Hyperlipidemia or heterozygous familial and nonfamilial hypercholesterolemia: Note: Begin treatment if after adequate trial of diet the following are present: LDL-C ≥190 mg/dL or LDL-C remains ≥160 mg/dL and positive family history of premature cardiovascular disease or meets NCEP classification (Ref). Therapy may be considered for children 8-9 years of age meeting the above criteria or for children with diabetes mellitus and LDL-C ≥130 mg/dL (Ref).
Children ≥10 years and Adolescents ≤16 years (female patients should be ≥1 year postmenarche): Oral:
Immediate release capsule: Initial: 20 mg once daily; may titrate dose or frequency (twice daily dosing) at 6-week intervals; maximum dose: 40 mg twice daily.
Extended release tablet: Should not be used to initiate therapy; may convert patient if total daily dose is 80 mg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Muscle symptoms (potential myopathy): Children ≥10 years and Adolescents: Discontinue use until symptoms can be evaluated; check creatine phosphokinase (CPK) level; based on experience in adult patients, also evaluate patient for conditions that may increase the risk for muscle symptoms (eg, hypothyroidism, reduced renal or hepatic function, rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases). Upon resolution (symptoms and any associated CPK abnormalities), resume the original or consider a lower dose of fluvastatin and retitrate. If muscle symptoms recur, discontinue fluvastatin use. After muscle symptom resolution, may then reinitiate a different statin at an initial low dose; gradually increase if tolerated. Based on experience in adult patients, if muscle symptoms or elevated CPK persists for 2 months in the absence of continued statin use, consider other causes of muscle symptoms. If determined to be due to another condition aside from statin use, may resume statin therapy at the original dose (Ref).
There are no pediatric specific recommendations; based on experience in adult patients, no adjustment may be necessary with mild to moderate impairment. With severe renal impairment, use with caution, particularly when using maximum doses (has not been studied).
All patients: There are no dosage adjustments provided in the manufacturer's labeling; systemic exposure may be increased in patients with liver disease; use is contraindicated in patients with active liver disease or unexplained transaminase elevations.
(For additional information see "Fluvastatin: Drug information")
Dosage guidance:
Dosing: Fluvastatin 80 mg/day is considered a moderate-intensity statin (generally reduces LDL-C by ~30% to 49%). Fluvastatin 20 to 40 mg/day is considered a low-intensity statin (reduces LDL-C <30%). If LDL-C must be lowered ≥50%, select an alternative high-intensity statin (atorvastatin or rosuvastatin). Assess response ~1 to 3 months after initiation of therapy or dose adjustment and every 3 to 12 months thereafter (Ref).
Clinical considerations: Use in conjunction with lifestyle modification (eg, diet, exercise). When initiating therapy and selecting dose intensity, consider age, baseline low-density lipoprotein cholesterol (LDL-C), 10-year atherosclerotic cardiovascular disease (ASCVD) risk, risk-enhancing factors, potential adverse effects, and drug interactions (Ref).
Heterozygous familial hypercholesterolemia (alternative agent):
Note: Use of fluvastatin should be limited to patients unable to tolerate a high-intensity statin. Multiple lipid-lowering therapies may be needed if statin monotherapy is not effective. Referral to a lipid specialist should be considered if treatment goals are not met (Ref).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral:
Immediate release: 40 mg twice daily (Ref).
Extended release: 80 mg once daily (Ref).
Homozygous familial hypercholesterolemia (alternative agent):
Note: Use of fluvastatin should be limited to patients unable to tolerate a high-intensity statin. Multiple lipid-lowering therapies may be needed if statin monotherapy is not effective. Referral to a lipid specialist should be considered if treatment goals are not met (Ref).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral:
Immediate release: 40 mg twice daily (Ref).
Extended release: 80 mg once daily (Ref).
Prevention of atherosclerotic cardiovascular disease:
Note: If LDL-C goal (eg, percent reduction or absolute goal) is not met with the initial dose, may consider switching to a high-intensity statin (atorvastatin or rosuvastatin) based on estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk (see ACC/AHA ASCVD Risk Estimator Plus online), LDL-C response, and tolerability. Additional lipid-lowering therapy may be warranted (Ref).
