Products
Most statins are commercially available in the form of film-coated tablets, and some are also available as capsules. The first active ingredient to be marketed was lovastatin from Merck in the United States in 1987. In many countries, simvastatin (Zocor) and, shortly thereafter, pravastatin (Selipran) were the first agents to be approved in 1990.
Structure and properties
The first statin, lovastatin, is a natural product isolated in 1978 as a fermentation product of mold. It is also found in red mold rice, a traditional Chinese food and medicine. The other first active ingredients – simvastatin and pravastatin – are closely related to lovastatin. The other active ingredients were developed fully synthetically. Lovastatin and simvastatin exist as lactones, cyclic esters. They are prodrugs and are hydrolyzed in the body to the active inhibitor. Statins are also divided into hydrophilic and lipophilic agents. Pravastatin and rosuvastatin belong to the hydrophilic representatives.
Effects
Statins (ATC C10AA) have lipid-lowering properties. The effects are based on inhibition of endogenous cholesterol formation through competitive inhibition of HMG-CoA reductase. This enzyme catalyzes an early and rate-determining step in cholesterol biosynthesis by conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) to mevalonic acid (mevalonate). This also stimulates LDL receptor synthesis and increases LDL particle uptake. Statins lower LDL, VLDL, total cholesterol, triglycerides, ApoB and increase HDL. Furthermore, statins exert so-called pleiotropic effects that are independent of cholesterol lowering. These include, for example, antioxidant, anti-inflammatory, immunomodulatory, cardioprotetcive, antiproliferative, and antithrombotic effects. Because statins interfere relatively early in the synthesis of cholesterol, the formation of other metabolites (isoprenoid intermediates) formed from mevalonate is also inhibited. This is one explanation for its diverse properties.
Indications
For the prevention of cardiovascular disease and reduction of mortality:
- For the reduction of elevated blood lipid levels (total cholesterol, LDL, triglycerides, ApoB) of various causes (hypercholesterolemia, hyperlipidemia).
- For the prevention of cardiovascular events (eg, myocardial infarction, stroke) in patients at high risk.
In addition to the classic indications, countless applications are discussed in the literature.
Dosage
According to the professional information. Medicines are usually taken once daily. Some medications are recommended to be taken in the evening. Others may be administered regardless of the time of day, but always at the same time.
Active ingredients
- Atorvastatin (Sortis, generic).
- Fluvastatin (Lescol, generics)
- Pitavastatin (Livazo)
- Pravastatin (Selipran, generics)
- Rosuvastatin (Crestor, generics)
- Simvastatin (Zocor, generics)
Other statins:
- Cerivastatin (Lipobay) was withdrawn from the market in 2001 due to severe adverse effects (see below).
- Lovastatin (Mevacor), the first statin, is not on the market in many countries.
- Mevastatin was discovered before lovastatin and played an important role in the development of the drug class. However, it has never been marketed as a drug.
Contraindications
Contraindications include hypersensitivity, liver disease, unexplained elevation of serum transaminases, myopathy, and pregnancy and lactation (select). Full details of precautions can be found in the Drug Information Leaflet.
Interactions
The active ingredients differ in their pharmacokinetic properties, metabolism, and potential for drug-drug interactions. Omeprazole, lovastatin, and atorvastatin are substrates of CYP3A. When combined with CYP inhibitors, concentrations may increase and the risk for adverse effects may increase. In contrast, the other statins interact less or hardly at all with CYP450, and some statins are substrates of transporters such as OATP and BCRP. The risk of skeletal muscle disease is increased in combination with certain agents. These include, for example, ciclosporin, CYP inhibitors of CYP substrates, fusidic acid, and fibrates.
Adverse effects
The most common possible adverse effects include:
- Digestive disturbances such as constipation, bloating, dyspepsia, nausea, and diarrhea
- Muscle and joint pain, muscle cramps, pain in the extremities, muscle cramps, joint swelling, back pain.
- Headache
- Respiratory infections
Statins can cause muscle disorders and very rarely life-threatening disintegration of skeletal muscle (rhabdomyolysis). Cerivastatin had to be withdrawn from the market because of this side effect. Statins can also occasionally cause liver disease such as hepatitis.
