Rosuvastatin

Products

Rosuvastatin is commercially available in the form of film-coated tablets (Crestor, generic, auto-generic). It was approved in many countries in 2006 (Netherlands: 2002, EU and US: 2003). The marketing authorization holder is AstraZeneca. The statin was originally developed at Shionogi in Japan. In the USA, generic versions came on the market in 2016. In many countries, the patent expired on June 30, 2017.

Structure and properties

Rosuvastatin (C22H28FN3O6S, Mr = 481.5 g/mol) is present in drugs as rosuvastatin calcium, a white, amorphous powder that is sparingly soluble in water. It is a synthetic statin.

Effects

Rosuvastatin (ATC C10AA07) has lipid-lowering, anti-inflammatory, and pleiotropic properties. It lowers LDL cholesterol, total cholesterol, triglycerides, ApoB, VLDL-C, and raises HDL cholesterol. The effects are due to selective and competitive inhibition of HMG-CoA reductase, which plays a central role in the endogenous synthesis of cholesterol. Rosuvastatin increases the number of LDL receptors on the cell surface of the liver, thereby increasing the uptake and degradation of LDL. It reduces the synthesis of VLDL in the liver, which decreases the number of VLDL and LDL particles. The drug has a deep bioavailability (20%) and a long half-life of 19 hours. Effects occur after two to four weeks.

Indications

  • For the treatment of disorders of lipid metabolism: hypercholesterolemia, mixed dyslipidemia (type IIb).
  • To reduce the risk of serious cardiovascular events in high-risk patients.
  • In some countries, other indications, for example, to inhibit the progression of atherosclerosis and to treat hypertriglyceridemia.

Dosage

According to the professional information. The film-coated tablets are taken once daily, regardless of meals. They may be taken at any time of day, but should always be taken at the same time.

Contraindications

  • Hypersensitivity
  • Active liver disease
  • Severe renal dysfunction
  • Myopathy
  • Combination with ciclosporin
  • Pregnancy and lactation
  • Women of childbearing potential without suitable contraception.

Additional contraindications apply to the 40 mg dosage. Full precautions can be found in the drug label.

Interactions

Rosuvastatin is metabolized only about 10%, primarily by CYP2C9. It is not an inhibitor or inducer of CYP450 isozymes. Unlike other statins, it is not expected to interact with CYP450. Rosuvastatin is a substrate of the hepatic OATP1B1 and the efflux transporter BCRP. Drug-drug interactions have been described with antacids, ciclosporin, colchicine, erythromycin, fenofibrate, fusidic acid, gemfibrozil, niacin, protease inhibitors, and vitamin K antagonists, among others.

Adverse effects

The most common potential adverse effects include headache, muscle pain, abdominal pain, weakness, and nausea. Statins may very rarely cause life-threatening disintegration of skeletal muscle (rhabdomyolysis). The risk is greater at the higher dose (40 mg). Rosuvastatin may promote the development of diabetes mellitus, especially if risk factors are present.