Primary prevention:
Patients without diabetes, 40 to 75 years of age, and LDL-C 70 to 189 mg/dL:
ASCVD 10-year risk 5% to <7.5%:
Note: Depending on baseline LDL-C and presence of risk-enhancing factors, consider statin therapy after shared decision-making with patient. Some experts suggest shared decision-making if ASCVD 10-year risk is 5% to 10%; however, in patients with a baseline LDL-C ≥160 mg/dL, statin therapy is usually recommended (Ref).
Moderate-intensity therapy: Oral:
Immediate release: 40 mg twice daily to reduce LDL-C by ~30% to 49% (Ref).
Extended release: 80 mg once daily to reduce LDL-C by ~30% to 49% (Ref).
ASCVD 10-year risk ≥7.5% to <20%:
Note: Depending on baseline LDL-C and presence of risk-enhancing factors, consider statin therapy after shared decision-making with patient. Some experts suggest initiating moderate-intensity statin therapy in most patients if ASCVD 10-year risk is >10% to <20% and LDL-C is >100 mg/dL (Ref).
Moderate-intensity therapy: Oral:
Immediate release: 40 mg twice daily to reduce LDL-C by ~30% to 49% (Ref).
Extended release: 80 mg once daily to reduce LDL-C by ~30% to 49% (Ref).
Note: Higher-risk patients with multiple risk-enhancing factors may benefit from a high-intensity statin therapy (ie, with atorvastatin or rosuvastatin) to reduce LDL-C by ≥50% (Ref).
ASCVD 10-year risk ≥20% (alternative agent):
Note: Use of fluvastatin should be limited to patients unable to tolerate high-intensity statin (Ref).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral:
Immediate release: 40 mg twice daily (Ref).
Extended release: 80 mg once daily (Ref).
Patients with diabetes:
40 to 75 years of age without additional ASCVD risk factors:
Moderate-intensity therapy: Oral:
Immediate release: 40 mg twice daily to reduce LDL-C by ~30% to 49% (Ref).
Extended release: 80 mg once daily to reduce LDL-C by ~30% to 49% (Ref).
ASCVD 10-year risk ≥7.5% or multiple ASCVD risk factors (alternative agent) :
Note: Use of fluvastatin should be limited to patients unable to tolerate high-intensity statin (Ref).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral:
Immediate release: 40 mg twice daily (Ref).
Extended release: 80 mg once daily (Ref).
Patients with LDL-C ≥190 mg/dL and 20 to 75 years of age (regardless of ASCVD risk estimate or coexisting diabetes mellitus) (alternative agent):
Note: Use of fluvastatin should be limited to patients unable to tolerate high-intensity statin (Ref).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral:
Immediate release: 40 mg twice daily (Ref).
Extended release: 80 mg once daily (Ref).
Secondary prevention in patients with established ASCVD (eg, coronary heart disease, cerebrovascular disease [ischemic stroke or transient ischemic attack], peripheral arterial disease) (alternative agent):
Note: Use of fluvastatin should be limited to patients unable to tolerate a high-intensity statin. Patients with high-risk ASCVD may require additional therapies to achieve LDL-C goal (eg, <70 mg/dL or <50 mg/dL if very high risk) (Ref).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral:
Immediate release: 40 mg twice daily (Ref).
Extended release: 80 mg once daily (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution, particularly at doses >40 mg/day (has not been studied).
