E-BP1) which enhances protein translation [58] [59] and has been confirmed following oral intake of leucine. [60] Modulation of eIF in this manner enhances muscle protein synthesis induced by p70S6K, and mTOR activation is a common anabolic pathway that is also tied into exercise (not activated acutely, but after a 1-2 hour time delay), [61] [62] insulin, [63] and a caloric excess. [64]

Similar to the other Branched Chain Amino Acids and different than insulin, leucine does not stimulate Akt/PKB activity (which is between the insulin receptor and mTOR, Akt and Protein Kinase B/PKB are interchangeable terms). [11] [12] Akt is able to enhance eIF2B which also positively promotes muscle protein synthesis induced by p70S6K [65] [66] and as such the lack of activation of Akt by leucine is theoretically less potent than if Akt signalling was also promoted like insulin.

mTOR activation from leucine has been confirmed in the tissue of humans following oral supplementation [67] [68] as well as p70S6K activation. [11] Akt activation has been investigated, and there has been a failure to find any alteration in activity in human muscle [11] which suggests that the release of insulin from the pancreas induced by leucine (noted to occur in humans [69] and insulin activates Akt) may not be relevant.

Leucine is able to stimulate mTOR activity and its subsequent protein synthesis signalling. Although Akt/PKB positively influences mTOR activity (so when Akt is activated, it activates mTOR) leucine appears to work via a different pathway and activate mTOR without affecting Akt. Regardless, anything that activates mTOR will then activate p70S6K and then promote muscle protein synthesis

This anabolic effect of leucine appears to favor skeletal muscle more than hepatic (liver) tissue [70] and appears to be augmented by physical exercise (muscle contractions) [71] with some studies suggesting preloading leucine to a workout is more effective than other times (in acutely increasing protein synthesis). [72] [73]

Leucine appears to be the most potent of all amino acids in stimulating muscle protein synthesis. [74]

5.2. Atrophy/Catabolism

Leucine is known to promote muscle protein synthesis at low concentrations in vitro while requiring higher concentrations to attenuate atrophy, despite synthesis rates plateuing. [75]

This muscle preserving effect has been noted in disease states characterized by muscular wasting such as cancer [76] as well as sepsis, burns, and trauma. [77] In these scenarios the benefits appear to be dose-dependent.

5.3. Hyperaminoacidemia

Hyper(aminoacid)emia is a term used to refer to an excess (hyper-) of amino acids in the blood (-emia), and similar to that hyperleucinemia refers to an excess of leucine in particular.

In older men, leucine has been found to increase muscle protein synthesis independent of hyperaminoacidemia. [20]

5.4. Sarcopenia

Sarcopenia is characterized by a decrease in skeletal muscle mass protein content and an increase in skeletal muscle fat content that occurs with aging. One of the reasons as to why sarcopenia may occur is due to a decrease in the metabolic response to L-Leucine's muscle preserving effects that occurs with cellular aging [79]. This effect can be negated in part by the addition of L-Leucine to protein containing foods. [80] [81] [82]

6 Nutrient-Nutrient Interactions

6.1. Carbohydrate

When the insulin receptor is activated, it can activate mTOR vicariously through Akt. [83] While Akt positively influences protein synthesis induced by S6K1 (which is activated when mTOR is activated [67] [68] ), leucine supplementation does not appear to directly activate Akt like insulin does in vitro . [11] [12] Leucine infusions in humans have been noted to not activate Akt significantly in skeletal muscle [11] which suggests that the insulin secretion induced by leucine [69] is insufficient to stimulate Akt.

Leucine has been found to work synergistically with ingested glucose in reducing blood glucose secondary to releasing more pancreatic insulin secretion. [84] [43] Interestingly, leucine is not additive with Yohimbine in inducing insulin secretion due to overlapping mechanisms. [43]

Leucine appears to be synergistic with dietary carbohydrate in promoting insulin secretion from the pancreas, and appears to be synergistic with insulin in promoting muscle protein synthesis

6.2. Resveratrol

Resveratrol is a wine phenolic that is known to interact with sirtuin proteins (mostly SIRT1) which is similar to leucine; the metabolites of KIC and HMB at 0.5mM are able to induce SIRT1 to 30-100% of baseline which is a comparable potency to 2-10μM resveratrol [25] although the combination of leucine (0.5mM) or HMB (0.5μM) and resveratrol (200nM) is able to synergistically induce SIRT1 and SIRT3 activity in both adipocytes and skeletal muscle cells. [85] KIC appears to be a more potent stimulator than HMB, [25] and synergism appears to be greater with leucine than with HMB (possibly indicative of KIC metabolism). [85]

When rats are fed the combination of leucine (24g/kg, up to 200% of the control diet) or HMB (2 or 10g/kg) with resveratrol (12.5 or 225mg/kg) and then sacrificed in a fasted state, the reductions in fat mass and body weight appear to also be synergistic. [85]

It has been noted that incubation of resveratrol with leucine or HMB actually increases AMPK activity (42-55%, respectively) and promoted a modest (18%) increase in fat oxidation despite incubation with 5mM glucose. [85]

Resveratrol and leucine both appear to positively influence mitochondrial biogenesis via SIRT1 activation, and they both appear synergistic in doing so when incubated or ingested together

6.3. Citrulline

Citrulline appears to restore muscle protein synthesis rates [86] [87] and muscular function [88] during aging and malnourishment in rats, and this appears to be mediated via the mTORc1 pathway (abolished by the mTORc1 inhibitor known as rapamycin). [89] [90]

For human studies, supplementation of 0.18g/kg citrulline for a week has failed to significantly modify leucine oxidation rates or whole body protein synthesis [91] but elsewhere at the same dose has been noted to improve nitrogen balance in humans in the fed state. [92] The reason for this discrepancy is unknown.

There is not too much evidence looking at the direct activation of citrulline on mTOR, but it appears to weakly induce proteins after mTOR (including 4E-BP1) to a degree lesser than leucine. [86] It is plausible that citrulline augments mTOR signalling since its benefits are mTOR dependent, in which case it should be synergistic with leucine; this has not been directly investigated.

Citrulline may positively mediate leucine's signalling through mTOR, which theoretically suggests that they are synergistic. The application of the combination towards weight lifters has not yet been investigated, so the synergism is currently just a hypothesis rather than a demonstrated fact

7 Safety and Toxicity

7.1. General

In a small study in 5 healthy men given graded leucine intake up to 1,250mg/kg (25-fold the estimated average requirement) noted that oral doses of 500-1,250 caused increases in serum ammonia and due to this the upper limited was said to be established at 500mg/kg (for a 150lb human, 34g). [93]

Scientific Support & Reference Citations

References

(Common misspellings for Leucine include loocine, lucine, leucin)

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Candiphen

CANDIPHEN contiene un agente antimicótico de amplio espectro, utilizado en el tratamiento de infecciones dérmicas causadas por una variedad de agentes patógenos. Está indicado en el tratamiento de micosis de la piel debidas a dermatófitos o levaduras, como dermatofitosis, Tinea pedis . Tinea cru­ris, Tinea corporis . candidiasis tópica y Tinea versicolor . También es activo en algunas infecciones cutáneas no debidas a hongos como eritrasma, una infección crónica bacteriana de los pliegues mayores de la piel causada por Corynebacterium minutissimum .

FARMACOCIN?TICA Y FARMACODINAMIA

El clotrimazol se absorbe de 3 a 10% después de una aplicación por vía vaginal y 0.5% de la dosis por vía ­tópica, se metaboliza rápidamente en el hígado y se excreta una pequeña porción por vía biliar, únicamente 1% del medicamento es activo por su metabolito activo. Es el 2-clorofenil-4-hidroxifenil-fenilmetano y se excreta por la orina.

Los estudios clínicos demuestran que el clotrimazol se absorbe poco por la piel (hasta 0.5%). Sin embargo, cuando se administra por vía oral, se absorbe rápida y casi completamente, y se distribuye en todo el organismo en cuestión de horas. Las mayores concentraciones se encuentran en hígado, tejido adiposo y piel. Aproximadamente 25% del fármaco se excreta en orina y el resto se excreta en heces durante 6 días.

Bajo condicio nes de prueba, las concentra ciones inhibito­rias mínimas se encuentran en niv eles de 0.0642-4 mg/l. El tipo de acción es principalmente fungistático, aunque a concentraciones superiores a la concentración mí­nima inhibitoria tiene actividad fungicida. Su modo de acción es alterando las propiedades de permeabilidad de la membrana micótica y de las levaduras. También inhibe la incorporación de acetato de ergosterol, alterando la integridad y función de la membrana mi­cótica.

Antes de aplicar CANDIPHEN lave el área afectada con agua y jabón, y seque bien.

Periodos habituales de tratamiento:

Dermatomicosis y eritrasma: De 2 a 4 semanas.

Pitiriasis versicolor: De 1 a 3 semanas.

Modo de aplicación: Aplicar una capa delgada de CANDIPHEN 2 a 3 veces al día, con un ligero masaje.

Una vez que hayan desaparecido los síntomas debe continuarse el tratamiento por unos 15 días más.

Si persisten los síntomas consulte a su médico.

MANIFESTACIONES Y MANEJO DE LA SOBREDOSIFICACI?N O INGESTA ACCIDENTAL

No se han reportado hasta la fecha.

Venta al público y exportación: Caja con tubo con 10, 20 y 30 g.

RECOMENDACIONES SOBRE ALMACENAMIENTO

Consérvese a temperatura ambiente a no más de 30°C.

LEYENDAS DE PROTECCI?N

No se deje al alcance de los niños. En niños menores de 12 años consulte a su médico. Si persisten las molestias consulte a su médico. Literatura exclusiva para médicos.

Hecho en México por:

LABORATORIOS QUIMICA SON´S, S. A. de C. V.

Reg. Núm. 187M98, SSA VI

Do-spertin, do-spertin

Official website of Sporting Clube de Portugal

Resumo Historico

Fundacao

Nos dias da fundacao, em 1906, Jose Alvalade profetizou o conhecido desejo de transformar o Sporting num ‘grande clube, tao grande como os maiores da Europa’. Hoje, passado um seculo, e extraordinario registar a confianca manifestada desde logo por Jose Alvalade nos principios, nos valores, na vocacao ganhadora e no ambicioso espirito desportivo manifestado pelos fundadores. Ousando desbravar caminhos muito mal conhecidos quando o desporto, em Portugal, era ainda uma actividade incipiente, com caracteristicas muito elitistas, os primeiros Sportinguistas conseguiram fixar bem fundo as raizes de uma colectividade poderosissima projectada ao nivel mundial, como e hoje o Sporting. Eis alguns numeros de registo: milhares de titulos conquistados, mais de tres milhoes de simpatizantes em todos os continentes e centenas de Nucleos, Filiais e Delegacoes.

'Vou pedir dinheiro ao meu avo e ele me dara dinheiro para fundar um outro clube', prometeu Jose Alvalade no momento em que ele, os irmaos Gavazzo e uma vintena de seguidores (todos amantes do desporto) abandonaram o Campo Grande Foot-Ball Club por discordarem da vertente mais social que o clube estava a seguir.

Reconhecido oficialmente o Sporting Clube de Portugal, em Maio de 1906, Jose Alvalade formulou o celebre voto: 'Queremos que o Sporting seja um grande clube, tao grande como os maiores da Europa'. A sua ambicao representou sempre, ao longo desta historia centenaria, uma meta permanente no horizonte de todos os atletas, equipas e adeptos Sportinguistas!

Jose Alvalade fez historia ao fundar um clube verdadeiramente ecletico numa altura em que a cultura desportiva em Portugal era ainda muito incipiente. Este jovem fundador (com apenas 21 anos), foi o 3? Presidente da historia do Sporting Clube de Portugal, integrou numerosas direccoes, mas foi sobretudo um extraordinario promotor de instalacoes desportivas, factor determinante para o rapido crescimento e primeiros sucessos desportivos do emblema leonino. Em sua homenagem, e porque os Estatutos do Clube assim o estabelecem, o principal recinto desportivo tem o seu nome.

Visite o Museu Mundo Sporting e conheca toda a nossa riquissima historia.

O dia 3 de Fevereiro de 1907 foi um dos dias mais importantes da historia do Sporting Clube de Portugal, pois foi quando os leoes realizaram o seu primeiro jogo de futebol, em terceiras categorias, frente ao Football Club Cruz Negra, integrado num torneio organizado pelo CIF. Algum tempo depois, os leoes conquistaram o seu primeiro trofeu de futebol, diante do Sport Club Estefania, poucos meses antes de se estrear no Campeonato de Lisboa.

E, entao, nessa prova que Sporting e o Grupo Sport Lisboa (que no ano seguinte viria a designar-se Sport Lisboa e Benfica) se encontraram pela primeira vez. A 1 de Dezembro de 1907, no Campo da Quinta Nova em Carcavelos, os leoes venceram a partida por 2-1 com golos leoninos de Candido Rodrigues e autogolo de Cosme Damiao. No final do Campeonato de Lisboa (apenas com 10 jornadas), os leoes ocuparam o segundo lugar, somente atras do Carcavelos, a melhor equipa nacional da epoca com muitos jogadores ingleses.

Ainda em 1907, a Casa Anjos de Lisboa, apresentou o primeiro emblema do Clube em forma circular com um leao rampante sobre as iniciais ‘SCP’, com fundo verde que teve origem em conversas tidas entre Jose Alvalade, os primos Jose Roquette, Antonio Rebelo de Andrade e D. Fernando de Castelo Branco (Pombeiro).

Visite o Museu Mundo Sporting e conheca toda a nossa riquissima historia.

Por ideia de Eduardo Francisco Quintela de Mendonca, o Sporting Clube de Portugal estreou as camisolas bipartidas (verde de um lado e branco do outro) com calcoes brancos, no dia 25 de Outubro de 1908, em jogo disputado com o ‘eterno rival’ Benfica.

As camisolas provenientes de Inglaterra eram folgadas, propicias a agarroes dos adversarios e pesadas em caso de intemporal. Os jogadores sabiam destes inconvenientes, mas gostavam do desenho delas, sobretudo o bolso preto onde o simbolo do Sporting Clube de Portugal ganhava um enorme destaque. Ate 1928, estas foram as camisolas leoninas, sendo posteriormente substituidas pelas camisolas listadas.

A 29 de Novembro de 1908, os leoes obtiveram a primeira goleada em futebol: 6-0 ao Ajudense (equipa da zona ocidental de Lisboa), em jogo a contar para a 3? jornada do Campeonato de Lisboa.

Ainda em 1908, destaque para a estreia de Francisco Stromp na equipa principal leonina (com apenas 16 anos), facto que se manteve ate 1924. Foi a primeira grande referencia do futebol verde-e-branco, tendo capitaneado os leoes durante 10 anos.

Visite o Museu Mundo Sporting e conheca toda a nossa riquissima historia.

