Lescol

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Lescol

Classes

HMG-CoA Reductase Inhibitors (Statins)

Administration

NOTE: Patients should also be placed on a standard cholesterol-lowering diet, and this diet should be continued throughout fluvastatin therapy. Serum lipoprotein concentrations should be determined periodically and dosage adjusted according to individual response and established NCEP treatment guidelines.
 

Oral Administration

If administered concomitantly with a bile-acid resin (e.g., colestipol, cholestyramine), administer fluvastatin at least 1 hour before (or possibly longer for the extended-release product) or 4 hours after the resin to avoid significant interactions.

Oral Solid Formulations

Regular-release Capsules: Fluvastatin may be administered without regard to meals. Do not open fluvastatin capsules prior to administration.
Extended-release Tablets: Fluvastatin may be administered without regard to meals since no differences in antilipemic effects have been observed when administered with the evening meal or 4 hours after the evening meal. Do not break, crush or chew fluvastatin extended-release tablets prior to administration.

Adverse Reactions
Severe

atrial fibrillation / Early / 2.4-2.4
immune-mediated necrotizing myopathy / Delayed / 0-1.0
pancreatitis / Delayed / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
myoglobinuria / Delayed / Incidence not known
hepatic necrosis / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
cirrhosis / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
lupus-like symptoms / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
vasculitis / Delayed / Incidence not known
muscle paralysis / Delayed / Incidence not known
cranial nerve palsies / Delayed / Incidence not known
myasthenia gravis / Delayed / Incidence not known

Moderate

hypertension / Early / 5.8-5.8
elevated hepatic enzymes / Delayed / 0.2-4.9
peripheral edema / Delayed / 4.4-4.4
constipation / Delayed / 3.3-3.3
myopathy / Delayed / Incidence not known
myasthenia / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
dyspnea / Early / Incidence not known
thrombocytopenia / Delayed / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
depression / Delayed / Incidence not known
memory impairment / Delayed / Incidence not known
confusion / Early / Incidence not known
amnesia / Delayed / Incidence not known
dysphagia / Delayed / Incidence not known
dysarthria / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
diabetes mellitus / Delayed / Incidence not known
impotence (erectile dysfunction) / Delayed / Incidence not known

Mild

headache / Early / 4.7-8.9
dyspepsia / Early / 3.5-7.9
influenza / Delayed / 5.1-7.1
abdominal pain / Early / 3.7-6.3
myalgia / Early / 2.2-5.0
diarrhea / Early / 3.3-4.9
sinusitis / Delayed / 2.6-3.5
nausea / Early / 2.5-3.2
arthropathy / Delayed / 3.2-3.2
pharyngitis / Delayed / 2.8-2.8
fatigue / Early / 1.6-2.7
insomnia / Early / 0.8-2.7
infection / Delayed / 1.6-2.7
flatulence / Early / 1.4-2.6
syncope / Early / 2.4-2.4
arthralgia / Delayed / 2.1-2.1
vomiting / Early / Incidence not known
anorexia / Delayed / Incidence not known
drowsiness / Early / Incidence not known
fever / Early / Incidence not known
malaise / Early / Incidence not known
weakness / Early / Incidence not known
muscle cramps / Delayed / Incidence not known
chills / Rapid / Incidence not known
alopecia / Delayed / Incidence not known
flushing / Rapid / Incidence not known
pruritus / Rapid / Incidence not known
purpura / Delayed / Incidence not known
photosensitivity / Delayed / Incidence not known
rash / Early / Incidence not known
urticaria / Rapid / Incidence not known
tremor / Early / Incidence not known
dysesthesia / Delayed / Incidence not known
vertigo / Early / Incidence not known
paresthesias / Delayed / Incidence not known
hypoesthesia / Delayed / Incidence not known
dizziness / Early / Incidence not known
anxiety / Delayed / Incidence not known
dysgeusia / Early / Incidence not known
gynecomastia / Delayed / Incidence not known
libido decrease / Delayed / Incidence not known
Co-Enzyme Q-10 deficiency / Delayed / Incidence not known

Common Brand Names

Lescol, Lescol XL

Dea Class

Rx

Description

Least potent, oral, HMG Co-A reductase inhibitor; used 1-2 times daily to treat hypercholesterolemia; indicated to reduce LDL and total cholesterol, plasma triglycerides, and apolipoprotein B; documented to slow the progression of coronary atherosclerosis in patients with CAD.

Dosage And Indications
For general dosing information in persons requiring moderate-intensity statin therapy. Oral dosage (immediate-release) Adults

40 mg PO twice daily.

Oral dosage (extended-release) Adults

80 mg PO once daily.

For general dosing information in persons requiring low-intensity statin therapy. Oral dosage (immediate-release) Adults

20 or 40 mg PO once daily.

For the treatment of hypercholesterolemia, including hyperlipidemia, hyperlipoproteinemia, or hypertriglyceridemia, as an adjunct to dietary controll, for the purpose of reducing the risk of cardiovascular events (e.g., myocardial infarction prophylaxis, stroke prophylaxis). Oral dosage (regular-release capsules) Adults

20 to 40 mg PO once daily (22% to 25% LDL reduction), titrated up to 40 mg PO twice daily (or switch to extended-release fluvastatin 80 mg PO once daily) to achieve 35% to 36% LDL reduction. In patients with coronary heart disease, fluvastatin 40 mg PO twice daily has been demonstrated to be effective for secondary prevention in post-PCI patients (LIPS trial).[27453] Serum lipid determinations and dosage adjustments should be made at intervals of 4 four weeks or more. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Due to the doubling of costs associated with twice daily administration of 40 mg regular-release capsules, consider reserving the twice daily dosage for those patients with inadequate LDL-lowering at 40 mg once daily (also see dosage information for the alternative extended-release 80 mg tablets designed for once-daily administration). The LIPS trial has demonstrated that initiation of fluvastatin 40 mg twice daily within days following PCI significantly reduces the risk of major cardiac events (cardiac death, nonfatal MI, coronary revascularization).[27453] Based on prior results from the 2.5-year LCAS trial [23946], the FDA, fluvastatin received approval for use to slow the progression of coronary atherosclerosis; the study utilized fluvastatin 20 mg twice daily in patients with coronary heart disease.

