simvastatin (Rx)

Brand and Other Names:Zocor
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 5mg
  • 10mg
  • 20mg
  • 40mg
  • 80mg

Hypercholesterolemia

Usual dosage range: 5-40 mg PO qDay

Initial: 10-20 mg PO qDay in the evening

Patients at high CHD risk: Start 40 mg/day

Homozygous Familial Hypercholesterolemia

Recommended dose: 40 mg PO qDay in the evening

See limitations for 80 mg/day, listed below

Prevention of Coronary Events

5-40 mg PO qDay in the evening

Moderate reduction of LDL-C desired: 5-10 mg PO qDay in the evening; adjust dose to achieve goal

Reduction of >40% of LDL-C desired: 40 mg PO qDay in the evening; adjust dose to achieve goal

Presence of CHD or at high risk for cardiovascular events, including patients with diabetes, PVD, history of stroke or other cerebrovascular disease: 40 mg PO qDay in the evening adjunct to diet therapy (initiate simultaneously); adjust dose to achieve goal

Primary and secondary prevention of atheroschlerotic cardiovascular disease (ASCVD)

ACC/AHA Cholesterol Guideline Recommendations (2013) for adults ≥21 years

Primary prevention

  • LDL-C ≥190 mg/dL: High-intensity therapy agent atorvastatin or rosuvastatin recommended
  • Type 1 or 2 diabetes (40-75 years of age): Moderate-intensity therapy: 20-40 mg simvastatin PO qDay
  • Type 1 or 2 diabetes (40-75 years of age and 10 year estimated risk of ASCVD ≥7.5%): High-intensity therapy agent atorvastatin or rosuvastatin recommended
  • 40-75 years of age and 10 year estimated risk of ASCVD ≥7.5% : Moderate-intensity therapy: 20-40 mg simvastatin PO qDay; may consider high-intensity therapy agent atorvastatin or rosuvastatin

Secondary prevention

  • Presence of ASCVD, including stroke/TIA or peripheral arterial disease believed to be of atherosclerotic origin or post-CABG
  • ≤75 years: Treat with high-intensity therapy agent atorvastatin or rosuvastatin
  • >75 years: Administer 20-40 mg simvastatin PO qDay (moderate-intensity therapy); not candidate for high-intensity therapy

Dosage Modifications

Severe renal impairment (CrCl <30 mL/min): 5 mg qDay initially

Coadministration with dronedarone, verapamil, or diltiazem: Do not exceed 10 mg/day

Coadministration with amiodarone, amlodipine, or ranolazine: Do not exceed 20 mg/day

Coadministration with lomitapide: Reduce simvastatin dose by 50%, and do not exceed 20 mg/day (or 40 mg/day in those previously tolerating 80 mg/day) when initiating lomitapide

Dosing Considerations

Lipid determinations should be performed after 4 weeks of therapy and periodically thereafter

Restricted dosing

  • 80 mg/day should be used only for individuals who have been taking simvastatin 80 mg chronically (eg, ≥12 months) without evidence of myopathy or rhabdomyolysis
  • Patients tolerating 80 mg who need to be initiated on an interacting drug that is contraindicated or associated with a maximum dose for simvastatin should be switched to an alternative statin with less potential for drug-drug interactions
  • Patients unable to achieve their LDL-C goal utilizing 40 mg/day should not be titrated to 80 mg (increased risk for myopathy) but should instead be placed on alternative LDL-C-lowering treatment that provides greater LDL-C lowering

Overdose management

  • Adverse drug reactions from overdose may include peripheral neuropathy, diarrhea, increased K+, myopathy, rhabdomyolysis, acute renal failure, elevated LFTs, and eye lens opacities
  • Treatment is supportive

Dosage Forms & Strengths

tablet

  • 5mg
  • 10mg
  • 20mg
  • 40mg
  • 80mg

Hypercholesterolemia

<10 years: Safety and efficacy not established

Heterozygous Familial Hypercholesterolemia

Adolescents aged 10-17 years

  • Initial: 10 mg PO qDay in the evening; not to exceed 40 mg/day
  • Recommended dosing range: 10-40 mg/day; adjustments should be made at intervals of 4 weeks or more
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Interactions

Interaction Checker

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            Contraindicated (29)

            • atazanavir

              atazanavir will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure

            • clarithromycin

              clarithromycin will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure

              clarithromycin will increase the level or effect of simvastatin by Other (see comment). Contraindicated. OATP1B1 inhibitors may increase risk of myopathy

            • cobicistat

              cobicistat will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Potential for serious reactions such as myopathy including rhabdomyolysis

            • cyclosporine

              cyclosporine will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure.

              cyclosporine will increase the level or effect of simvastatin by Other (see comment). Contraindicated. OATP1B1 inhibitors may increase risk of myopathy

            • danazol

              danazol increases toxicity of simvastatin by decreasing metabolism. Contraindicated. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure.

