Brand name: Lescol
Drug class: HMG-CoA Reductase Inhibitors

Medically reviewed by Drugs.com on Jul 10, 2024. Written by ASHP.

Introduction

Antilipemic agent; hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (i.e., statin).

Uses for Fluvastatin Sodium

Reduction in Risk of Cardiovascular Events

Adjunct to diet and lifestyle modifications in adults with coronary heart disease (CHD) to reduce the risk of undergoing coronary revascularization procedures and slow progression of coronary atherosclerosis.

Also has been used for primary prevention^{† [off-label]} of atherosclerotic cardiovascular disease (ASCVD).

Extensive evidence demonstrates that statins can substantially reduce LDL-cholesterol concentrations and associated risk of ASCVD; may be used for secondary or primary prevention in high-risk patients.

AHA/ACC cholesterol management guideline states that lifestyle modification is the foundation of ASCVD risk reduction. Patients with established ASCVD or high risk of ASCVD should also be treated with a statin.

Because relative ASCVD risk reduction is correlated with degree of LDL-cholesterol lowering, use maximum tolerated intensity of a statin to achieve greatest benefit. High-intensity statin therapy (defined as reducing LDL-cholesterol concentrations by ≥50%) is recommended; if high-intensity statin therapy not possible (e.g., because of a contraindication or intolerable adverse effect), may consider moderate-intensity statin therapy (defined as reducing LDL-cholesterol concentrations by 30–49%). AHA/ACC considers fluvastatin 40 mg twice daily (or extended-release fluvastatin 80 mg daily) to be a moderate-intensity statin.

The addition of a nonstatin drug (e.g., ezetimibe, PCSK9 inhibitor) to statin therapy may be considered in certain high-risk patients who require further reduction in LDL-cholesterol concentrations, particularly if there is evidence from randomized controlled studies suggesting that the addition of the nonstatin drug further reduces ASCVD events.

When considering whether to initiate statin therapy for primary prevention, AHA/ACC recommends an individualized approach and shared decision making between patient and clinician. According to the guidelines, statin therapy may be considered in certain high-risk groups such as adults 20–75 years of age with LDL cholesterol ≥190 mg/dL, adults 40–75 years of age with diabetes mellitus, adults 40–75 years of age without diabetes mellitus but with LDL-cholesterol levels ≥70 mg/dL and an estimated 10-year ASCVD risk ≥7.5%, adults 40–75 years of age with chronic kidney disease (not treated with dialysis or transplantation) and LDL-cholesterol concentrations of 70–189 mg/dL who have a 10-year ASCVD risk ≥7.5%.

Dyslipidemias

Adjunct to nondrug therapies (e.g., dietary management) to decrease elevated serum total cholesterol, LDL-cholesterol, apolipoprotein B (apo B), and triglyceride concentrations and to increase HDL-cholesterol concentrations in the management of primary hypercholesterolemia (heterozygous familial and nonfamilial) or mixed dyslipidemia (Fredrickson type IIa or IIb).

Adjunct to nondrug therapies (e.g., dietary management) to decrease elevated serum total cholesterol, LDL-cholesterol, and apo B concentrations in the management of heterozygous familial hypercholesterolemia in boys and girls (≥1 year postmenarchal) 10–16 years of age who, despite an adequate trial of dietary management, have a serum LDL-cholesterol concentration of ≥190 mg/dL or a serum LDL-cholesterol concentration of ≥160 mg/dL and either a family history of premature cardiovascular disease or ≥2 other cardiovascular risk factors.

Fluvastatin Sodium Dosage and Administration

General

Pretreatment Screening

• Obtain baseline liver enzyme tests (e.g., AST, ALT) in all patients.

• Obtain baseline hepatic panel in appropriate patients with chronic stable liver disease (including non-alcoholic fatty liver disease).

• Obtain baseline fasting lipid panel.

Patient Monitoring

• Perform fasting lipid panel periodically 4–12 weeks after statin initiation or dose adjustment; monitoring should continue every 3–12 months thereafter as clinically indicated.

• Periodically reinforce adherence to lifestyle modifications. Antilipemic therapy is an adjunct to, not a substitute for, lifestyle modification therapies that reduce the risk of ASCVD.

• Perform repeat liver function tests (e.g., AST, ALT, total bilirubin, alkaline phosphatase) when clinically indicated (i.e., symptoms suggesting hepatotoxicity); routine monitoring in the absence of symptoms is not recommended.

• Monitor hepatic panel in appropriate patients with chronic stable liver disease (including non-alcoholic fatty liver disease).