Children and Adolescents 10 to 17 years (females should be at least 1 year post-menarche)

20 mg PO once daily; may titrate up to 40 mg twice daily. Adjust dosage at intervals of 6 weeks or more to attain desired cholesterol reduction. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In 2 open-label studies of heterozygous familial hypercholesterolemia (n = 114, age 9 to 16 years) serum total cholesterol and LDL were decreased by 21% to 22% and 27% to 28%, respectively, after two years of treatment with fluvastatin. The majority of patients in both studies were titrated to the maximum dosage (80 mg/day).

Oral dosage (extended-release tablets) Adults

Patients requiring 25% or more LDL reduction may be started on extended-release fluvastatin 80 mg PO once daily (35% LDL reduction). Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. For patients requiring lower LDL reductions, see dosage information for regular-release capsules. In general, the recommended dosage range for fluvastatin is 20 to 80 mg/day PO. Elderly patients may have greater LDL reductions at usual doses. Serum lipid determinations and dosage adjustments should be made at intervals of 4 weeks or more.

Children and Adolescents 10 to 17 years (females should be at least 1 year post-menarche)

Patients who have been titrated up to 40 mg PO twice daily of fluvastatin may be transitioned to 80 mg PO once daily of the extended-release formulation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In 2 open-label studies of heterozygous familial hypercholesterolemia (n = 114, age 9 to 16 years), the majority of patients in both studies were titrated to the maximum dosage (80 mg/day). In these trials, serum total cholesterol and LDL decreased by 21% to 22% and 27% to 28%, respectively, after 2 years of treatment with fluvastatin.

Dosing Considerations
Hepatic Impairment

Contraindicated in patients with active hepatic disease or with unexplained or persistent hepatic transaminase elevations.

Renal Impairment

No initial dosage adjustment is needed for adult patients mild to moderate renal impairment. Fluvastatin has not been evaluated at doses more than 40 mg/day in adult patients with severe renal impairment; therefore, use caution when treating such patients at higher doses. Specific recommendations for dosage adjustment in pediatric patients with renal impairment are not available.
 
Intermittent hemodialysis
The hemodialyzability of fluvastatin is unknown.