            • darunavir

              darunavir will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

            • erythromycin base

              erythromycin base will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure

              erythromycin ethylsuccinate increases toxicity of simvastatin by Other (see comment). Contraindicated. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure

              erythromycin lactobionate increases toxicity of simvastatin by Other (see comment). Contraindicated. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure

              erythromycin stearate increases toxicity of simvastatin by Other (see comment). Contraindicated. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • fosamprenavir

              fosamprenavir will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure

            • gemfibrozil

              gemfibrozil, simvastatin. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Contraindicated with other lipid-lowering drugs that can cause myopathy.

              gemfibrozil will increase the level or effect of simvastatin by Other (see comment). Contraindicated. OATP1B1 inhibitors may increase risk of myopathy

            • idelalisib

              idelalisib will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors increase systemic statin exposure and risk of myopathy, including rhabdomyolysis

            • indinavir

              indinavir will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

              simvastatin will increase the level or effect of indinavir by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

              indinavir increases toxicity of simvastatin by Other (see comment). Contraindicated. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • itraconazole

              itraconazole will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated during and 2 weeks after itraconazole treatment. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure.

            • ketoconazole

              ketoconazole will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure

              ketoconazole increases toxicity of simvastatin by Other (see comment). Contraindicated. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • letermovir

              letermovir increases levels of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of letermovir and simvastatin is not recommended. When letermovir is coadministered with cyclosporine, use of either simvastatin is contraindicated due to significantly increased pitavastatin or simvastatin concentrations and risk of myopathy or rhabdomyolysis. .

            • lonafarnib

              lonafarnib will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • lopinavir

              lopinavir increases levels of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure.

            • mifepristone

              mifepristone increases levels of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated due to increased risk of rhabdomyolysis.

              mifepristone increases toxicity of simvastatin by Other (see comment). Contraindicated. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • nefazodone

              nefazodone will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure.

            • nelfinavir

              nelfinavir will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

              simvastatin will increase the level or effect of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

              nelfinavir increases toxicity of simvastatin by Other (see comment). Contraindicated. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir

              ombitasvir/paritaprevir/ritonavir & dasabuvir will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increased risk of myopathy, including rhabdomyolysis

              ombitasvir/paritaprevir/ritonavir & dasabuvir increases toxicity of simvastatin by Other (see comment). Contraindicated. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • posaconazole

              posaconazole will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure

              posaconazole will increase the level or effect of simvastatin by P-glycoprotein (MDR1) efflux transporter. Contraindicated. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure

            • red yeast rice

              simvastatin, red yeast rice. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. May increase creatine kinase levels and increase risk of myopathy or rhabdomyolysis; red yeast rice contains monocolin K (reportedly identical to lovastatin).

            • ritonavir

              ritonavir will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

              simvastatin will increase the level or effect of ritonavir by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

              ritonavir increases toxicity of simvastatin by Other (see comment). Contraindicated. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • saquinavir

              simvastatin will increase the level or effect of saquinavir by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

              saquinavir increases levels of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure.

              saquinavir increases toxicity of simvastatin by Other (see comment). Contraindicated. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • tipranavir

              tipranavir increases levels of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. This interaction is the net effect of tipranavir being coadministered with ritonavir (boosted therapy); increased risk of myopathy including rhabdomyolysis.

            Serious - Use Alternative (76)

            • abametapir

              abametapir will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • afatinib

              simvastatin increases levels of afatinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Reduce afatinib daily dose by 10 mg if not tolerated when coadministered with P-gp inhibitors.

            • amiodarone

              amiodarone increases toxicity of simvastatin by decreasing metabolism. Avoid or Use Alternate Drug. Do not exceed simvastatin 20 mg daily when given concurrently. Potential for increased risk of myopathy/rhabdomyolysis.

            • amlodipine

              amlodipine increases levels of simvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: Benefits of combination therapy should be carefully weighed against the potential risks of combination. Potential for increased risk of myopathy/rhabdomyolysis. Limit simvastatin dose to no more than 20 mg/day when used concurrently.

            • apalutamide

              apalutamide will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

            • aprepitant

              aprepitant will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • armodafinil

              armodafinil will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • artemether/lumefantrine

              artemether/lumefantrine will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • bosentan

              bosentan will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • bosutinib

              simvastatin increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • butabarbital

              butabarbital will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • butalbital

              butalbital will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • carbamazepine

              carbamazepine will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • cimetidine

              cimetidine will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • colchicine

              colchicine, simvastatin. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of rhabdomyolysis (incl a fatality).

