Fluvastatin; Uses, Dosage, Side Effects, Drug Interactions

Fluvastatin; Uses, Dosage, Side Effects, Drug Interactions

Fluvastatin is a synthetic lipid-lowering agent with antilipidemic and potential antineoplastic properties. Fluvastatin competitively inhibits hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, a key step in cholesterol synthesis. This agent lowers plasma cholesterol and lipoprotein levels and modulates immune responses through the suppression of MHC II (major histocompatibility complex II) on interferon gamma-stimulated antigen-presenting cells such as human vascular endothelial cells. Due to its anti-inflammatory effects mediated by alterations of lipid metabolism, fluvastatin may possess chemopreventive and therapeutic antineoplastic properties.

Fluvastatin is a member of the statin drug class, used to treat hypercholesterolemia, lower cholesterol and triglyceride levels associated with primary hypercholesterolemia, mixed dyslipidemia and to prevent cardiovascular disease & antilipemic agent that competitively inhibits hydroxymethyl-glutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonic acid, the rate-limiting step in cholesterol biosynthesis. Fluvastatin belongs to a class of medications called statins and is used to reduce plasma cholesterol levels and prevent cardiovascular disease.

Mechanism of Action of Fluvastatin

Fluvastatin selectively and competitively inhibits the hepatic enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate, the rate-limiting step in cholesterol biosynthesis. Inhibition results in a decrease in hepatic cholesterol levels which stimulates the synthesis of LDL receptors and increases hepatic uptake of LDL cholesterol. The end result is decreased levels of plasma total and LDL cholesterol. Although similar to lovastatin, simvastatin, and pravastatin, fluvastatin has a shorter half-life, no active metabolites, extensive protein binding, and minimal CSF penetration. Fluvastatin acts primarily in the liver. It is prepared as a racemate of two erythro enantiomers of which the 3R,5S enantiomer exerts the pharmacologic effect.

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Statins are largely used in clinics in the treatment of patients with cardiovascular diseases for their effect on lowering circulating cholesterol. Lectin-like oxidized low-density lipoprotein (LOX-1), the primary receptor for ox-LDL, plays a central role in the pathogenesis of atherosclerosis and cardiovascular disorders. We have recently shown that chronic exposure of cells to lovastatin disrupts LOX-1 receptor cluster distribution in plasma membranes, leading to a marked loss of LOX-1 function. Here we investigated the molecular mechanism of statin-mediated LOX-1 inhibition and we demonstrate that all tested statins /including fluvastatin/ are able to displace the binding of fluorescent ox-LDL to LOX-1 by a direct interaction with LOX-1 receptors in a cell-based binding assay. Molecular docking simulations confirm the interaction and indicate that statins completely fill the hydrophobic tunnel that crosses the C-type lectin-like (CTLD) recognition domain of LOX-1. Classical molecular dynamics simulation technique applied to the LOX-1 CTLD, considered in the entire receptor structure with or without a statin ligand inside the tunnel, indicates that the presence of a ligand largely increases the dimer stability. Electrophoretic separation and western blot confirm that different statins binding stabilize the dimer assembly of LOX-1 receptors in vivo. The simulative and experimental results allow us to propose a CTLD clamp motion, which enables the receptor-substrate coupling. These findings reveal a novel and significant functional effect of statins

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Indications of Fluvastatin

  • Dyslipidemia
  • High cholesterol
  • High cholesterol, familial heterozygous
  • Hyperlipoproteinemia
  • Hyperlipoproteinemia Type IIa, Elevated LDL
  • Hyperlipoproteinemia Type IIb, Elevated LDL VLDL
  • Atherosclerosis
  • Atherosclerotic cardiovascular diseases
  • Cardiovascular disease
  • Coronary heart disease
  • Heterozygous familial hypercholesterolemia
  • Hypercholesterolemia, Familial
  • Mixed hypercholesterolemia
  • Treatment of primary hypercholesterolemia and mixed dyslidipidemia.
  • To be used as an adjunct to dietary therapy to prevent cardiovascular events. May be used as secondary prevention in patients with coronary heart disease (CHD) to reduce the risk of requiring coronary revascularization procedures, for reducing progression of coronary atherosclerosis in hypercholesterolemic patients with CHD, and for the treatment of primary hypercholesterolemia and mixed dyslidipidemia.
  • In patients with clinically evident coronary heart disease (CHD), fluvastatin capsules are indicated to: reduce the risk of undergoing coronary revascularization procedures and slow the progression of coronary atherosclerosis.
  • Fluvastatin has reduced total and LDL-cholesterol concentrations in a few patients with hypercholesterolemia associated with or exacerbated by diabetes mellitus (diabetic dyslipidemia), renal insufficiency, cardiac or renal transplantation, or nephrotic syndrome (nephrotic hyperlipidemia). Fluvastatin also has been shown to decrease proteinuria in patients with immunoglobulin A nephropathy. Additional studies are necessary to determine the role if any, of fluvastatin therapy in patients with these disorders.