• Obtain creatine kinase (CK) levels in patients with severe statin-associated muscle weakness; routine monitoring in the absence of symptoms is not recommended.

• Evaluate patients who develop clinical evidence of endocrine dysfunction.

Administration

Oral Administration

Administer orally without regard to meals. Available as immediate-release capsules or extended-release tablets.

Immediate-release Capsules

Administer orally once (in the evening) or twice daily; do not administer two 40-mg capsules at one time. Do not open capsules prior to administration.

Administer a missed dose as soon as possible; if more than 12 hours has elapsed since the last dose, do not administer until the next scheduled dose is due. Do not administer 2 doses at the same time.

Extended-release Tablets

Administer orally as a single dose at any time of day. Do not break, crush, or chew tablets.

Dosage

Available as fluvastatin sodium; dosage expressed in terms of fluvastatin.

Dosage modifications may be necessary when used concomitantly with certain drugs.

Pediatric Patients

Dyslipidemias

Oral

Immediate-release capsules: Children 10–16 years of age: Initially, 20 mg once daily. Adjust dosage at 6-week intervals until desired effect or a daily dosage of 80 mg (administered as 40 mg twice daily) is reached.

Extended-release tablets: Children 10–16 years of age: 80 mg once daily, following initial titration with immediate-release capsules.

Adults

Reduction in Risk of Cardiovascular Events

Oral

Use maximally tolerated statin intensity to achieve optimal ASCVD risk reduction. High-intensity statin therapy (defined as reducing LDL-cholesterol concentrations by ≥50%) is preferred; if high-intensity statin therapy not possible (e.g., because of a contraindication or intolerable adverse effect), may consider moderate-intensity statin therapy (defined as reducing LDL-cholesterol concentrations by 30–49%).

The AHA/ACC guideline panel considers fluvastatin 40 mg twice daily (or extended-release fluvastatin 80 mg daily) to be a moderate-intensity statin.

For patients who require a high-intensity statin or are unable to achieve their LDL-cholesterol goal receiving fluvastatin, an alternative LDL-cholesterol lowering treatment is recommended.

Immediate-release capsules: Initially, 40 mg once daily in the evening or 40 mg twice daily. Recommended dosage range is 20–80 mg/day in a single-dose or 2 divided doses.

Extended-release tablets: 80 mg once daily.

Dyslipidemias

Oral

Immediate-release capsules: Patients who require reductions in LDL-cholesterol concentrations of <25%: Initially, 20 mg once daily in the evening.

Immediate-release capsules: Patients who require reductions of >25% in LDL-cholesterol concentrations or patients with primary hypercholesterolemia or mixed dyslipidemia: Initially, 40 mg once daily in the evening or 40 mg twice daily.

Adjust dosage at intervals of ≥4 weeks until the desired effect on lipoprotein concentrations is observed. Usual maintenance dosage is 20–80 mg daily.

Extended-release tablets: 80 mg once daily.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

Dosage modification not necessary in patients with mild to moderate renal impairment.

Dosages >40 mg daily have not been studied in patients with severe renal impairment; use caution when administering higher dosages to such patients.

Geriatric Patients

No specific dosage recommendations. Cautious dosage selection recommended.

Pharmacogenomic Considerations in Dosing

Dosage adjustments or alternative therapy recommended based on SLCO1B1 function and CYP2C9 metbolizer status.

SLCO1B1 decreased or possible decreased function phenotype: No recommended dosage adjustment. SLCO1B1 poor function phenotype: Initial dosage ≤40 mg/day.

CYP2C9 intermediate metabolizer (activity score 1 and 1.5) phenotype: Initial dosage ≤40 mg/day. CYP2C9 poor metabolizer phenotype: Initial dosage ≤20 mg/day.

SLCO1B1 decreased or possible decreased function and CYP2C9 intermediate metabolizer: Initial dosage ≤20 mg/day.

SLCO1B1 decreased or possible decreased function and CYP2C9 poor metabolizer: Alternative statin recommended.

SLCO1B1 poor function and CYP2C9 intermediate or poor metabolizer: Alternative statin recommended.

Cautions for Fluvastatin Sodium

Contraindications

• Hypersensitivity to fluvastatin or any component of the formulation; anaphylaxis, angioedema, and Stevens-Johnson syndrome have been reported.

• Immediate-release capsules: Active liver disease or unexplained, persistent elevations of serum transaminases.

• Extended-release tablets: Acute liver failure or decompensated cirrhosis.

• Immediate-release capsules: Nursing mothers. Manufacturer states that this formulation is contraindicated in women who are pregnant or may become pregnant; however, because statins may prevent serious or potentially fatal cardiovascular events in certain high-risk patients who are pregnant, FDA has requested that the contraindication in pregnant women be removed from the prescribing information for all statins.