            • conivaptan

              conivaptan will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • darifenacin

              darifenacin will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • darolutamide

              darolutamide will increase the level or effect of simvastatin by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).

            • dasatinib

              dasatinib will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • dexamethasone

              dexamethasone will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • diltiazem

              diltiazem will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Benefits of combination therapy should be carefully weighed against the potential risks of combination. Limit simvastatin dose to no more than 10 mg/day and dilitazem dose to no more than 240 mg/day when used concurrently.

            • eltrombopag

              eltrombopag will increase the level or effect of simvastatin by Other (see comment). Avoid or Use Alternate Drug. OATP1B1 inhibitors may increase risk of myopathy

            • eluxadoline

              simvastatin increases levels of eluxadoline by decreasing metabolism. Avoid or Use Alternate Drug. Decrease eluxadoline dose to 75 mg PO BID if coadministered with OATP1B1 inhibitors. .

            • enzalutamide

              enzalutamide will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • etravirine

              etravirine will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • fenofibrate

              fenofibrate, simvastatin. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Fenofibrate may further increase risk for rhabdomyolysis when added to optimal statin regimen to further decrease TG and increase HDLs.

            • fenofibrate micronized

              fenofibrate micronized, simvastatin. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Fenofibrate may further increase risk for rhabdomyolysis when added to optimal statin regimen to further decrease TG and increase HDLs.

            • fenofibric acid

              fenofibric acid, simvastatin. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Fenofibrate may further increase risk for rhabdomyolysis when added to optimal statin regimen to further decrease TG and increase HDLs.

            • fexinidazole

              fexinidazole will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • fluconazole

              fluconazole will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • glecaprevir/pibrentasvir

              glecaprevir/pibrentasvir increases levels of simvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: Increased statin concentrations resulting from OATP1B1 inhibition may increase risk of myopathy, including rhabdomyolysis. Coadministration of glecaprevir/pibrentasvir with simvastatin is not recommended.

            • grapefruit

              grapefruit will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid consuming large quantities of grapefruit or juice (ie, >1 quart/day)

            • griseofulvin

              griseofulvin will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • hydrocortisone

              hydrocortisone will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • isoniazid

              isoniazid will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ivosidenib

              ivosidenib will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • lapatinib

              lapatinib will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • lasmiditan

              lasmiditan increases levels of simvastatin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

              lasmiditan increases effects of simvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: Lasmiditan inhibits BCRP in vitro. Avoid coadministration of lasmiditan with BCRP substrates.

            • lomitapide

              lomitapide increases levels of simvastatin by decreasing metabolism. Avoid or Use Alternate Drug. Reduce simvastatin dose by 50% when initiating lomitapide dosing.

            • lumefantrine

              lumefantrine will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • marijuana

              marijuana will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • mesterolone

              mesterolone increases toxicity of simvastatin by decreasing metabolism. Avoid or Use Alternate Drug. Risk of rhabdomyolysis (theoretical interaction based on case reports of combination of danazol and >20 mg/day lovastatin).

            • methylprednisolone

              methylprednisolone will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • metronidazole

              metronidazole will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • miconazole vaginal

              miconazole vaginal will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • modafinil

              modafinil will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • nafcillin

              nafcillin will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • nevirapine

              nevirapine will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • niacin

              niacin, simvastatin. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of rhabdomyolysis (>1 g/day niacin).

            • nifedipine

              nifedipine will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • nilotinib

              nilotinib will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • pentobarbital

              pentobarbital will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • pexidartinib

              simvastatin and pexidartinib both increase inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

            • phenobarbital

              phenobarbital will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • phenytoin

              phenytoin will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • pomalidomide

              simvastatin increases levels of pomalidomide by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • prednisone

              prednisone will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • pretomanid

              simvastatin, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

            • primidone

              primidone will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ranolazine

              ranolazine increases levels of simvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: Benefits of combination therapy should be carefully weighed against the potential risks of combination. Potential for increased risk of myopathy/rhabdomyolysis. Limit simvastatin dose to no more than 20 mg/day when used concurrently. .

            • rifabutin

              rifabutin will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • rifampin

              rifampin will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • rifapentine

              rifapentine will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • riociguat

              simvastatin will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed

            • rufinamide

              rufinamide will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • secobarbital

              secobarbital will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • St John's Wort

              St John's Wort will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • topiramate

              topiramate will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tucatinib

              tucatinib will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • verapamil

              verapamil will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Do not exceed simvastatin 10 mg daily when given concurrently. Potential for increased risk of myopathy/rhabdomyolysis.

