Drug information of fluvastatin

Mechanism of effect

Acts by competitively inhibiting 3-hydroxyl-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the reduction ofHMG-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.

In addition to the ability of HMG-CoA reductase inhibitors to decrease levels of highsensitivity C-reactive protein (hsCRP), they also possess pleiotropic properties including improved endothelial function, reduced inflammation atthe site of the coronary plaque, inhibition of platelet aggregation, and anticoagulant effects (de Denus 2002; Ray 2005).

Pharmacodynamic

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.

Pharmacokinetics

Onset of action: Peak effect: Maximal LDL-C reductions achieved within 4 weeks

Distribution: Vdss: 0.35 L/kg

Protein binding: 98%

Metabolism: Hepatic to inactive and active

Half-life elimination: Immediate-release: ~3 hours; Extended-release: 7.3 to 10.5 hours

Excretion: Feces (~90%; <2% unchanged); urine (~5%)

Drug indications

Prevention of Cardiovascular Disease

Dosage

Heterozygous familial and nonfamilial hypercholesterolemia: Oral:

Immediate release: 40 mg once daily in the evening or 40 mg twice daily

Extended release: 80 mg once daily (anytime)

Mixed dyslipidemia: Oral:

Immediate release: 40 mg once daily in the evening or 40 mg twice daily

Extended release: 80 mg once daily (anytime)

Patients requiring ≥25% decrease in LDL-C: Oral:

Immediate release: Initial: 40 mg once daily in the evening or 40 mg twice daily

Extended release: Initial: 80 mg once daily (anytime)

Patients requiring <25% decrease in LDL-C: Oral: Initial: Immediate release: 20 mg once daily in the evening; may increase based on

tolerability and response to a maximum recommended dose of 80 mg/day, given in 2 divided doses (immediate release) or as a single dailydose (extended release)

Prevention of cardiovascular disease/reduce the risk of ASCVD:

Adults ≥21 years:

Primary prevention:

LDL-C ≥190 mg/dL: High-intensity therapy necessary; use alternate statin therapy (eg, atorvastatin, rosuvastatin)

Type 1 or 2 diabetes and age 40 to 75 years: Moderate intensity therapy:

Immediate release: 40 mg twice daily.

Extended release: 80 mg once daily.

Type 1 or 2 diabetes, age 40 to 75 years, and an estimated 10-year ASCVD risk ≥7.5%: High-intensity therapy necessary; use alternate

statin therapy (eg, atorvastatin, rosuvastatin).

Age 40 to 75 years and an estimated 10-year ASCVD risk ≥7.5%: Moderate- to high-intensity therapy:

Immediate release: 40 mg twice daily or consider using high-intensity statin therapy (eg, atorvastatin, rosuvastatin).

Extended release: 80 mg once daily or consider using high-intensity statin therapy (eg, atorvastatin, rosuvastatin).

Secondary prevention:

Patient has clinical ASCVD (eg, coronary heart disease, stroke/TIA, or peripheral arterial disease presumed to be of atherosclerotic

origin) and:

Age ≤75 years: High-intensity therapy necessary; use alternate statin therapy (eg, atorvastatin, rosuvastatin).

Age >75 years or not a candidate for high-intensity therapy: Moderate-intensity therapy:

Immediate release: 40 mg twice daily.

Extended release: 80 mg once daily.

Concomitant use with cyclosporine or fluconazole: Immediate release: Do not exceed fluvastatin 20 mg twice daily

Drug contraindications

Active liver disease

Side effects

Sinusitis , Insomnia , Diarrhea , Headache , nausea , dyspepsia , myalgia , tiredness , Abdominal pain

Interactions

Gemfibrozil , Repaglinide , Cyclosporine , Fluconazole , Phenytoin , Warfarin , Carvedilol , Colchicine , Cholestyramine , Niacin , phosphination , Daptomycin , Cyproterone , teriflunomide , Mifepristone , Eltrombopag , Mibefradil , ELBASVIR/GRAZOPREVIR , Cannabidiol

Alerts

• Diabetes mellitus: Increases in HbA1c and fasting blood glucose have been reported with HMG-CoA reductase inhibitors; however, the benefits of statin therapy (eg, reduction in the risk of MI or stroke) far outweigh the risk of dysglycemia. If a patient develops diabetes

mellitus during therapy, continue use of fluvastatin and encourage patient to adhere to healthy lifestyle regimens (eg, heart healthy dietary pattern, engage in physical activity, achieve and maintain a healthy body weight)

• Hepatotoxicity: Increased AST or ALT has been reported; in most cases, elevations were transient and resolved or improved on continued therapy or after a brief interruption in therapy.

. If serious hepatotoxicity with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, interrupt therapy promptly.

. Ethanol may enhance the potential of adverse hepatic effects;

Use has been found to be safe in those with active hepatitis C

• Myopathy/rhabdomyolysis: Rhabdomyolysis with acute renal failure secondary to myoglobinuria and/or myopathy has been reported; patients should be monitored closely. This risk is dose related and is increased with concurrent use of cyclosporine, erythromycin, or

other lipid-lowering medications (eg, fibrates, niacin at doses ≥1 g/day). Use caution in patients with inadequately treated hypothyroidism, and those taking other drugs associated with myopathy (eg, colchicine); these patients are predisposed to myopathy.

Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or brown urine, particularly if accompanied by malaise or fever. Discontinue therapy if markedly elevated CPK levels occur or myopathy is diagnosed/suspected.

• Use caution in patients with conditions or on medications that reduce steroidogenesis.
• Use with caution in patients who consume large amounts of ethanol or have a history of liver

disease. Use is contraindicated in patients with active liver disease or unexplained transaminase elevations.

• Use with caution in patients with renal impairment; these patients are predisposed to myopathy.
• Use with caution in patients with advanced age; these patients are predisposed to myopathy.

Points of recommendation

Oral: Patient should be placed on a standard cholesterol-lowering diet before and during treatment. Administer without regard to meals. Do not

break, chew, or crush extended release tablets; do not open immediate-release capsules. Do not administer two 40 mg immediate-release capsulesat once.

Pregnancy level

X

Related drugs

Atorvastatin , Pitavastatin , pravastatin , Simvastatin , Lovastatin , Rosuvastatin