Drug Interactions

Amiodarone: (Moderate) In theory, concurrent use CYP2C9 inhibitors, such as amiodarone, and fluvastatin, a CYP2C9 substrate, may result in reduced metabolism of fluvastatin and potential for toxicity, including myopathy and rhabdomyolysis.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Concomitant administration of omeprazole with fluvastatin can decrease fluvastatin clearance by 18 to 23%, and increase AUC by 24 to 33%. (Moderate) Rare reports of rhabdomyolysis have been reported in patients taking clarithromycin and fluvastatin. Use together with caution and monitor for symptoms of myopathy and/or rhabdomyolysis.
Aprepitant, Fosaprepitant: (Minor) Use caution if fluvastatin and aprepitant are used concurrently and monitor for a possible decrease in the efficacy of fluvastatin. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Fluvastatin is a CYP2C9 substrate and aprepitant is a CYP2C9 inducer. Administration of a CYP2C9 substrate, tolbutamide, on days 1, 4, 8, and 15 with a 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) decreased the tolbutamide AUC by 23% on day 4, 28% on day 8, and 15% on day 15. The AUC of tolbutamide was decreased by 8% on day 2, 16% on day 4, 15% on day 8, and 10% on day 15 when given prior to oral administration of aprepitant 40 mg on day 1, and on days 2, 4, 8, and 15. The effects of aprepitant on tolbutamide were not considered significant. When a 3-day regimen of aprepitant (125 mg/80 mg/80 mg) given to healthy patients on stabilized chronic warfarin therapy (another CYP2C9 substrate), a 34% decrease in S-warfarin trough concentrations was noted, accompanied by a 14% decrease in the INR at five days after completion of aprepitant.
Aspirin, ASA; Omeprazole: (Moderate) Concomitant administration of omeprazole with fluvastatin can decrease fluvastatin clearance by 18 to 23%, and increase AUC by 24 to 33%.
Atazanavir: (Moderate) Concurrent use of atazanavir with fluvastatin should be done cautiously. Concomitant use may increase the risk of myopathy and rhabdomyolysis. Atazanavir inhibits CYP3A4 metabolism. Because fluvastatin does not rely exclusively on CYP3A4 for its metabolism, atazanavir may not interact to the same extent as expected with other HMG-CoAA reductase inhibitors.
Atazanavir; Cobicistat: (Major) The plasma concentrations of fluvastatin may increase when administered with cobicistat. Use the lowest starting dose of fluvastatin and carefully titrate while monitoring for adverse events. (Moderate) Concurrent use of atazanavir with fluvastatin should be done cautiously. Concomitant use may increase the risk of myopathy and rhabdomyolysis. Atazanavir inhibits CYP3A4 metabolism. Because fluvastatin does not rely exclusively on CYP3A4 for its metabolism, atazanavir may not interact to the same extent as expected with other HMG-CoAA reductase inhibitors.
Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like HMG-CoA reductase inhibitors; the risk of peripheral neuropathy may be additive.
Bupivacaine; Meloxicam: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with fluvastatin is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and fluvastatin is a weak CYP2C9 inhibitor.
Cholestyramine: (Moderate) Concomitant administration of cholestyramine with fluvastatin (immediate-release capsules) significantly reduces fluvastatin serum concentrations (reduces AUC by 89%). Cholestyramine produces a complex with fluvastatin that is unavailable for absorption. However, administration of fluvastatin 4 hours after cholestyramine resulted in a clinically significant additive effect compared with that achieved with either component drug. If a patient is to receive both medications, administration times should be staggered by at least 4 hours to avoid impairing fluvastatin bioavailability.
Cimetidine: (Moderate) Use HMG-CoA reductase inhibitors with caution with concomitant drugs that may decrease the levels or activity of endogenous steroids, such as cimetidine. Evaluate patients with signs and symptoms of endocrine dysfunction appropriately. HMG-CoA reductase inhibitors interfere with cholesterol synthesis and theoretically might blunt adrenal and/or gonadal steroid production.
Clarithromycin: (Moderate) Rare reports of rhabdomyolysis have been reported in patients taking clarithromycin and fluvastatin. Use together with caution and monitor for symptoms of myopathy and/or rhabdomyolysis.
Cobicistat: (Major) The plasma concentrations of fluvastatin may increase when administered with cobicistat. Use the lowest starting dose of fluvastatin and carefully titrate while monitoring for adverse events.
Colchicine: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
Cyclosporine: (Major) Do not exceed 40 mg/day of fluvastatin when coadministered with cyclosporine. The risk of developing myopathy/rhabdomyolysis increases when fluvastatin is used concomitantly with cyclosporine. Monitor patients for any signs or symptoms of muscle pain, weakness, or tenderness. The serious risk of myopathy or rhabdomyolysis should be weighed carefully against the benefits of combined therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage. The fluvastatin AUC was increased by 90% with the concomitant cyclosporine administration.
Daclatasvir: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Daptomycin: (Major) Temporarily suspend HMG-CoA reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. Both agents can cause myopathy and rhabdomyolysis when given alone and the risk may be increased when given together.
Darolutamide: (Moderate) Monitor for an increase in fluvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with darolutamide is necessary. Concomitant use may increase fluvastatin exposure. Fluvastatin is a substrate of OATP1B3; darolutamide is an inhibitor of OATP1B3.
Darunavir: (Moderate) Concurrent use of darunavir with fluvastatin should be done cautiously. Concomitant use may increase the risk of myopathy and rhabdomyolysis. Darunavir inhibits CYP3A4 metabolism. Because fluvastatin does not rely exclusively on CYP3A4 for its metabolism, darunavir may not interact to the same extent as expected with other HMG-CoAA reductase inhibitors.
Darunavir; Cobicistat: (Major) The plasma concentrations of fluvastatin may increase when administered with cobicistat. Use the lowest starting dose of fluvastatin and carefully titrate while monitoring for adverse events. (Moderate) Concurrent use of darunavir with fluvastatin should be done cautiously. Concomitant use may increase the risk of myopathy and rhabdomyolysis. Darunavir inhibits CYP3A4 metabolism. Because fluvastatin does not rely exclusively on CYP3A4 for its metabolism, darunavir may not interact to the same extent as expected with other HMG-CoAA reductase inhibitors.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) The plasma concentrations of fluvastatin may increase when administered with cobicistat. Use the lowest starting dose of fluvastatin and carefully titrate while monitoring for adverse events. (Moderate) Concurrent use of darunavir with fluvastatin should be done cautiously. Concomitant use may increase the risk of myopathy and rhabdomyolysis. Darunavir inhibits CYP3A4 metabolism. Because fluvastatin does not rely exclusively on CYP3A4 for its metabolism, darunavir may not interact to the same extent as expected with other HMG-CoAA reductase inhibitors.