            • voriconazole

              voriconazole will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Simvastatin prescribing information recommends a reduced simvastatin dose be considered when coadministered with voriconazole to reduce the risk of myopathy, including rhabdomyolysis

            • voxelotor

              voxelotor will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            • zafirlukast

              zafirlukast will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            Monitor Closely (89)

            • amitriptyline

              simvastatin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • apalutamide

              apalutamide will decrease the level or effect of simvastatin by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and weakly induces BCRP and may decrease systemic exposure of drugs that are substrates of both UGT and BCRP.

            • atorvastatin

              simvastatin will increase the level or effect of atorvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • azithromycin

              azithromycin will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • bazedoxifene/conjugated estrogens

              simvastatin will increase the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • bempedoic acid

              bempedoic acid increases levels of simvastatin by unknown mechanism. Modify Therapy/Monitor Closely. Avoid concomitant use with simvastatin dose >20 mg.

            • budesonide

              simvastatin will increase the level or effect of budesonide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • carbamazepine

              carbamazepine will increase the level or effect of simvastatin by Other (see comment). Use Caution/Monitor. OATP1B1 inhibitors may increase risk of myopathy

            • caspofungin

              caspofungin will increase the level or effect of simvastatin by Other (see comment). Use Caution/Monitor. OATP1B1 inhibitors may increase risk of myopathy

            • cenobamate

              cenobamate will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • ceritinib

              simvastatin increases levels of ceritinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • cholestyramine

              cholestyramine decreases levels of simvastatin by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            • cholic acid

              simvastatin increases toxicity of cholic acid by decreasing elimination. Modify Therapy/Monitor Closely. Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP). May exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is necessary, monitor serum transaminases and bilirubin.

            • clobetasone

              simvastatin will increase the level or effect of clobetasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • clotrimazole

              clotrimazole will increase the level or effect of simvastatin by Other (see comment). Use Caution/Monitor. OATP1B1 inhibitors may increase risk of myopathy

            • conjugated estrogens

              simvastatin will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • conjugated estrogens, vaginal

              simvastatin will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • cortisone

              simvastatin will increase the level or effect of cortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • crizotinib

              crizotinib increases levels of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • crofelemer

              crofelemer increases levels of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

            • dabrafenib

              dabrafenib will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • daptomycin

              simvastatin, daptomycin. Either increases toxicity of the other by Other (see comment). Modify Therapy/Monitor Closely. Comment: Coadministration of daptomycin with HMG-CoA reductase inhibitors may increase CPK levels and risk for myopathy; consider temporary suspension of HMG-CoA reductase inhibitors during daptomycin therapy.

            • deferasirox

              deferasirox will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • deflazacort

              simvastatin will increase the level or effect of deflazacort by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • dexamethasone

              simvastatin will increase the level or effect of dexamethasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • digoxin

              simvastatin will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • docetaxel

              simvastatin will increase the level or effect of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • dronedarone

              dronedarone will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for signs and symptoms of myopathy in patients receiving dronedarone concurrently with simvastatin

            • duvelisib

              duvelisib will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

            • efavirenz

              efavirenz will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • elagolix

              elagolix will increase the level or effect of simvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              elagolix decreases levels of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • elbasvir/grazoprevir

              elbasvir/grazoprevir increases levels of simvastatin by unknown mechanism. Modify Therapy/Monitor Closely. If coadministered, use lowest necessary simvastatin dose.

            • eliglustat

              eliglustat increases levels of simvastatin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.

            • eluxadoline

              eluxadoline increases levels of simvastatin by decreasing metabolism. Use Caution/Monitor. Eluxadoline may increase the systemic exposure of coadministered BCRP substrates. .

            • encorafenib

              encorafenib, simvastatin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Dose adjustment of some statins may be needed if a clinically significant change in lipids is noted.

            • estradiol

              simvastatin will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • estropipate

              simvastatin will increase the level or effect of estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • fedratinib

              fedratinib will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fludrocortisone

              simvastatin will increase the level or effect of fludrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • fostemsavir

              fostemsavir will increase the level or effect of simvastatin by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits OATP1B1/3 and BCRP transporters. If possible, avoid coadministration or modify dose of OATP1B1/3 or BCRP substrates coadministered with fostemsavir. Use lowest possible starting dose for statins and monitor for associated adverse events.