Use is contraindicated in patients with active acute liver failure, unexplained persistent transaminase elevations, or decompensated cirrhosis.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
1% to 10%:
Gastrointestinal: Abdominal pain (5%; including upper abdominal pain), diarrhea (5%), dyspepsia (8%), nausea (3%)
Genitourinary: Urinary tract infection (2%)
Hepatic: Increased serum transaminases (≤5%)
Nervous system: Fatigue (3%), headache (9%), insomnia (3%)
Neuromuscular & skeletal: Arthropathy (3%)
Respiratory: Bronchitis (2% to 3%), flu-like symptoms (7%), sinusitis (3% to 4%)
<1%: Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (>10 × normal), myopathy
Frequency not defined: Cardiovascular: Chest pain
Postmarketing:
Dermatologic: Alopecia, dermatitis (including bullous dermatitis), eczema, lichen planus, pruritus, skin changes (including changes in nails, changes of hair, cutaneous nodule, dry mucous membranes, nodule, skin discoloration, xeroderma), skin rash
Endocrine & metabolic: Decreased libido, elevated glycosylated hemoglobin, gynecomastia, increase in fasting plasma glucose, thyroid dysfunction
Gastrointestinal: Anorexia, dysgeusia, pancreatitis (Tysk 2002), vomiting
Genitourinary: Cystitis (interstitial) (Huang 2015), erectile dysfunction
Hepatic: Cholestatic jaundice, fulminant hepatic necrosis, hepatic cirrhosis, hepatic failure, hepatic neoplasm, hepatitis, hyperbilirubinemia, increased gamma-glutamyl transferase, increased serum alkaline phosphatase, liver steatosis
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis, angioedema)
Immunologic: Dermatomyositis (Visconti 2020)
Nervous system: Anxiety, cranial nerve disorder (including facial paresis, impairment of extraocular movement), depression, dysesthesia, hypoesthesia, myasthenia, paresthesia, peripheral nerve palsy, peripheral neuropathy, psychic disorder, tremor, vertigo
Neuromuscular & skeletal: Arthralgia, muscle cramps, muscle spasm, myoglobinuria, myositis (Alanazi 2021), rhabdomyolysis (Baek 2011)
Ophthalmic: Ophthalmoplegia, progression of cataract
Respiratory: Interstitial lung disease
Hypersensitivity (anaphylaxis, angioedema, and Stevens-Johnson syndrome) to fluvastatin or any component of the formulation; acute liver failure or decompensated cirrhosis.
Canadian labeling: Additional contraindications (not in the US labeling): Unexplained persistent elevated transaminases; breastfeeding; pregnancy.
Concerns related to adverse effects:
• 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 myocardial infarction 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) (AHA/ACC [Grundy 2019]).
• 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. Postmarketing reports of fatal and nonfatal hepatic failure have been reported and are rare. If serious hepatotoxicity with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, interrupt therapy promptly. If an alternate etiology is not identified, do not restart fluvastatin. Possible drug-related hepatitis (rare) was observed that resolved upon discontinuation of treatment. Liver enzyme tests should be obtained at baseline and as clinically indicated and if signs/symptoms of liver injury occur. Ethanol may enhance the potential of adverse hepatic effects; instruct patients to avoid excessive ethanol consumption. Use has been found to be safe in those with active hepatitis C (Kondo 2012; Kurincic 2014).
• 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, fluconazole, or other lipid-lowering medications (eg, fibrates, niacin at doses ≥1 g/day). Use caution in patients with uncontrolled hypothyroidism, and those taking other drugs associated with myopathy (eg, colchicine); these patients are predisposed to myopathy. Immune-mediated necrotizing myopathy associated with HMG-CoA reductase inhibitors use has also been reported. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or brown urine, particularly if accompanied by malaise or fever. Prior to initiating a different HMG-CoA reductase inhibitor consider risk of immune-mediated necrotizing myopathy; monitor closely.
Disease-related concerns:
• Hepatic impairment and/or ethanol use: Use with caution in patients who consume large amounts of ethanol or have a history of liver disease.
• Myasthenia gravis: May rarely worsen or precipitate myasthenia gravis (MG); monitor for worsening MG if treatment is initiated (AAN [Narayanaswami 2021]).
• Renal impairment: Use with caution in patients with renal impairment; these patients are predisposed to myopathy.
Special populations:
• Older adult: Use with caution in patients with advanced age; these patients are predisposed to myopathy.
• Surgical patients: Based on current research and clinical guidelines, HMG-CoA reductase inhibitors should be continued in the perioperative period for noncardiac and cardiac surgery (ACC/AHA [Hillis 2011]; ACC/AHA [Fleisher 2014]). Perioperative discontinuation of statin therapy is associated with an increased risk of cardiac morbidity and mortality.
