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Active ingredient: Fluvastatin - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

  • Free Radical Scavengers
  • Antioxidants
  • Anticholesteremic Agents
  • HMG-CoA Reductase Inhibitors

Dosage Forms

  • Capsules
  • Tablets (extended-release)

Brands / Synonyms

Cranoc; Fluindostatin; Fluindostatin: Lescol; Fluvastatina [Inn-Spanish]; Fluvastatine [Inn-French]; Fluvastatinum [Inn-Latin]; Lescol; Lescol XL; Lescol XL


For management as an adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels in patients with primary hypercholesterolemia and mixed dyslipidemia


Fluvastatin, the first synthetically-prepared HMG-CoA reductase inhibitor, is used as an antilipemic to lower cholesterol and triglyceride levels associated with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson types IIa and IIb) and to slow the progression of coronary atherosclerosis in patients with coronary artery disease. Although similar to lovastatin, simvastatin, and pravastatin, Fluvastatin has a shorter half-life, no active metabolites, extensive protein binding, and minimal CSF penetration.

Mechanism of Action

Fluvastatin selectively and competitively inhibits the hepatic enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. As HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate, this results in a decrease in mevalonate, a precursor of cholesterol, and a subsequent decrease in hepatic cholesterol levels and increase in uptake of LDL cholesterol.


24% (range 9%-50%).


Variety of GI complaints and an increase in transaminase values (i.e., SGOT and SGPT).

Biotrnasformation / Drug Metabolism




Hypersensitivity to any component of this medication. Lescol (fluvastatin sodium) and
Lescol XL (fluvastatin sodium) are contraindicated in patients with active liver disease
or unexplained, persistent elevations in serum transaminases
Pregnancy and Lactation

Atherosclerosis is a chronic process and discontinuation of lipid-lowering drugs during
pregnancy should have little impact on the outcome of long-term therapy of primary
hypercholesterolemia. Cholesterol and other products of cholesterol biosynthesis are
essential components for fetal development (including synthesis of steroids and cell
membranes). Since HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly
the synthesis of other biologically active substances derived from cholesterol, they may
cause fetal harm when administered to pregnant women. Therefore, HMG-CoA reductase
inhibitors are contraindicated during pregnancy and in nursing mothers. Fluvastatin
sodium should be administered to women of childbearing age only when such patients are
highly unlikely to conceive and have been informed of the potential hazards. If the
patient becomes pregnant while taking this class of drug, therapy should be discontinued
and the patient apprised of the potential hazard to the fetus.

Drug Interactions

The below listed drug interaction information is derived from studies using immediate release fluvastatin. Similar studies have not been conducted using the Lescol XL tablet.

Immunosuppressive Drugs, Gemfibrozil, Niacin (Nicotinic Acid), Erythromycin .

In vitro data indicate that fluvastatin metabolism involves multiple Cytochrome P450 (CYP) isozymes. CYP2C9 isoenzyme is primarily involved in the metabolism of fluvastatin (~75%), while CYP2C8 and CYP3A4 isoenzymes are involved to a much less extent, i.e. ~5% and ~20%, respectively. If one pathway is inhibited in the elimination process of fluvastatin other pathways may compensate.

In vivo drug interaction studies with CYP3A4 inhibitors/substrates such as cyclosporine, ery-thromycin, and itraconazle result in minimal changes in the pharmacokinetics of fluvastatin, confirming less involvement of CYP3A4 isozyme. Concomitant administration of fluvastatin and phenytoin increased the levels of phenytoin and fluvastatin, suggesting predominant involvement of CYP2C9 in fluvastatin metabolism.

Niacin/Propranolol: Concomitant administration of immediate release fluvastatin sodium with niacin or propranolol has no effect on the bioavailability of fluvastatin sodium.

Cholestyramine: Administration of immediate release fluvastatin sodium concomitantly with, or up to 4 hours after cholestyramine, results in fluvastatin decreases of more than 50% for AUC and 50%-80% for Cmax. However, administration of immediate release fluvastatin sodium 4 hours after cholestyramine resulted in a clinically significant additive effect compared with that achieved with either component drug.

Cyclosporine: Plasma cyclosporine levels remain unchanged when fluvastatin (20 mg daily) was administered concurrently in renal transplant recipients on stable cyclosporine regimens. Fluvastatin AUC increased 1.9 fold, and Cmax increased 1.3 fold compared to historical controls.

Digoxin: In a crossover study involving 18 patients chronically receiving digoxin, a single 40 mg dose of immediate release fluvastatin had no effect on digoxin AUC, but had an 11% increase in digoxin Cmax and small increase in digoxin urinary clearance.

Erythromycin: Erythromycin (500 mg, single dose) did not affect steady-state plasma levels of fluvastatin (40 mg daily).

Itraconazole: Concomitant administration of fluvastatin (40 mg) and itraconazole (100 mg daily x 4 days) does not affect plasma itraconazole or fluvastatin levels.

Gemfibrozil: There is no change in either fluvastatin (20 mg twice daily) or gemfibrozil (600 mg twice daily) plasma levels when these drugs are co-administered.

Phenytoin: Single morning dose administration of phenytoin (300 mg extended release) increased mean steady-state fluvastatin (40 mg) Cmax by 27% and AUC by 40% whereas fluvastatin increased the mean phenytoin Cmax by 5% and AUC by 20%. Patients on phenytoin should continue to be monitored appropriately when fluvastatin therapy is initiated or when the fluvastatin dosage is changed.