O Sporting Clube de Portugal foi, desde a sua fundacao, um Clube marcadamente ecletico. Em 1909, praticavam-se as seguintes modalidades: futebol, corridas e saltos (atletismo), tenis, exercicios fisicos (ginastica), luta de traccao a corda, tenis, cricket e hoquei em campo.

Os grandes destaques neste ano vao para duas modalidades: o atletismo obteve os seus primeiros titulos, sendo que o atleta Alfredo Camecelha estabeleceu o recorde nacional do peso com 9,38 metros. Por outro lado, assinala-se a vitoria da equipa de luta de traccao a corda, no festival a favor das vitimas do terramoto de Messina, em Italia. Durante varios anos, o Sporting Clube de Portugal manteve uma total hegemonia nesta modalidade muito conceituada na epoca.

Visite o Museu Mundo Sporting e conheca toda a nossa riquissima historia.

Ambicao e dinamica de vitoria

O Sporting Clube de Portugal comemorou em 2006, portanto, cem anos bem contados, com respeito pelo rigor historico. Outros somam anos a partir da fundacao de entidades que lhes deram origem ou ignoram longos periodos de inactividade que se seguiram a uma efemera existencia. Sao criterios. Para ser mais ‘idoso’, como outros se dizem, o Sporting poderia ter fixado como data da sua fundacao a do Sport Club de Belas (1902) ou mesmo a do Campo Grande F Club (1904), mas nao o fez.

Nesses dias de 1906 ficou tracado o caminho: futebol sim, mas eclectismo tambem, correspondendo a vocacao atletica multidisciplinar de alguns dos seus fundadores. O clube nasceu com cinco modalidades: tenis, futebol, corridas e saltos (atletismo), exercicios fisicos (ginastica) e luta de traccao a corda. No ano seguinte ja de praticava o criquete e o hoquei em campo, logo seguido da esgrima. O ciclismo surge em 1911 e por ai fora. Eles eram ao mesmo tempo dirigentes e atletas, jogavam futebol, faziam atletismo, praticavam tenis, traccao a corda, esgrima, criquete, ginastica, hoquei em campo.

Em 1907, D. Fernando de Castelo Branco (Pombeiro) autorizou que o leao rampante do seu brasao fosse utilizado como simbolo do Sporting, ‘. Nao de oiro armado de vermelho em campo azul, como nos Pombeiros, mas de prata armado em preto, em campo verde, como correspondia as limpidas, firmes e esperancadas intencoes dos seus fundadores’, recorda Julio de Araujo. O verde fora, de facto, sugerido pelo Visconde de Alvalade, simbolizando a sua esperanca no novo clube que tanto ajudara a formar.

A 3 de Fevereiro de 1907 realizou-se o primeiro jogo de futebol do Sporting. Nao se pode dizer que tenha estado a altura dos exitos vindouros: derrota por 5-1, em segundas categorias, frente ao Cruz Negra, em partida disputada em Alcantara. Do lado dos vencedores jogaram alguns desportistas que depois ingressaram no Sporting: Alipio da Motta Veiga, Octavio Teixeira Bastos, Antonio das Neves Vital, entre outros. D. Joao de Vila Franca marcou o golo de honra desse jogo, que assim se tornou o primeiro da historia do Sporting.

Em 1 de Dezembro de 1907 nasceu uma longa e eterna rivalidade. O Sporting Clube de Portugal e o Sport Lisboa (que so viria a designar-se Sport Lisboa e Benfica no ano seguinte) disputaram o seu primeiro jogo de futebol, no Campo da Quinta Nova, em Sete Rios. O Sporting, que nos primeiros tempos vestira de branco, estreou nesse encontro o seu equipamento de camisola bipartida verticalmente numa faixa verde e outra branca (hoje conhecida por ‘Stromp’), com calcoes brancos. O Sporting venceu por 2-1 (golos de Candido Rosa Rodrigues e de Cosme Damiao, na propria baliza) no primeiro jogo entre os dois grandes rivais do desporto nacional.

O clube ja dispunha, nessa altura, daquele que era considerado o melhor campo de Portugal, no Sitio das Mouras. Localizava-se no n? 73 da entao Alameda do Lumiar, hoje Alameda das Linhas de Torres, em terrenos disponibilizados pelo Visconde de Alvalade na sua quinta. Comecou a funcionar ainda em Maio de 1906 e foi melhorado logo em 1907. O complexo desportivo integrava campo de futebol, pista de atletismo, dois campos de tenis, pavilhao com chuveiros e banhos de imersao e ate uma cozinha. Um luxo para o tempo.

Em 1910 o eclectismo estava enraizado. O Sporting evidenciava-se, campeoes nacionais em tenis por equipas e ganhou os titulos do salto a vara, do lancamento do peso e do salto em comprimento. Este foi o ano em que Jose Alvalade assumiu a presidencia, que manteve ate 1916.

Em tempos de instabilidade decorrente da implantacao da Republica em Portugal, destaque especial para o primeiro jogo com espectadores pagantes: o bilhete para o ‘derby’ Sporting - Benfica realizado no Campo do Lumiar, no dia 27 de Fevereiro de 1910, custava 120 reis. O Diario de Noticias (na sua edicao de 1 de Marco) escrevia: ‘Entradas pagas! Oh! Oh! Agora fia mais fino. Ja o senhor Manuel Ceguinho, o Chico da Rira e outros mais, assiduos frequentadores da tasca e dos desafios, nao poderao ir manifestar-se (…) pois pagar 120 reis nao esta escrito no seu orcamento’.

Ainda em 1910, registo para o primeiro contacto internacional, atraves de um convite do Recreativo de Huelva ao CIF, que deixara excelente imagem aquando da digressao a Espanha, tres anos antes. Desta feita, porem, o CIF, reconhecendo o seu momento menos bom, sugeriu o Sporting Clube de Portugal, o qual so aceitou mediante a possibilidade da formacao de um misto de equipas lisboetas, cuja constituicao ficou a cargo do capitao leonino Joao Bentes. A 27 de Agosto de 1910, o seleccionado portugues triunfou 4-0 em Huelva, com golos de Francisco Stromp (2) e Antonio Rosa Rodrigues (2).

Extra-futebol, Jose Alvalade assumiu a Presidencia do Sporting Clube de Portugal, solicitando a Francisco Vieira que tratasse da confeccao da primeira bandeira do Clube.

Inicio do ciclismo no Sporting, destacando-se Laranjeira Guerra como principal figura atraves da na mitica prova Porto-Lisboa: 365km atraves de estradas muito dificeis e em bicicletas pesadas.

Os Triunfos Iniciais

O rumo do clube estava tracado: o das vitorias. O Sporting ganhou o seu primeiro Campeonato de Lisboa de Futebol, ainda em quartas categorias, no ano de 1912. O feito foi reeditado em 1915, mas ja na categoria de Honra, a que se juntou a Taca de Honra, com vitoria sobre o Benfica na final (3-1). O Campeonato de Lisboa de 1915 foi o primeiro de uma longa serie de 19 (chegaram a ser seis consecutivos) ganhos ate 1947, quando a competicao foi extinta. Ainda em 1915, as equipas do Sporting passaram a usar calcoes pretos com a camisola ‘Stromp’.

Laranjeira Guerra venceu o Porto-Lisboa em ciclismo no ano de 1912, competicao que tambem era uma epopeia com as estradas, os meios e os equipamentos de entao, tornando-se um precursor de ciclistas brilhantes como Alfredo Trindade, Joao Roque, Leonel Miranda, Marco Chagas e o maior de todos, o saudoso Joaquim Agostinho. Classificacoes brilhantes na Volta a Franca, que correu por 13 vezes, entre elas dois terceiros lugares, e um segundo lugar na Volta a Espanha – sem contar os grandes triunfos em Portugal – transformaram Agostinho numa das lendas e simbolos do Sporting e de Portugal.

Numa modalidade muito em voga a epoca, a luta de traccao a corda, o Sporting revelou-se a grande potencia: nunca foi derrotado enquanto se realizaram competicoes da especialidade.

Ainda no ano de 1912, o tambem polivalente Antonio Stromp brilhou nas provas de 100 (quarto lugar na eliminatoria) e 200 metros dos Jogos Olimpicos de Estocolmo, que foram fatais para o maratonista portugues Francisco Lazaro. Antonio Stromp foi pois o primeiro atleta olimpico Sportinguista, iniciando uma caminhada que transformou o Clube na maior potencia olimpica do Pais, tanto em numero de representantes como de medalhas conquistadas. Tambem em 1912 o Sporting venceu o primeiro da longa serie de Campeonatos Nacionais de Corta-Mato.

Em 1917 o Sporting mudou de instalacoes. Jose Alvalade fizera construir o Stadium de Lisboa, em 1914, mas divergencias quanto a sua utilizacao entre o fundador e a Direccao eleita em 1916 levaram os responsaveis Sportinguistas em exercicio a procurar outra solucao. Arrendaram o Campo Grande 412, campo onde actuava a Lisboa F. C. que entretanto se extinguiu, fazendo importantes beneficiacoes sob projecto do arquitecto Antonio do Couto, sendo esta a casa do Sporting durante 30 anos. A vida do recinto, porem, prolongou-se por mais algumas epocas pois foi utilizado pelo Benfica, com solidariedade do Sporting, quando se mudou das Amoreiras. Ficou popularmente conhecido pela ‘estancia de madeira’.

A convite da Federacao espanhola, o jogador leonino Jorge Vieira arbitra o Espanha-Belgica em Bilbau, tornando-se assim o primeiro portugues a arbitrar um jogo internacional

O 1? Campeonato e o novo equipamento

Nos anos vinte aconteceu a primeira vitoria do Sporting no Campeonato de Portugal de futebol (1922/23), a competicao que atribuia o titulo nacional, embora disputada em sistema de eliminatorias. O jogo decisivo foi em Faro, em 24 de Junho de 1923, com uma vitoria por 3-0 frente a Academica de Coimbra. Os campeoes foram: Torres Pereira, Jaime Goncalves, Francisco Stromp, Joao Francisco Maia, Carlos Fernandes, Jose Leandro, Filipe dos Santos, Joaquim Ferreira, Cipriano dos Santos, Jorge Vieira e Henrique Portela. Joaquim Ferreira marcou dois golos e Francisco Stromp, lenda do Sporting e do desporto portugues, pioneiro dos tempos da fundacao, cavalheiro e atleta sobredotado, marcou o outro e abandonaria o futebol no ano seguinte, em 1924.

As seccoes de natacao, polo aquatico e raguebi iniciaram entao a actividade. Foram o historico atleta e dirigente Salazar Carreira e o Sporting que introduziram o raguebi em Portugal.

Em 1928 o Sporting estreou no futebol as suas camisolas as riscas horizontais verdes e brancas, uma mudanca que, em boa parte, foi proporcionada pelo raguebi. Aconteceu numa historica viagem ao Brasil, a primeira de um clube portugues, e ficou a dever-se ao facto de os equipamentos as listas usados pelo raguebi serem mais frescos que os do futebol – camisola bipartida verde e branca e calcoes pretos, de flanela. Uma circunstancia fortuita, como tantas vezes acontece na Historia, originou um modelo de equipamento que se tornou profundamente apreciado em Portugal e no estrangeiro, muito procurado pela sua originalidade. A opcao pelas listas horizontais no raguebi fora trazida por Salazar Carreira, inspirado no equipamento do Racing de Paris, embora este utilizasse o azul e branco. No regresso do Brasil a equipa de futebol voltou ao vestuario original mas em Outubro de 1928, num jogo frente ao Benfica disputado sob temporal, os jogadores mudaram de equipamento ao intervalo e regressaram para a segunda parte com as camisolas do raguebi. Nao se sabe ao certo as razoes, mas Sporting ganhou o jogo e. um novo equipamento.

A serie de vitorias nos Campeonatos de Portugal em futebol prosseguiu nos anos trinta: 1933/34, 1935-36 e 1937-38. Nesta decada, o Clube somou titulos em tenis, ciclismo, raguebi (ao nivel regional), tiro, hoquei em patins (vitoria no Campeonato Nacional em 1937-38 - primeira edicao da prova), patinagem, ginastica e esgrima.

Alfredo Trindade, com numerosos titulos em varias especialidades do ciclismo, venceu a Volta a Portugal em 1933, a primeira vitoria individual e colectiva do Sporting na mais importante prova velocipedica portuguesa. Trindade ficou na historia pelos seus feitos individuais mas tambem pela intensa rivalidade, temperada com respeito e grande amizade, com o benfiquista Jose Maria Nicolau. Os seus duelos empolgaram os portugueses de entao, mesmo sem a dinamica mediatica que hoje existe. A eles se deve a implantacao nacional dos dois grandes clubes rivais do desporto nacional. Jose Albuquerque, o 'Faisca', venceu a Volta a Portugal de 1940.

O lendario avancado-centro Fernando Peyroteo, que ingressara no Sporting em 1937, emergiu em 1938 como melhor marcador do Campeonato da I Liga, com 34 golos. Ele viria a ser uma figura central dos anos de ouro que se seguiram.

Comemoracao das ‘Bodas de Prata’ do Sporting Clube de Portugal com a entrega de 32 Medalhas de Merito, em prata e cobre. O momento solene acontece a 4 de Julho

Os Anos de Ouro

Os anos de quarenta e cinquenta foram fabulosos para o Sporting. Dez titulos de Campeao Nacional de futebol conquistados nesses 20 anos, aos quais se juntaram quatro Tacas de Portugal que figuram no quadro de honra do Clube. De 1946-47 a 1953-54 o Sporting venceu sete dos oito campeonatos em disputa, juntando um tricampeonato e um tetracampeonato – ficando a epoca de 1949-50 de permeio. Foram os anos dos ‘Cinco Violinos’, de grandes e historicas equipas que conquistaram enorme fama nacional e internacional. A propria designacao ‘Cinco Violinos’ foi atribuida pelo jornalista e treinador Tavares da Silva a uma linha avancada formada por Jesus Correia, Vasques, Peyroteo, Travassos e Albano. Eles e os seus companheiros formavam uma orquestra a jogar, tal o espirito colectivo e a eficacia em campo. Nesses anos, em 1946-47, o Sporting chegou aos 123 golos (quase cinco por jogo!) num campeonato que tinha entao 26 jornadas, tendo Peyroteo marcado 43 golos em 19 encontros (media de 2,26 golos por jogo), recordes impossiveis de serem batidos.

Esses tempos foram de tal maneira impressionantes aquem e alem-fronteiras que, apesar de nao ser entao campeao nacional em titulo, o Sporting foi convidado para participar na primeira edicao da Taca dos Clubes Campeoes Europeus, em 1955-56. Foi pena que a UEFA nao tivesse lancado a competicao alguns anos mais cedo. Para a Historia fica ainda o facto de o Sporting ter inaugurado a Taca dos Campeoes num jogo com o Partizan de Belgrado (3-3), no Estadio Nacional. Joao Martins marcou o primeiro golo desta historica e hoje milionaria competicao.

