Getz Pharma


Getz Bros
Full Prescribing Info
Simvastatin is a lipid-lowering agent that is derived synthetically from a fermentation of product of Aspergillus terreus.
Simvastatin is butanoic acid, 2,2-dimethyl,1,2,3,7,8, 8a-hexahydro-3, 7-dimethyl-8-[2-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)] ethyl-1-naphthalenyl ester,(1S-[1α,3α,7β,8β(2S,4S),8aβ]).
Simvastatin's molecular formula is C25H39O6.
Pharmacology: Mechanism of Action: After oral ingestion, simvastatin, which is an inactive lactone, is hydrolyzed to the corresponding β-hydroxyacid form. This is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, which an early and rate-limiting step in the biosynthesis of cholesterol.
Pharmacokinetics: Simvastatin is absorbed from the GIT and is hydrolyzed to its active β-hydroxyacid form. Other active metabolites have been detected and a number of inactive metabolites are also formed. Simvastatin undergoes intensive first-pass metabolism in the liver, its primary site of action. Less than 5% of the oral dose has been reported to reach the circulation as active metabolites. Both simvastatin and its β-hydroxyacid metabolite are about 95% bound to plasma proteins. It is mainly excreted in the feces via the bile as metabolites. About 10-15% is recovered in the urine, mainly in inactive form. The t½ of active metabolite is 1.9 hrs.
Reductions in Risk of Coronary Heart Disease (CHD) Mortality and Cardiovascular Events: In patients at high risk of coronary events because of existing CHD, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease. Simvoget is indicated to: Reduce the risk of total mortality by reducing CHD deaths, non-fatal myocardial infarction and stroke.
Reduce the need for coronary and non-coronary revascularization procedures.
Patients with Hypercholesterolemia Requiring Modifications of Lipid Profiles: Simvastatin is indicated to: Reduce elevated Total-C, LDL-C, Apo B and TG, and to increase HDL-C on patients with primary hypercholesterolemia (heterozygous familial and non-familial) and mixed dyslipidemia (Fredrickson types IIa and IIb4).
Treat patients with hypertriglyceridemia (Fredrickson type IV hyperlipidemia).
Treat patients with primary dysbetalipoproteinemia (Fredrickson type III hyperlipidemia).
Reduce Total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) or if such treatments are unavailable.
Adolescent Patients with Heterozygous Familial Hypercholesterolemia (HeFM): Simvoget is indicated as an adjunct to diet to reduce total-C, LDL-C and Apo B levels in adolescent boys and girls who are at least 1 year post-menarche, 10-17 years, with heterozygous familial hypercholesterolemia, if after an adequate trial of diet therapy the following findings are present: LDL cholesterol remains 190 or 160 mg/dL.
There is a positive family history of premature cardiovascular disease (CVD) or 2 or more CVD risk factors are present in the adolescent patient.
The minimum goal of treatment in pediatric and adolescent patients is to achieve a mean LDL-C <130 mg/dL.
Dosage/Direction for Use
The patient should be placed on a standard cholesterol-lowering diet before receiving Simvoget and should continue on this diet during treatment with Simvoget. In patients with CHD or at high risk of CHD, Simvastatin can be started simultaneously with diet. Lipid determination should be performed at intervals of no less than 4 weeks and the dosage should be individualized according to the goals of therapy and the patient's response. (For the treatment of adult dyslipidemia, see table of NCEP Treatment Guidelines.) (See table.)

