rosuvastatin/ezetimibe (Rx)

Brand and Other Names:Roszet
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

rosuvastatin/ezetimibe

tablet

  • 5mg/10mg
  • 10mg/10mg
  • 20mg/10mg
  • 40mg/10mg

Hyperlipidemia

Indicated as an adjunct to diet for primary nonfamilial hyperlipidemia to reduce LDL-C

Dosage range: Rosuvastatin/ezetimibe 10mg/10mg to 40mg/10mg PO qDay

Recommended dosage depends on indication, LDL-C, and individual risk for cardiovascular events

Switching to rosuvastatin/ezetimibe from coadministration of a statin and ezetimibe: Starting dose determined by rosuvastatin dose plus ezetimibe 10 mg

Homozygous Familial Hypercholesterolemia

Indicated alone or with other LDL-C lowering therapies in adults with homozygous familial hypercholesterolemia (HoFH) to recue LDL-C

Dosage range: Rosuvastatin/ezetimibe 10mg/10mg to 40mg/10mg PO qDay

Recommended dosage depends on indication, LDL-C, and individual risk for cardiovascular events

Switching to rosuvastatin/ezetimibe from coadministration of a statin and ezetimibe: Starting dose determined by rosuvastatin dose plus ezetimibe 10 mg

Dosage Modifications

Dosing in Asian patients

  • Start at 5 mg/10mg qDay, owing to genotypic slow metabolism resulting in increased rosuvastatin plasma concentrations
  • Consider risk/benefit when not adequately controlled at doses up to 20mg/10mg qDay

Dosage adjustment for rosuvastatin with concomitant therapy

  • Coadministered with darolutamide: Not to exceed rosuvastatin 5 mg/ezetimibe 10 mg qDay
  • Coadministered with regorafenib: Not to exceed rosuvastatin 10 mg/ezetimibe 10 mg qDay
  • Antivirals
    • Coadministered with sofosbuvir/velpatasvir/voxilaprevir or ledipasvir/sofosbuvir: Not recommended
    • Patients taking simeprevir, dasabuvir/ombitasvir/paritaprevir/ritonavir, elbasvir/grazoprevir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, atazanavir/ritonavir, and lopinavir/ritonavir: Initiate rosuvastatin/ezetimibe at 5 mg/10mg qDay; not to exceed 10mg/10mg qDay
    • Coadministered with fosamprenavir/ritonavir or tipranavir/ritonavir: No dosage adjustment necessary

Renal impairment

  • Mild or moderate (CrCl ≥30 mL/min/1.73m2): No dosage adjustment necessary
  • Severe (CrCl <30 mL/min/1.73m2) and not on hemodialysis: Initiate at 5 mg/10mg qDay; not to exceed 10 mg/10mg qDay

Hepatic impairment

  • Active liver disease or decompensated cirrhosis: Contraindicated
  • Chronic alcoholic liver disease: Use with caution; known to increase rosuvastatin exposure

Dosing Considerations

Monitoring parameters

  • Assess LDL-C when clinically appropriate, as early as 2 weeks after initiating therapy and adjusting dosage, if necessary

Safety and efficacy not established

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Interactions

Interaction Checker

and rosuvastatin/ezetimibe

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            Contraindicated (2)

            • gemfibrozil

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

            • red yeast rice

              rosuvastatin, 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).

            Serious - Use Alternative (20)

            • atazanavir

              atazanavir increases levels of rosuvastatin by unknown mechanism. Avoid or Use Alternate Drug. Potential for increased toxicity. Use alternatives if available. Increased risk of myopathy and rhabdomyolysis. Limit rosuvastatin dose to 10 mg/day; ritonavir component of atazanavir/ritonavir regimen decreases rosuvastatin metabolism.

            • clarithromycin

              clarithromycin increases toxicity of rosuvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • colchicine

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

            • cyclosporine

              cyclosporine, ezetimibe. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Monitor for potential adverse effects of cyclosporine and ezetimibe if coadministered, especially in patients with severe renal impairment.

              cyclosporine increases toxicity of rosuvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • darolutamide

              darolutamide will increase the level or effect of rosuvastatin 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; dose of rosuvastatin should not exceed 5 mg once daily (refer BCRP substrate prescribing information).