O tetracampeonato do Sporting, o primeiro do futebol portugues, arrancou em 1950-51 com os seguintes jogadores: Mario Wilson, Juca, Jesus Correia, Manuel Passos, Juvenal, Vasques, Galileu, Verissimo, Travassos, Martins, Tormenta, Carlos Gomes, Leandro, Caldeira, Barros, Canario, Jose Travassos, Cesar Nascimento, Anacleto, Manuel Marques, Pacheco Nobre, Mateus e Pacheco. O treinador era o britanico Randolph Galloway, que tinha como adjunto Fernando Vaz.

Em 1955, Jose Travassos foi o primeiro futebolista portugues a ser convocado para uma Seleccao da Europa. Jogou em Belfast perante a equipa da Gra-Bretanha e mereceu referencias muito elogiosas da imprensa internacional, assim conquistando para sempre o cognome de ‘Ze da Europa’.

No atletismo, o Sporting comecou em 1941 a sua inigualavel colheita de Campeonatos Nacionais em pista, que hoje prossegue galopante: 12 entre 1940 e 1960. Em corta-mato, ou crosse, foram dez as vitorias colectivas no mesmo periodo.

De notar que em 1945 o Sporting fundou as primeiras escolas de natacao em Portugal: ‘um pais de marinheiros’ mas onde mal se nadava. O Sporting ja fora pioneiro ao abrir um posto nautico no inicio dos anos vinte, dai as vitorias em polo aquatico nos primeiros anos da modalidade.

Em 1941 comecou a era dos titulos em andebol, com a vitoria no Campeonato Regional na variante de Onze, a que existia ao tempo, jogada em campos de futebol. A serie de vitorias nacionais no andebol de sete foi inaugurada em 1951-52, sendo o Sporting nesta modalidade (como em muitas outras) a Maior Potencia Desportiva Nacional.

Na decada de cinquenta, alem dos titulos nas modalidades de maior divulgacao ha a registar os conquistados em bilhar, esgrima, tiro, tenis de mesa, badminton, automobilismo, os dois primeiros campeonatos nacionais de voleibol (53-54 e 55-56), o primeiro campeonato nacional de basquetebol, em 1956.

Em 1956, a 10 de Junho, o Sporting inaugurou o Estadio Jose Alvalade, um feito que assinalou a grande vitalidade, a dinamica e a capacidade de mobilizacao do Clube e dos seus dedicados associados, que se desdobraram em iniciativas e sacrificios para que tal obra gigantesca fosse possivel. O Sporting tinha regressado as origens, ao Stadium ou Estadio do Lumiar em 1937. Este foi o cenario dos recitais dos ‘Cinco Violinos’, que rapidamente se tornou pequeno para a extraordinaria envergadura do Clube a medida que se aproximava dos seus primeiros 50 anos de vida. A necessidade de um novo estadio tornou-se premente logo no inicio da decada de cinquenta e acabou por ser uma realidade em 1956, assentando sobre a area do antigo Stadium. Foi baptizado com o nome do fundador Jose Alvalade que teve sempre como preocupacao a qualidade das instalacoes do Clube. Alias a designacao ja fora adoptada anteriormente, a partir de 1947, ao remodelado Estadio do Lumiar. O socio n? 1 do Sporting ao tempo da inauguracao do grandioso Estadio era Francisco Gavazzo, um dos fundadores e um dos jovens veraneantes de Belas em 1902.

Mais tarde, em 1983, por accao da presidencia de Joao Rocha, concretizou-se outra das ambicoes Sportinguistas em termos de instalacoes – o ‘fecho’ do Estadio atraves da construcao da denominada Bancada Nova, que substituiu o peao herdado do recinto anterior. A 6 de Junho de 1960, o Sporting foi declarado Instituicao de Utilidade Publica.

Manuel Faria, fundista de grande prestigio, antecessor de Manuel de Oliveira, Carlos Lopes, Fernando Mamede e dos irmaos Castro, venceu as famosas corridas de Sao Silvestre de Sao Paulo em 1957 e 1958, ate entao os maiores feitos do atletismo portugues juntamente com o quarto lugar do saltador em comprimento Alvaro Dias no Campeonato da Europa.

O Sporting alcanca a tao ambicionada tripleta do momento: Campeonato de Lisboa, Taca de Portugal e o Nacional da 1? Divisao

Gloria Europeia

Na decada de sessenta o ponto mais alto do futebol foi a conquista europeia da Taca dos Vencedores das Tacas, em 1963-64. Uma epopeia que passou por tres jogos suplementares, incluindo a final, uma vitoria de 5-0 sobre o Manchester United e uma goleada de 16-1 sobre o Apoel de Chipre (que ainda hoje e recorde das competicoes europeias de clubes). A vitoria nessa gesta, na qual poucos acreditavam a partida tanto mais que a carreira interna nao era famosa, foi obra de uma equipa unida e psicologicamente fortissima, liderada primeiro por Gentil Cardoso, depois pelo arquitecto Anselmo Fernandez, e na qual pontificavam, entre alguns outros, grandes nomes do futebol leonino e nacional como Carvalho, Pedro Gomes, Mario Lino, Alexandre Baptista, Jose Carlos, Hilario, Fernando Mendes (o grande capitao), Geo, Perides, Osvaldo Silva, Figueiredo, Mascarenhas e Joao Morais, autor do canto directo na finalissima em Antuerpia com o qual se decidiu o vencedor da prova.

Com a extincao da Taca dos Vencedores das Tacas na temporada de 1998-99 e respectiva fusao com a Taca UEFA, o Sporting tornou-se assim o unico clube portugues a poder ostentar este titulo historico.

Entre 1960 e 1999, a equipa de futebol venceu mais seis Campeonatos Nacionais, o ultimo dos quais em 1981-82, e mais sete Tacas de Portugal, entre elas a de 1994-95, que assinalou um regresso da equipa principal aos titulos de ambito nacional depois de um prolongado interregno. Em 1974, com 46 golos, Hector Yazalde, ponta-de-lanca do Sporting, conquistou a Bota de Ouro dos goleadores europeus. O seu recorde ainda hoje se mantem. Em 2002, Mario Jardel tornou-se o segundo jogador do Sporting a conquistar essa distincao europeia.

No hoquei em patins o Sporting registou uma gloriosa vaga europeia entre 1975 e 1990, com uma Taca dos Campeoes Europeus – era a melhor equipa do Mundo na altura –, tres Tacas das Tacas e uma Taca CERS.

O atletismo foi e continua a ser uma constante fonte de orgulho para o Sporting: Carlos Lopes conquistou tres Campeonatos Mundiais de Corta-Mato, uma medalha de ouro e uma medalha de prata em Jogos Olimpicos. O corredor do Sporting empolgou Portugal com a vitoria na maratona olimpica de Los Angeles, em 1984. Os seus trofeus foram precursores de varios outros de ambito olimpico, mundial e europeu de que hoje o Sporting se orgulha.

Fernando Mamede foi recordista mundial dos 10.000 metros durante cinco anos e recordista europeu da mesma prova durante 15 anos. O Sporting somou entretanto, ate aos dias de hoje, 14 Tacas dos Campeoes Europeus em Corta-Mato.

No ano 2000, a equipa de atletismo venceu a Taca dos Clubes Campeoes Europeus em pista, feito unico no desporto portugues que foi conseguido sobre uma equipa russa que era praticamente a seleccao nacional de uma das potencias mundiais e olimpicas da modalidade. Depois de Carlos Lopes, Fernando Mamede e os irmaos Castro, todos eles com medalhas e recordes internacionais, Rui Silva, Naide Gomes, Francis Obikwelu, o homem mais veloz da Europa, Yuri Bilonog e Ionela Tirlea sao atletas da geracao do centenario com expressao mundial que interpretam a vocacao ganhadora do Sporting alem-fronteiras.

O andebol, outra das modalidades com uma mistica especial no Clube, conquistou um pentacampeonato entre 1969 e 1973, feito ainda por igualar em Portugal.

Joao Roque, Leonel Miranda, Joaquim Agostinho e Marco Chagas, entre outros, brilharam no ciclismo, em estradas portuguesas e estrangeiras. Agostinho (terceiro lugar numa Volta a Franca, segundo numa Volta a Espanha e vencedor de tres Voltas a Portugal) morreu a 10 de Maio de 1984, na sequencia de uma queda provocada por um cao quando seguia com a camisola amarela na Volta ao Algarve, em representacao do Sporting. O seu nome esta perpetuado numa curva da terrivel escalada do Alpe D'Huez, na Volta a Franca, como homenagem a epica vitoria do ciclista portugues nessa mitica etapa.

O tenis de mesa do Sporting amealhou titulos nacionais numa quantidade recorde insuperavel a curto prazo. Entre 1984-85 e 1994-95 ganhou todos os Campeonatos Nacionais. 11 no seu total.

O Sporting conquista o prestigiante Torneio Teresa Herrera, realizado na Corunha. A prova contou com a participacao do Reims e os leoes bateram os franceses por 3-2, arrecandando o trofeu no dia 29 de Junho

Um Novo Ciclo

Em 1996 o Sporting iniciou um novo ciclo de vida: aprovou Estatutos adequados a realidade dos tempos modernos, lancou as bases de um grupo empresarial e criou uma Sociedade Desportiva de Futebol, SAD, admitida na Bolsa, em 1998. Alem disso, o Clube assumiu e dinamizou medidas no sentido de estabelecer a transparencia no desporto e nas relacoes deste sector de actividade com as instancias fiscais e de seguranca social.

No ambito do processo transformador o Sporting avancou de maneira determinada, e ainda antes de Portugal se abalancar na candidatura a organizacao do Euro 2004, para a modernizacao das suas infraestruturas.

As accoes integradas neste novo ciclo ficaram conhecidas como ‘Projecto Roquette’, entendido globalmente como uma dinamica de modernizacao do Clube em tres frentes: a desportiva, com racionalizacao e valorizacao de meios atraves de formas actualizadas de funcionamento; a patrimonial, capaz de proporcionar a transformacao de bens inertes em estruturas desportivas e multifuncionais rentaveis; e a organizacional, caracterizada pelo funcionamento de todo o Clube de forma inovadora, conjugando a dedicacao com a profissionalizacao de acordo com as condicoes reais, valorizando o presente sem hipotecar o futuro.

Ainda em 1998 o Sporting iniciou todo o processo de idealizacao e construcao de um estadio de nova geracao, ao nivel dos melhores do mundo, que veio a ser inaugurado em 6 de Agosto de 2003 numa noite emocionante e inesquecivel para todos os Sportinguistas (vitoria 3-1 sobre o Manchester United).

Em 2002 entrou em funcionamento a Academia Sporting, no concelho de Alcochete, um empreendimento a que corresponde um grande esforco para aprofundar a capacidade e a qualidade desde sempre revelada pela famosa escola de talentos do Sporting e que proporciona excelentes condicoes de trabalho ao futebol profissional.

Pouco tempos antes, o Sporting viria a tornar-se o primeiro Campeao Nacional do novo milenio. Em 2000, atraves de uma campanha seguida apaixonadamente por todos os Sportinguistas, os leoes voltaram a festejar depois de 17 anos de ‘jejum’. No jogo decisivo, vitoria por 4-0 no terreno do Salgueiros, seguindo-se uma festa de ambito nacional, estendida a todos os sitios do mundo onde ha portugueses, que nao teve paralelo ate hoje.

Dois anos mais tarde, nova celebracao atraves da conquista da ‘tripleta’: Campeonato Nacional, Taca de Portugal e uma Supertaca Nacional reforcaram a nova dinamica do futebol do Sporting dentro do ciclo transformador e que teve expressao de relevo mundial em 2005 com a chegada a final da Taca UEFA atraves de um percurso empolgante. O novo Estadio Jose Alvalade viveu uma jornada de alto nivel em 18 de Maio de 2005: o Sporting perdeu por 1-3 com o CSKA de Moscovo ao cabo de 14 jogos nos quais espalhou a qualidade do seu futebol atraves da Europa, mas o inexito derradeiro nao apaga a importancia da campanha.

Ao longo da sua Historia, o futebol do Sporting atingiu por duas vezes finais europeias – uma das quais ganhou – e chegou por duas vezes as meias-finais, uma na Taca dos Vencedores das Tacas, em 1974, outra na Taca UEFA, em 1991. Em ambos os casos perdeu com o vencedor da prova, Magdeburgo e Inter de Milao, assim respectivamente.

Podemos concluir, entao, que a ambicao de ganhar e de fazer do Sporting um dos maiores clubes da Europa que orientou os fundadores, desde os remotos tempos de um jogo do efemero Sport Club de Belas contra um grupo de Sintra, teve o desejado sucesso. A obra de todos os Sportinguistas ai esta, erguida dia-a-dia de mais de 100 anos, numa interminavel estafeta caracterizada por dedicacao, paixao e ambicao, independentemente de quem transporta o testemunho: um Sporting que e desportivamente o maior clube portugues e um dos maiores da Europa e do Mundo.