Warnings/Precautions

Musculoskeletal Effects

Myopathy (manifested as muscle pain, tenderness, or weakness and serum CK concentration increases >10 times the ULN) reported.

Rhabdomyolysis reported; rare fatalities have occurred.

Risk of myopathy is increased in geriatric patients (≥65 years of age) and patients with renal impairment or inadequately treated hypothyroidism; use with caution.

Concomitant use of statins with certain other drugs (e.g., cyclosporine, fluconazole, erythromycin, and other lipid-lowering drugs) also may increase risk of myopathy and/or rhabdomyolysis.

AHA/ACC recommends measurement of CK levels in patients with severe statin-associated muscle symptoms; however, routine monitoring is not useful.

Consider myopathy in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked CK elevation. Discontinue therapy if serum CK concentrations become markedly elevated or if myopathy is diagnosed or suspected.

Temporarily withhold therapy in any patient experiencing an acute or serious condition predisposing to the development of acute renal failure secondary to rhabdomyolysis (e.g., sepsis; shock or hypotension; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; uncontrolled seizures).

Immune-mediated Necrotizing Myopathy

Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, reported rarely in patients receiving statins. Characterized by proximal muscle weakness and elevated CK concentrations that persist despite discontinuance of statin therapy, positive anti-HMG CoA reductase antibody, muscle biopsy showing necrotizing myopathy, and improvement following therapy with immunosuppressive agents.

Additional neuromuscular and serologic testing may be necessary.

Discontinue if IMNM suspected. Consider risk of IMNM prior to initiating therapy with another statin; monitor for signs and symptoms.

Hepatic Effects

Increases in serum aminotransferase (AST, ALT) concentrations reported. Generally transient and resolve or improve with continued therapy or after temporary interruption in therapy.

Persistent aminotransferase elevations (>3 times the ULN on 2 consecutive weekly measurements) are more common at higher dosages (40 or 80 mg daily). Most cases occurred within 12 weeks of therapy.

Fatal and nonfatal hepatic failure reported rarely. Possibly drug-related hepatitis, which resolved following discontinuance of therapy, reported very rarely.

Perform liver function tests before initiation of therapy and as clinically indicated. Serious statin-related liver injury is rare and unpredictable, and routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury. AHA/ACC cholesterol management guideline states that it is reasonable to obtain liver function tests in patients with symptoms of hepatotoxicity (e.g., unusual fatigue or weakness, loss of appetite, abdominal pain, dark colored urine, yellowing of skin or sclera); however, routine monitoring not recommended.

Use with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease.

Contraindicated in patients with active liver disease (acute failure or decompensated cirrhosis), including unexplained, persistent elevations in serum aminotransferase concentrations.

If serious liver injury with clinical manifestations and/or hyperbilirubinemia or jaundice occurs, promptly interrupt fluvastatin therapy. If an alternate etiology is not found, do not restart fluvastatin.

Hyperglycemic Effects

Increases in HbA_1c and fasting serum glucose concentrations reported. Possible increased risk of developing diabetes.

AHA/ACC cholesterol management guideline states that in patients with increased risk of diabetes mellitus or new-onset diabetes mellitus, statin therapy and lifestyle modifications should be continued to reduce risk of ASCVD.

Endogenous Steroid Production

Statins interfere with cholesterol synthesis and theoretically may blunt adrenal and/or gonadal steroid production.

Fluvastatin had no effect on nonstimulated cortisol concentrations, adrenal response to corticotropin (adrenocorticotropic hormone, ACTH) stimulation, or thyroid metabolism. Small declines in total serum testosterone concentrations reported, but no commensurate elevation in luteinizing hormone (LH) concentrations, and no effect on follicular stimulating hormone (FSH) concentrations in men. Data insufficient to determine effect on female sex hormones.

If clinical evidence of endocrine dysfunction is present, evaluate patients appropriately.

Caution advised if a statin or another antilipemic agent is used concomitantly with drugs that may decrease concentrations or activity of endogenous steroid hormones (e.g. ketoconazole, spironolactone, cimetidine).

Specific Populations

Pregnancy

All statins were previously contraindicated in pregnant women because fetal risk was thought to outweigh any possible benefit. However, the totality of evidence to date indicates limited potential for statins to cause malformations and other adverse embryofetal effects; FDA has therefore requested removal of the contraindication. Most pregnant patients should still discontinue statins because of the possibility of fetal harm; however, some patients (e.g., those with homozygous familial hypercholesterolemia or established cardiovascular disease) may benefit from continued therapy. Consider patient's individual risks and benefits.