Deferasirox: (Moderate) Deferasirox inhibits CYP2C8. Fluvastatin is a substrate for CYP2C8. The concomitant administration of deferasirox and the CYP2C8 substrate repaglinide (single dose of 0.5 mg) resulted in an increase in repaglinide Cmax by 62% and an increase in AUC 2.3-fold. Although specific drug interaction studies of deferasirox and fluvastatin are not available, a similar interaction may occur. The dose of fluvastatin may need to be decreased if coadministered with deferasirox.
Delavirdine: (Moderate) Concurrent use of delavirdine with fluvastatin should be done cautiously. Coadministration of fluvastatin with delavirdine may increase the risk of myopathy and rhabdomyolysis. Delavirdine inhibits CYP2C9, which is the isoenzyme primarily responsible for the metabolism of fluvastatin.
Diclofenac: (Moderate) If possible, avoid concurrent use of diclofenac with inhibitors of CYP2C9, such as fluvastatin; if coadministration is required, do not exceed a total daily diclofenac dose of 100 mg. When used with a CYP2C9 inhibitor the systemic exposure to diclofenac (a CYP2C9 substrate) may increase, potentially resulting in adverse events. In addition, exposure to fluvastatin may also be increased during concurrent use.
Diclofenac; Misoprostol: (Moderate) If possible, avoid concurrent use of diclofenac with inhibitors of CYP2C9, such as fluvastatin; if coadministration is required, do not exceed a total daily diclofenac dose of 100 mg. When used with a CYP2C9 inhibitor the systemic exposure to diclofenac (a CYP2C9 substrate) may increase, potentially resulting in adverse events. In addition, exposure to fluvastatin may also be increased during concurrent use.
Digoxin: (Moderate) Due to data that indicate high doses of fluvastatin, 80mg/day, increase digoxin serum concentrations, the manufacturer recommends closer monitoring of patients stabilized on digoxin if fluvastatin is added.
Dronabinol: (Moderate) Use caution if coadministration of dronabinol with fluvastatin is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; fluvastatin is a weak inhibitor of CYP2C9. Concomitant use may result in elevated plasma concentrations of dronabinol.
Efavirenz: (Moderate) Efavirenz inhibits CYP2C9, which is the isoenzyme primarily responsible for the metabolism of fluvastatin. Coadministration of fluvastatin with efavirenz may increase the risk of myopathy and rhabdomyolysis.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Efavirenz inhibits CYP2C9, which is the isoenzyme primarily responsible for the metabolism of fluvastatin. Coadministration of fluvastatin with efavirenz may increase the risk of myopathy and rhabdomyolysis.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Efavirenz inhibits CYP2C9, which is the isoenzyme primarily responsible for the metabolism of fluvastatin. Coadministration of fluvastatin with efavirenz may increase the risk of myopathy and rhabdomyolysis.
Elbasvir; Grazoprevir: (Moderate) The manufacturer of elbasvir; grazoprevir recommends caution during concurrent administration with fluvastatin. Although this interaction has not been studied, use of these drugs together may result in elevated fluvastatin plasma concentrations. Use the lowest effective fluvastatin dose and monitor patients for statin-related adverse events (such as myopathy).
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for an increase in fluvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with elexacaftor is necessary. Concomitant use may increase fluvastatin exposure. Fluvastatin is a substrate of OATP1B3; elexacaftor is an inhibitor of OATP1B3. (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as fluvastatin. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
Eltrombopag: (Moderate) Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as fluvastatin, may exhibit an increase in systemic exposure if coadministered with eltrombopag; monitor patients for adverse reactions if these drugs are coadministered.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) The plasma concentrations of fluvastatin may increase when administered with cobicistat. Use the lowest starting dose of fluvastatin and carefully titrate while monitoring for adverse events.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) The plasma concentrations of fluvastatin may increase when administered with cobicistat. Use the lowest starting dose of fluvastatin and carefully titrate while monitoring for adverse events.
Enasidenib: (Moderate) Monitor for an increase in fluvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with enasidenib is necessary. Concomitant use may increase fluvastatin exposure. Fluvastatin is a substrate of OATP1B3; enasidenib is an inhibitor of OATP1B3.
Encorafenib: (Moderate) Monitor for an increase in fluvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with encorafenib is necessary. Concomitant use may increase fluvastatin exposure. Fluvastatin is a substrate of OATP1B3; encorafenib is an inhibitor of OATP1B3.
Erythromycin: (Major) The risk of developing myopathy and/or rhabdomyolysis with HMG-CoA reductase inhibitors, such as fluvastatin, is increased if coadministered with erythromycin. Fluvastatin is partially metabolized by CYP3A4, and erythromycin is a potent CYP3A4 inhibitor. However, according to the manufacturer, coadministration of erythromycin did not significantly alter the pharmacokinetic disposition of fluvastatin.
Esomeprazole: (Moderate) Concomitant administration of cimetidine, ranitidine, or omeprazole with fluvastatin can decrease fluvastatin clearance by 18 to 23%, and increase AUC by 24 to 33%. A similar interaction might be expected with esomeprazole.
Etravirine: (Moderate) The risk of myopathy, including rhabdomyolysis, may be increased when antiretrovirals are given in combination with HMG-CoA reductase inhibitors. Concomitant use of fluvastatin (CYP2C9 substrate) may result in higher fluvastatin plasma concentrations; dose adjustments may be necessary.
Everolimus: (Moderate) Carefully weigh the benefits of combined use of everolimus and fluvastatin against the potential risks. The risk of myopathy/rhabdomyolysis may increase with concurrent use. Guidelines recommend limiting the dose of fluvastatin to 40 mg/day if combined with everolimus.
Fenofibrate: (Major) Use caution when coadministering fluvastatin and fenofibrate. The risk of myopathy increases when HMG-Co-A reductase inhibitors ('statins'), including fluvastatin, are administered concurrently with fibric acid derivatives. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Fenofibric Acid: (Major) Use caution when coadministering fluvastatin and fenofibric acid. The risk of myopathy increases when HMG-Co-A reductase inhibitors ('statins'), including fluvastatin, are administered concurrently with fibric acid derivatives. The serious risk of myopathy or rhabdomyolysis should be weighed carefully versus the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Fluconazole: (Major) Coadministration of fluconazole and fluvastatin increases fluvastatin exposure, therefore increasing the risk of myopathy and rhabdomyolysis. If used together, limit fluvastatin to 20 mg PO twice daily in adult patients. Fluconazole is an inhibitor of CYP2C9 and fluvastatin is a major CYP2C9 substrate.
