Fluvastatin is a member of the

statin Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. Low- ...

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...

class, used to treat

hypercholesterolemia Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia (high levels of lipids in the blood), hyperlipoproteinemia (high levels of lipoproteins in the blood), ...

and to prevent

cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...

. It was patented in 1982 and approved for medical use in 1994. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...

Adverse effects

Adverse effects are comparable to other statins. Common are

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

indigestion Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier t ...

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

and headache.

Myalgia Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likel ...

(muscle pain), and rarely

rhabdomyolysis Rhabdomyolysis (also called rhabdo) is a condition in which damaged skeletal muscle breaks down rapidly. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some of th ...

, characteristic side effects for statins, can also occur.

Interactions

Contrary to

lovastatin Lovastatin, sold under the brand name Mevacor among others, is a statin medication, to treat hypercholesterolemia, high blood cholesterol and reduce the risk of cardiovascular disease. Its use is recommended together with lifestyle changes. It ...

simvastatin Simvastatin, sold under the brand name Zocor among others, is a statin, a type of lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease elevated lipid levels. It is also used to decrease the risk of heart ...

and

atorvastatin Atorvastatin is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a first-line treatment. It is taken by mouth. Common ...

, fluvastatin has no relevant interactions with drugs that inhibit the liver enzyme

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...

, and a generally lower potential for interactions than most other statins.

Fluconazole Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to prevent ...

, a potent inhibitor of

CYP2C9 Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the prote ...

, does increase fluvastatin levels.

Pharmacology

Mechanism of action

Fluvastatin works by blocking the liver enzyme

HMG-CoA reductase HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, official symbol HMGCR) is the rate-controlling enzyme (NADH-dependent, ; NADPH-dependent, ) of the mevalonate pathway, the metabolic pathway that produces cholesterol and oth ...

, which facilitates an important step in

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

synthesis.

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%.

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 In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

is lower: about 24–30% according to different sources. Over 98% of the substance is bound to plasma proteins. Several

cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

enzymes (mainly CYP2C9, but also CYP3A4 and

CYP2C8 Cytochrome P4502C8 (abbreviated CYP2C8), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. Cytochrome P4502C8 also possesses epoxygenase activity, i.e. it metabolizes long-cha ...

) 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 Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

. Brandnames include Lescol, Canef, Vastin.

Research

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

References

{{Statins Carboxylic acids Diols Indoles Fluoroarenes Statins Isopropyl compounds Novartis brands