Fluvastatin
Template:Short description Template:Drugbox 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.[3]
Pharmacology
Mechanism of action
Script error: No such module "Labelled list hatnote". 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%[6][4] according to different sources. Over 98% of the substance is bound to plasma proteins.[4]
Several cytochrome P450 enzymes (mainly CYP2C9, but also CYP3A4 and CYP2C8)[7] 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.[4][3]
93–95% of the drug is excreted via the feces, less than 2% of which in form of the original substance.[4]
Names
Fluvastatin is the INN.[8] Brandnames include Lescol, Canef, Vastin.
Research
Data from the Cholesterol Treatment Trialists' (CTT) publication[9] 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.[5]
References
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ a b c Script error: No such module "citation/CS1".
- ↑ a b c d e Script error: No such module "citation/CS1".
- ↑ a b Script error: No such module "Citation/CS1".
- ↑ Cite error: Invalid
<ref>tag; no text was provided for refs namedPK - ↑ Lescol Template:Drugs.com on Drugs.com.
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "Citation/CS1".