            • glyburide

              glyburide increases toxicity of simvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • hydrocortisone

              simvastatin will increase the level or effect of hydrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • iloperidone

              iloperidone increases levels of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

            • irinotecan liposomal

              simvastatin will increase the level or effect of irinotecan liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • istradefylline

              istradefylline will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

              istradefylline will increase the level or effect of simvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

            • itraconazole

              simvastatin will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ivacaftor

              ivacaftor increases levels of simvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • ivermectin

              simvastatin will increase the level or effect of ivermectin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lanthanum carbonate

              lanthanum carbonate decreases levels of simvastatin by cation binding in GI tract. Use Caution/Monitor. Administer statin at least 2 hr before or 2 hr after lanthanum. Monitor serum concentrations.

            • levamlodipine

              levamlodipine will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily.

            • loperamide

              simvastatin will increase the level or effect of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lorlatinib

              lorlatinib will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lovastatin

              simvastatin will increase the level or effect of lovastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • mestranol

              simvastatin will increase the level or effect of mestranol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • methylprednisolone

              simvastatin will increase the level or effect of methylprednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • metyrapone

              metyrapone increases toxicity of simvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • mipomersen

              mipomersen, simvastatin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

            • mitotane

              mitotane decreases levels of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • paclitaxel

              simvastatin will increase the level or effect of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              paclitaxel increases toxicity of simvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • paclitaxel protein bound

              simvastatin will increase the level or effect of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • paliperidone

              simvastatin will increase the level or effect of paliperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • pazopanib

              simvastatin increases toxicity of pazopanib by Other (see comment). Use Caution/Monitor. Comment: Increased risk of elevated LFTs with pazopanib when coadministered with simvastatin.

              pazopanib will increase the level or effect of simvastatin by Other (see comment). Use Caution/Monitor. OATP1B1 inhibitors may increase risk of myopathy

            • pioglitazone

              pioglitazone increases toxicity of simvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • ponatinib

              ponatinib increases levels of simvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              ponatinib increases levels of simvastatin by Other (see comment). Use Caution/Monitor.

            • posaconazole

              simvastatin will increase the level or effect of posaconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • prednisolone

              simvastatin will increase the level or effect of prednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • prednisone

              simvastatin will increase the level or effect of prednisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • repaglinide

              repaglinide increases toxicity of simvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • ribociclib

              ribociclib will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifampin

              rifampin will increase the level or effect of simvastatin by Other (see comment). Use Caution/Monitor. OATP1B1 inhibitors may increase risk of myopathy

            • risperidone

              simvastatin will increase the level or effect of risperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • rosiglitazone

              rosiglitazone increases toxicity of simvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • sacubitril/valsartan

              simvastatin will increase the level or effect of sacubitril/valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • sarecycline

              sarecycline will increase the level or effect of simvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

            • silodosin

              simvastatin will increase the level or effect of silodosin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • sirolimus

              simvastatin will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • sofosbuvir/velpatasvir

              sofosbuvir/velpatasvir will increase the level or effect of simvastatin by Other (see comment). Modify Therapy/Monitor Closely. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates. Coadministration may significantly increase simvastatin serum concentration, which is associated with increased risk of myopathy, including rhabdomyolysis.

            • stiripentol

              stiripentol, simvastatin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

              stiripentol will increase the level or effect of simvastatin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

            • tacrolimus

              simvastatin will increase the level or effect of tacrolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              tacrolimus increases toxicity of simvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • tazemetostat

              tazemetostat will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • ticagrelor

              ticagrelor increases levels of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid simvastatin doses greater than 40 mg.

            • tolvaptan

              simvastatin will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • valsartan

              simvastatin will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • vinblastine

              simvastatin will increase the level or effect of vinblastine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vincristine

              simvastatin will increase the level or effect of vincristine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vincristine liposomal

              simvastatin will increase the level or effect of vincristine liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • warfarin

              simvastatin, warfarin. Either increases effects of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Competition by each drug for CYP3A4-mediated metabolism may result in increased INR and increased risk of rhabdomyolysis.

            Minor (15)

            • aliskiren

              simvastatin will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • alvimopan

              simvastatin will increase the level or effect of alvimopan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • ambrisentan

              simvastatin will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • armodafinil

              simvastatin will increase the level or effect of armodafinil by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • coenzyme Q10

              simvastatin decreases levels of coenzyme Q10 by unspecified interaction mechanism. Minor/Significance Unknown.

            • colestipol

              colestipol decreases levels of simvastatin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • fexofenadine

              simvastatin will increase the level or effect of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • isradipine

              isradipine decreases levels of simvastatin by unknown mechanism. Minor/Significance Unknown.

            • loratadine

              simvastatin will increase the level or effect of loratadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • orlistat

              orlistat increases effects of simvastatin by pharmacodynamic synergism. Minor/Significance Unknown.