Fluoxetine: (Moderate) In theory, concurrent use CYP2C9 inhibitors, such as fluoxetine, and fluvastatin, a CYP2C9 substrate, may result in reduced metabolism of fluvastatin and potential for toxicity including myopathy and rhabdomyolysis.
Fluvoxamine: (Moderate) In theory, concurrent use CYP2C9 inhibitors, such as fluvoxamine, and fluvastatin, a CYP2C9 substrate, may result in reduced metabolism of fluvastatin and potential for toxicity including myopathy and rhabdomyolysis.
Fosamprenavir: (Moderate) Concurrent use of fosamprenavir with fluvastatin should be done cautiously. Concomitant use may increase the risk of myopathy and rhabdomyolysis. Fosamprenavir inhibits CYP3A4 metabolism. Because fluvastatin does not rely exclusively on CYP3A4 for its metabolism, fosamprenavir may not interact to the same extent as expected with other HMG-CoAA reductase inhibitors.
Fosphenytoin: (Moderate) Monitor for a decrease in fluvastatin efficacy and for an increase in phenytoin/fosphenytoin-related adverse effects if concomitant use is necessary. Concomitant use may decrease fluvastatin exposure and may increase phenytoin/fosphenytoin concentrations.
Fostemsavir: (Moderate) Use the lowest possible starting dose for fluvastatin when administered concurrent with fostemsavir and monitor for signs of fluvastatin-associated adverse events, such as rhabdomyolysis. Use of these drugs together may increase the systemic exposure of fluvastatin. Fluvastatin is a substrate for the transporter OATP1B1 and fostemsavir is an inhibitor of OATP1B1.
Gemfibrozil: (Major) Avoid the concomitant administration of fluvastatin and gemfibrozil. The risk of myopathy/rhabdomyolysis increases when HMG-CoA reductase inhibitors are administered concurrently with gemfibrozil. The serious risk of myopathy or rhabdomyolysis should be weighed carefully against the benefits of combined 'statin' and fibrate therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Glecaprevir; Pibrentasvir: (Major) Use the lowest approved fluvastatin dose (i.e., 20 mg PO once daily) when coadministered with glecaprevir due to an increased risk of myopathy, including rhabdomyolysis. If a higher dose is necessary, use the lowest necessary dose based on a risk/benefit assessment. Coadministration may increase the plasma concentrations of fluvastatin. Fluvastatin is a substrate of the drug transporters OATP1B1 and BRCP; glecaprevir is an inhibitor of these transporters. Additionally, glecaprevir is a P-gp substrate and fluvastatin is a P-gp inhibitor; concentrations of glecaprevir may also be increased. (Major) Use the lowest approved fluvastatin dose (i.e., 20 mg PO once daily) when coadministered with pibrentasvir due to an increased risk of myopathy, including rhabdomyolysis. If a higher dose is necessary, use the lowest necessary dose based on a risk/benefit assessment. Coadministration may increase the plasma concentrations of fluvastatin. Fluvastatin is a substrate of the drug transporters OATP1B1 and BRCP; pibrentasvir is an inhibitor of these transporters. Additionally, pibrentasvir is a P-gp substrate and fluvastatin is a P-gp inhibitor; concentrations of pibrentasvir may also be increased.
Glimepiride: (Moderate) Glimepiride is metabolized by CYP2C9. It is possible for serum concentrations of glimepiride to rise when coadministered with drugs that inhibit CYP2C9 like fluvastatin. Monitor serum glucose concentrations if glimepiride is coadministered with fluvastatin. Dosage adjustments may be necessary.
Glyburide: (Moderate) Monitor the blood glucose of patients on glyburide when fluvastatin therapy is initiated or when the fluvastatin dose is changed. Concurrent administration results in increased glyburide exposure, which could lead to hypoglycemia and other adverse effects. Glyburide is a CYP2C9 substrate; fluvastatin inhibits this enzyme. The glyburide AUC increased by 70% when glyburide 5 to 20 mg daily for 22 days was coadministered with fluvastatin 40 mg daily for 8 days.
Glyburide; Metformin: (Moderate) Monitor the blood glucose of patients on glyburide when fluvastatin therapy is initiated or when the fluvastatin dose is changed. Concurrent administration results in increased glyburide exposure, which could lead to hypoglycemia and other adverse effects. Glyburide is a CYP2C9 substrate; fluvastatin inhibits this enzyme. The glyburide AUC increased by 70% when glyburide 5 to 20 mg daily for 22 days was coadministered with fluvastatin 40 mg daily for 8 days.
Imatinib: (Moderate) Monitor for evidence of fluvastatin-related toxicity including myopathy and rhabdomyolysis if fluvastatin is coadministered with imatinib. Concurrent use may result in clinically significant increased levels of fluvastatin. Imatinib is a moderate CYP3A4 inhibitor; fluvastatin is a CYP3A4 substrate.
Indinavir: (Moderate) Concurrent use of indinavir with fluvastatin should be done cautiously. Concomitant use may increase the risk of myopathy and rhabdomyolysis. Indinavir inhibits CYP3A4 metabolism. Because fluvastatin does not rely exclusively on CYP3A4 for its metabolism, indinavir may not interact to the same extent as expected with other HMG-CoAA reductase inhibitors.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors. Monitor serum lipid concentrations during coadministration of rifampin with fluvastatin.
Isoniazid, INH; Rifampin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors. Monitor serum lipid concentrations during coadministration of rifampin with fluvastatin.
Ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as fluvastatin. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Rare reports of rhabdomyolysis have been reported in patients taking clarithromycin and fluvastatin. Use together with caution and monitor for symptoms of myopathy and/or rhabdomyolysis.
Lanthanum Carbonate: (Major) To limit absorption problems, HMG-CoA reductase inhibitors ("statins") should not be taken within 2 hours of dosing with lanthanum carbonate. Oral drugs known to interact with cationic antacids, like statin cholesterol treatments, may also be bound by lanthanum carbonate. Separate the times of administration appropriately. Monitor the patient's lipid profile to ensure the appropriate response to statin therapy is obtained.
Leflunomide: (Major) Consider reducing the dose of HMG-CoA reductase inhibitors ("Statins" including atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin) during use of leflunomide and monitor patients closely for signs and symptoms of myopathy. For a patient taking leflunomide, the dose of rosuvastatin should not exceed 10 mg once daily. Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Teriflunomide is an inhibitor of the organic anion transporting polypeptide OATP1B1, and some statins are substrates for the OATP transporters. Teriflunomide may increase the exposure (AUC) of these statins. Increased concentrations of the statins increases the risk for myopathy and other statin-related side effects.
Leniolisib: (Moderate) Monitor for an increase in fluvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with leniolisib is necessary. Concomitant use may increase fluvastatin exposure. Fluvastatin is a substrate of OATP1B3; leniolisib is an inhibitor of OATP1B3.
