Products
Simvastatin is commercially available in the form of film-coated tablets (Zocor, generics). It is also combined fixed with ezetimibe (Inegy, generic). Simvastatin has been approved in many countries since 1990.
Structure and properties
Simvastatin (C25H38O5, Mr = 418.6 g/mol) exists as a white crystalline powder that is practically insoluble in water. It is a lactone obtained from a fermentation product of mold. Simvastatin, unlike newer statins, is a prodrug that is not biotransformed to the active beta-hydroxy acid until it reaches the organism.
Effects
Simvastatin (ATC C10AA01) has lipid-lowering properties. It lowers cholesterol levels, LDL-C, and triglycerides and increases HDL-C. The effects are due to inhibition of an early step in endogenous cholesterol biosynthesis by inhibition of HMG-CoA reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate. Simvastatin further has pleiotropic effects.
Indications
For treatment of dyslipidemia (hypercholesterolemia, hyperlipidemia) and prevention of cardiovascular complications.
Dosage
According to the SmPC. Tablets are usually taken once daily in the evening.
Contraindications
- Hypersensitivity
- Active liver disease
- Unresolved and persistent elevation of serum transaminases.
- Pregnancy and lactation
- Combination with strong CYP3A4 inhibitors.
- Combination with gemfibrozil, ciclosporin and danazol.
Full details of precautions and interactions can be found in the drug label.
Interactions
Simvastatin is a substrate of CYP3A4. Corresponding drug-drug interactions are possible and must be considered. Co-administration with fibrates such as gemfibrozil may increase the risk of muscle disease. Other interactions have been described.
Adverse effects
The most common potential adverse effects include respiratory infections, headache, abdominal pain, constipation, and nausea. Statins can rarely cause muscle disease, life-threatening skeletal muscle breakdown, and liver disease.
