Overview
11 DESCRIPTION Fluvastatin sodium, USP is a water-soluble cholesterol lowering agent which acts through the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Fluvastatin sodium, USP is [ R *, S *-( E )]-(±)-7-[3-(4-fluorophenyl)-1-(1-methylethyl)-1 H -indol-2-yl]-3,5-dihydroxy-6-heptenoic acid, monosodium salt. Its structural formula is: C 24 H 25 FNNaO 4 M.W. 433.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Fluvastatin sodium is a competitive inhibitor of HMG-CoA reductase, the rate limiting enzyme that converts 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to mevalonate, a precursor of sterols, including cholesterol. The inhibition of cholesterol biosynthesis reduces the cholesterol in hepatic cells, which stimulates the synthesis of LDL receptors and thereby increases the uptake of LDL particles. The end result of these biochemical processes is a reduction of the plasma cholesterol concentration. 12.3 Pharmacokinetics Absorption: Following oral administration of the capsule, fluvastatin reaches peak concentrations in less than 1 hour. The absolute bioavailability is 24% (range 9% to 50%) after administration of a 10 mg dose.
Indications
- 1 INDICATIONS AND USAGE Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other non-pharmacologic measures alone has been inadequate. Fluvastatin capsules are an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: Reduce elevated TC, LDL-C, Apo B, and TG, and to increase HDL-C...
Common Doses
- 20 mg
- 80 mg
- 40 mg
Dosage
2 DOSAGE AND ADMINISTRATION Dose range: 20 mg to 80 mg/day ( 2.1 ) Fluvastatin capsules can be taken with or without food. ( 2.1 ) Do not open fluvastatin capsules prior to administration ( 2.1 ) Adults: the recommended starting dose is 40 mg to 80 mg (administered as one fluvastatin capsule, 40 mg twice daily) ( 2.2 ) Do not take two fluvastatin capsules, 40 mg at one time Children with heterozygous familial hypercholesterolemia (ages 10 to 16, inclusive): the recommended starting dose is fluvastatin capsule, 20 mg once daily ( 2.3 ) 2.
Contraindications
- 4 CONTRAINDICATIONS Hypersensitivity to any component of this medication ( 4 ) Active liver disease or unexplained, persistent elevations in serum transaminases ( 4 , 5.3 ) Women who are pregnant or may become pregnant ( 4 , 8.1 ) Nursing mothers ( 4 , 8.3 ) 4.1 Hypersensitivity to any Component of This Medication Fluvastatin capsules are contraindicated in patients with hypersensitivity to any component of this medication. 4.
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the label: Rhabdomyolysis with myoglobinuria and acute renal failure and myopathy (including myositis) [ see Warnings and Precautions ( 5.1 ) ]. Liver Enzyme Abnormalities [ see Warnings and Precautions ( 5.3 ) ]. Most frequent adverse reactions (rate ≥ 2% and > placebo) are: headache, dyspepsia, myalgia, abdominal pain and nausea ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.
Interactions
- 7 DRUG INTERACTIONS Cyclosporine: Combination increases fluvastatin exposure. Limit fluvastatin dose to 20 mg ( 2.4 , 7.1 ) Fluconazole: Combination increases fluvastatin exposure. Limit fluvastatin dose to 20 mg ( 2.5 , 7.2 ) Concomitant lipid-lowering therapies: Use with fibrates or lipid-modifying doses (≥ 1 g/day) of niacin increases the risk of adverse skeletal muscle effects. Caution should be used when prescribing with fluvastatin ( 5.1 , 7.3 , 7.