Fluvastatin

Routes of
administrationBy mouth (capsules, tablets)ATC codeLegal statusLegal status Pharmacokinetic dataBioavailability24–30%^[1][2]Protein binding>98%^[2]MetabolismHepatic: CYP2C9 (75%), CYP3A4 (20%), CYP2C8 (5%)^[2][3]Elimination half-life1–3 hours (capsule), 9 hours (XR formulations)^[2][3]ExcretionFaeces (95%), urine (5%)^[2]IdentifiersCAS NumberPubChem CIDIUPHAR/BPSDrugBankChemSpiderUNIIKEGGChEBIChEMBLCompTox Dashboard (EPA)ECHA InfoCard100.224.327 Chemical and physical dataFormulaC₂₄H₂₆FNO₄Molar mass411.473 g·mol⁻¹3D model (JSmol)  (verify)

Fluvastatin is a member of the statin drug class, used to treat hypercholesterolemia and to prevent cardiovascular disease.

It was patented in 1982 and approved for medical use in 1994.^[4] It is on the World Health Organization's List of Essential Medicines.^[5]

Adverse effects

Adverse effects are comparable to other statins. Common are nausea, indigestion, insomnia and headache. Myalgia (muscle pain), and rarely rhabdomyolysis, characteristic side effects for statins, can also occur.^[6]

Interactions

Contrary to lovastatin, simvastatin and atorvastatin, fluvastatin has no relevant interactions with drugs that inhibit the liver enzyme CYP3A4, and a generally lower potential for interactions than most other statins. Fluconazole, a potent inhibitor of CYP2C9, does increase fluvastatin levels.^[6]

Pharmacology

Mechanism of action

Fluvastatin works by blocking the liver enzyme HMG-CoA reductase, which facilitates an important step in cholesterol synthesis.^[1]

Pharmacodynamics

In a Cochrane systematic review the dose-related magnitudes of fluvastatin on blood lipids was determined. Over the dose range of 10 to 80 mg/day total cholesterol was reduced by 10.7% to 24.9%, LDL cholesterol by 15.2% to 34.9%, and triglycerides by 3% to 17.5%.^[7]

Pharmacokinetics

The drug is quickly and almost completely (98%) absorbed from the gut. Food intake slows down absorption, but does not decrease it. Due to its first-pass effect, bioavailability is lower: about 24–30%^[2][1] according to different sources. Over 98% of the substance is bound to plasma proteins.^[1]

Several cytochrome P450 enzymes (mainly CYP2C9, but also CYP3A4 and CYP2C8)^[8] are involved in the metabolism of fluvastatin, which makes is less liable to interactions than most other statins. The main metabolite is inactive and is called "N-desisopropyl propionic acid" in the literature.^[1][6]

93–95% of the drug is excreted via the feces, less than 2% of which in form of the original substance.^[1]

Names

Fluvastatin is the INN.^[9] Brandnames include Lescol, Canef, Vastin.

Research

Data from the Cholesterol Treatment Trialists’ (CTT) publication^[10] was used to determine the effects of fluvastatin, atorvastatin and rosuvastatin on LDL cholesterol lowering and reduction of myocardial infarction. In two RCTs an average dose of 72 mg/day fluvastatin reduced LDL cholesterol by 31.9%, and reduced myocardial infarction, relative risk, 0.68 (95% CI 0.55 to 0.85) as compared to placebo. In five RCTs a mean atorvastatin dose of 26 mg/day reduced LDL cholesterol by 44.0% and reduced myocardial infarction, relative risk, 0.67 (95% CI 0.58 to 0.77) as compared to placebo. In four RCTs a mean rosuvastatin dose of 16 mg/day reduced LDL cholesterol by 48.8% and reduced myocardial infarction, relative risk, 0.82 (95% CI 0.73 to 0.93) as compared to placebo. Thus despite reducing LDL cholesterol by a much lesser amount with fluvastatin than atorvastatin and rosuvastatin, fluvastatin reduced myocardial infarction similarly to atorvastatin and to a greater degree than rosuvastatin.^[7]

References