Click on icon to see table/diagram/image

Dose Range: 5-80 mg/day. Starting Dose: 20-40 mg once daily in the evening.
Reductions in Risk of CHD Mortality and Cardiovascular Events: For patients at high risk for a CHD event due to existing coronary heart disease, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, the recommended starting dose is 40 mg/day. Lipid determinations should be performed after 4 weeks of therapy and periodically, thereafter.
Patients with Homozygous Familial Hypercholesterolemia: Recommended Dose: 40 mg/day in the evening or 80 mg/day in 3 divided doses of 20 mg, 20 mg and an evening dose of 40 mg.
Simvoget should be used as and adjunct to other lipid-lowering treatments (eg, LDL apheresis) in these patients or if such treatments are unavailable.
Patients with Heterozygous Familial Hypercholesterolemia: Adolescents 10-17 years: Starting Dose: 10 mg once daily in the evening. Recommended dosing range is 10-40 mg/day. Maximum Dose: 40 mg/day. Doses should be individualized according to the recommended goal of therapy. Adjustment should be made at intervals of ≥4 weeks. Doses >40 mg have not been studied in this population.
Concomitant Lipid-lowering Therapy: Simvoget is effective alone or when used concomitantly with bile-acid sequestrants. Maximum Dose: 10 mg/day, if Simvoget is used in combination with gemfibrozil.
Patients Taking Cyclosporine or Danazol: Starting Dose: 5 mg/day. Maximum Dose: 10 mg/day.
Patients Taking Amiodarone or Verapamil: Maximum Dose: 20 mg/day.
Patients with Renal Insufficiency: Because Simvoget does not undergo significant renal excretion, modification of dosage should not be necessary in patients with mild to moderate renal insufficiency. However caution should be exercised when Simvoget is administered to patients with severe renal insufficiency. Such patients should be started at 5 mg/day and be closely monitored.
Patients with hypersensitivity to any component of Simvoget. Active liver disease or unexplained persistent elevations of serum transaminase.
Simvastatin is also contraindicated in combination with potent inhibitor of cytochrome P-450 3A4 including itraconazole, ketoconazole, HIV protease inhibitors, erythromycin, clarithromycin, telithromycin and nefazodone.
Pregnancy and lactation.
Special Precautions
General: Simvoget should be used with caution in patients who consume substantial quantities of alcohol.
Myopathy/Rhabdomyolysis: All patients starting therapy with simvastatin, or whose dose of simvastatin is being increased, should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness. Caution should be exercised in patients with predisposing factors for rhabdomyolysis.
If muscle pain, weakness or cramps occur while a patient is receiving treatment with a statin, their CK levels should be measured. If these levels are found, in the absence of strenuous exercise, to be significantly elevated (>5 x ULN), treatment should be stopped.
If symptoms resolve and CK levels return to normal, then re-introduction of the statin or introduction of an alternative statin may be considered at the lowest dose and with close monitoring.
Therapy with simvastatin should be temporarily stopped a few days prior to elective major surgery and when any major medical or surgical condition supervenes.
Hepatic Effect: It is recommended that liver function tests be performed before treatment begins and thereafter when clinically indicated. Patients titrated to the 80-mg dose should receive an additional test prior to titration, 3 months after titration to the 80-mg dose, and periodically thereafter (eg, semi-annually) for the 1st yr of treatment. Special attention should be paid to patients who develop elevated serum transaminase levels, and in these patients, measurements should be repeated promptly and then performed more frequently. If the transaminase levels show evidence of progression, particularly if they rise to 3 x ULN and are persistent, simvastatin should be discontinued.
Use in children: Simvastatin has not been studied in patients <10 years, nor in pre-menarchal girls.
Use In Pregnancy & Lactation
Contraindicated during pregnancy and lactation.
Adverse Reactions
Simvastatin is generally well-tolerated and side effects are rare. Minor side effects include constipation, diarrhea, fatigue, gas, heartburn and headache. Major side effects include abdominal pain or cramps, blurred vision, dizziness, easy bruising or bleeding, itching, muscle pain or cramps, rash and yellowing of the skin or eyes.
Drug Interactions
Diltiazem: The dose of simvastatin should not exceed 40 mg daily in patients receiving concomitant medication with diltiazem, unless the clinical benefit is likely to outweigh the increased risk of myopathy and rhabdomyolysis.
Grapefruit Juice: Intake of 240 mL of grapefruit juice in the morning and simvastatin in the evening resulted in a 1.9-fold increase of simvastatin concentration. Intake of grapefruit juice during treatment with simvastatin should therefore be avoided.
Oral Anticoagulants: In patients taking coumarin anticoagulants, prothrombin time should be determined before starting simvastatin and frequently enough during early therapy to ensure that no significant alteration of prothrombin time occurs. Once a stable prothrombin time has been documented, prothrombin times can be monitored at the intervals usually recommended for patients on coumarin anticoagulants.
Store at temperatures not exceeding 30°C. Protect from sunlight and moisture.
ATC Classification
C10AA01 - simvastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the treatment of hyperlipidemia.
FC tab 10 mg x 10's. 20 mg x 10's. 40 mg x 10's.
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