No

Antilipemic Agent (HMG-CoA Reductase Inhibitor)

Adjunct to dietary therapy to decrease elevated serum total and LDL cholesterol concentrations in primary hypercholesterolemia

X

Clinical effects on the fetus: Skeletal malformations have occurred in animals following agents with similar structure; avoid use in women of childbearing age; discontinue if pregnancy occurs

Breast-feeding/lactation: Avoid use in nursing mothers

Hypersensitivity to fluvastatin or any component; active liver disease; unexplained persistent elevations of serum transaminases; pregnancy

Liver function must be monitored by periodic laboratory assessment. Rhabdomyolysis with acute renal failure has occurred with other HMG-CoA reductase inhibitors. Risk is increased with concurrent use of clarithromycin, danazol, diltiazem, fluvoxamine, indinavir, nefazodone, nelfinavir, ritonavir, verapamil, troleandomycin, cyclosporine, fibric acid derivatives, erythromycin, niacin, or azole antifungals. The risk of combining any of these drugs with fluvastatin is minimal. Temporarily discontinue in any patient experiencing an acute or serious condition predisposing to renal failure secondary to rhabdomyolysis. Use caution in patients with previous liver disease or heavy alcohol use. Treatment in patients <18 years of age is not recommended.

1% to 10%:

Central nervous system: Headache (8.9%; similar to placebo), fatigue (2.7%), insomnia (2.7%)

Gastrointestinal: Dyspepsia (7.9%), diarrhea (4.9%), abdominal pain (4.9%), nausea (3.2%), flatulence (2.6%), constipation (3.1%)

Neuromuscular & skeletal: Myalgia (5%), arthritis (2.1%)

Respiratory: Sinusitis (2.6%)

Miscellaneous: Allergy (2.3%)

<1% including additional class-related events (not necessarily reported with fluvastatin therapy) and postmarketing case reports: Myopathy, arthralgia, muscle cramps, increased CPK (>10x normal), rhabdomyolysis, renal failure (secondary to rhabdomyolysis), blurred vision, alteration in taste, impaired extraocular muscle movement, facial paresis, tremor, dizziness, memory loss, vertigo, paresthesia, peripheral neuropathy, peripheral nerve palsy, anxiety, depression, psychic disturbance, hypersensitivity reaction, angioedema, anaphylaxis, systemic lupus erythematosus-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, increased ESR, eosinophilia, arthritis, urticaria, photosensitivity, fever, chills, flushing, malaise, dyspnea, rash, toxic epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome, pancreatitis, hepatitis, cholestatic jaundice, fatty liver, cirrhosis, fulminant hepatic necrosis, hepatoma, anorexia, vomiting, alopecia, pruritus, nodules, skin discoloration, dryness of skin/mucous membranes, nail changes, gynecomastia, decreased libido, erectile dysfunction, impotence, cataracts, ophthalmoplegia, elevated transaminases, increased alkaline phosphatase, increased GGT, hyperbilirubinemia, thyroid dysfunction

No symptomatology has been reported in cases of significant overdosage, however, supportive measure should be instituted, as required; dialyzability is not known

CYP2C9 enzyme substrate; CYP2C9, 2C18, and 2C19 enzyme inhibitor

Cholestyramine reduces fluvastatin absorption. Separate administration times by at least 4 hours.

Cholestyramine and colestipol (bile acid sequestrants): Cholesterol-lowering effects are additive.

Clofibrate and fenofibrate may increase the risk of myopathy and rhabdomyolysis.

Gemfibrozil: Increased risk of myopathy and rhabdomyolysis.

Omeprazole increases fluvastatin blood levels

Ranitidine increases fluvastatin blood levels.

Rifampin decreases fluvastatin blood levels.

Ritonavir increases fluvastatin blood levels.

Warfarin: Hypoprothrombinemic response is increased; monitor INR closely when fluvastatin is initiated or discontinued.

Acts by competitively inhibiting 3-hydroxyl-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the reduction of HMG-CoA to mevalonate; this is an early rate-limiting step in cholesterol biosynthesis. HDL is increased while total, LDL and VLDL cholesterols, apolipoprotein B, and plasma triglycerides are decreased.

Protein binding: >98%

Metabolism: Undergoes extensive first pass hepatic extraction; metabolized to inactive and active metabolites although the active forms do not circulate systemically

Bioavailability: Absolute (24%); T_max: less than or equal to 1 hour

Half-life: 1.2 hours

Elimination: Urine (5%), feces (90%)

Adults: Oral:

Usual dose: 20-80 mg at bedtime

Note: Splitting the 80 mg dose into a twice daily regimen may provide a modest improvement in LDL response. Maximum response occurs within 4-6 weeks. Decrease dose and monitor effects carefully in patients with hepatic insufficiency.

Before initiation of therapy, patients should be placed on a standard cholesterol-lowering diet for 3-6 months and the diet should be continued during drug therapy.

Increased serum transaminases, CPK, alkaline phosphatase, and bilirubin and thyroid function tests

HMG-CoA reductase inhibitors are effective in secondary prevention of cardiovascular events in patients with hyperlipidemia. In these situations, the target of therapy is a reduction in LDL cholesterol to <100 mg/dL. HMG-CoA reductase inhibitors have also been shown to be effective in primary prevention of coronary artery disease in individuals without established cardiovascular disease but who have multiple risk factors. Selection of lipid-lowering therapy should be based on the patient's lipid profile, concomitant disease states, and the cost of therapy. The benefits of lipid-lowering are also compelling in women and in the elderly. Important side effects relate to elevated liver enzymes and rhabdomyolysis. LFTs need to be monitored at specified intervals.

May cause dizziness, insomnia, or drowsiness

None reported

No information available to require special precautions

No effects or complications reported

Take at bedtime since highest rate of cholesterol synthesis occurs between midnight and 5 AM. Follow diet and exercise regimen as prescribed. Have periodic ophthalmic exam to check for cataract development. Avoid prolonged exposure to the sun and other ultraviolet light. Report unexplained muscle pain or weakness, especially if accompanied by fever or malaise. Pregnancy/breast-feeding precautions: Do not get pregnant or engage in sexual activity during therapy and for 1 month following therapy unless using barrier contraceptive measures. Breast-feeding is not recommended while on this drug and for several weeks after last dose. This drug may cause severe fetal defects. Do not donate blood during or for 1 month following therapy. Breast-feeding is not recommended.

Capsule: 20 mg, 40 mg

Levy RI, Troendle AJ, and Fattu JM, "A Quarter Century of Drug Treatment of Dyslipoproteinemia With a Focus on the New HMG-CoA Reductase Inhibitor Fluvastatin," Circulation, 1993, 87(4 Suppl):III45-53.

"Summary of the Second Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II)," JAMA, 1993, 269(23):3015-23.

Tse FL, Jaffe JM, and Troendle A, "Pharmacokinetics of Fluvastatin After Single and Multiple Doses in Normal Volunteers," J Clin Pharmacol, 1992, 32(7):630-8.