            • eltrombopag

              eltrombopag increases toxicity of rosuvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • fenofibrate

              fenofibrate, rosuvastatin. 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, rosuvastatin. 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, rosuvastatin. 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.

            • gemfibrozil

              gemfibrozil, rosuvastatin. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Gemfibrozil may further increase risk for rhabdomyolysis when added to optimal statin regimen to further decrease TG and increase HDLs. If concomitant use cannot be avoided, initiate rosuvastatin at 5 mg once daily; the dose of rosuvastatin should not exceed 10 mg once daily.

            • indinavir

              indinavir increases toxicity of rosuvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Risk of myopathy and rhabdomyolysis increased when atorvastatin coadministered with CYP3A4 inhibitors; use lowest statin dose possible.

              indinavir increases toxicity of rosuvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • ketoconazole

              ketoconazole increases toxicity of rosuvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • lasmiditan

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

            • lopinavir

              lopinavir increases levels of rosuvastatin by decreasing metabolism. Avoid or Use Alternate Drug. Limit rosuvastatin dose to 10 mg/day; ritonavir component of lopinavir/ritonavir decreases rosuvastatin metabolism.

            • mifepristone

              mifepristone increases toxicity of rosuvastatin by Other (see comment). Avoid or Use Alternate Drug.

            • nelfinavir

              nelfinavir increases toxicity of rosuvastatin by Other (see comment). Avoid or Use Alternate Drug.

            • niacin

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

            • ombitasvir/paritaprevir/ritonavir & dasabuvir

              ombitasvir/paritaprevir/ritonavir & dasabuvir increases toxicity of rosuvastatin by Other (see comment). Avoid or Use Alternate Drug.

            • ritonavir

              ritonavir increases toxicity of rosuvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • saquinavir

              saquinavir increases toxicity of rosuvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            Monitor Closely (56)

            • acalabrutinib

              acalabrutinib increases levels of rosuvastatin by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.

            • aluminum hydroxide

              aluminum hydroxide decreases levels of rosuvastatin by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

            • apalutamide

              apalutamide will decrease the level or effect of ezetimibe by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and weakly induces OATP1B1 and may decrease systemic exposure of drugs that are substrates of both UGT and OATP1B1.

              apalutamide will decrease the level or effect of rosuvastatin by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and weakly induces BCRP and OATP1B1. Drugs that are eliminated via these pathways may have decreased systemic exposure if coadministered with apalutamide.

            • atazanavir

              atazanavir increases levels of rosuvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. Use alternatives if available. Increased risk of myopathy and rhabdomyolysis. .

            • cholestyramine

              cholestyramine decreases levels of ezetimibe by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2-4 hours.

            • calcium carbonate

              calcium carbonate decreases levels of rosuvastatin by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

            • carbamazepine

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

            • caspofungin

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

            • cholestyramine

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

            • clotrimazole

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

            • cobicistat

              cobicistat will increase the level or effect of rosuvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. For HMG-CoA reductase inhibitors that are not contraindicated with cobicistat, dose should not exceed 20 mg/day.

            • crofelemer

              crofelemer increases toxicity of rosuvastatin by Other (see comment). Use Caution/Monitor. Comment: Crofelemer has the potential to inhibit transporters MRP2 and OATP1A2 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

            • daptomycin

              rosuvastatin, 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.

            • darunavir

              darunavir will increase the level or effect of rosuvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. For HMG-CoA reductase inhibitors that are not contraindicated with cobicistat, dose should not exceed 20 mg/day.

            • dasabuvir

              dasabuvir increases toxicity of rosuvastatin by Other (see comment). Modify Therapy/Monitor Closely. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • elagolix

              elagolix decreases levels of rosuvastatin by unknown mechanism. Modify Therapy/Monitor Closely. Consider increasing the dose of rosuvastatin.

            • elbasvir/grazoprevir

              elbasvir/grazoprevir increases levels of rosuvastatin by unknown mechanism. Modify Therapy/Monitor Closely. If coadministered, do not exceed rosuvastatin dose of 10 mg/day.