Lesinurad: (Moderate) Use lesinurad and fluvastatin together with caution; fluvastatin may increase the systemic exposure of lesinurad. Fluvastatin is a mild inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
Lesinurad; Allopurinol: (Moderate) Use lesinurad and fluvastatin together with caution; fluvastatin may increase the systemic exposure of lesinurad. Fluvastatin is a mild inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
Letermovir: (Moderate) Closely monitor for fluvastatin-related adverse events (myopathy, rhabdomyolysis) and consider a fluvastatin dose reduction if administered with letermovir. Do not exceed a fluvastatin dose of 20 mg daily if the patient is also receiving cyclosporine. The magnitude of this interaction may be increased if letermovir is given with cyclosporine. Concurrent administration of letermovir, an organic anion-transporting polypeptide (OATP1B1) inhibitor, with fluvastatin, an OATP1B1 substrate, may result in a clinically relevant increase in fluvastatin plasma concentration.
Lonafarnib: (Major) Avoid coadministration of lonafarnib and fluvastatin; concurrent use may increase the exposure of lonafarnib and the risk of adverse effects. If coadministration is unavoidable, closely monitor patients for lonafarnib-related adverse reactions. Lonafarnib is a CYP2C9 substrate and fluvastatin is a CYP2C9 inhibitor.
Lopinavir; Ritonavir: (Moderate) Monitor for fluvastatin-related adverse reactions (myopathy, rhabdomyolysis) during concurrent administration with lopinavir as use of these drugs together may increase fluvastatin exposure. Fluvastatin is a substrate of the organic anion transporting peptide (OATP1B1); lopinavir inhibits OATP1B1. (Moderate) Ritonavir is an inhibitor of CYP3A4 and may increase exposure to drugs metabolized by this enzyme, such as fluvastatin. Because fluvastatin does not rely exclusively on CYP3A4 for its metabolism (approximately 20%), ritonavir may not interact to the same extent as expected with other HMG-CoA reductase inhibitors. Elevated serum concentrations of fluvastatin may increase the risk for adverse reactions, such as myopathy.
Lumacaftor; Ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as fluvastatin. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
Maralixibat: (Minor) Maralixibat may reduce the oral absorption of HMG-CoA reductase inhibitors, also known as statins, which may reduce their efficacy. This risk is greatest with maralixibat doses greater than 4.75 mg. Monitor statin therapy and adjust the dose as needed based on clinical response. Maralixibat is a OATP2B1 inhibitor and statins are OATP2B1 substrates.
Meloxicam: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with fluvastatin is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and fluvastatin is a weak CYP2C9 inhibitor.
Mifepristone: (Major) When mifepristone is used chronically in the treatment of hormonal conditions, such as Cushing's syndrome, and given with fluvastatin, the lowest dose of fluvastatin should be used and the patient monitored closely for an increased risk for fluvastatin-related adverse events, such as myopathy and rhabdomyolysis. Consider an alternative to fluvastatin if possible. Mifepristone inhibits CYP2C8/C9 and CYP3A4. In drug interaction studies, significantly increased the exposure of fluvastatin. Fluvastatin is primarily metabolized by CYP2C9, and to a lesser extent, CYP2C8 and CYP3A4. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Nanoparticle Albumin-Bound Sirolimus: (Moderate) Carefully weigh the benefits of combined use of sirolimus and fluvastatin against the potential risks. The risk of myopathy/rhabdomyolysis may increase with concurrent use. Guidelines recommend limiting the dose of fluvastatin to 40 mg/day if combined with sirolimus.
Naproxen; Esomeprazole: (Moderate) Concomitant administration of cimetidine, ranitidine, or omeprazole with fluvastatin can decrease fluvastatin clearance by 18 to 23%, and increase AUC by 24 to 33%. A similar interaction might be expected with esomeprazole.
Nelfinavir: (Moderate) Concurrent use of nelfinavir with fluvastatin should be done cautiously. Concomitant use may increase the risk of myopathy and rhabdomyolysis. Nelfinavir inhibits CYP3A4 metabolism. Because fluvastatin does not rely exclusively on CYP3A4 for its metabolism, nelfinavir may not interact to the same extent as expected with other HMG-CoAA reductase inhibitors.
Niacin, Niacinamide: (Major) There is no clear indication for routine use of niacin in combination with fluvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with fluvastatin. If coadministered, consider lower starting and maintenance does of fluvastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue fluvastatin immediately if myopathy is diagnosed or suspected.
Niacin; Simvastatin: (Major) There is no clear indication for routine use of niacin in combination with fluvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with fluvastatin. If coadministered, consider lower starting and maintenance does of fluvastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue fluvastatin immediately if myopathy is diagnosed or suspected.
Nirmatrelvir; Ritonavir: (Moderate) Ritonavir is an inhibitor of CYP3A4 and may increase exposure to drugs metabolized by this enzyme, such as fluvastatin. Because fluvastatin does not rely exclusively on CYP3A4 for its metabolism (approximately 20%), ritonavir may not interact to the same extent as expected with other HMG-CoA reductase inhibitors. Elevated serum concentrations of fluvastatin may increase the risk for adverse reactions, such as myopathy.
Olanzapine; Fluoxetine: (Moderate) In theory, concurrent use CYP2C9 inhibitors, such as fluoxetine, and fluvastatin, a CYP2C9 substrate, may result in reduced metabolism of fluvastatin and potential for toxicity including myopathy and rhabdomyolysis.
Omeprazole: (Moderate) Concomitant administration of omeprazole with fluvastatin can decrease fluvastatin clearance by 18 to 23%, and increase AUC by 24 to 33%.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Concomitant administration of omeprazole with fluvastatin can decrease fluvastatin clearance by 18 to 23%, and increase AUC by 24 to 33%. (Minor) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors. To evaluate this interaction, monitor serum lipid concentrations during coadministration of rifamycins with HMG-CoA reductase inhibitors.
Omeprazole; Sodium Bicarbonate: (Moderate) Concomitant administration of omeprazole with fluvastatin can decrease fluvastatin clearance by 18 to 23%, and increase AUC by 24 to 33%.
Oritavancin: (Moderate) Fluvastatin is metabolized by CYP2C9; oritavancin is a weak CYP2C9 inhibitor. Coadministration may result in elevated fluvastatin plasma concentrations. If these drugs are administered concurrently, monitor patients for signs of fluvastatin toxicity, such as muscle aches, muscle pain or tenderness, general weakness or fatigue, side or back pain, or decreased urination.
Phenytoin: (Moderate) Monitor for a decrease in fluvastatin efficacy and for an increase in phenytoin-related adverse effects if concomitant use is necessary. Concomitant use may decrease fluvastatin exposure and may increase phenytoin concentrations.
