Fluvastatin Explained

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.[1] It is on the World Health Organization's List of Essential Medicines.[2]

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.[3]

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.

Pharmacology

Mechanism of action

Fluvastatin works by blocking the liver enzyme HMG-CoA reductase, which facilitates an important step in cholesterol synthesis.[4]

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%.[5]

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% according to different sources. Over 98% of the substance is bound to plasma proteins.

Several cytochrome P450 enzymes (mainly CYP2C9, but also CYP3A4 and CYP2C8)[6] 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.

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

Names

Fluvastatin is the INN.[7] Brandnames include Lescol, Canef, Vastin.

Research

Data from the Cholesterol Treatment Trialists’ (CTT) publication[8] 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.

Notes and References

  1. Book: Fischer J, Ganellin CR . Analogue-based Drug Discovery . 2006 . John Wiley & Sons . 9783527607495 . 472 . en.
  2. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 22nd list (2021) . 2021 . 10665/345533 . World Health Organization . World Health Organization . Geneva . WHO/MHP/HPS/EML/2021.02 . free .
  3. Book: Arzneistoff-Profile. Dinnendahl, V, Fricke, U. Govi Pharmazeutischer Verlag. Eschborn, Germany. 2012. 26. 2. 978-3-7741-9846-3. German.
  4. Book: Austria-Codex. Haberfeld H . Österreichischer Apothekerverlag . Vienna . 2015 . German.
  5. Adams SP, Sekhon SS, Tsang M, Wright JM . Fluvastatin for lowering lipids . The Cochrane Database of Systematic Reviews . 2018 . CD012282 . March 2018 . 3 . 29508377 . 6494196 . 10.1002/14651858.cd012282.pub2 . John Wiley & Sons, Ltd .
  6. Lescol on Drugs.com.
  7. Web site: International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names (Rec. INN): List 30 . World Health Organization . 29 November 2016 . 1990.
  8. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R . 6 . Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins . Lancet . 366 . 9493 . 1267–78 . October 2005 . 16214597 . 10.1016/s0140-6736(05)67394-1 . 10716362 .