            • sacubitril/valsartan

              sacubitril/valsartan increases toxicity of simvastatin by Other (see comment). Minor/Significance Unknown. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • telmisartan

              telmisartan increases toxicity of simvastatin by Other (see comment). Minor/Significance Unknown. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • trazodone

              trazodone increases levels of simvastatin by unspecified interaction mechanism. Minor/Significance Unknown.

            • valsartan

              valsartan increases toxicity of simvastatin by Other (see comment). Minor/Significance Unknown. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • voclosporin

              voclosporin will increase the level or effect of simvastatin by Other (see comment). Minor/Significance Unknown. Information suggests voclosporin (an OATP1B1 inhibitor) may increase in the concentration of OATP1B1 substrates is possible. Monitor for adverse reactions of OATP1B1 substrates when coadministered with voclosporin.

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            Adverse Effects

            1-10%

            CPK elevation (>3x ULN) (5%)

            Constipation (2%)

            Upper respiratory infection (9%)

            Flatulence (1-2%)

            Transaminases increased (>3x ULN) (1%)

            Headache (3-7%)

            Myalgia (5%)

            Eczema (5%)

            Vertigo (5%)

            Abdominal pain (7%)

            <1%

            Myalgia

            Myopathy

            Arthralgia

            Arthritis

            Eosinophilia

            Chills

            Angioedema

            Rhabdomyolysis

            Abdominal pain

            Postmarketing Reports

            Erectile dysfunction

            Interstitial lung disease

            Rare reports of cognitive impairment (eg, memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use

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            Warnings

            Contraindications

            Hypersensitivity to simvastatin

            Active liver disease or unexplained transaminase elevation

            Strong CYP3A4 inhibitors (eg, itraconazole, ketoconazole, erythromycin, clarithromycin, posaconazole, voriconazole, HIV protease inhibitors, cobicistat, nefazodone), gemfibrozil, cyclosporine, and danazol

            Cautions

            Rule out secondary causes of hyperlipidemia prior to initiating therapy

            Nonserious and reversible cognitive side effects may occur

            Increased blood sugar and glycosylated hemoglobin (HbA1c) levels reported with statin intake

            Heavy alcohol use, history of liver disease, renal failure

            Monitor LFTs before initiating treatment and thereafter when clinically indicated; reports of fatal and nonfatal hepatic failure in patients taking statins

            Discontinue if markedly elevated CPK levels occur or myopathy is diagnosed or suspected

            Increases in HbA1c and fasting serum glucose levels reported with simvastatin

            Severe electrolyte, endocrine, or metabolic disorders

            Grapefruit juice increases simvastatin systemic exposure; avoid large quantities of grapefruit juice (ie, ≥1 quart/day)

            Simvastatin and myopathy risk

            • Myopathy/rhabdomyolysis with acute renal failure and/or myopathy reported; monitor patient closely
            • Dose adjustment required when coadministered with niacin, amiodarone, verapamil, diltiazem, amlodipine, and ranolazine
            • Predisposing factors for myopathy include advanced age (>65 years), uncontrolled hypothyroidism, and renal impairment
            • Withhold or discontinue if myopathy, renal failure, or transaminase levels >3x ULN develop
            • Risk of myopathy is greater in patients taking simvastatin 80 mg/day, especially in the 1st year of treatment

            Immune-mediated necrotizing myopathy

            • Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, reported with statin use
            • IMNM is characterized by muscle biopsy showing necrotizing myopathy without significant inflammation improvement with immunosuppressive agents, proximal muscle weakness, and elevated serum creatine kinase, which persist despite discontinuation of statin treatment
            • Treatment with immunosuppressive agents may be required
            • Advice all patients starting therapy or whose dose is being increased, about the risk of myopathy, including rhabdomyolysis
            • Patients should report promptly any unexplained muscle pain, tenderness, or weakness particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing therapy; additional neuromuscular and serologic testing may be necessary
            • Therapy should be discontinued immediately if myopathy is diagnosed or suspected
            • Discontinue therapy if markedly elevated creatine kinase (CK) levels occur or if myopathy diagnosed or suspected
            • Therapy should be temporarily withheld in any patient experiencing an acute or serious condition predisposing to development of renal failure secondary to rhabdomyolysis, eg, sepsis; hypotension; dehydration; major surgery; trauma; severe metabolic, endocrine, and electrolyte disorders; or uncontrolled epilepsy
            • Consider risk of IMNM carefully prior to initiation of a different statin
            • If therapy is initiated with a different statin, monitor for signs and symptoms of IMNM
            • Additional neuromuscular and serologic testing may be necessary
            • Treatment with immunosuppressive agents may be required
            • Consider risk of IMNM carefully prior to initiation of a different statin
            • If therapy is initiated with a different statin, monitor for signs and symptoms of IMNM