O Sporting volta a conquistar o titulo nacional, com mais dois pontos que o Porto. No final da epoca, mais uma digressao pioneira e triunfal a Angola. Foram 11 dias inesqueciveis com a presenca de 120 atletas de varias modalidades, mais um grande servico prestado a Portugal

O Sporting Clube de Portugal alcanca no futebol a primera tripleta (moderna) da sua historia: Campeonato Nacional, Taca de Portugal e Supertaca Candido de Oliveira. Rui Jordao, Manuel Fernandes e Antonio Oliveira apontam 72 golos no conjunto destas competicoes

Carlos Lopes ganha o Ouro Olimpico na maratona de Los Angeles e Fernando Mamede e recordista mundial nos 10.000 metros em Estocolmo. Outras vitorias colectivas de importante registo viriam a suceder: Taca dos Clubes Campeoes Europeus em corta-mato e a Taca CERS no hoquei em patins

O Sporting goleia por 7-1, em pleno Estadio Jose Alvalade o ‘eterno rival’ Benfica, com 4 golos do capitao Manuel Fernandes. O ‘homem das maos de ouro’, Manuel Marques, foi justamente homenageado antes desse encontro ao contemplar 50 anos ao servico do Sporting Clube de Portugal

Conquista da Supertaca Candido de Oliveira com uma dupla vitoria sobre o ‘eterno rival’ Benfica (a espantosa vitoria por 3-0 na Luz, na segunda mao, em Alvalade, os leoes ganham com um golo solidario de Silvinho)

O Napoles de Diego Armando Maradona e dos brasileiros Careca e Alemao foi o ‘carrasco’ dos leoes na 1? eliminatoria da Taca UEFA, numa decisao sem golos em 210 minutos. So os ‘penalties’ resolveram a questao e, neste aspecto, os italianos foram mais certeiros. De reter, a aposta de 100 dolares de Ivkovic a Maradona

Estreia de Luis Figo na primeira equipa leonina, a 1 de Abril, frente ao Maritimo, curiosamente o mesmo adversario aquando da sua despedida, na Final da Taca de Portugal, em Junho de 1995. A Taca dos Campeoes de corta-mato vai pela decima vez para Alvalade

O hoquei em patins leonino conquista a sua quarta taca europeia, desta vez, a Taca das Tacas, repetindo a proeza de 1985, batendo os italianos do Novara, na final

Ano repleto de acontecimentos: o verao quente (com a contratacao de Paulo Sousa e Pacheco ao Benfica), a bancarrota no Casino de Salzsburgo para a Taca UEFA (e consequente troca de Robson por Carlos Queiroz), o acidente do russo Cherbakov e a digressao a Mocambique e a Africa do Sul vencendo os tres jogos disputados

No ano de despedida de dois genios (Balakov e Figo), o Sporting ganha a sua 12? Taca de Portugal. Um bis do bulgaro Iordanov garantiu o triunfo diante do Maritimo. Treze anos volvidos, os leoes voltaram a festejar

Conquista da Supertaca Candido de Oliveira, com um expressivo 3-0 ao Porto, numa final realizada em Paris, em homenagem a todos os imigrantes: golos de Sa Pinto e ‘penalty’ de Carlos Xavier

O Sporting Clube de Portugal participa pela primeira vez na ‘Champions League’, tendo derrotado no primeiro jogo os franceses do Monaco por 3-0. O grupo leonino seria constituido, tambem, pelos belgas do Lierse e, os alemaes do Bayern Leverkusen

O Sporting contrata Peter Schmeichel que tinha acabado de vencer a ‘Champions League’ ao servico do Manchester United. Extra-futebol, Rui Silva sagra-se Campeao da Europa dos 1.500 metros (Sub-23), Francis Obikwelu Campeao de Africa dos 4x100 e nos 100 metros, Ines Monteiro Campea da Europa de Corta-Mato (juniores), Pedro Grilo Campeao Europeu de Bilhar Pool Individual e Rita Costa Campea do Mundo de Duplo Mini-Trampolim

Apos recuperar um atraso de 7 pontos (face ao lider FC Porto), os leoes acabaram o Campeonato Nacional com 4 pontos de avanco, facto da qualidade e espirito de sacrificio do plantel leonino. As comemoracoes do titulo transformaram-se numa verdadeira festa nacional que extravasou pelo Mundo, atraves de todas as comunidades portuguesas, sinal evidente da pujanca e vitalidade do Sporting Clube de Portugal.

Para alem do futebol, o atletismo voltou a dar grandes alegrias: em masculinos, os leoes escreveram mais uma pagina dourada na modalidade, sagrando-se pela primeira vez campeoes europeus de pista, em Vila Real de Santo Antonio, diante da poderosa equipa do Luch – a base da seleccao da Russia.

Por ultimo, a presenca de 17 atletas do Sporting Clube de Portugal nos Jogos Olimpicos de Sidney, constituiram um feito unico no Mundo, tendo cinco atletas disputado finais: Mercy Nku, Carlos Calado, Teresa Machado, Valentina Fedyushina e Manuel da Silva.

O Sporting Clube de Portugal iniciou as obras de construcao do novo Estadio Jose Alvalade a 16 de Janeiro, tendo apresentado publicamente, a 4 de Julho, a versao actual do seu emblema (o 5? da historia leonina). No futebol os leoes conquistaram, a 16 de Maio, a 4? Supertaca ‘Candido de Oliveira’ ao vencer, em jogo de desempate disputado em Coimbra, o FC Porto por 1-0 com golo do avancado argentino Beto Acosta aos 31 minutos. O ano de 2001 ficara (tambem) gravado a letras de ouro para o atletismo leonino: Rui Silva conquistou em pleno Pavilhao Atlantico (pista coberta) a primeira medalha mundial para Portugal, numa disciplina tao exigente como os 1.500 metros com o tempo de 3.51,06. Na mesma competicao, outro atleta leonino brilhou: Carlos Calado alcancou a medalha de bronze no salto em comprimento.

Pela segunda vez no historial leonino, o futebol ganhou todos os titulos nacionais em disputa: Campeonato, Taca e Supertaca ‘Candido de Oliveira’. A titulo individual, destaque para o avancado brasileiro Mario Jardel que conquistou a ‘Bota de Ouro’ europeia com 42 golos em 30 jogos disputados no campeonato. Face ao sucesso desportivo interno, o Sporting Clube de Portugal foi quem mais jogadores cedeu a Seleccao Nacional para a fase final do Campeonato do Mundo disputado na Coreia/Japao, num total de 7 atletas: Nelson, Beto, Rui Jorge, Hugo Viana, Paulo Bento, Joao Pinto e Pedro Barbosa. Ainda no que diz respeito ao futebol, a Academia Sporting (situada em Alcochete) foi inaugurada a 21 de Junho, possibilitando assim excelentes condicoes de trabalho para a equipa profissional, bem como para os atletas mais jovens. Por ultimo, destaque para o sucesso do atletismo leonino, em Viena, nos campeonatos europeus de pista coberta: Rui Silva sagrou-se campeao europeu nos 1.500 metros, Francis Obikwelu conquistou as medalhas de prata nos 100 e 200 metros, enquanto Naide Gomes alcancou um feito historico para Portugal com a primeira medalha numa prova combinada de atletismo (pentatlo moderno).

O novo Estadio Jose Alvalade foi inaugurado, a 6 de Agosto, num espectaculo inolvidavel de cor, luz e som. O jogo entre Sporting e Manchester United terminou com uma vitoria leonina por 3-1: Luis Filipe fez o primeiro golo do novo recinto desportivo, enquanto Joao Vieira Pinto bisou numa partida que viria a ser a ultima de Cristiano Ronaldo com a camisola verde e branca. Devido a sua genial exibicao, dias depois seria apresentado em ‘Old Trafford’. Com Fernando Santos no comando tecnico, a equipa leonina venceu 4-2 no primeiro jogo oficial do novo Estadio (2? jornada, frente ao Belenenses): Fabio Rochemback apontou de penalty o primeiro golo oficial do novo recinto leonino. Extra-futebol, o grande destaque vai para o tenis de mesa: dominio absoluto em Portugal (Campeonato, Taca e Supertaca) com uma impressionante marca de 45 vitorias consecutivas em jogos do campeonato nacional. A nivel individual, o mesatenista Joao Pedro Monteiro voltou a sagrar-se campeao de Portugal.

O Euro-2004 foi o grande evento desportivo do ano em Portugal, sendo que os leoes cederam tres jogadores a Seleccao Nacional: Ricardo, Beto e Rui Jorge. Durante a competicao, a Seleccao das ‘Quinas’ ficou instalada na Academia Sporting e o Estadio Jose Alvalade foi palco de 5 jogos desta importante competicao, sendo ali que Portugal se qualificou para a final (vitoria 2-1 sobre a Holanda). No entanto, o grande destaque do Clube vai novamente para o atletismo leonino: dos 8 atletas que representaram Portugal no campeonato mundial de pista coberta, em Budapeste, 7 pertenciam aos leoes, sendo que Naide Gomes sagrou-se campea mundial em pentatlo. Poucos meses depois, nos Jogos Olimpicos de Atenas, 4 medalhas para atletas do Sporting Clube de Portugal: Yuri Bilonog (ouro no lancamento do peso); Francis Obikwelu (prata nos 100 metros, com novo recorde da Europa – 9,86 segundos); Iolena Tirlea (prata nos 400 metros barreiras) e Rui Silva (bronze nos 1.500 metros).

Do paraiso ao inferno, em dois actos: o final da epoca 2004/2005 foi uma desilusao para todos os Sportinguistas. Em poucos dias, os leoes perderam o Campeonato Nacional frente ao ‘eterno rival’ Benfica e a Taca UEFA, em pleno Estadio Jose Alvalade apos estarem a vencer, ao intervalo, os russos do CSKA de Moscovo por 1-0 (golo de Rogerio). A 1 de Julho de 2005, iniciaram-se as comemoracoes do 1? Centenario do Sporting Clube de Portugal, com um mega-jantar do 99? Aniversario do Clube e que contou com dois mil Sportinguistas, em pleno relvado do Estadio Jose Alvalade. Nas modalidades destaque para o andebol (Campeao Nacional da Divisao de Elite e Taca de Portugal), futsal (Supertaca) e bilhar (Vice-Campeoes da Europa). A nivel individual, Naide Gomes conquistou o ouro na prova de salto em comprimento, no campeonato europeu de pista coberta, em Madrid. De referir, igualmente, que a entidade maxima do futebol europeu (UEFA) distinguiu o Estadio Jose Alvalade como ‘Estadio 5 Estrelas’, a maior distincao para complexos desportivos de ultima geracao.

Sob o lema ‘A honra do passado, o orgulho do presente, a conquista do futuro’, o Sporting Clube de Portugal celebrou 100 anos de vida efectiva, a 1 de Julho de 2006, atraves de 141 iniciativas de grande relevo associativo, cultural, social e desportivo. Correspondendo a excelencia da Academia Sporting, recentemente inaugurada em 2002, os jovens leoes conquistaram todos os campeonatos nacionais e distritais de futebol, em iniciados, juvenis e juniores. Feito inedito na formacao leonina! No futebol profissional, Paulo Bento assumiu o comando tecnico tendo obtido o 2? lugar na Liga Nacional que possibilitou aos leoes estrearem o novo Estadio Jose Alvalade na fase de grupos da milionaria Liga dos Campeoes: vitoria 1-0 frente ao poderoso Inter de Milao. Em termos internacionais, dois grandes destaques: Francis Obikwelu ganhou duas medalhas de ouro nos 100 e 200 metros do Campeonato da Europa de pista, em Gotemburgo, e o piloto Rodrigo Gallego voltaria a conquistar mais um titulo no Campeonato do Mundo de F1 Historicos (apos o sucesso em 2004).

Depois de ter (novamente) assegurado o 2? lugar na Liga Nacional, o futebol leonino conquistou a 14? Taca de Portugal, no Jamor, frente ao Belenenses com um golo solitario de Liedson perto do final do encontro. Meses mais tarde, os leoes viriam a conquistar a Supertaca ‘Candido de Oliveira’, no Estadio Municipal de Leiria, diante do campeao FC Porto atraves de um remate de longa distancia do recem-contratado jogador russo Marat Izmailov. No atletismo, Naide Gomes voltou as grandes conquistas: medalha de ouro, no salto em comprimento, no Campeonato da Europa de pista coberta, realizado em Birmingham com a marca de 6,89 (novo recorde nacional). No meeting de Madrid, segunda classificada, bateu o recorde nacional no salto em comprimento, ultrapassando a mitica barreira dos 7 metros, alcancando a marca de 7,01.

Apos Luis Figo ter sido consagrado em 2001, Cristiano Ronaldo foi eleito, pela FIFA, o melhor jogador do Mundo de futebol: o Sporting Clube de Portugal passava assim a ser o unico Clube do Mundo com duas distincoes. No futebol, os leoes conquistaram (pelo segundo ano consecutivo) a Taca de Portugal e a Supertaca ‘Candido de Oliveira’, vencendo ambos os jogos ao FC Porto por 2-0 (bis de Tiui no Jamor e bis de Yannick Djalo na Supertaca disputada no Algarve). No atletismo, Naide Gomes sagrou-se campea mundial no salto em comprimento, em pista coberta, vencendo ainda os meetings de Estocolmo (onde bateu o seu recorde nacional com 7,12), Lausanne e Estugarda. Em ano de Jogos Olimpicos, o Sporting Clube de Portugal foi quem mais atletas (8) cedeu a representacao portuguesa, passando a contabilizar 109 atletas olimpicos em dez diferentes modalidades, so superado na Europa pelo FC Barcelona.

Em Santarem, nos dias 28 e 29 de Marco, teve lugar o 8? Congresso Leonino sob o lema ‘Pensar o Futuro’, com a presenca de cerca de meio milhar de delegados. As quatro seccoes de debate eram: ‘Socios e Adeptos’, ‘Modelo Estrategico do Futebol’, ‘Desafios do Ecletismo’ e ‘Sustentabilidade Financeira’, tendo sido aprovadas no final um total de 126 recomendacoes. Na milionaria Liga dos Campeoes, o Sporting Clube de Portugal atingiu pela primeira vez os oitavos-de-final (com 4 vitorias em 6 jogos da fase de grupos), apos estar num grupo verdadeiramente vencedor: Barcelona (viria a ganhar a Liga dos Campeoes), Shakhtar Donetsk (conquistaria a Liga Europa) e os suicos do Basileia. Face ao sucesso galopante do projecto ‘Escolas Academia Sporting’, o Sporting contabilizou mais de 10 mil atletas a praticar desporto com a camisola verde-e-branca, alargando assim a sua base de recrutamento para futuros campeoes.

Uma Nova Era Desportiva

A 24 de Marco de 2013, comeca uma nova Era no Sporting Clube de Portugal. Bruno de Carvalho, a votos pela 2.? vez (em 2011 perdera para Godinho Lopes), venceu as eleicoes e trouxe para o Clube uma nova visao.

Focado em cortar com o passado mais recente, apostou numa contencao de custos e uma estrategia de "fazer mais com menos". Vindo da pior epoca do Futebol do Sporting, em que a equipa se ficou por um terrivel 7.? lugar, rapidamente as novas praticas impostas pelo Presidente comecaram a dar resultados: sob o comando de Leonardo Jardim, a equipa alcancou um 2.? lugar, debatendo-se pelo titulo ate as ultimas jornadas. No campo financeiro, sucederam-se trimestres positivos e umas contas cada vez mais equilibradas, salvando-se o clube de um cenario negro.

Em 2014/15, ja com Marco Silva como treinador da equipa principal, o Sporting voltou finalmente aos titulos, conquistando a Taca de Portugal numa epica vitoria, nos penaltis, frente ao ao Sp. Braga, no Estadio do Jamor. No campeonato, a equipa ficou-se pelo 3.? lugar, falhando o apuramento directo para a Liga dos Campeoes. Agora, e Jorge Jesus, treinador acabado de se sagrar bicampeao pelo arqui-rival, que toma as redeas da equipa e faz os adeptos voltar a sonhar com o grande objectivo: a conquista do Campeonato Nacional.

No futebol, depois de afastados da Liga dos Campeoes sem derrotas, e devido a deploravel arbitragem no jogo de Lisboa, com os italianos da Fiorentina. a que se seguiu o primeiro lugar na fase de grupos da Liga Europa, os leoes ultrapassaram o Everton (derrota 2-1 em Inglaterra e vitoria 3-0 em Alvalade), tendo sido eliminados de forma ingloria, nos 16-avos, perante os futuros vencedores da mesma: o Atletico de Madrid, apos 2 empates, com afastamento devido ao menor n? de golos marcados fora. De realcar, o extraordinario apoio na capital espanhola de cinco mil Sportinguistas no jogo da 1? mao, a 11 de Marco.