Contra-Indications of Fluvastatin

  • alcoholism
  • Uncontrolled epilepsy
  • Hemorrhage in the brain
  • Severely low blood pressure
  • Liver problems
  • Rhabdomyolysis
  • Recent operation
  • Loss of memory
  • High blood sugar
  • Abnormal liver function tests
  • Trauma
  • Pregnancy
  • A mother who is producing milk and breastfeeding
  • Muscle pain or tenderness with increase creatine kinase
  • Metabolic syndrome X
  • Muscle damage due to auotimmunity

Dosage of Fluvastatin

Strengths: 20 mg; 40 mg; 80 mg

High cholesterol

For oral dosage form (capsules)

  • Adults—At first, 20 or 40 milligrams (mg) once a day in the evening. Some patients may need 40 mg two times a day (one in the morning and one in the evening). Your doctor may increase your dose as needed.
  • Children 10 to 16 years of age—At first, 20 mg once a day in the evening. Your doctor may increase your dose as needed. However, the dose is usually not more than 40 mg two times a day (one in the morning and one in the evening).
  • Children younger than 10 years of age—Use and dose must be determined by your doctor.
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For oral dosage form (extended-release tablets)

  • Adults—80 milligrams (mg) once a day.
  • Children 10 to 16 years of age—80 mg once a day.
  • Children younger than 10 years of age—Use and dose must be determined by your doctor.

Hyperlipidemia

Immediate Release Capsules

  • Low-density lipoprotein cholesterol (LDL-C) reduction to a goal of 25% or greater: Initial dose of 40 mg orally once a day in the evening or 40 mg orally twice a day
  • LDL-C reduction to a goal of less than 25%: Initial dose of 20 mg orally once a day
  • Maintenance dose: 20 mg to 80 mg per day

Extended Release Tablets

  • 80 mg orally once a day, at any time of day

Hyperlipoproteinemia Type IIa (Elevated LDL)

Immediate Release Capsules

  • Low-density lipoprotein cholesterol (LDL-C) reduction to a goal of 25% or greater: Initial dose of 40 mg orally once a day in the evening or 40 mg orally twice a day
  • LDL-C reduction to a goal of less than 25%: Initial dose of 20 mg orally once a day
  • Maintenance dose: 20 mg to 80 mg per day

Extended Release Tablets

  • 80 mg orally once a day, at any time of day

Dyslipidemia

Immediate Release Capsules

  • Low-density lipoprotein cholesterol (LDL-C) reduction to a goal of 25% or greater: Initial dose of 40 mg orally once a day in the evening or 40 mg orally twice a day
  • LDL-C reduction to a goal of less than 25%: Initial dose of 20 mg orally once a day
  • Maintenance dose: 20 mg to 80 mg per day

Extended Release Tablets

  • 80 mg orally once a day, at any time of day

Cardiovascular Disease

Immediate Release Capsules

  • LDL-C reduction to a goal of 25% or greater: Initial dose of 40 mg orally once a day in the evening or 40 mg orally twice a day
  • LDL-C reduction to a goal of less than 25%: Initial dose of 20 mg orally once a day
  • Maintenance dose: 20 mg to 80 mg per day

Extended Release Tablets

  • 80 mg orally once a day, at any time of day

Pediatric Heterozygous Familial Hypercholesterolemia

10 to 16 years

  • Initial dose: 20 mg orally once a day
  • Maintenance dose: 20 mg to 80 mg per day
  • Maximum dose: 40 mg twice a day (immediate release); 80 mg once a day (extended release)
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Side Effects of Fluvastatin

The most common

 Common

Less common

Drug Interactions of Fluvastatin

Fluvastatin may interact with following drugs, supplements & may change the efficacy of the drug

Pregnancy & Lactation of Fluvastatin

FDA pregnancy category X

Pregnancy

Fluvastatin should not be taken by pregnant women. If you become pregnant while taking fluvastatin, stop taking the medication immediately and contact your doctor.

Lactation

It is not known whether fluvastatin passes into breast milk. Women taking fluvastatin should breastfeeds-feed.

References

 

Fluvastatin

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