            Coadministration with niacin

            • Myopathy/rhabdomyolysis observed with simvastatin coadministered with lipid-modifying niacin doses (ie, ≥1 g/day); also observed when coadministered with daptomycin
            • Risk of myopathy is greater in Chinese patients, and therefore, coadministration of simvastatin with lipid-modifying niacin doses is not recommended in Chinese patients
            • Unknown if this risk applies to other patients of Asian descent
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            Pregnancy & Lactation

            Pregnancy

            Owing to HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, fetal harm may occur when administered to pregnant females; discontinue therapy as soon as pregnancy is recognized; limited published data are insufficient to determine a drug-associated risk of major congenital malformations or miscarriage

            Contraception

            Advise females of reproductive potential to use effective contraception during treatment

            FDA MedWatch

            • On July 20, 2021, the FDA request to remove the contraindication against HMG-CoA reductase inhibitors in pregnant females
            • Despite the changes, most females found to be pregnant should stop therapy

            Lactation

            There is no available information on effects of drug on breastfed infant or on milk production

            Unknown whether is present in human milk; it has been shown that drugs in this class pass into human milk and atorvastatin is present in rat milk

            Not recommended during treatment

            FDA MedWatch

            • On July 20, 2021, the FDA request to remove the contraindication against HMG-CoA reductase inhibitors in pregnant females
            • Breastfeeding is still not recommended if taking statins; drug may still pass through milk and pose a risk breastfed children
            • For patients with lower risk, temporarily stop statin therapy until breastfeeding ends
            • Patients who are at high risk of heart attack or stroke who require statins after delivery should not breastfeed and should use alternatives such as infant formula

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            HMG-CoA reductase inhibitor; inhibits the rate-limiting step in cholesterol biosynthesis by competitively inhibiting HMG-CoA reductase

            Absorption

            Bioavailability: <5%

            Onset of action: >3 days

            Peak plasma time: 1.3-2.4 hr

            Maximum effect: 4-6 weeks

            Distribution

            Protein bound: 95%

            Metabolism

            First pass in liver

            Converted to maximally active simvastatin acid by nonenzymatic pathways and nonspecific enzymes

            Metabolites: Beta-hydroxyacid and 6'-hydroxy, 6'-hydroxymethyl, and 6'-exomethylene derivatives (all active)

            Simvastatin acid also converted to other active metabolites by CYP3A4

            Elimination

            Excretion: Feces (60%); urine (13%)

            Pharmacogenomics

            SLCO1B1 (OATP1B1) CC genotype significantly increases AUCs of parent drug and metabolites compared with the CT or TT genotypes

            This polymorphism is proposed to reduce transport into the liver, the main site of statin metabolism and elimination, resulting in elevated plasma concentrations

            SLCO1B1 polymorphism is thought to have a lesser effect on the more hydrophilic statins (eg, rosuvastatin, fluvastatin) compared with those that are more lipophilic (eg, atorvastatin, simvastatin)

            Other genetic polymorphisms of elimination (eg, CYP450, P-glycoprotein) for each individual drug must also be considered, to explain variability for statin clearance among patients that exhibit SCLO1B1 polymorphism

            SLCO1B1 CC genotype is most common in Caucasians and Asians (15%)

            Risk of myopathy is 2.6- to 4.3-fold higher if the C allele is present and 16.9-fold higher in CC homozygotes than in TT homozygotes

            Genetic testing laboratories

            • Optivia Biotechnology, Inc (http://optiviabio.com)
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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Zocor oral
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            40 mg tablet
            Zocor oral
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            Zocor oral
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            20 mg tablet
            Zocor oral
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            80 mg tablet
            simvastatin oral
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            10 mg tablet
            simvastatin oral
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            10 mg tablet
            simvastatin oral
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            5 mg tablet
            simvastatin oral
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            simvastatin oral
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            simvastatin oral
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            simvastatin oral
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            simvastatin oral
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            simvastatin oral
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            simvastatin oral
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            80 mg tablet
            simvastatin oral
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            simvastatin oral
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            40 mg tablet
            simvastatin oral
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            simvastatin oral
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            simvastatin oral
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            5 mg tablet
            simvastatin oral
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            simvastatin oral
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            20 mg tablet
            simvastatin oral
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            Patient Handout

            Patient Education
            simvastatin oral

            SIMVASTATIN - ORAL

            (SIM-va-STAT-in)