As modalidades voltaram a obter importantes vitorias: o futsal conquistou o titulo nacional no pavilhao do ‘eterno rival’ Benfica, enquanto a equipa de andebol triunfou na Taca Challenge, tornando o emblema leonino no primeiro portugues a vencer uma prova europeia da modalidade. No caminho para esta ardua conquista, o Sporting eliminou equipas da Grecia, Romenia, Eslovenia e Polonia com um total de 238 golos marcados e 200 sofridos!

Individualmente, Joao Pina sagrou-se campeao europeu de judo (medalha de ouro), no Grande Premio de Roterdao, na categoria de -73 kg.

No futebol leonino destaque para o ultimo jogo de Liedson a 4 de Fevereiro: o avancado brasileiro representou o Clube durante 8 anos, tendo apontado 173 golos oficiais, dos quais 26 em jogos das competicoes europeias (melhor marcador da historia do Sporting em jogos da UEFA).

No atletismo, a equipa feminina alcancou o 3? lugar do Grupo A da Taca dos Clubes Campeoes, conquistando a melhor classificacao de sempre do Clube e de qualquer equipa portuguesa nesta competicao internacional. O futsal viveu uma epoca de sonho: apos vitorias na Supertaca, Taca de Portugal e o 2? lugar europeu, os leoes ganharam ao Benfica e sagraram-se bicampeoes nacionais em apenas tres jogos (7-4, 4-2 e 5-4). No mes de Dezembro, a equipa de natacao sagrou-se, pela 1? vez na historia da modalidade no Clube, campea nacional em masculinos. A titulo individual, as grandes proezas foram para Joao Pina com a medalha de ouro e Joana Ramos com prata no Campeonato da Europa de Judo e, Diogo Neves com o titulo mundial de K1 na categoria de -67kg.

Adicionalmente, destacamos dois momentos de verdadeiro orgulho leonino: em Outubro, mais de 4 mil atletas participaram na 1? edicao da Corrida Jubas e 10km, batendo o recorde em estreias de provas do genero. Em Novembro, o Sporting Clube de Portugal foi distinguido com o Premio de Elevado Merito Desportivo atribuido pela Confederacao do Desporto de Portugal.

No futebol leonino destaque para o ultimo jogo de Liedson a 4 de Fevereiro: o avancado brasileiro representou o Clube durante 8 anos, tendo apontado 173 golos oficiais, dos quais 26 em jogos das competicoes europeias (melhor marcador da historia do Sporting em jogos da UEFA).

No atletismo, a equipa feminina alcancou o 3? lugar do Grupo A da Taca dos Clubes Campeoes, conquistando a melhor classificacao de sempre do Clube e de qualquer equipa portuguesa nesta competicao internacional. O futsal viveu uma epoca de sonho: apos vitorias na Supertaca, Taca de Portugal e o 2? lugar europeu, os leoes ganharam ao Benfica e sagraram-se bicampeoes nacionais em apenas tres jogos (7-4, 4-2 e 5-4). No mes de Dezembro, a equipa de natacao sagrou-se, pela 1? vez na historia da modalidade no Clube, campea nacional em masculinos. A titulo individual, as grandes proezas foram para Joao Pina com a medalha de ouro e Joana Ramos com prata no Campeonato da Europa de Judo e, Diogo Neves com o titulo mundial de K1 na categoria de -67kg.

Adicionalmente, destacamos dois momentos de verdadeiro orgulho leonino: em Outubro, mais de 4 mil atletas participaram na 1? edicao da Corrida Jubas e 10km, batendo o recorde em estreias de provas do genero. Em Novembro, o Sporting Clube de Portugal foi distinguido com o Premio de Elevado Merito Desportivo atribuido pela Confederacao do Desporto de Portugal.

No futebol leonino destaque para o ultimo jogo de Liedson a 4 de Fevereiro: o avancado brasileiro representou o Clube durante 8 anos, tendo apontado 173 golos oficiais, dos quais 26 em jogos das competicoes europeias (melhor marcador da historia do Sporting em jogos da UEFA).

No atletismo, a equipa feminina alcancou o 3? lugar do Grupo A da Taca dos Clubes Campeoes, conquistando a melhor classificacao de sempre do Clube e de qualquer equipa portuguesa nesta competicao internacional. O futsal viveu uma epoca de sonho: apos vitorias na Supertaca, Taca de Portugal e o 2? lugar europeu, os leoes ganharam ao Benfica e sagraram-se bicampeoes nacionais em apenas tres jogos (7-4, 4-2 e 5-4). No mes de Dezembro, a equipa de natacao sagrou-se, pela 1? vez na historia da modalidade no Clube, campea nacional em masculinos. A titulo individual, as grandes proezas foram para Joao Pina com a medalha de ouro e Joana Ramos com prata no Campeonato da Europa de Judo e, Diogo Neves com o titulo mundial de K1 na categoria de -67kg.

Adicionalmente, destacamos dois momentos de verdadeiro orgulho leonino: em Outubro, mais de 4 mil atletas participaram na 1? edicao da Corrida Jubas e 10km, batendo o recorde em estreias de provas do genero. Em Novembro, o Sporting Clube de Portugal foi distinguido com o Premio de Elevado Merito Desportivo atribuido pela Confederacao do Desporto de Portugal.

No futebol leonino destaque para o ultimo jogo de Liedson a 4 de Fevereiro: o avancado brasileiro representou o Clube durante 8 anos, tendo apontado 173 golos oficiais, dos quais 26 em jogos das competicoes europeias (melhor marcador da historia do Sporting em jogos da UEFA).

No atletismo, a equipa feminina alcancou o 3? lugar do Grupo A da Taca dos Clubes Campeoes, conquistando a melhor classificacao de sempre do Clube e de qualquer equipa portuguesa nesta competicao internacional. O futsal viveu uma epoca de sonho: apos vitorias na Supertaca, Taca de Portugal e o 2? lugar europeu, os leoes ganharam ao Benfica e sagraram-se bicampeoes nacionais em apenas tres jogos (7-4, 4-2 e 5-4). No mes de Dezembro, a equipa de natacao sagrou-se, pela 1? vez na historia da modalidade no Clube, campea nacional em masculinos. A titulo individual, as grandes proezas foram para Joao Pina com a medalha de ouro e Joana Ramos com prata no Campeonato da Europa de Judo e, Diogo Neves com o titulo mundial de K1 na categoria de -67kg.

Adicionalmente, destacamos dois momentos de verdadeiro orgulho leonino: em Outubro, mais de 4 mil atletas participaram na 1? edicao da Corrida Jubas e 10km, batendo o recorde em estreias de provas do genero. Em Novembro, o Sporting Clube de Portugal foi distinguido com o Premio de Elevado Merito Desportivo atribuido pela Confederacao do Desporto de Portugal.

No futebol leonino destaque para o ultimo jogo de Liedson a 4 de Fevereiro: o avancado brasileiro representou o Clube durante 8 anos, tendo apontado 173 golos oficiais, dos quais 26 em jogos das competicoes europeias (melhor marcador da historia do Sporting em jogos da UEFA).

No atletismo, a equipa feminina alcancou o 3? lugar do Grupo A da Taca dos Clubes Campeoes, conquistando a melhor classificacao de sempre do Clube e de qualquer equipa portuguesa nesta competicao internacional. O futsal viveu uma epoca de sonho: apos vitorias na Supertaca, Taca de Portugal e o 2? lugar europeu, os leoes ganharam ao Benfica e sagraram-se bicampeoes nacionais em apenas tres jogos (7-4, 4-2 e 5-4). No mes de Dezembro, a equipa de natacao sagrou-se, pela 1? vez na historia da modalidade no Clube, campea nacional em masculinos. A titulo individual, as grandes proezas foram para Joao Pina com a medalha de ouro e Joana Ramos com prata no Campeonato da Europa de Judo e, Diogo Neves com o titulo mundial de K1 na categoria de -67kg.

Adicionalmente, destacamos dois momentos de verdadeiro orgulho leonino: em Outubro, mais de 4 mil atletas participaram na 1? edicao da Corrida Jubas e 10km, batendo o recorde em estreias de provas do genero. Em Novembro, o Sporting Clube de Portugal foi distinguido com o Premio de Elevado Merito Desportivo atribuido pela Confederacao do Desporto de Portugal.

Carvedilol side effects in detail, cardival

Carvedilol Side Effects

Commonly reported side effects of carvedilol include: hyperglycemia. Other side effects include: angina pectoris, hypotension, visual disturbance, nausea, orthostatic hypotension, vomiting, and rales. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to carvedilol: oral capsule extended release, oral tablet

In addition to its needed effects, some unwanted effects may be caused by carvedilol. In the event that any of these side effects do occur, they may require medical attention.

Major Side Effects

You should check with your doctor immediately if any of these side effects occur when taking carvedilol:

More common:

Allergy

chest pain, discomfort, tightness, or heaviness

dizziness, lightheadedness, or fainting

generalized swelling or swelling of the feet, ankles, or lower legs

pain

shortness of breath

slow heartbeat

weight gain

Less common:

Ankle, knee, or great toe joint pain

anxiety

arm, back, or jaw pain

blood in the urine

bloody, black or tarry stools

chills

cloudy urine

cold sweats

coma

confusion

convulsions

cool pale skin

cough

dark urine

decreased appetite

decreased frequency or amount of urine

depression

difficulty with breathing

dizziness, faintness, or lightheadedness when getting up suddenly from a lying position

dry mouth

fainting

fast or irregular heartbeat

fever

flu-like symptoms

flushed, dry skin

fruit-like breath odor

headache, sudden and severe

inability to speak

increased blood pressure

increased hunger

increased thirst

increased urination

itching

joint stiffness or swelling

large amount of cholesterol in the blood

loss of appetite

loss of consciousness

lower back, side, or stomach pain

mental depression

muscle pain or cramps

nervousness

nightmares

noisy, rattling breathing

numbness or tingling in the hands, feet, or lips

pinpoint red or purple spots on the skin

pounding in the ears

pounding, slow heartbeat

rapid breathing

seizures

shakiness

slurred speech

stomachache

sweating

swelling of the fingers or hands

temporary blindness

tenderness on the upper right side of the body

trouble with breathing even at rest

unexplained weight loss

unusual bleeding or bruising

weakness in the arm and/or leg on one side of the body, sudden and severe

weakness or heaviness of the legs

yellow eyes or skin

Incidence not known:

Sores, ulcers, or white spots on the lips or in the mouth

swollen or painful glands

wheezing

Minor Side Effects

Some of the side effects that can occur with carvedilol may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common:

Back pain

diarrhea

prickling or tingling sensation

unusual tiredness or weakness

Less common:

Abdominal or stomach pain

bleeding gums

blurred vision

burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings

changes in vision

cold hands and feet

decreased interest in sexual intercourse

decreased tearing

difficulty with moving

feeling of constant movement of self or surroundings

general feeling of discomfort or illness

headache

inability to have or keep an erection

increased sweating

joint or muscle pain

lack or loss of strength

loose teeth

loss of sexual ability, desire, or performance

loss of strength or energy

muscle aches, stiffness, or weakness

nausea

persistent breath odor or bad taste in your mouth

redness and swelling of the gums

sensation of spinning

sleepiness or unusual drowsiness

sore throat

stuffy or runny nose

sugar in the urine

trouble sleeping

unusual weak feeling

vomiting

weight loss

For Healthcare Professionals

Applies to carvedilol: oral capsule extended release, oral tablet

General

In placebo-controlled trials, carvedilol monotherapy was discontinued due to adverse events in 4.9% of patients versus 5.2% of placebo patients.

In a review of heart failure trials, beta-blockers (i. e. carvedilol, metoprolol, bisoprolol) were associated with increased risks of hypotension, dizziness, and bradycardia, but not fatigue compared with placebo. In addition, beta-blocker therapy was associated with fewer overall all-cause withdrawals and less heart failure deterioration than placebo. [Ref ]

Cardiovascular

Patients with liver disease complicated by ascites are at greater risk of systemic hypotension associated with the use of carvedilol as this drug is a potent portal hypotensive agent.

The incidence of dizziness or hypotension is increased by hypovolemia (dehydration, over-diuresis) and thus may be a more common problem in diuretic-treated subjects and the elderly. [Ref ]

Cardiovascular side effects have included bradycardia (9% to 10%), hypotension (9% to 14%), syncope (3% to 8%), angina pectoris (2% to 6%), edema generalized (5% to 6%), edema dependent (4%), peripheral edema (2% to 7%), leg edema (greater than 1% to less than or equal to 3%), postural hypotension (1% to less than or equal to 3%), myocardial ischemia (less than 1%), tachycardia (less than 1%), fluid overload (greater than 1% to less than or equal to 3%), aggravated angina pectoris (greater than 1% to less than or equal to 3%), palpitations (greater than 1% to less than or equal to 3%), hypertension (greater than 1% to less than or equal to 3%), AV block (greater than 1% to less than or equal to 3%), bundle branch block (less than 1%), peripheral vascular disorder (greater than 1% to less than or equal to 3%), peripheral ischemia (greater than 0.1% to less than or equal to 1%), and cerebrovascular accident (greater than 1% to less than or equal to 3%). Cardiovascular side effects including cardiac failure have been reported rarely. [Ref ]

Nervous system

The incidence of dizziness or hypotension is increased by hypovolemia (dehydration, over-diuresis) and thus may be a more common problem in diuretic-treated subjects and the elderly. [Ref ]

Nervous system side effects have included dizziness (24% to 32%), headache (5% to 8%), hypesthesia (greater than 1% to less than or equal to 3%), cerebrovascular accident (greater than 1% to less than or equal to 3%), vertigo (greater than 1% to less than or equal to 3%), paresthesia (greater than 1% to less than or equal to 3%), hypokinesia (greater than 0.1% to less than or equal to 1%), neuralgia (less than 0.1%), paresis (less than 0.1%), tinnitus (greater than 0.1% to less than or equal to 1%), dry mouth (greater than 0.1% to less than or equal to 1%), sweating increased (greater than 0.1% to less than or equal to 1%), cerebrovascular disorder (less than or equal to 0.1%), convulsions (less than or equal to 0.1%), migraine (less than or equal to 0.1%), and decreased hearing (less than or equal to 0.1%). [Ref ]

Respiratory

Respiratory side effects have included increased cough (5% to 8%), rales (4%), dyspnea (greater than 3%), lung edema (greater than 3%), asthma (greater than 0.1% to less than or equal to 1%), bronchospasm (less than or equal to 0.1%), pulmonary edema (less than or equal to 0.1%), and respiratory alkalosis (less than or equal to 0.1%). [Ref ]

Gastrointestinal

Gastrointestinal side effects have included diarrhea (5% to 12%), nausea (4% to 9%), vomiting (1% to 6%), gastrointestinal pain (greater than 1% to less than or equal to 3%), melena (greater than 0.1% to less than 1%), periodontitis (greater than 0.1% to less than 1%), and GI hemorrhage (less than 0.1%). [Ref ]

Renal

Renal side effects have included renal insufficiency (greater than 1% to less than or equal to 3%), and albuminuria (greater than 1% to less than or equal to 3%). [Ref ]

Hematologic

Hematologic side effects have included thrombocytopenia (greater than 1% to less than or equal to 3%), purpura (greater than 1% to less than or equal to 3%), hypovolemia (greater than 1% to less than or equal to 3%), prothrombin decreased (greater than 1% to less than or equal to 3%), anemia (greater than 0.1% to less than or equal to 1%), leucopenia (greater than 0.1% to less than or equal to 1%), pancytopenia (less than or equal to 0.1%), atypical lymphocytes (less than or equal to 0.1%). Decreases in hematocrit, red blood cells, and hemoglobin concentration have also been reported. Rarely, aplastic anemia has been reported in postmarketing experience. [Ref ]

Dermatologic

Dermatologic side effects have included pruritus (0.1% to less than or equal to 1%), rash erythematous (0.1% to less than or equal to 1%), rash maculopapular (0.1% to less than or equal to 1%), rash psoriaform (0.1% to less than or equal to 1%), photosensitivity reactions (0.1% to less than or equal to 1%), exfoliative dermatitis (less than 0.1%), and alopecia (less than 0.1%). [Ref ]

Hepatic

Hepatic side effects have included SGPT increased (greater than 1% to less than or equal to 3%), SGOT increased (greater than 1% to less than or equal to 3%), and increased hepatic enzymes (greater than 0.1% to less than or equal to 1%). Elevations in serum transaminases (ALT or AST) have also been reported. At least one case of hepatotoxicity has been reported.