Patients who become pregnant or suspect that they are pregnant while receiving a statin should notify their clinician; clinician should advise patient on the appropriate course of action.

Increased risk of miscarriage reported in pregnant women exposed to statins; however, not clear whether drug-related or due to other confounding factors.

Lactation

Distributed into milk in animals. Use is contraindicated in nursing women; women who require fluvastatin therapy should not breast-feed their infants. Many patients can stop statin therapy temporarily until breast-feeding is complete; patients who require ongoing statin treatment should not breast-feed and should use alternatives such as infant formula.

Females and Males of Reproductive Potential

May cause fetal harm when administered to a pregnant woman.

Women (including adolescents) of childbearing age who are sexually active should be counseled to use reliable contraception.

Small declines in total serum testosterone concentrations reported, no commensurate elevation in LH concentrations, and no effect on FSH concentrations in men.

Data insufficient to determine effect on female sex hormones.

Pediatric Use

Safety and efficacy not established in children <10 years of age with heterozygous familial hypercholesterolemia (HeFH) or in children with other types of hyperlipidemia. However, experts state statins may be considered in patients as young as 8 years of age in the presence of concerning family history, extremely elevated LDL-cholesterol levels, or elevated lipoprotein (a), in the context of informed shared decision-making and counseling with the patient and family.

Geriatric Use

Fluvastatin exposures not substantially different between patients ≥65 years of age and younger adults.

Patients >75 years of age may have a higher risk of adverse effects and lower adherence to therapy; consider expected benefits versus adverse effects before initiating statin therapy in this population.

Hepatic Impairment

Patients with hepatic impairment due to liver cirrhosis may have increased exposure and peak plasma concentration.

Use with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease.

Contraindicated in patients with active liver disease (acute failure or decompensated cirrhosis) or unexplained, persistent increases in liver function test results.

Renal Impairment

Moderate to severe renal impairment (Cl_cr 10 –40 mL/minute): AUC and peak plasma concentration increased approximately 1.2 fold.

End-stage renal disease on hemodialysis: AUC increased approximately 1.5 fold.

Extended-release preparation not evaluated in patients with renal impairment; systemic exposures after administration lower than the 40 mg immediate-release capsule.

Monitor patients with renal impairment for the development of myopathy.

Pharmacogenomic Considerations

Genetic variation in the solute carrier organic anion transporter (SLCO) family member (SLCO1B1), ABCG2 (also known as breast cancer resistance protein [BCRP]), and CYP2C9 genes alter systemic exposure to statins, which can increase the risk for statin-associated musculoskeletal symptoms.

In patients with phenotypes that result in increased statin exposure, consider potential for other patient-specific issues that may increase statin exposure (e.g., renal and hepatic function, drug-drug interactions).

Experts state statin therapy should neither be discontinued nor avoided based on SLCO1B1, ABCG2, or CYP2C9 genotype results for patients with an indication for statin therapy.

SLCO1B1 decreased or possible decreased function phenotype poor function phenotypes: Increased exposure.

CYP2C9 intermediate metabolizer or poor metabolizer phenotypes: Increased exposure.

Combined SLCO1B1 (decreased or possible decreased or poor function) and CYP2C9 intermediate or poor metabolizer phenotypes: Increased exposure.

Patients with such phenotypes may require lower doses or an alternative statin.

Common Adverse Effects

Common adverse effects (≥2%) in patients receiving immediate-release capsules: headache, dyspepsia, myalgia, abdominal pain, nausea.

Common adverse effects (≥2.5%) in patients receiving extended-release tablets: influenza-like symptoms, sinusitis, dyspepsia, urinary tract infection, bronchitis, nausea.

Drug Interactions

Metabolized principally by CYP2C9; CYP2C8 and CYP3A4 also contribute to fluvastatin metabolism. Inhibits CYP2C9.

Substrate of organic anion transporter protein (OATP) 1B1, 1B3, and 2B1.

Drug interaction studies not performed with extended-release fluvastatin.

Drugs Affecting or Affected by Hepatic Microsomal Enzymes

CYP2C9 inhibitors: Possible decreased fluvastatin clearance and increased AUC.

CYP2C9 inducers: Possible increased fluvastatin clearance and decreased AUC.

CYP2C9 substrates: Possible increased exposure and increased pharmacodynamic effects of such substrates.

Drugs Affecting or Affected by Transport Systems

OATP1B1, 1B3, or 2B1 inhibitors: Possible increased exposure and increased risk of statin-induced toxicity (e.g., myopathy).