Other warnings/precautions:
• Appropriate use: Drug therapy should be only one component of multiple risk factor intervention in patients at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. In patients with congenital heart defect (CHD) or multiple risk factors for CHD, initiate therapy simultaneously with diet.
• Hyperlipidemia: Secondary causes of hyperlipidemia should be ruled out prior to therapy.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Generic: 20 mg, 40 mg
Tablet Extended Release 24 Hour, Oral:
Lescol XL: 80 mg
Generic: 80 mg
Yes
Capsules (Fluvastatin Sodium Oral)
20 mg (per each): $5.00 - $5.01
40 mg (per each): $5.00 - $5.01
Tablet, 24-hour (Fluvastatin Sodium ER Oral)
80 mg (per each): $8.76 - $9.24
Tablet, 24-hour (Lescol XL Oral)
80 mg (per each): $16.38
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Generic: 20 mg, 40 mg
Tablet Extended Release 24 Hour, Oral:
Lescol XL: 80 mg [DSC]
Oral: Fluvastatin may be taken without regard to meals.
Immediate-release capsules: Do not open capsules; do not use two 40 mg capsules for an 80 mg once daily dose; extended release formulation should be used.
Extended-release tablet: Do not break, chew, or crush; swallow whole.
Oral: Administer without regard to meals. Do not break, chew, or crush ER tablets; do not open IR capsules. Do not administer two 40 mg IR capsules at once.
Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Switch to IR capsule.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.
Adjunct to dietary therapy to reduce elevated total-C, LDL-C, and apo-B levels in patients with heterozygous familial hypercholesterolemia (HFH) and if LDC-C remains ≥190 mg/dL or if ≥160 mg/dL with family history of premature cardiovascular disease or presence of ≥2 cardiovascular risk factors [FDA approved in ages 10-16 years (girls ≥1 year postmenarche)]. Adjunct to dietary therapy to reduce elevated total cholesterol (total-C), LDL-C, triglyceride, and apolipoprotein B (apo-B) levels and to increase HDL-C in primary hypercholesterolemia, and mixed dyslipidemia (Fredrickson types IIa and IIb) (FDA approved in adults); to slow the progression of coronary atherosclerosis in patients with coronary heart disease (FDA approved in adults); to reduce risk of coronary revascularization procedures in patients with coronary heart disease (FDA approved in adults)
Fluvastatin may be confused with fluoxetine, nystatin, pitavastatin
HMG-CoA reductase inhibitors (when referred to as "statins") may be confused with nystatin.
Substrate of CYP2C8 (minor), CYP2C9 (major), CYP2D6 (minor), CYP3A4 (minor), OATP1B1/1B3 (SLCO1B1/1B3); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Abiraterone Acetate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Acipimox: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Atazanavir: May increase the serum concentration of Fluvastatin. Management: When used with atazanavir/cobicistat, initiate fluvastatin at the lowest recommended dose and monitor clinical response (particularly any evidence of toxicity) to dose titration. Risk D: Consider therapy modification
Belumosudil: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid coadministration of belumosudil with these substrates of OATP1B1/1B3 for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the OATP1B1/1B3 substrate may be required. Risk D: Consider therapy modification
Bezafibrate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Bezafibrate may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). More specifically, bezafibrate may increase the serum concentration of fluvastatin Management: Avoid use of bezafibrate and HMG-CoA reductase inhibitors (statins) unless strictly indicated due to the increased of muscle toxicity (including rhabdomyolysis). In patients who may be predisposed to myopathy, concomitant use is contraindicated. Risk D: Consider therapy modification
Bulevirtide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Coadministration of bulevirtide with OATP1B1/1B3 (also known as SLCO1B1/1B3) substrates should be avoided when possible. If used together, close clinical monitoring is recommended. Risk D: Consider therapy modification
Bulevirtide: May increase the serum concentration of NTCP Substrates. Management: Coadministration of bulevirtide with sodium taurocholate co-transporting polypeptide (NTCP) substrate should be avoided when possible. If used together, close clinical monitoring is recommended. Risk D: Consider therapy modification
Ceftobiprole Medocaril: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Cholestyramine Resin: May decrease the serum concentration of Fluvastatin. Management: Separate the administration of fluvastatin and cholestyramine to maximize fluvastatin absorption. Administer fluvastatin 2 to 4 hours, or longer, after cholestyramine administration. Risk D: Consider therapy modification