Genitourinary

Genitourinary side effects have included impotence (greater than 1% to less than or equal to 3%), decreased libido (male) (greater than 0.1% to less than or equal to 1%), micturition frequency increased (greater than 0.1% to less than or equal to 1%), and hematuria (greater than 1% to less than or equal to 3%). Rarely, genitourinary side effects including urinary incontinence in women have been reported in postmarketing experience. [Ref ]

Hypersensitivity

Hypersensitivity side effects have included allergy (greater than 1% to less than or equal to 3%), and anaphylactoid reaction (less than or equal to 0.1%). Rarely, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and hypersensitivity reactions (including anaphylactic reactions, angioedema, and urticaria) have been reported in postmarketing experience.

Metabolic

Metabolic side effects have included hyperglycemia (5% TO 12%), weight increase (10% TO 12%), BUN increase (6%), NPN increased (6%), hypercholesterolemia (1% TO 4%), edema peripheral (2% TO 7%). Metabolic side effects reported greater than 1% to less than 3% have included hyperuricemia, hypoglycemia, hyponatremia, increased alkaline phosphatase, glycosuria, hypervolemia, diabetes mellitis, GGT increased, weight loss, and creatinine increased. Metabolic side effects reported greater than 0.1% to less than or equal to 1% have included hypokalemia and hypertriglyceridemia.

Psychiatric

Psychiatric side effects have included somnolence (greater than 1% to less than or equal to 3%), insomnia (1% to 3% or greater), nervousness (greater than 0.1% to less than or equal to 1%), sleep disorder (greater than 0.1% to less than or equal to 1%), aggravated depression (greater than 0.1% to less than or equal to 1%), impaired concentration (greater than 0.1% to less than or equal to 1%), abnormal thinking (greater than 0.1% to less than or equal to 1%), paranoia (greater than 0.1% to less than or equal to 1%), emotional lability (greater than 0.1% to less than or equal to 1%), and aggravated depression (greater than 1% to less than or equal to 3%).

Musculoskeletal

Musculoskeletal side effects have included arthralgia (1% to 6%), muscle cramps (greater than 1% to less than or equal to 3%), gout (greater than 1% to less than or equal to 3%), hypotonia (greater than 1% to less than or equal to 3%), and arthritis (greater than 1% to less than or equal to 3%).

Ocular

Ocular side effects have included abnormal vision (5%) and blurred vision (greater than 1% to less than or equal to 3%).

Other

Other side effects have included fatigue (24%), asthenia (7% to 11%), digoxin level increased (2% to 5%), malaise (greater than 1% to less than or equal to 3%), fever (greater than 1% to less than or equal to 3%), and flu syndrome (greater than 1% and less than or equal to 3%).

References

1. Kohno M, Takeda T, Ishii M, Saruta T, Mizuno Y, Yoshimura M, Kubo S, Fukiyama K, Fujishima M "Therapeutic benefits and safety of carvedilol in the treatment of renal hypertension. An open, short term study. Carvedilol Renal Hypertension Study Group in Japan." Drugs 36 Suppl 6 (1988): 129-35

2. Krum H, Sacknerbernstein JD, Goldsmith RL, Kukin ML, Schwartz B, Penn J, Medina N, Yushak M, Horn E, Katz SD, Levin HR, Neu "Double-blind, placebo-controlled study of the long-term efficacy of carvedilol in patients with severe chronic heart failure." Circulation 92 (1995): 1499-506

3. "Product Information. Coreg (carvedilol)." SmithKline Beecham, Philadelphia, PA.

4. Meyer-Sabellek W, Agrawal B "Antihypertensive profile of carvedilol." Clin Investig 70 Suppl 1 (1992): s43-52

5. Ko DT, Hebert PR, Coffey CS, et al. "Adverse effects of beta-blocker therapy for patients with heart failure: a quantitative overview of randomized trials." Arch Intern Med 164 (2004): 1389-94

6. Takeda T, Kohno M, Ishii M, Kubo S, Saruta T, Mizuno Y, Fukiyama K, Fujishima M, Yoshimura M "Efficacy and safety of carvedilol in renal hypertension. A multicenter open trial." Eur J Clin Pharmacol 38 Suppl 2 (1990): s158-63

7. Colucci WS, Packer M, Bristow MR, Gilbert EM, Cohn JN, Fowler MB, Krueger SK, Hershberger R, Uretsky BF, Bowers JA, Sackne "Carvedilol inhibits clinical progression in patients with mild symptoms of heart failure." Circulation 94 (1996): 2800-6

8. Forrest EH, Bouchier IAD, Hayes PC "Acute haemodynamic changes after oral carvedilol, a vasodilating beta-blocker, in patients with cirrhosis." J Hepatol 25 (1996): 909-15

9. Morgan T "Clinical pharmacokinetics and pharmacodynamics of carvedilol." Clin Pharmacokinet 26 (1994): 335-46

10. Forrest EH, Bouchier IA, Hayes PC "Acute haemodynamic changes after oral carvedilol, a vasodilating beta - blocker, in patients with cirrhosis." J Hepatol 25 (1996): 909-15

11. Dunn CJ, Lea AP, Wagstaff AJ "Carvedilol: A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disorders." Drugs 54 (1997): 161-85

12. Packer M, Bristow MR, Cohn JN, et al. "The effect of carvedilol on morbidity and mortality in patients with chronic heart failure." N Engl J Med 334 (1996): 1349-55

13. Ruffolo RR, Boyle DA, Brooks DP, Feuerstein GZ, Venuti RP, Lukas MA, Poste G "Carvedilol: a novel cardiovascular drug with multiple actions." Cardiovasc Drug Rev 10 (1992): 127-57

14. Dupont AG "Effects of carvedilol on renal function." Eur J Clin Pharmacol 38 Suppl 2 (1990): s96-100

Not all side effects for carvedilol may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here .

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Important Notice: The Drugs. com international database is in BETA release. This means it is still under development and may contain inaccuracies. It is not intended as a substitute for the expertise and judgement of your physician, pharmacist or other healthcare professional. It should not be construed to indicate that the use of any medication in any country is safe, appropriate or effective for you. Consult with your healthcare professional before taking any medication.

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Diclofenac (Sofarin)

Diclofenac is used primarily for the treatment of inflammation and pain caused by conditions such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. It is also effective in treating soft tissue inflammations due to tendinitis and bursitis, and treating dysmenorrhea (menstrual cramps). Diclofenac is an NSAID. NSAIDs treat the symptoms of pain and inflammation. They do not treat the disease that causes those symptoms.

Use Diclofenac as directed by your doctor!

Take Diclofenac by mouth. It may be taken with food if it upsets your stomach. Taking it with food may not lower the risk of stomach or bowel problems (eg, bleeding, ulcers). Talk with your doctor or pharmacist if you have persistent stomach upset.

Take Diclofenac with a full glass of water (8 oz/240 mL) as directed by your doctor.

If you miss a dose of Diclofenac, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Diclofenac.

Store Diclofenac at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Diclofenac out of the reach of children and away from pets.

Do NOT use Diclofenac if:

you are allergic to any ingredient in Diclofenac or to bovine (cow) protein

you have had a severe allergic reaction (eg, severe rash, hives, trouble breathing, growths in the nose, dizziness) to aspirin or an NSAID (eg, ibuprofen, celecoxib)

you have recently had or will be having bypass heart surgery

you have severe kidney problems

you are in the last 3 months of pregnancy.

Contact your doctor or health care provider right away if this applies to you.

Some medical conditions may interact with Diclofenac. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding

if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

if you have allergies to medicines, foods, or other substances

if you have a history of kidney or liver problems, diabetes, or stomach or bowel problems (eg, bleeding, perforation, ulcers)

if you have a history of swelling or fluid buildup, asthma, growths in the nose (nasal polyps), or mouth inflammation

if you have high blood pressure, blood disorders (eg, porphyria), bleeding or clotting problems, heart problems (eg, heart failure), or blood vessel disease, or if you are at risk for any of these diseases

if you have poor health, dehydration or low fluid volume, or low blood sodium levels, you smoke, drink alcohol, or have a history of alcohol abuse

if you are taking an antibiotic or an anti-seizure medicine. The risk of liver problems may be increased with some of these medicines.

Some medicines may interact with Diclofenac. Tell your health care provider if you are taking any other medicines, especially any of the following:

Anticoagulants (eg, warfarin), aspirin, clopidogrel, corticosteroids (eg, prednisone), heparin and other blood thinners (eg, dalteparin), or selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine) because the risk of stomach bleeding may be increased

Acetaminophen because the risk of liver problems may be increased

Probenecid because it may increase the risk of Diclofenac's side effects

Cyclosporine, lithium, metformin, methotrexate, oral NSAIDs (eg, ibuprofen), or quinolones (eg, ciprofloxacin) because the risk of their side effects may be increased by Diclofenac

Angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril) or diuretics (eg, furosemide, hydrochlorothiazide) because their effectiveness may be decreased by Diclofenac.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Diclofenac may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

Important safety information:

Diclofenac may cause dizziness or drowsiness. These effects may be worse if you take it with alcohol or certain medicines. Use Diclofenac with caution. Do not drive or perform other possible unsafe tasks until you know how you react to it.

Serious stomach ulcers or bleeding can occur with the use of Diclofenac. Taking it in high doses, for a long time, smoking, or drinking alcohol increases the risk of these side effects. Taking Diclofenac with food will NOT reduce the risk of these effects. If you have severe stomach or back pain; black, tarry stools; vomit that looks like blood or coffee grounds; or unusual weight gain or swelling, contact your doctor or emergency room right away.

Do NOT take more than the recommended dose or use for longer than prescribed without checking with your doctor.

Diclofenac is an NSAID. Before you start any new medicine, check the label to see if it has an NSAID (eg, ibuprofen) in it too. If it does or if you are not sure, check with your doctor or pharmacist.

Do not take aspirin while you are using Diclofenac unless your doctor tells you to.

Check with your doctor or pharmacist before you take acetaminophen while you are taking Diclofenac. The risk of liver problems may be increased.

Do not switch between different forms of Diclofenac (eg, enteric-coated tablets, immediate-release tablets, capsules) unless your doctor tells you to. They may not provide the same amount of medicine to your body.

Lab tests, including kidney function, liver function, blood electrolyte levels, complete blood cell counts, and blood pressure, may be performed while you use Diclofenac. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.

Use Diclofenac with caution in the elderly; they may be more sensitive to its effects, especially stomach bleeding and kidney problems.

Diclofenac should be used with extreme caution in children; safety and effectiveness in children have not been confirmed.

Pregnancy and breast-feeding: Diclofenac may cause harm to the fetus. Do not use it during the last 3 months of pregnancy. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of using Diclofenac while you are pregnant. It is not known if Diclofenac is found in breast milk. Do not breastfeed while taking Diclofenac.

All medicines may cause side effects, but many people have no, or minor, side effects.

Check with your doctor if any of these most common side effects persist or become bothersome:

Constipation; diarrhea; dizziness; drowsiness; headache; mild stomach pain or heartburn; nausea; vomiting.

Seek medical attention right away if any of these severe side effects occur:

Severe allergic reactions (rash; hives; itching; trouble breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody or black, tarry stools; change in the amount of urine produced; chest pain; confusion; depression; fainting; fast or irregular heartbeat; fever, chills, or persistent sore throat; mental or mood changes; numbness of an arm or leg; one-sided weakness; persistent flu-like symptoms; red, swollen, blistered, or peeling skin; ringing in the ears; seizures; severe headache or dizziness; severe or persistent stomach pain or nausea; severe vomiting or diarrhea; shortness of breath; sudden or unexplained weight gain; swelling of the hands, legs, or feet; symptoms of liver problems (eg, dark urine, pale stools, persistent loss of appetite, yellowing of the skin or eyes); unusual bruising or bleeding; unusual joint or muscle pain; unusual tiredness or weakness; vision or speech changes; vomit that looks like coffee grounds.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider.

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I have viagra

Viagra

This leaflet answers some common questions about Viagra.

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Viagra against the benefits they expect it will have for you.

It should be used only under strict medical supervision.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What Viagra is used for

Viagra is used to treat erectile dysfunction, more commonly known as impotence, in men. This is when a man cannot get, or keep, a hard erect penis suitable for sexual activity.

Viagra belongs to a group of medicines called phosphodiesterase type 5 inhibitors.

It works by relaxing the blood vessels in your penis when you are sexually excited. This allows blood to flow into your penis, allowing you to get an erection in the natural way.

Viagra will work only if you are sexually excited.

Viagra will not increase your sex drive.

Viagra is not for use in women.

This medicine is available only with a doctor's prescription.

Before you take Viagra

When you must not take it

YOU MUST NOT TAKE VIAGRA IF YOU ARE TAKING NITRATES OR NITRITE MEDICATIONS. IT MAY LEAD TO A SEVERE DROP IN YOUR BLOOD PRESSURE, WHICH MAY BE DIFFICULT TO TREAT.

BECAUSE SEXUAL ACTIVITY MAY PLACE A STRAIN ON YOUR HEART, YOUR DOCTOR WILL NEED TO CHECK WHETHER YOU ARE FIT ENOUGH TO TAKE VIAGRA.

Do not take Viagra if you are being treated for angina (chest pain) or other heart conditions with medicines called nitrates.