Pioglitazone; Glimepiride: (Moderate) Glimepiride is metabolized by CYP2C9. It is possible for serum concentrations of glimepiride to rise when coadministered with drugs that inhibit CYP2C9 like fluvastatin. Monitor serum glucose concentrations if glimepiride is coadministered with fluvastatin. Dosage adjustments may be necessary.
Probenecid; Colchicine: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
Raltegravir: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Ranitidine: (Moderate) Concomitant administration of ranitidine with fluvastatin can decrease fluvastatin clearance by 18 to 23%, and increase AUC by 24 to 33%.
Red Yeast Rice: (Contraindicated) Since compounds in red yeast rice claim to have HMG-CoA reductase inhibitor activity, red yeast rice should not be used in combination with HMG-CoA reductase inhibitors. The administration of more than one HMG-CoA reductase inhibitor at one time would be duplicative therapy and perhaps increase the risk of drug-related toxicity including myopathy and rhabdomyolysis.
Regorafenib: (Moderate) Monitor for an increase in fluvastatin-related adverse reactions including myopathy and rhabdomyolysis if coadministration with regorafenib is necessary. Fluvastatin is a BCRP substrate and regorafenib is a BCRP inhibitor.
Rifabutin: (Minor) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors. To evaluate this interaction, monitor serum lipid concentrations during coadministration of rifamycins with HMG-CoA reductase inhibitors.
Rifampin: (Moderate) Rifampin has been reported to significantly increase the plasma clearance and decrease the serum concentrations of fluvastatin, with the potential for reduced antilipemic efficacy. Although not studied, a similar interaction can be expected between other rifamycins (e.g., rifabutin, rifapentine) and other HMG-CoA reductase inhibitors. Monitor serum lipid concentrations during coadministration of rifampin with fluvastatin.
Ritonavir: (Moderate) Ritonavir is an inhibitor of CYP3A4 and may increase exposure to drugs metabolized by this enzyme, such as fluvastatin. Because fluvastatin does not rely exclusively on CYP3A4 for its metabolism (approximately 20%), ritonavir may not interact to the same extent as expected with other HMG-CoA reductase inhibitors. Elevated serum concentrations of fluvastatin may increase the risk for adverse reactions, such as myopathy.
Rucaparib: (Moderate) Monitor for an increase in fluvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with rucaparib is necessary. Fluvastatin is a CYP2C9 substrate and rucaparib is a weak CYP2C9 inhibitor.
Saquinavir: (Moderate) Concurrent use of saquinavir with fluvastatin should be done cautiously. Concomitant use may increase the risk of myopathy and rhabdomyolysis. Saquinavir inhibits CYP3A4 metabolism. Because fluvastatin does not rely exclusively on CYP3A4 for its metabolism, saquinavir may not interact to the same extent as expected with other HMG-CoAA reductase inhibitors.
Sirolimus: (Moderate) Carefully weigh the benefits of combined use of sirolimus and fluvastatin against the potential risks. The risk of myopathy/rhabdomyolysis may increase with concurrent use. Guidelines recommend limiting the dose of fluvastatin to 40 mg/day if combined with sirolimus.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Caution is advised when administering voxilaprevir with fluvastatin. Taking these drugs together may increase fluvastatin plasma concentrations; thereby increasing the risk for adverse events, such as myopathy or rhabdomyolysis. Initiate fluvastatin at the lowest approved dose. If higher doses are needed, use the lowest necessary dose based on risk and benefit assessment.
Sulfonamides: (Moderate) In theory, concurrent use CYP2C9 inhibitors, such as sulfonamides, and fluvastatin, a CYP2C9 substrate, may result in reduced metabolism of fluvastatin and potential for toxicity.
Tacrolimus: (Moderate) Carefully weigh the benefits of combined use of tacrolimus and fluvastatin against the potential risk of statin-induced myopathy/rhabdomyolysis. Guidelines recommend lower doses of statins in combination with tacrolimus. A maximum dose of fluvastatin of 40 mg/day is recommended.
Terbinafine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering fluvastatin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9; fluvastatin is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
Teriflunomide: (Major) Consider reducing the dose of HMG-CoA reductase inhibitors ("Statins" including atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin) during use of teriflunomide and monitor patients closely for signs and symptoms of myopathy. For a patient taking teriflunomide, the dose of rosuvastatin should not exceed 10 mg once daily. Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Teriflunomide is an inhibitor of the organic anion transporting polypeptide OATP1B1, and some statins are substrates for the OATP transporters. Teriflunomide may increase the exposure (AUC) of these statins. Increased concentrations of the statins increases the risk for myopathy and other statin-related side effects.
Tezacaftor; Ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as fluvastatin. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
Tipranavir: (Moderate) Concurrent use of tipranavir with fluvastatin should be done cautiously. Concomitant use may increase the risk of myopathy and rhabdomyolysis. Tipranavir inhibits CYP3A4 metabolism. Because fluvastatin does not rely exclusively on CYP3A4 for its metabolism, saquinavir may not interact to the same extent as expected with other HMG-CoAA reductase inhibitors.
Trofinetide: (Moderate) Monitor for an increase in fluvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with trofinetide is necessary. Concomitant use may increase fluvastatin exposure. Fluvastatin is a substrate of OATP1B3; trofinetide is an inhibitor of OATP1B3.
Vemurafenib: (Moderate) Concomitant use of vemurafenib and fluvastatin may result in increased fluvastatin concentrations. Vemurafenib is a CYP2C9 inhibitor and fluvastatin is a CYP2C9 substrate. Patients should be monitored for toxicity.
Voclosporin: (Moderate) Monitor for an increase in fluvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with voclosporin is necessary. Concomitant use may increase fluvastatin exposure. Fluvastatin is a substrate of OATP1B3; voclosporin is an inhibitor of OATP1B3.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Rare reports of rhabdomyolysis have been reported in patients taking clarithromycin and fluvastatin. Use together with caution and monitor for symptoms of myopathy and/or rhabdomyolysis.
Voriconazole: (Moderate) The risk of developing myopathy, rhabdomyolysis, and acute renal failure is increased if fluvastatin is administered concomitantly with CYP 3A4 inhibitors including voriconazole.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with fluvastatin is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Fluvastatin is a weak CYP2C9 inhibitor and the S-enantiomer, the active metabolite of warfarin, is a CYP2C9 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Zafirlukast: (Minor) Zafirlukast inhibits the CYP2C9 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP2C9, such as fluvastatin.