            • eluxadoline

              eluxadoline increases levels of rosuvastatin by decreasing metabolism. Use Caution/Monitor. Eluxadoline may increase the systemic exposure of coadministered OATP1B1 or BCRP substrates. Potential for increased risk of myopathy/rhabdomyolysis with rosuvastatin. Decrease rosuvastatin to lowest effective dose.

            • erythromycin base

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

            • erythromycin ethylsuccinate

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

            • erythromycin lactobionate

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

            • erythromycin stearate

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

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of rosuvastatin 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.

            • fostamatinib

              fostamatinib will increase the level or effect of rosuvastatin by decreasing metabolism. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of BCRP substrate drugs. Monitor for toxicities of BCRP substrate drug that may require dosage reduction when given concurrently with fostamatinib.

            • fostemsavir

              fostemsavir will increase the level or effect of ezetimibe by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits OATP1B1/3 transporter. If possible, avoid coadministration or modify dose of OATP1B1/3 substrates coadministered with fostemsavir.

              fostemsavir will increase the level or effect of rosuvastatin 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.

            • glecaprevir/pibrentasvir

              glecaprevir/pibrentasvir increases levels of rosuvastatin by Other (see comment). Modify Therapy/Monitor Closely. Comment: Increased statin concentrations resulting from OATP1B1 inhibition may increase risk of myopathy, including rhabdomyolysis. If coadministered, do not exceed 10 mg/day of rosuvastatin.

              glecaprevir/pibrentasvir will increase the level or effect of ezetimibe by Other (see comment). Use Caution/Monitor. Coadministration with glecaprevir/pibrentasvir may increase plasma concentration of drugs that are substrates of OATP1B1 or OATP1B3

            • glyburide

              glyburide increases toxicity of rosuvastatin by Other (see comment). Use Caution/Monitor. Comment: Coadministration of rosuvastatin with OATP1B1 inhibitors may increase rosuvastatin levels and risk for myopathy.

            • letermovir

              letermovir increases levels of ezetimibe by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

            • lanthanum carbonate

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

            • ledipasvir/sofosbuvir

              ledipasvir/sofosbuvir will increase the level or effect of rosuvastatin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ledipasvir/sofosbuvir with rosuvastatin may be associated withincreased risk of myopathy,including rhabdomyolysis. Monitor closely.

            • letermovir

              letermovir increases levels of rosuvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of letermovir with fluvastatin may require a dosage reduction. Closely monitor patients for myopathy and rhabdomyolysis. When letermovir is coadministered with cyclosporine, the dose of rosuvastatin should not exceed 5 mg PO qDay . .

            • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

              rosuvastatin increases levels of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Coadministration of rosuvastatin and certain combined hormonal contraceptives (CHCs) containing EE increase AUC values for EE by approximately 20-25%.

            • mesterolone

              mesterolone increases toxicity of rosuvastatin by decreasing metabolism. Use Caution/Monitor. Risk of rhabdomyolysis (theoretical interaction based on case reports of combination of danazol and >20 mg/day lovastatin).

            • metyrapone

              metyrapone increases toxicity of rosuvastatin by Other (see comment). Use Caution/Monitor.

            • mipomersen

              mipomersen increases toxicity of rosuvastatin by Other (see comment). Use Caution/Monitor.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir

              ombitasvir/paritaprevir/ritonavir & dasabuvir will increase the level or effect of rosuvastatin by decreasing hepatic clearance. Modify Therapy/Monitor Closely. Maximum daily dose of rosuvastatin should be limited to 10 mg/day

            • paclitaxel

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

            • pazopanib

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

            • pioglitazone

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

            • ponatinib

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

            • ranolazine

              ranolazine increases toxicity of rosuvastatin by Other (see comment). Modify Therapy/Monitor Closely. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • regorafenib

              regorafenib will increase the level or effect of rosuvastatin by Other (see comment). Modify Therapy/Monitor Closely. Regorafenib likely inhibits BCRP (ABCG2) transport. Coadministration with a BCRP substrate may increase systemic exposure to the substrate and related toxicity.

            • repaglinide

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

            • rifampin

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

            • ritonavir

              ritonavir will increase the level or effect of rosuvastatin by decreasing metabolism. Use Caution/Monitor.