Ciprofibrate: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Management: Avoid the use of HMG-CoA reductase inhibitors and ciprofibrate if possible. If concomitant therapy is considered, benefits should be carefully weighed against the risks, and patients should be monitored closely for signs/symptoms of muscle toxicity. Risk D: Consider therapy modification
Cobicistat: May increase the serum concentration of Fluvastatin. Risk C: Monitor therapy
Colchicine: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). HMG-CoA Reductase Inhibitors (Statins) may increase the serum concentration of Colchicine. Risk C: Monitor therapy
CycloSPORINE (Systemic): May increase the serum concentration of Fluvastatin. Management: Limit fluvastatin to 20 mg twice daily and avoid use of fluvastatin extended-release tablets in patients who are also receiving cyclosporine and monitor for fluvastatin toxicities (eg, myalgia, myopathy, rhabdomyolysis). Risk D: Consider therapy modification
CYP2C9 Inducers (Moderate): May decrease the serum concentration of Fluvastatin. Risk C: Monitor therapy
CYP2C9 Inhibitors (Moderate): May increase the serum concentration of Fluvastatin. Management: Fluvastatin should be used at the lowest effective dose and should not exceed 20 mg twice daily when combined with moderate CYP2C9 inhibitors. Avoid coadministration of fluvastatin extended-release tablets with moderate CYP2C9 inhibitors. Risk D: Consider therapy modification
Daclatasvir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
DAPTOmycin: HMG-CoA Reductase Inhibitors (Statins) may enhance the adverse/toxic effect of DAPTOmycin. Specifically, the risk of skeletal muscle toxicity may be increased. Management: Consider temporarily stopping statin (HMG-CoA reductase inhibitor) therapy prior to daptomycin. If daptomycin is used with a statin, creatine phosphokinase (CPK) monitoring could be considered. Risk D: Consider therapy modification
Darolutamide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Elbasvir and Grazoprevir: May increase the serum concentration of Fluvastatin. Risk C: Monitor therapy
Eltrombopag: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Encorafenib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Etravirine: May increase the serum concentration of Fluvastatin. Risk C: Monitor therapy
Fenofibrate and Derivatives: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Fosphenytoin-Phenytoin: Fluvastatin may increase the serum concentration of Fosphenytoin-Phenytoin. Fosphenytoin-Phenytoin may increase the serum concentration of Fluvastatin. Risk C: Monitor therapy
Fostemsavir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Use the lowest possible starting statin dose and monitor patients closely for statin-related adverse effects (eg, muscle aches and pains) during coadministration with fostemsavir. Risk D: Consider therapy modification
Fusidic Acid (Systemic): May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Specifically, the risk for muscle toxicities, including rhabdomyolysis may be significantly increased. Management: Avoid concurrent use whenever possible. Use is listed as contraindicated in product characteristic summaries in several countries, although UK labeling suggests that use could be considered under exceptional circumstances and with close supervision. Risk X: Avoid combination
Gemfibrozil: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk X: Avoid combination
Glecaprevir and Pibrentasvir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Use the lowest statin dose possible if combined with glecaprevir/pibrentasvir and monitor for increased statin effects/toxicities. Avoid concomitant use with atorva-, simva-, or lovastatin. Limit rosuvastatin to 10 mg daily and reduce pravastatin dose 50% Risk D: Consider therapy modification
GlyBURIDE: May increase the serum concentration of Fluvastatin. Fluvastatin may increase the serum concentration of GlyBURIDE. Risk C: Monitor therapy
Lanthanum: May decrease the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Administer HMG-CoA reductase inhibitors (eg, statins) at least two hours before or after lanthanum. Risk D: Consider therapy modification
Leflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Leniolisib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Letermovir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor therapy
Niacin: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May increase the serum concentration of Fluvastatin. Management: Canadian product labeling recommends use of the lowest fluvastatin dose with this combination. Risk C: Monitor therapy
Pretomanid: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Raltegravir: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Red Yeast Rice: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Risk X: Avoid combination
Repaglinide: HMG-CoA Reductase Inhibitors (Statins) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy
RifAMPin: May decrease the serum concentration of Fluvastatin. Specifically, this occurs with prolonged coadministration. RifAMPin may increase the serum concentration of Fluvastatin. Specifically, this occurs upon rifampin initiation. Risk C: Monitor therapy
Rifapentine: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Risk C: Monitor therapy
Roxadustat: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Rupatadine: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Specifically, the risk for increased CPK and/or other muscle toxicities may be increased. Risk C: Monitor therapy
Simeprevir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Teriflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Trabectedin: HMG-CoA Reductase Inhibitors (Statins) may enhance the myopathic (rhabdomyolysis) effect of Trabectedin. Risk C: Monitor therapy
Trofinetide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid concurrent use with OATP1B1/1B3 substrates for which small changes in exposure may be associated with serious toxicities. Monitor for evidence of an altered response to any OATP1B1/1B3 substrate if used together with trofinetide. Risk D: Consider therapy modification
Vadadustat: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): HMG-CoA Reductase Inhibitors (Statins) may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Voclosporin: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Voxilaprevir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Use the lowest statin dose possible if combined with voxilaprevir and monitor patients for increased statin effects/toxicities. Avoid concomitant use of voxilaprevir with rosuvastatin or pitavastatin, and limit pravastatin doses to 40 mg daily. Risk D: Consider therapy modification
Food reduces rate but not the extent of absorption. Management: Administer without regard to meals.
Generally, patients should be placed on a standard cholesterol-lowering diet and other lifestyle modifications for 3 to 6 months prior to the initiation of drug therapy. The diet should be continued during drug therapy. However, for patients with advanced risk factors (eg, known coronary heart disease), drug therapy may be initiated concurrently with diet modification.
Red yeast rice contains variable amounts of several compounds that are structurally similar to HMG-CoA reductase inhibitors, primarily monacolin K (or mevinolin) which is structurally identical to lovastatin; concurrent use of red yeast rice with HMG-CoA reductase inhibitors may increase the incidence of adverse and toxic effects (Lapi 2008; Smith 2003).
Adequate contraception is recommended if an HMG-CoA reductase inhibitor (statin) is required in patients who may become pregnant (AHA/ACC [Grundy 2019]; CCS [Pearson 2021]). Use of fluvastatin is contraindicated in patients who could become pregnant. Patients planning to become pregnant should discuss their lifetime risk of cardiovascular disease, as well as risks and benefits of statin therapy with their health care team (CCS [Pearson 2021]). When appropriate, statins can be discontinued 1 to 2 months prior to conception (AHA/ACC [Grundy 2019]).
When a statin is needed in a patient of reproductive potential, a more hydrophilic option (eg, pravastatin, rosuvastatin) may be preferred to limit placental transfer (CCS [Pearson 2021]).
In healthy pregnancies, changes in lipid synthesis occur that are required for normal placental and fetal growth. Low-density lipoprotein cholesterol and triglycerides increase as pregnancy progresses and decline postpartum. HMG-CoA reductase inhibitors (statins) decrease the synthesis of cholesterol and substances derived from cholesterol. Therefore, based on the mechanism of action, in utero exposure may cause fetal harm (Lecarpentier 2012); however, data from available studies have not shown an increased risk of major congenital anomalies following first-trimester exposure (Bateman 2015; Chang 2021; Vahedian-Azimi 2021a). Additional data are needed to evaluate other pregnancy outcomes, such as miscarriage (Vahedian-Azimi 2021b).
Because there is potential for fetal harm, statins should be discontinued once pregnancy is recognized (AHA/ACC [Grundy 2019]; Brunham 2018). If lipid-lowering therapy during pregnancy is required, it should be individualized based on the therapeutic needs of the patient, considering the lifetime risk of untreated disease, use of nonstatin therapies, as well as the known risks and benefits of statins. Based on limited data, when a statin is needed in a pregnant patient, a more hydrophilic option (eg, pravastatin, rosuvastatin) may be preferred. Lipophilic statins (eg, atorvastatin, fluvastatin, lovastatin, simvastatin, pitavastatin) may be more likely to cross the placenta and increase the risk of congenital malformations (AHA/ACC [Grundy 2019]; CCS [Pearson 2021]; Lecarpentier 2012).