How Supplied

Fluvastatin/Fluvastatin Sodium/Lescol Oral Cap: 20mg, 40mg
Fluvastatin/Fluvastatin Sodium/Lescol XL Oral Tab ER: 80mg

Maximum Dosage
Adults

80 mg/day PO.

Geriatric

80 mg/day PO.

Adolescents

 80 mg/day PO.

Children

10 to 12 years: 80 mg/day PO.
1 to 9 years: Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mechanism Of Action

Fluvastatin interferes with the activity of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, a hepatic enzyme. Inhibition of HMG-CoA reductase interrupts the pathway within the body responsible for the majority of human cholesterol biosynthesis. The amount of mevalonic acid, a precursor of cholesterol, is reduced. Cholesterol levels in hepatic cells are subsequently reduced, stimulating uptake of LDL cholesterol. Fluvastatin reduces plasma total cholesterol, LDL cholesterol, and serum triglycerides; and it raises plasma HDL-cholesterol concentrations.
 
HMG-CoA reductase inhibitors have been reported to decrease endogenous CoQ10 serum concentrations; the clinical significance of these effects is unknown.

Pharmacokinetics

Fluvastatin is administered orally. It is highly (> 98%) bound to protein and does not cross the blood-brain barrier. Hepatic metabolism occurs primarily (75%) via CYP2C9 isoenzymes; other metabolic pathways include CYP 2C8 (5%) and CYP 3A4 (20%). Active hydroxylated metabolites do not circulate systemically. The mean half-life ranges from 2.5—2.7 hours for the immediate-release capsules. Following administration of the extended-release tablets (Lescol XL), the half-life is approximately 9 hours. It is completely metabolized before excretion via the bile into the feces. About 5% is excreted by the renal route.
 
Affected cytochrome P450 (CYP450) enzymes: CYP2C8, CYP2C9, CYP3A4
Fluvastatin is completely metabolized and hepatic metabolism occurs primarily (75%) via CYP2C9 isoenzymes; other metabolic pathways include CYP2C8 (5%) and CYP3A4 (20%). If one pathway is inhibited in the elimination process, in theory, other pathways may compensate. Drugs that are CYP2C9 inhibitors or inducers have greater potential to alter plasma concentrations and cause potential toxicity relative to drugs which affect the CYP3A4 pathway. Fluvastatin also is a CYP2C9 inhibitor.
 

Oral Route

Following administration of regular-release fluvastatin, absorption of the active form from the stomach is rapid and almost complete, but a significant first-pass effect reduces mean absolute bioavailability to 24% following a 10 mg dose (range 9—50%). In the fasting state, bioavailability is dose-dependent and is subject to first-pass metabolism. Food reduces the rate but not extent of absorption. Following administration of the regular-release formulation (20 or 40 mg capsules), peak fluvastatin concentrations are achieved in less than an hour in the fasting state and can be delayed up to 6 hours post-dose when administered with food. The pharmacokinetics following administration of extended-release fluvastatin (Lescol XL 80 mg tablets) is highly variable due to its absorption characteristics and first-pass metabolism, especially following a high-fat meal. Extended-release fluvastatin tablets result in peak concentrations in about 3 hours in the fasting state, with a mean relative bioavailability of 29% (range 9—66%) compared to the regular-release capsules. Administration of Lescol XL tablets with a high-fat meal delayed the absorption (Tmax 6 hours) and increased the bioavailability by about 50%. However, Lescol XL may be administered without regard to meals since no differences in antilipemic effects have been observed when administered with the evening meal or 4 hours after the evening meal, despite pharmacokinetic differences. Once absorption of Lescol XL begins, fluvastatin plasma concentrations rise rapidly; multiple peaks in plasma concentrations may occur. Fluvastatin is highly (>98%) bound to protein. It does not cross the blood-brain barrier. Fluvastatin undergoes significant first-pass metabolism. Both human and animal studies suggest a saturable first-pass effect.

Pregnancy And Lactation
Pregnancy

Fluvastatin is contraindicated for use during pregnancy because of the potential effects of HMG-CoA reductase inhibitors on cholesterol pathways and the potential for fetal harm. Cholesterol and other products of the cholesterol biosynthesis pathway are essential components for fetal development, including synthesis of steroids and cell membranes. Treatment should be immediately discontinued as soon as pregnancy is recognized. Other HMG-CoA reductase inhibitors have been shown to cause malformations of vertebrae and ribs in fetal rats when given in high doses. In a prospective review of about 100 pregnancies in women exposed to simvastatin or another structurally related HMG-CoA reductase inhibitor, the incidence of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed what would be expected in the general population. However, atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. If the patient becomes pregnant while taking this drug, fluvastatin should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus. Fluvastatin should only be administered to females of child-bearing potential, including adolescents at least 1 year post-menarche, when such patients are highly unlikely to conceive and have been informed of the potential hazards. Contraception requirements are advised; females of child-bearing potential should be counseled regarding appropriate methods of contraception while on therapy. The effects of statins on spermatogenesis and fertility have not been studied in adequate numbers of patients. The effects, if any, of fluvastatin on the pituitary-gonadal axis in pre-menopausal females are unknown. Patients treated with fluvastatin who display clinical evidence of endocrine dysfunction should be evaluated appropriately.