Products
Atorvastatin is commercially available in the form of film-coated tablets (Sortis, generic, auto-generic). It has been approved in many countries since 1997. Atorvastatin is also available as a fixed combination with ezetimibe; see Atorvastatin and Ezetimibe.
Structure and Properties
Atorvastatin (C33H35FN2O5, Mr = 558.64 g/mol) is present in drugs as atorvastatin calcium trihydrate, (atorvastatin)2– – Ca2+ – 3 H2O. It is a white crystalline powder that is very slightly soluble in water.
Effects
Atorvastatin (ATC C10AA05) has lipid-lowering properties. It results in lowering LDL, the triglycerides, apolipoprotein B, and increases HDL. The effects are due in part to inhibition of HMG-CoA reductase. This enzyme catalyzes an early step in cholesterol biosynthesis by converting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) to mevalonic acid (mevalonate). Atorvastatin also has numerous pleiotropic effects that are partially independent of lipid metabolism.
Indications
Atorvastatin is used to reduce elevated total cholesterol, LDL cholesterol, apolipoprotein B, and triglyceride levels and to prevent cardiovascular events in high-risk patients (primary and secondary prevention).
Dosage
According to the drug label. Tablets are usually administered once daily, independent of meals. They can be taken at any time of the day.
Contraindications
- Hypersensitivity
- Active liver disease
- Permanent elevation of serum transaminases
- Cholestasis
- Muscle diseases
- Pregnancy and lactation
Full precautions can be found in the drug label.
Interactions
Atorvastatin is biotransformed by CYP3A4 to partially active metabolites; therefore, drug-drug interactions are possible via CYP3A4. These should be noted because there is (presumably) an increased risk of muscle disease with elevated atorvastatin concentrations. For example, potent CYP3A4 inhibitors such as itraconazole, clarithromycin, and ritonavir can lead to significant increases in atorvastatin concentrations. Ciclosporin, fibrates, and niacin may also increase the risk of muscle disease. Atorvastatin is transported by OATP1B1, so interactions via OATP1B1 are also possible. Full and comprehensive information on interactions can be found in the Drug Information Leaflet.
Adverse effects
The most common possible adverse effects include digestive disturbances such as bloating, constipation, and nausea; inflammation of the nasopharynx; headache; muscle and joint pain; muscle cramps; and swollen joints. Serious side effects, which occur rarely, include dissolution of striated muscle (rhabdomyolysis), severe allergic reactions, and severe skin reactions and liver damage.