Diclofenac: Concurrent administration of fluvastatin (40 mg) increased the mean Cmax and AUC of diclofenac by 60% and 25% respectively.

Tolbutamide: In healthy volunteers, concurrent administration of either single or multiple daily doses of fluvastatin sodium (40 mg) with tolbutamide (1 g) did not affect the plasma levels of either drug to a clinically significant extent.

Glibenclamide (Glyburide): In glibenclamide-treated NIDDM patients (n=32), administration of fluvastatin (40 mg twice daily for 14 days) increased the mean Cmax, AUC, and t1/2 of glibenclamide approximately 50%, 69% and 121%, respectively. Glibenclamide (5-20 mg daily) increased the mean Cmax and AUC of fluvastatin by 44% and 51%, respectively. In this study there were no changes in glucose, insulin and C-peptide levels. However, patients on concomitant therapy with glibenclamide (glyburide) and fluvastatin should continue to be monitored appropriately when their fluvastatin dose is increased to 40 mg twice daily.

Losartan: Concomitant administration of fluvastatin with losartan has no effect on the bioavailability of either losartan or its active metabolite.

Cimetidine/Ranitidine/Omeprazole: Concomitant administration of immediate release fluvastatin sodium with cimetidine, ranitidine and omeprazole results in a significant increase in the fluvastatin Cmax (43%, 70% and 50%, respectively) and AUC (24%-33%), with an 18%-23% decrease in plasma clearance.

Rifampicin: Administration of immediate release fluvastatin sodium to subjects pretreated with rifampicin results in significant reduction in Cmax (59%) and AUC (51%), with a large increase (95%) in plasma clearance.

Warfarin: In vitro protein binding studies demonstrated no interaction at therapeutic concentrations. Concomitant administration of a single dose of warfarin (30 mg) in young healthy males receiving immediate release fluvastatin sodium (40 mg/day x 8 days) resulted in no elevation of racemic warfarin concentration. There was also no effect on prothrombin complex activity when compared to concomitant administration of placebo and warfarin. However, bleeding and/or increased prothrombin times have been reported in patients taking coumarin anticoagulants concomitantly with other HMG-CoA reductase inhibitors. Therefore, patients receiving warfarin-type anticoagulants should have their prothrombin times closely monitored when fluvastatin sodium is initiated or the dosage of fluvastatin sodium is changed.

Endocrine Function

HMG-CoA reductase inhibitors interfere with cholesterol synthesis and lower circulating cholesterol levels and, as such, might theoretically blunt adrenal or gonadal steroid hormone production.

Fluvastatin exhibited no effect upon non-stimulated cortisol levels and demonstrated no effect upon thyroid metabolism as assessed by TSH. Small declines in total testosterone have been noted in treated groups, but no commensurate elevation in LH occurred, suggesting that the observation was not due to a direct effect upon testosterone production. No effect upon FSH in males was noted. Due to the limited number of premenopausal females studied to date, no conclusions regarding the effect of fluvastatin upon female sex hormones may be made.

Two clinical studies in patients receiving fluvastatin at doses up to 80 mg daily for periods of 24 to 28 weeks demonstrated no effect of treatment upon the adrenal response to ACTH stimulation. A clinical study evaluated the effect of fluvastatin at doses up to 80 mg daily for 28 weeks upon the gonadal response to HCG stimulation. Although the mean total testosterone response was significantly reduced (p<0.05) relative to baseline in the 80 mg group, it was not significant in comparison to the changes noted in groups receiving either 40 mg of fluvastatin or placebo.

Patients treated with fluvastatin sodium who develop clinical evidence of endocrine dysfunction should be evaluated appropriately. Caution should be exercised if an HMG-CoA reductase inhibitor or other agent used to lower cholesterol levels is administered to patients receiving other drugs (e.g., keto-conazole, spironolactone, or cimetidine) that may decrease the levels of endogenous steroid hormones.

CNS Toxicity

CNS effects, as evidenced by decreased activity, ataxia, loss of righting reflex, and ptosis were seen in the following animal studies: the 18-month mouse carcinogenicity study at 50 mg/kg/day, the 6-month dog study at 36 mg/kg/day, the 6-month hamster study at 40 mg/kg/day, and in acute, high-dose studies in rats and hamsters (50 mg/kg), rabbits (300 mg/kg) and mice (1500 mg/kg). CNS toxicity in the acute high-dose studies was characterized (in mice) by conspicuous vacuolation in the ventral white columns of the spinal cord at a dose of 5000 mg/kg and (in rat) by edema with separation of myelinated fibers of the ventral spinal tracts and sciatic nerve at a dose of 1500 mg/kg. CNS toxicity, characterized by periax-onal vacuolation, was observed in the medulla of dogs that died after treatment for 5 weeks with 48 mg/kg/day; this finding was not observed in the remaining dogs when the dose level was lowered to 36 mg/kg/day. CNS vascular lesions, characterized by perivascular hemorrhages, edema, and mononuclear cell infiltration of perivascular spaces, have been observed in dogs treated with other members of this class. No CNS lesions have been observed after chronic treatment for up to 2 years with fluvastatin in the mouse (at doses up to 350 mg/kg/day), rat (up to 24 mg/kg/day), or dog (up to 16 mg/kg/day).

Prominent bilateral posterior Y suture lines in the ocular lens were seen in dogs after treatment with 1, 8, and 16 mg/kg/day for 2 years.


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