            • rolapitant

              rolapitant will increase the level or effect of rosuvastatin by Other (see comment). Use Caution/Monitor. Monitor for adverse reactions when unable to avoid rolapitant coadministration with narrow therapeutic index BCRP substrates. Use the lowest effective dose of rosuvastatin.

            • rosiglitazone

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

            • safinamide

              safinamide will increase the level or effect of rosuvastatin by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • sodium bicarbonate

              sodium bicarbonate decreases levels of rosuvastatin by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

            • sodium citrate/citric acid

              sodium citrate/citric acid decreases levels of rosuvastatin by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

            • sofosbuvir/velpatasvir

              sofosbuvir/velpatasvir increases levels of ezetimibe by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

              sofosbuvir/velpatasvir will increase the level or effect of rosuvastatin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of sofosbuvir/velpatasvir with rosuvastatin may significantly increase the concentration of rosuvastatin, which may increase risk of myopathy,including rhabdomyolysis. Rosuvastatin may beadministered with sofosbuvir/velpatasvir at a dose that does not exceed 10 mg.

              sofosbuvir/velpatasvir will increase the level or effect of rosuvastatin 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 rosuvastatin serum concentration, which is associated with increased risk of myopathy, including rhabdomyolysis. If coadministered, do not exceed rosuvastatin dose of 10 mg/day.

            • stiripentol

              stiripentol will increase the level or effect of rosuvastatin by Other (see comment). Modify Therapy/Monitor Closely. Stiripentol is a BCRP transport inhibitor. Consider dosage reduction for BCRP substrates if adverse effects are experienced when coadministered.

            • tafamidis

              tafamidis will increase the level or effect of rosuvastatin by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.

            • tafamidis meglumine

              tafamidis meglumine will increase the level or effect of rosuvastatin by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.

            • tipranavir

              tipranavir increases levels of rosuvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. This interaction is the net effect of tipranavir being coadministered with ritonavir (boosted therapy); increased risk of myopathy including rhabdomyolysis; do not exceed rosuvastatin dose of 10 mg/day.

            • warfarin

              rosuvastatin increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.

            Minor (16)

            • coenzyme Q10

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

            • colestipol

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

            • erythromycin base

              erythromycin base decreases levels of rosuvastatin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate decreases levels of rosuvastatin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • erythromycin lactobionate

              erythromycin lactobionate decreases levels of rosuvastatin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • erythromycin stearate

              erythromycin stearate decreases levels of rosuvastatin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • ethinylestradiol

              rosuvastatin increases levels of ethinylestradiol by unspecified interaction mechanism. Minor/Significance Unknown.

            • fenofibrate

              fenofibrate increases levels of ezetimibe by unspecified interaction mechanism. Minor/Significance Unknown.

            • fenofibrate micronized

              fenofibrate micronized increases levels of ezetimibe by unspecified interaction mechanism. Minor/Significance Unknown.

            • fenofibric acid

              fenofibric acid increases levels of ezetimibe by unspecified interaction mechanism. Minor/Significance Unknown.

            • gemfibrozil

              gemfibrozil increases levels of ezetimibe by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • isradipine

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

            • mestranol

              rosuvastatin increases levels of mestranol by unspecified interaction mechanism. Minor/Significance Unknown.

            • orlistat

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

            • trazodone

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

            • voclosporin

              voclosporin will increase the level or effect of ezetimibe 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.

              voclosporin will increase the level or effect of rosuvastatin 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

            >10%

            Rosuvastatin H4

            • Myalgia (2.8-12.7%)
            • Arthralgia (10.1%)

            1-10%

            Rosuvastatin

            • Headache (5.5-6.4%)
            • Dizziness (4%)
            • Nausea (3.4%)
            • Asthenia (2.7%)
            • Increased CPK (2.6%)
            • Constipation (2.4%)
            • Abdominal (2.4%)
            • ALT >3x ULN (2.2%)