            COMMON BRAND NAME(S): Zocor

            USES: Simvastatin is used along with a proper diet to help lower "bad" cholesterol and fats (such as LDL, triglycerides) and raise "good" cholesterol (HDL) in the blood. It belongs to a group of drugs known as "statins." It works by reducing the amount of cholesterol made by the liver. Lowering "bad" cholesterol and triglycerides and raising "good" cholesterol decreases the risk of heart disease and helps prevent strokes and heart attacks.In addition to eating a proper diet (such as a low-cholesterol/low-fat diet), other lifestyle changes that may help this medication work better include exercising, losing weight if overweight, and stopping smoking. Consult your doctor for more details.

            HOW TO USE: Take this medication by mouth as directed by your doctor, usually once daily in the evening. If you are using the tablet form of this medication, you may take this medication with or without food.If you are using the liquid form of this medication, take this medication on an empty stomach. Shake the bottle well for at least 20 seconds before each dose. Carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose.The dosage is based on your medical condition, response to treatment, age, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).The usual maximum dose for this medication is 40 milligrams a day. If you have been instructed by your doctor to take more than 40 milligrams, continue on that same dose. However, promptly talk with him or her about the risks and benefits of your higher dose.Do not increase your dose or take this medication more often than prescribed. Your condition will not improve any faster, and the risk of serious side effects may be increased.Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor instructs you otherwise. Grapefruit can increase the amount of this medication in your bloodstream. Consult your doctor or pharmacist for more details.Take this medication regularly in order to get the most benefit from it. Remember to take it at the same time each day. Keep taking this medication even if you feel well. Most people with high cholesterol or triglycerides do not feel sick.It is very important to continue to follow your doctor's advice about diet and exercise. It may take up to 4 weeks before you get the full benefit of this drug.

            SIDE EFFECTS: Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.A very small number of people taking simvastatin may have mild memory problems or confusion. If these rare effects occur, talk to your doctor.Rarely, statins may cause or worsen diabetes. Talk to your doctor about the benefits and risks.This drug may rarely cause muscle problems (which can rarely lead to very serious conditions called rhabdomyolysis and autoimmune myopathy). Females, older adults, and Chinese people may be at higher risk. Tell your doctor right away if you develop any of these symptoms during treatment and if these symptoms last after your doctor stops this drug: muscle pain/tenderness/weakness (especially with fever or unusual tiredness), signs of kidney problems (such as change in the amount of urine).This medication may rarely cause liver problems. If you notice any of the following rare but serious side effects, tell your doctor right away: yellowing eyes/skin, dark urine, severe stomach/abdominal pain, persistent nausea/vomiting.A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking simvastatin, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, kidney disease, alcohol use.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Limit alcoholic beverages. Daily use of alcohol may increase your risk for liver problems, especially when combined with simvastatin. Ask your doctor or pharmacist for more information.Older adults may be more sensitive to the side effects of this drug, especially muscle problems.This medication must not be used during pregnancy. Simvastatin may harm an unborn baby. It is important to prevent pregnancy while taking this medication. Consult your doctor for more details and to discuss the use of reliable forms of birth control (such as condoms, birth control pills) while taking this medication. If you become pregnant or think you may be pregnant, tell your doctor right away.It is unknown if this medication passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: See also How to Use section.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: "blood thinners" (such as warfarin), cyclosporine, danazol, daptomycin, gemfibrozil.Other medications can affect the removal of simvastatin from your body, which may affect how simvastatin works. Examples include certain azole antifungals (such as itraconazole, ketoconazole, posaconazole, voriconazole), boceprevir, cobicistat, colchicine, delavirdine, macrolide antibiotics (such as clarithromycin, erythromycin), nefazodone, HIV protease inhibitors (such as nelfinavir, ritonavir), telaprevir, telithromycin, among others.Chinese people should not take niacin at doses used to lower cholesterol (1 gram or more) when taking this medication. Doing so may increase the risk of side effects (especially muscle problems). Talk with your doctor for details.Do not take any red yeast rice products while you are taking simvastatin because some red yeast rice products may also contain a statin called lovastatin. Taking simvastatin and red yeast rice products together can increase your risk of serious muscle and liver problems.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

            NOTES: Do not share this medication with others.Laboratory and/or medical tests (such as blood cholesterol/triglyceride levels) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

            MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store at room temperature away from light and moisture. Storage temperature ranges differ according to different manufacturers, so consult your pharmacist for more information. Do not refrigerate or freeze. Do not store in the bathroom. Discard the suspension form of this medication one month after opening the bottle, even if there is medication left. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.