Specific Drugs

Fluvastatin Sodium Pharmacokinetics

Pharmacokinetic data in pediatric patients not available.

Absorption

Bioavailability

Rapidly absorbed.

Absolute bioavailability of immediate-release capsules is 24%.

The mean relative bioavailability of extended-release tablets is approximately 29% compared with immediate-release capsules administered under fasting conditions.

Mean peak plasma concentrations occur within 1 or 3 hours following oral administration of immediate-release capsules or extended-release tablets, respectively.

Onset

Maximal response occurs within 4 weeks.

Food

Peak plasma concentration decreased and time to peak plasma concentrations increased following administration of fluvastatin immediate-release capsules with the evening meal; however, no substantial differences in lipid-lowering effects following administration with food.

Bioavailability increased and absorption delayed following administration of extended-release tablets with a high-fat meal; however, peak plasma concentrations achieved with the extended-release tablets following a high-fat meal are much less than those achieved with a single or twice-daily dose of 40 mg immediate-release caspules.

Distribution

Extent

Distributed mainly to the liver.

Distributed into human milk (milk to plasma ratio 2:1).

Plasma Protein Binding

About 98%.

Elimination

Metabolism

Metabolized in the liver, principally by CYP2C9 and to a lesser extent by CYP3A4 and CYP2C8.

Elimination Route

Excreted in feces (90%) and urine (5%) mainly as metabolites; <2% excreted as unchanged drug.

Half-life

Approximately 3 hours (immediate-release capsules) and 3–5 hours (extended-release tablets).

Special Populations

Patients with Cl_cr 10–40 mL/minute or with end-stage renal disease on hemodialysis have increased AUC and peak plasma concentrations.

Patients with hepatic impairment due to liver cirrhosis have increased exposure and peak plasma concentrations.

No significant difference in drug concentrations in patients > 65 years of age compared to patients 21–49 years of age.

AUC is higher in females 21-49 years of age compared to males of the same age group; body weight adjustment decreases magnitude of observed differences. No significant differences in exposure between males and females in other age groups. AUC increased 67% and 77% for women compared to men under fasted and high-fat meal conditions, respectively, following administration of the extended-release preparation.

Patients with certain solute carrier organic anion transporter (SLCO) 1B1 phenotypes (i.e., decreased, possible decreased, or poor function) or certain CYP2C9 phenotypes (i.e., intermediate or poor metabolizer) will have increased fluvastatin exposure compared to those with normal function.

Stability

Storage

Oral

Immediate-release Capsules

20–25°C. Protect from light.

Extended-release Tablets

20–25°C (excursions permitted to 15–30°C). Protect from light.

Actions

• Inhibits HMG-CoA reductase, causing subsequent reduction in hepatic cholesterol synthesis. Reduces serum concentrations of total cholesterol, LDL-cholesterol, apo B, and triglycerides.

• Other favorable (pleitropic) effects include an antiproliferative influence on smooth muscle cells, reconstruction of endothelial activity, antioxidant, antithrombotic, anticancer, and anti-inflammatory effects.

Advice to Patients

• Advise patients of the importance of adhering to nondrug therapies and measures, including adherence to a heart-healthy diet, regular exercise, avoidance of tobacco products, and maintenance of a healthy weight.

• Advise patients of the risk of myopathy and/or rhabdomyolysis; risk is increased when used concomitantly with certain other drugs. Advise patients on the importance of promptly reporting unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever, or if manifestations persist after discontinuance of therapy.

• Advise patients of the risk of adverse hepatic effects and the importance of promptly reporting any symptoms suggestive of liver injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice).

• Advise patients of the risk of nonserious, reversible cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion).

• Advise patients of the risk of increased glucose concentrations and development of type 2 diabetes.

• Advise patients that fluvastatin immediate-release capsules should be administered at the same time each day with or without food. When fluvastatin immediate-release is taken twice daily, the capsules may be administered once in the morning and once in the evening. Fluvastatin capsules should not be opened.

• If a dose of immediate-release fluvastatin is missed, advise patients to take the missed as soon as possible. If it has been more than 12 hours since the last dose, advise patients to not take a dose until the next scheduled dose is due; do not administer 2 doses at the same time.

• Advise patients that fluvastatin extended-release tablets should be administered one time each day, at any time of day, with or without food. Fluvastatin extended-release tablets must be swallowed whole with a liquid and should not be broken, crushed, or chewed prior to administration.

• Advise females of reproductive potential (including adolescents) of the risk to a fetus and to use effective contraception during treatment. Advise women to contact their clinician if they become pregnant or suspect pregnancy during therapy.

• Advise women not to breastfeed during treatment with fluvastatin.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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