P - Contraindicated in pregnancy
L - Contraindicated in lactation
FI - Food *
Simvastatin, (marketed under the trade names Zocor, Simlup, Simcard, Simvacor, and others, as well as generically) is a hypolipidemic drug belonging to the class of pharmaceuticals called "statins". It is used to control hypercholesterolemia (elevated cholesterol levels) and to prevent cardiovascular disease. Simvastatin is a synthetic derivate of a fermentation product of Aspergillus terreus.
Simvastatin is a prodrug metabolised in the liver to form the active β-hydroxyacid derivative. This inhibits the conversion of HMG-CoA to mevalonic acid by blocking HMG-CoA reductase, an early and rate-limiting step in cholesterol biosynthesis. It reduces total cholesterol, LDL-cholesterol and triglycerides and increases HDL-cholesterol levels.
Absorbed from the GI tract (oral).
Extensively hepatic; undergoes metabolism by CYP3A4.
Mainly excreted in the faeces as metabolites. Urine (10-15% inactive form); 1.9 hours (elimination half-life, active metabolite).
Information Not Available
Headache, nausea, flatulence, heartburn, abdominal pain, diarrhoea/constipation, dysgeusia; myopathy features like myalgia and muscle weakness; serum transaminases and CPK elevations; hypersensitivity; lens opacities; blurring of vision; dizziness; sexual dysfunction; insomnia; depression and upper respiratory symptoms.
Potentially Fatal: Severe rhabdomyolysis with acute renal failure.
Monitor LFTs before initiation of treatment and periodically thereafter. Check lipid profile after 4 weeks of therapy and periodically thereafter. Monitor CPK levels periodically.
History of liver disease. Increased risk of rhabdomyolysis in severe infection, hypotension, major surgical trauma, uncontrolled seizures or severe metabolic, endocrine and electrolyte disorder. Alcoholism; premenarcheal females; children <10 years. Discontinue treatment if there is marked or persistent increase in serum-aminotransferase concentrations.
May cause slight elevation of serum digoxin. May increase risk of bleeding when used with coumarins and fluindione. Serum levels may be increased when used with ranolazine, itraconazole, verapamil, diltiazem and imatinib. Reduced serum levels when used with carbamazepine and rifampicin. Increased risk of myopathy when used with amiodarone, colchicine, danazol, clarithromycin and nefazodone.
Potentially Fatal: Concurrent use with ciclosporin, gemfibrozil, niacin or protease inhibitors may increase the risk of rhabdomyolysis and acute renal failure.
Concurrent admin with large amounts of grapefruit juice may increase serum levels of simvastatin. Serum levels may be reduced by St John's wort.
Adult: Initially, 10-20 mg/day, to be taken in the evening. May start with 40 mg once daily in patients with high CV risk or require a large reduction in cholesterol. For patients with moderate CV risk, initiate with 10 mg once daily. May adjust dose at intervals of at least 4 weeks. Max: 80 mg once daily. For patients with homozygous familial hypercholesterolaemia: 40 mg once daily in the evening or 80 mg daily (given in 3 divided doses of 20 mg, 20 mg and an evening dose of 40 mg).
Renal impairment:Severe impairment: initially, 5 mg once daily. Doses >10 mg daily should be used with caution.
Cardiovascular risk reduction
Adult: In high-risk patients (e.g. patients with diabetes mellitus or atherosclerotic cardiovascular disease): 20-40 mg once daily. Moderate-risk patients: 10 mg once daily.
For patients taking drugs that interact with simvastatin, initially, 5 mg once daily. Max: 10 mg/day (for patients taking ciclosporin, fibrates or nicotinic acid) and 20 mg/day (for patients taking amiodarone or verapamil).
May be taken with or without food. (Avoid excessive consumption (> 1 L/day) of grapefruit juice.)
Contraindicated in pregnancy
Category X: Studies in animals or human beings have demonstrated foetal abnormalities or there is evidence of foetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.
Contraindicated in lactation
Safety and efficacy not established in children younger than 10 years of age with heterozygous familial hypercholesterolemia
No overall difference in safety between older and younger patients.
Acute liver disease or unexplained persistent elevations of serum transaminases. Pregnancy, lactation. Porphyria.
Store at 5-30°C
Store at 5-30°C