Nitrate medicines include glyceryl trinitrate (also called nitroglycerin). Common trade names for glyceryl trinitrate tablets include Anginine and Lycinate.

Common trade names for glyceryl trinitrate patches include Nitro-Dur, Transiderm-Nitro, Nitroderm TTS, and Minitran.

Common trade names for glyceryl trinitrate sprays include Nitrolingual and Glytrin.

Trade names for glyceryl trinitrate injections include Glyceryl Trinitrate Concentrate and Glyceryl Trinitrate.

Common trade names for other nitrate preparations include Imdur Durules, Monodur Durules, Sorbidin, Isordil, Imtrate, Duride, Isomonit, Ikorel and Sodium Nitroprusside.

There may be other trade names not listed here.

Do not take Viagra if you are taking guanylate cyclase stimulators (GCS), such as Adepmas (riociguat).

GCS is a type of medicine used to treat high blood pressure in the blood vessels in the lungs caused by blood clots in the lungs (chronic thromboembolic pulmonary hypertension, CTEPH) or narrowing of the vessels that carry blood from the heart to the lungs (pulmonary arterial hypertension or PAH).

Do not take Viagra if you:

have heart or blood vessel problems that make sexual intercourse inadvisable

have suffered a heart attack or stroke in the last 6 months

have severe liver problems

have blood pressure that is unusually high or low or is not effectively treated

have loss of vision in one or both eyes from an eye disease called non-arteritic anterior ischaemic optic neuropathy (NAION)

have an eye disease called retinitis pigmentosa.

Do not take Viagra if you have an allergy to sildenafil or similar medicines or any of the ingredients listed at the end of this leaflet

An allergic reaction can include:

hives, itching or skin rash

swelling of the face, lips or tongue which may lead to difficulty swallowing or breathing.

Do not take Viagra if the packaging is torn or shows signs of tampering, or does not look quite right even if the tablets may look alright.

Do not take Viagra if the expiry date on the pack has passed.

If it has expired or is damaged, return it to your pharmacist for disposal.

Before you start to take it

Tell your doctor if you:

have any allergies to any other medicines or any other substances such as foods, preservatives or dyes.

have any other heart or blood vessel problems.

have previously had sudden loss of eyesight in one or both eyes.

have any of the following medical conditions:

diabetes, especially if you also have eye problems

kidney or liver problems

leukaemia (cancer of the blood cells)

multiple myeloma (a cancer of the bone marrow)

any disease or deformity of your penis

any bleeding disorder such as haemophilia

a disease of the blood called sickle cell anaemia

colour vision problems

previously experienced sudden decrease or loss of hearing.

are taking or using any other treatment for impotence

are taking any medicines to treat high blood pressure in the vessels of the lungs (pulmonary arterial hypertension) including Tracleer (bosentan) or Revatio which also contains sildenafil.

Tell your doctor if you have any other medical conditions.

If you have not told your doctor or pharmacist about any of the above, tell him/her before you start taking Viagra.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including medicines you buy without a prescription from a pharmacy, supermarket or health food shop.

Do not take Viagra if you are taking or using nitrate medicines for angina.

Do not take Viagra if you are taking guanylate cyclase stimulators (GCS), such as Adepmas (riociguat).

Some medicines and Viagra may interfere with each other. These include:

cimetidine, a medicine used to treat ulcers

some medicines used to treat fungal infections including ketoconazole and itraconazole

some antibiotics including erythromycin and rifampicin

some protease inhibitors such as ritonavir and saquinavir for the treatment of HIV infection

medicines called alpha-blockers. These are used to treat high blood pressure or prostate problems

Tracleer (bosentan), a medicine used to treat high blood pressure in the vessels of the lungs.

You may need different amounts of your medicine or you may need to take different medicines. Your doctor or pharmacist can tell you what to do if you are taking any of these medicines. They also have a more complete list of medicines to be careful with or avoid while taking Viagra.

Ask your doctor or pharmacist, if you are not sure if you are taking any of these medicines.

How to take Viagra

Take Viagra exactly as your doctor has prescribed.

Follow all directions given to you by your doctor and pharmacist carefully.

They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

How much to take

Your doctor will decide the correct dose for you depending on your condition and response.

This can be one 25 mg tablet a day or one 50 mg tablet a day or one 100 mg tablet a day.

Do not take more than one dose of Viagra a day.

How to take it

Swallow the tablet whole with a full glass of water.

When to take it

Take your dose of Viagra about one hour before you intend to have sex.

The amount of time Viagra takes to start working varies from person to person, but it normally takes between half an hour and one hour.

You may find Viagra takes longer to work if you take it with a heavy meal.

Viagra will work only if you are sexually excited.

If you take too much (Overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26) for advice or go to Accident and Emergency at the nearest hospital if you think that you or anyone else may have taken too much Viagra.

Do this even if there are no signs of discomfort or poisoning.

While you are taking it

Things you must do

Stop taking Viagra if you have a loss of eyesight in one or both eyes, experience loss of hearing or have an erection that persists more than 4 hours. Seek medical attention urgently.

If Viagra does not help you get an erection or if your erection does not last long enough to complete sexual intercourse, tell your doctor.

In these cases, your doctor may decide that you need a higher dose.

If you are about to start taking any new medicines, especially nitrates, or Adepmas (riociguat), tell your doctor and pharmacist that you are taking Viagra.

See "Before you take Viagra" for a list of common nitrate medications.

Tell any other doctors, dentists and pharmacists who are treating you that you are taking Viagra.

Things you must not do

Do not use drugs containing amyl nitrite (sometimes called "poppers") while you are taking Viagra.

If you get an angina attack do not take nitrate medicines to relieve the pain but tell your doctor immediately. Make sure your doctor knows you are taking Viagra.

Do not give Viagra to anyone else, even if they have the same condition as you.

Things to be careful of

Be careful drinking alcohol while taking Viagra.

Drinking alcohol can temporarily impair the ability to get an erection.

Do not drink large amounts of alcohol before sexual activity.

If you experience changes in vision, or dizziness, when taking Viagra, you should not drive or operate machinery.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Viagra.

While Viagra helps most people, it can cause some unwanted side effects in a few people. All medicines have side effects. If unwanted effects occur, most are likely to be minor and temporary. However, some may be serious and need medical attention.

Do not be alarmed by this list of possible side effects.

You may not get any of them.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

How Viagra can mess up your marriage

AFP-Getty Images file

Did the makers of Viagra and its cousins, Levitra and Cialis, foresee the side effects — physical and otherwise — that the drugs could cause?

By Judith Newman, Prevention

updated 4/22/2011 9:34:36 AM ET 2011-04-22T13:34:36

Be careful what you wish for, I think as my husband reaches again for his new toy. Tragically, it's not a Ferrari or the latest Mac laptop — it's his Penis 2.0—the new, pharmaceutically enhanced model.

I married an older man, and lucky for us both, the only part on him that's given out is his knees. But since I was writing about erectile dysfunction (ED) drugs, I wanted him to help me out. Would he try one? The little blue pill enables older men to sexually respond like 18-year-olds. "Wouldn't that be interesting," I asked him, "journalistically speaking?"

John was skeptical. "What if I take this and things never work without the pill again?" he asked. I pointed out that the label of a leading brand, Viagra, does not list physical dependence as a side effect (although it does mention headaches and an upset stomach). True to promise, when John used Viagra, everything was perfectly fine. But to my chagrin, it was perfectly fine a lot.

Don't miss these Health stories

Rates of women who are opting for preventive mastectomies, such as Angeline Jolie, have increased by an estimated 50 percent in recent years, experts say. But many doctors are puzzled because the operation doesn't carry a 100 percent guarantee, it's major surgery -- and women have other options, from a once-a-day pill to careful monitoring.

And therein lies a problem I wonder whether the makers of Viagra and its pharmaceutical cousins Levitra and Cialis foresaw. While men of a certain age are undoubtedly thrilled to have their sexual potency restored, maybe their wives' enthusiasm is a bit more subdued?

What at first glance seems an obvious win-win situation for both husbands and wives can have a raft of unintended consequences. Don't get me wrong: Viagra is a wonder drug. Since the early '90s, when researchers testing a new heart medication called Sildenafil discovered that it had a startling side effect in men, erectile dysfunction drugs have become more than a billion-dollar industry.

One study conducted by Express Scripts, a pharmacy benefit management company, found that nearly 20% of all American men over age 45 have tried them. And since, according to the National Institutes of Health, approximately 5 percent of 40-year-old men and from 15 to 25 percent of 65-year-old men experience ED (for reasons ranging from narrowing of the blood vessels with age to high blood pressure, diabetes, obesity, and neurological problems), these drugs have been a godsend to millions.

ED drugs can also, indirectly, be lifesavers. Thirty-four to 70 percent of all men who take antidepressants experience sexual dysfunction as a side effect, and of those who have this problem, almost 90 percent stop taking the antidepressants so their sex lives can go back to normal.

But ED drugs are so readily available, so much a jokey part of the cultural landscape, that few of us really know how they work and what the potential dangers are. This leads to misuse — not so much life-threatening as knuckleheaded.

Essentially, ED drugs work like this: What gives a man an erection is blood flow to the penis. The vessels dilate, and blood flows in. There is an enzyme that counteracts the dilation. ED drugs inhibit that enzyme, allowing dilation to occur more easily and last longer. They can also diminish a man's refractory time, meaning that after orgasm he can more quickly get an erection again.

The one thing most people know about Viagra and its cohorts is that they are not supposed to be used by men who take nitroglycerin, a common medication for heart patients that also dilates the blood vessels. But ask around. That little piece of knowledge has translated into "Viagra is bad if you have a heart condition."

Not so, says Arthur S. Agatston, MD, a cardiologist and associate professor of medicine at the University of Miami Miller School of Medicine and Prevention editorial advisory board member. In fact, Dr. Agatston says, because Viagra keeps the blood vessels from becoming "sticky" and helps blood flow through them smoothly, not just in the penis but throughout the body, in the future, many of us—women included—may end up taking some small amount of Viagra daily, the way we take baby aspirin, which has the same nonsticking effect on blood itself.

So when a man takes Viagra, he has to avoid anything that dilates the blood vessels, not just nitroglycerides. Drinking, lying in the sun — both are problematic. Viagra won't give him a heart attack, but, taken with too much alcohol, it could make him pass out, Dr. Agatston says.

Perhaps more damaging than ignorance of the physical ramifications of ED drugs is ignorance of their potential interpersonal blowback. When not discussed frankly, Viagra can cause a lot of misunderstanding and hurt between couples. "There is something about a hard erection that is extremely important to a man's identity," says Steven Lamm, MD, an internist in New York City and author of The Hardness Factor. "And of course most couples would prefer that the man be able to have one. But there are some who may have adjusted to life without sex. Perhaps the woman doesn't really want it anymore, for one reason or another. And for those couples, the introduction of an ED drug can throw them seriously out of sync."

That leads to what is perhaps the biggest complicating factor: the reality that a woman's postmenopause genital health can put her physically at odds with her partner's newfound, drug-assisted prowess. As women age, their hormonal balances change. Reduced estrogen levels often mean less sexual desire but also decreased vaginal elasticity and lubrication, and thus more potential for sex to be painful.

The problem can be especially daunting for older women who are widowed or divorced or just beginning to date after years of being alone or with one man. Certainly this was the case for Marjorie P. a 60-something woman who complained about the drugs on a 50+ Web site: "Men have been saved from their middle-age sexual issues by Viagra and Cialis. They can be thirty again, while I have to deal with the sexual issues of being my age. It's put the world on 'tilt.'" Andrea D. a twice-divorced physician from Santa Monica, CA, and an over-50 dater, put it more bluntly. "Viagra has been liberating for men, but unless a woman is taking hormone therapy, she may have vaginal dryness and really not be that interested in the kind of driving, pounding intercourse he's now capable of."

There is also fallout from the erroneous belief that Viagra causes not just greater blood flow but also greater desire. The hormone testosterone is the driving force behind libido; a man with little or no testosterone will not have any desire to have sex, Viagra or no. Moreover, even with normal amounts of testosterone, "Viagra does not just instantly give a man an erection," says Abraham Morgentaler, MD, associate clinical professor of urology at Harvard Medical School and author of The Viagra Myth.

"You have to be in a sexual situation, you need to have desire and intent, in order for the drug to work." Dr. Morgentaler tells the story of a patient who was very upset because Viagra didn't do the trick for him. "He said, 'Doc, I followed your directions exactly. I took the pill an hour in advance. Then I watched a baseball game on TV and waited.' The man's wife was in the other room, waiting too; neither of them realized that the drug would be effective only if they were together, doing what couples do."

The misunderstandings cut all ways: Some women think ED drugs make men amorous and that their presence isn't required. "What a lot of women need to be turned on is the feeling that they're desired," adds Virginia A. Sadock, MD, director of the program in human sexuality at New York University Langone Medical Center. "So with Viagra, they think, Oh, it's not me he wants; it's the Viagra talking. In my practice, I spend a lot of time reassuring them that this isn't the case — and I tell men they must reassure the women too."

Another big issue for many women: ED drugs drastically shorten the interval between climaxing and achieving another erection. Men look at this differently than women do. For them, it's not a bug, it's a feature. And for the woman?

"We want maybe twenty or thirty great minutes of sex," says Susan K. a mother of two in Connecticut. "We don't want an interminable two hours." Not to mention the fact that prolonged intercourse, particularly without sufficient lubrication, can do damage. It can lead to vaginal abrasions and even tearing and can expose a woman to risk of getting yeast infections and — particularly for a woman who is dating or divorced — to sexually transmitted diseases.

There are, too, single women who worry that men with new-and-improved sexual abilities will be less likely to commit to marriage, and wives who worry that their husbands will be more apt to look outside the marriage for sex.

"A partner's Viagra use is now another reason some women give when I ask why they've come to see me," says Miami plastic surgeon Lee Gibstein, MD, who has performed breast implants, face-lifts, and even vaginal rejuvenation on women concerned about turning back the clock.

Which is not to say that Viagra hasn't ever led to straying—but not for the reasons women think. "I've seen problems when a wife or partner objects to ED drugs on the grounds that sex should be natural and spontaneous," says Dr. Morgentaler. So if the man is unable to have erections on his own, and the woman shoots down the idea of a pill, then the guy is really stuck. The relationship can get into trouble, because one person wants sex and the other doesn't or only wants it on her terms.

So how can you make sure, if ED drugs come into your marriage, that they help rather than hamper your relationship?

"Couples really need to talk about what each partner in the relationship expects," says New York couples counselor Jane Greer, PhD, author of What About Me. Stop Selfishness from Ruining Your Relationship. "The drug can highlight problems about which member of the couple puts him or herself first, which one is thoughtful and which isn't — creating all sorts of conflict."

Adds Andrea, whose own Viagra dating experiences and the experiences of similarly aged friends have ranged from excellent to Emergency Care Needed:

"You have to be crystal clear about what works for you and what doesn't. Because even with someone you really, really adore. sometimes you just want to get back to reading your book!"