Additional data are needed to clarify the role of statins for the prevention of atherosclerotic cardiovascular disease in at-risk pregnant patients (AHA/ACC [Grundy 2019]; CCS [Pearson 2021]; Parikh 2021).
Manufacturer's labeling: Consider neuromuscular and serologic testing if immune-mediated necrotizing myopathy is suspected.
Pediatric patients: Baseline: ALT, AST, and creatine phosphokinase levels (CPK); fasting lipid panel (FLP) and repeat ALT and AST should be checked after 4 weeks of therapy; if no myopathy symptoms or laboratory abnormalities, then monitor FLP, ALT, and AST every 3 to 4 months during the first year and then every 6 months thereafter (NHLBI 2011).
Adults:
2013 ACC/AHA Blood Cholesterol Guideline recommendations (Stone 2013):
Lipid panel (total cholesterol, HDL, LDL, triglycerides): Baseline lipid panel; fasting lipid profile within 4 to 12 weeks after initiation or dose adjustment and every 3 to 12 months (as clinically indicated) thereafter. If 2 consecutive LDL levels are <40 mg/dL, consider decreasing the dose.
Hepatic transaminase levels: Baseline measurement of hepatic transaminase levels (ie, ALT); measure hepatic function if symptoms suggest hepatotoxicity (eg, unusual fatigue or weakness, loss of appetite, abdominal pain, dark-colored urine or yellowing of skin or sclera) during therapy.
CPK: CPK should not be routinely measured. Baseline CPK measurement is reasonable for some individuals (eg, family history of statin intolerance or muscle disease, clinical presentation, concomitant drug therapy that may increase risk of myopathy). May measure CPK in any patient with symptoms suggestive of myopathy (pain, tenderness, stiffness, cramping, weakness, or generalized fatigue).
Evaluate for new-onset diabetes mellitus during therapy; if diabetes develops, continue statin therapy and encourage adherence to a heart-healthy diet, physical activity, a healthy body weight, and tobacco cessation.
If patient develops a confusional state or memory impairment, may evaluate patient for nonstatin causes (eg, exposure to other drugs), systemic and neuropsychiatric causes, and the possibility of adverse effects associated with statin therapy.
Manufacturer recommendations: Liver enzyme tests at baseline and repeated when clinically indicated. Measure CPK when myopathy is being considered. Upon initiation or titration, lipid panel should be analyzed at 4 weeks.
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. In addition to the ability of HMG-CoA reductase inhibitors to decrease levels of high-sensitivity C-reactive protein (hsCRP), they also possess pleiotropic properties including improved endothelial function, reduced inflammation at the site of the coronary plaque, inhibition of platelet aggregation, and anticoagulant effects (de Denus 2002; Ray 2005).
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 metabolites (oxidative metabolism via CYP2C9 [~75%], CYP2C8 [~5%], and CYP3A4 [~20%] isoenzymes); active forms do not circulate systemically; extensive (saturable) first-pass hepatic extraction
Bioavailability: Absolute: Immediate-release: 24%; Extended-release: ~29% (increased by ~50% when administered with a high-fat meal)
Half-life elimination: Immediate-release: ~3 hours; Extended-release: 7.3 to 10.5 hours (due to prolonged absorption time) (Barilla 2004)
Time to peak:
Immediate-release: <1 hour (delayed more than 2-fold when administered with food as compared to administering 4 hours after the evening meal)
Extended-release: ~3 hours (minimally affected by low-fat meals; however, with a high-fat meal, delayed by 2-fold)
Excretion: Feces (~90%; <2% unchanged); urine (~5%)
Altered kidney function: In moderate to severe renal impairment (CrCl 10 to 40 mL/minute), AUC and Cmax increased ~1.2-fold after administration of a single dose of 40 mg immediate-release fluvastatin; in ESRD on hemodialysis, the AUC increased ~1.5-fold.
Hepatic function impairment: AUC and Cmax increase ~2.5-fold after administration of a single dose of 40 mg immediate-release fluvastatin.
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