Moreover, women need to stop lying about what they like and don't like to protect the male ego, because that's a recipe for sexual dissatisfaction. "Women can cheat themselves out of good sex because they don't take responsibility for their own feelings, both physically and emotionally," says Dr. Sadock. This means: If you need to buy lubricant to make sex more comfortable, do it; if you need to tell him you're perfectly happy having intercourse for a few minutes, do that too.

After my husband's little panic about never being able to function without the wonders of pharmaceuticals again, well, it took only a week before he was back to his old self. But here's the interesting thing. He told me at the time that he threw out the Viagra. Last night, I noticed it was still in his drawer. I guess it's nice to have an insurance policy.

Copyright© 2012 Rodale Inc. All rights reserved. No reproduction, transmission or display is permitted without the written permissions of Rodale Inc.

PATIENT INFORMATION

VIAGRA® (vi-AG-rah) (sildenafil citrate) Tablets

What is the most important information I should know about VIAGRA?

VIAGRA can cause your blood pressure to drop suddenly to an unsafe level if it is taken with certain other medicines. Do not take VIAGRA if you take any other medicines called “nitrates.” Nitrates are used to treat chest pain (angina ). A sudden drop in blood pressure can cause you to feel dizzy, faint, or have a heart attack or stroke .

Do not take VIAGRA if you take medicines called guanylate cyclase stimulators which include:

Riociguat (Adempas®) a medicine that treats pulmonary arterial hypertension and chronicthromboembolic pulmonary hypertension.

Tell all your healthcare providers that you take VIAGRA. If you need emergency medical care for a heart problem, it will be important for your healthcare provider to know when you last took VIAGRA.

Stop sexual activity and get medical help right away if you get symptoms such as chest pain, dizziness, or nausea during sex.

Sexual activity can put an extra strain on your heart, especially if your heart is already weak from a heart attack or heart disease. Ask your doctor if your heart is healthy enough to handle the extra strain of having sex.

VIAGRA does not protect you or your partner from getting sexually transmitted diseases, including HIV —the virus that causes AIDS .

VIAGRA is a prescription medicine used to treat erectile dysfunction (ED). You will not get an erection just by taking this medicine. VIAGRA helps a man with erectile dysfunction get and keep an erection only when he is sexually excited (stimulated).

VIAGRA is not for use in women or children.

It is not known if VIAGRA is safe and effective in women or children under 18 years of age.

Who should not take VIAGRA?

Do not take VIAGRA if you:

take medicines called nitrates (such as nitroglycerin)

use street drugs called “poppers” such as amyl nitrate or amyl nitrite, and butyl nitrate

take any medicines called guanylate cyclase stimulators such as riociguat (Adempas)

are allergic to sildenafil, as contained in VIAGRA and REVATIO, or any of the ingredients in VIAGRA. See the end of this leaflet for a complete list of ingredients in VIAGRA.

What should I tell my healthcare provider before taking VIAGRA?

Before you take VIAGRA, tell your healthcare provider if you:

have or have had heart problems such as a heart attack, irregular heartbeat, angina, chest pain, narrowing of the aortic valve or heart failure

have had heart surgery within the last 6 months

have pulmonary hypertension

have had a stroke

have low blood pressure. or high blood pressure that is not controlled

have a deformed penis shape

have had an erection that lasted for more than 4 hours

have problems with your blood cells such as sickle cell anemia. multiple myeloma. or leukemia

have retinitis pigmentosa. a rare genetic (runs in families) eye disease

have ever had severe vision loss, including an eye problem called non-arteritic anterior ischemic optic neuropathy (NAION)

have bleeding problems

have or have had stomach ulcers

have liver problems

have kidney problems or are having kidney dialysis

have any other medical conditions

Tell your healthcare provider about all the medicines you take*, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

VIAGRA may affect the way other medicines work, and other medicines may affect the way VIAGRA works causing side effects. Especially tell your healthcare provider if you take any of the following:

medicines called nitrates (see “What is the most important information I should know about VIAGRA?” )

medicines called guanylate cyclase stimulators, such as riociguat (Adempas)

medicines called alpha blockers such as Hytrin (terazosin HCl), Flomax (tamsulosin HCl), Cardura (doxazosin mesylate), Minipress (prazosin HCl), Uroxatral (alfuzosin HCl), Jalyn (dutasteride and tamsulosin HCl), or Rapaflo (silodosin). Alpha-blockers are sometimes prescribed for prostate problems or high blood pressure. In some patients, the use of VIAGRA with alpha-blockers can lead to a drop in blood pressure or to fainting .

medicines called HIV protease inhibitors, such as ritonavir (Norvir), indinavir sulfate (Crixivan), saquinavir (Fortovase or Invirase) or atazanavir sulfate (Reyataz)

some types of oral antifungal medicines, such as ketoconazole (Nizoral), and itraconazole (Sporanox)

some types of antibiotics, such as clarithromycin (Biaxin), telithromycin (Ketek), or erythromycin

other medicines that treat high blood pressure

other medicines or treatments for ED

VIAGRA contains sildenafil, which is the same medicine found in another drug called REVATIO. REVATIO is used to treat a rare disease called pulmonary arterial hypertension (PAH ). VIAGRA should not be used with REVATIO or with other PAH treatments containing sildenafil or any other PDE5 inhibitors (such as Adcirca [tadalafil]).

Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure.

Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine.

How should I take VIAGRA?

Take VIAGRA exactly as your healthcare provider tells you to take it.

Your healthcare provider will tell you how much VIAGRA to take and when to take it.

Your healthcare provider may change your dose if needed.

Take VIAGRA about 1 hour before sexual activity. You may take VIAGRA between 30 minutes to 4 hours before sexual activity if needed.

VIAGRA can be taken with or without food. If you take VIAGRA after a high fat meal (such as a cheeseburger and french fries), VIAGRA may take a little longer to start working

Do not take VIAGRA more than 1 time a day.

If you accidentally take too much VIAGRA, call your doctor or go to the nearest hospital emergency room right away.

What are the possible side effects of VIAGRA?

VIAGRA can cause serious side effects. Rarely reported side effects include:

an erection that will not go away (priapism). If you have an erection that lasts more than 4 hours, get medical help right away. If it is not treated right away, priapism can permanently damage your penis.

sudden vision loss in one or both eyes. Sudden vision loss in one or both eyes can be a sign of a serious eye problem called non-arteritic anterior ischemic optic neuropathy (NAION). Stop taking VIAGRA and call your healthcare provider right away if you have sudden vision loss in one or both eyes.

sudden hearing decrease or hearing loss. Some people may also have ringing in their ears (tinnitus ) or dizziness. If you have these symptoms, stop taking VIAGRA and contact a doctor right away.

The most common side effects of VIAGRA are:

headache

flushing

upset stomach

abnormal vision, such as changes in color vision (such as having a blue color tinge) and blurred vision

stuffy or runny nose

back pain

muscle pain

nausea

dizziness

rash

In addition, heart attack, stroke, irregular heartbeats and death have happened rarely in men taking VIAGRA. Most, but not all, of these men had heart problems before taking VIAGRA. It is not known if VIAGRA caused these problems.

Tell your healthcare provider if you have any side effect that bothers you or does not go away.

These are not all the possible side effects of VIAGRA. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1800-FDA-1088.

How should I store VIAGRA?

Store VIAGRA at room temperature between 68°F to 77°F (20°C to 25°C).

Keep VIAGRA and all medicines out of the reach of children.

General information about the safe and effective use of VIAGRA.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use VIAGRA for a condition for which it was not prescribed. Do not give VIAGRA to other people, even if they have the same symptoms that you have. It may harm them.

This Patient Information leaflet summarizes the most important information about VIAGRA. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about VIAGRA that is written for health professionals.

For more information, go to www. viagra. com, or call 1-888-4VIAGRA

What are the ingredients in VIAGRA?

Active ingredient: sildenafil citrate

Inactive ingredients: microcrystalline cellulose, anhydrous dibasic calcium phosphate, croscarmellose sodium, magnesium stearate, hypromellose, titanium dioxide, lactose, triacetin, and FD & C Blue #2 aluminum lake

This Patient Information has been approved by the U. S. Food and Drug Administration.

Last reviewed on RxList: 10/3/2015 This monograph has been modified to include the generic and brand name in many instances.

Viagra (sildenafil) facts

What is Viagra?

Viagra is the trade name for a drug called Sildenafil. Viagra is one of a class of drugs known as PDE-5 (Phosphodiesterase type 5) inhibitors.

Viagra and the other PDE-5 inhibitors can help men with erectile dysfunction (male impotence) by enhancing the erectile response when a man is sexually stimulated. Aside from Viagra, the other drugs in this class are Cialis (Tadalafil) and Levitra (Vardenafil).

How does Viagra work?

Viagra does not cause a man to be sexually aroused. Viagra is only effective if you are sexually aroused. To understand how it works you need to understand the mechanics of how a man gets an erection. When you get sexually stimulated, the nervous system in the erectile tissue of your penis releases nitric oxide (NO).

The nitric oxide stimulates an enzyme that produces something called a messenger cyclic guanosine monophosphate (cGMP). The cGMP relaxes the smooth muscle cells. One result of this is that the arteries in your penis dilate and the blood can flow into your penis more easily. Another result is that the erectile tissue itself fills with blood. Both of these process result in an erection. Viagra works by maintaining the level of cGMP in the smooth muscle cells.

If you are not turned on, your brain will not stimulate the release of any nitric oxide and you will not produce any cGMP.

Is Viagra effective?

Clinical studies have shown that when compared to placebo, Viagra and the other drugs in the same class, result in significant improvement in erectile function. Although established to be a safe and effective drug, Viagra isn't appropriate for everyone and may not work in all cases.

How does it affect blood pressure?

Viagra can slightly lower blood pressure. This is not a problem for most men. But Viagra's effect on blood pressure is exaggerated if the Viagra is taken with a nitrate drug.

Nitrates are one of the treatments doctors prescribe for angina. If you take Viagra when you are also taking nitrates, the combined effect of the Viagra and the nitrates can lower your blood pressure to such an extent that it could prove fatal. Never take Viagra at the same time as taking nitrates.

If I have a heart condition can I take it?

If you have a heart condition it is important that you discuss this with the doctor before taking Viagra. Viagra may not be appropriate because of the danger of interacting with the nitrates.

Can women take it?

Viagra is not currently licensed for use by women.

How quickly does it work?

On average, Viagra becomes effective in just under an hour when you take a tablet on an empty stomach. Viagra can remain effective for between four and six hours. If you take it after a meal that has a high fat content, it may take longer than an hour to become effective.

Why are there different doses?

Viagra is available in three dosages: 25mg, 50mg and 100mg. Some men may respond to a lower dose of Viagra. Some men may already be taking medicines that interact with Viagra and thus need to adjust the Viagra dosage they are taking.

What dose is right for me?

The doctor needs to decide which dosage of Viagra is most appropriate. The doctor will take into account potential drug interactions, your age, the severity of your erectile dysfunction and any previous experience you have had with Viagra.

What if it does not work the first time I use it?

Viagra might not work the first time you take it. Most doctors advise taking Viagra at least eight times before trying a different medicine.

What are the side-effects?

Viagra's Side effects are generally mild and brief. Viagra's most common side-effects are headache and facial flushing. Less frequently, men taking Viagra have reported indigestion, a stuffy nose and a blue tint to the vision.

Does it interact with other medicines?

Viagra interacts with many drugs. The following list is not complete but it is important to inform the doctor of all prescription and non-prescription medication taken, especially:

nitrate medications (e. g. glyceryl trinitrate (GTN), nitroglycerin, isosorbide mononitrate or dinitrate)

nitroprusside

cimetidine

erythromycin

azole antifungals (e. g. itraconazole, ketoconazole)

mibefradil

rifamycins (e. g. rifampicin)

Alpha blockers, prescribed for prostate disease or high blood pressure

Ritonavir, Amyl, Butyl or Isopropyl nitrates ('Poppers')

Who shouldn't use it?

Men who have any of the following conditions should also avoid taking it:

severe heart or liver problems

recent stroke or heart attack

low blood pressure

certain rare inherited eye diseases

Does it treat the underlying causes of impotence?

Viagra will resolve the underlying cause of erectile dysfunction although if the cause is primarily psychological, it may help to break the cycle of anxiety and failure associated with being unable to achieve a satisfactory erection.

What kind of tests might highlight the underlying causes of male impotence?

A blood test for diabetes should be performed along with cholesterol and triglyceride blood tests. It is becoming increasingly accepted among doctors that sex hormone levels (Testosterone) should also be checked by way of a blood test.

What other impotence treatments are available?

The other drugs, Levitra and Cialis work in similar ways. Viagra is generally prescribed as the first line treatment. Cialis has a much longer half-life than Viagra and Levitra and therefore its effect lasts much longer.

This does not mean one has prolonged erections but the length of time available for further erections is increased without the need to take further doses. It also means however that the side effects if present will last longer. Levitra, like Cialis, can be taken with food whereas Viagra should be taken on an empty stomach.

Some studies have shown Levitra to be more suitable for men suffering from diabetes. Other treatments include Caverject ('Alprostadil'), which is a medication injected directly into the penis and MUSE (another form of 'Alprostadil'), which is a pellet inserted into the urethra. These may be of use for men who have to take Nitrates and are therefore unable to take the PDE5 inhibitors.

The use of vacuum pumps and other mechanical devices for producing and maintaining erections are alternatives to taking medication.

Lanfine mansion house ayrshire, lanafine

Lanfine House

Lanfine House was built for John Brown (1729-1802) a successful textile manufacturer and banker. He was also a bailie in the city of Glasgow and became wealthy enough to buy Waterhaughs, the property of his maternal grandfather. He acquired 400 acres at Lanfine presumably when Cessnock Estate was sold by the Hume family in 1769 and immediately set about the construction of the mansion house.

Lanfine House

The building work was undertaken by James Armour of Mauchline, who was to become the father-in-law of Robert Burns. Lanfine House was completed in 1772.

On the death of John Brown in 1802, his son Nicol Brown took over as Laird of Lanfine and Waterhaughs. About 1811, he planted Lanfine Woods. After the death of Nicol Brown in 1829, the estate was inherited by his cousin Thomas Brown, a physician in Glasgow, and for a time, Professor of Botany at Glasgow University. Thomas Brown indulged his interest in botany by planting many exotic trees, shrubs and large areas of woodlands. These are now mature specimen trees that can be seen today in the beauty of the tree-clad landscape extending from Newmilns to Darvel on the south of the river. He also cultivated less hardy species in the large greenhouses within the walled garden.

The estate of Lanfine grew from the original 400 acres acquired by John Brown in 1769, to over 10,000 acres. The mansion was also extended by each generation into what can be seen today.

There is a large apartment in the mansion available for holidays. For more information on Lanfine Estate, visit the website www. lanfinehouse. com .

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