            Ezetimibe

            • Diarrhea (4.1%)
            • Arthralgia (3%)
            • Sinusitis (2.8%)
            • Pain in extremity (2.7%)
            • Fatigue (2.4%)
            • Influenza (2%)
            • Nasopharyngitis (3.7%)
            • Myalgia (3.2%)
            • Upper respiratory tract infection (2.9%)
            • Arthralgia (2.6%)
            • Diarrhea (2.5%)
            • Back pain (2.4%)
            • Influenza (2.2%)
            • Pain in extremity (2.1%)
            • Fatigue (2%)

            <1%

            Ezetimibe

            • Elevations (≥3x ULN) in hepatic transaminase levels

            Frequency Not Defined

            Rosuvastatin

            • Abdominal pain
            • Hypersensitivity (including rash, pruritus, urticaria, and angioedema)
            • Pancreatitis
            • Dipstick-positive proteinuria and microscopic hematuria
            • Elevated CPK, transaminases, glucose, glutamyl transpeptidase, alkaline phosphatase, and bilirubin
            • Thyroid function abnormalities

            Postmarketing Reports

            Rosuvastatin

            • Arthralgia
            • Peripheral neuropathy
            • Depression and sleep disorders (including insomnia and nightmares)
            • Fatal and nonfatal hepatic failure, hepatitis, jaundice
            • Thrombocytopenia
            • Gynecomastia
            • Interstitial lung disease
            • Immune-mediated necrotizing myopathy
            • Cognitive impairment (eg, memory loss, forgetfulness, amnesia, memory impairment, confusion)

            Ezetimibe

            • Hepatitis/liver function test abnormalities (LFTs elevated slightly higher in combination with statin than with statin alone)
            • Hypersensitivity reactions (including anaphylaxis, angioedema, rash, urticaria)
            • Erythema multiforme
            • Elevated creatinine phosphokinase
            • Myopathy/rhabdomyolysis
            • Thrombocytopenia
            • Back pain
            • Abdominal pain
            • Pancreatitis
            • Nausea
            • Dizziness
            • Paresthesia
            • Depression
            • Headache
            • Cholelithiasis and cholecystitis
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            Warnings

            Contraindications

            Acute liver failure or decompensated cirrhosis.

            Hypersensitivity to rosuvastatin, ezetimibe, or any excipients in drug product(s)

            Cautions

            Increased fasting blood glucose and glycosylated hemoglobin (HbA1c) levels reported with statin intake; in some instances, these increases may exceed the threshold for the diagnosis of diabetes mellitus; optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices

            Hematuria and proteinuria reported in clinical trials; findings were more frequent with rosuvastatin 40 mg compared to lower doses of rosuvastatin or other statins; effects are generally transient and was not associated with worsening renal function; consider dosage reduction if unexplained hematuria and proteinuria persists

            Myopathy and rhabdomyolysis

            • May cause myopathy (muscle pain, tenderness, or weakness with creatinine kinase [CK] >10x ULN) and rhabdomyolysis
            • Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis with statins, including rosuvastatin
            • Risk factors: Age ≥65 years, uncontrolled hypothyroidism, renal impairment, concurrent use with certain other drugs including other lipid-lowering therapies, higher rosuvastatin/ezetimibe dosage, or patients of Asian descent or ethnicity
            • Discontinue if markedly elevated CK levels occur or myopathy is diagnosed or suspected; muscle symptoms and CK increases may resolve if therapy is discontinued
            • Temporarily withhold in patients with an acute, serious condition at high risk of developing of renal failure secondary to rhabdomyolysis (eg, sepsis; hypotension; dehydration; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; uncontrolled seizures)
            • Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing dosage
            • Instruct to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever

            Immune-mediated necrotizing myopathy

            • Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, reported with statin use
            • IMNM is characterized by
              • Proximal muscle weakness
              • Elevated serum CK, which persist despite discontinuation of statin treatment
              • Positive anti-HMG CoA reductase antibody
              • Muscle biopsy showing necrotizing myopathy
              • Improvement with immunosuppressive agents
            • Treatment with immunosuppressive agents may be required
            • 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 initiated with a different statin, monitor for signs and symptoms of IMNM

            Hepatic dysfunction

            • Increases in serum transaminases have occurred
            • In most cases, elevations appeared soon after initiation, were transient, were not accompanied by symptoms, and resolved or improved on continued therapy or after a brief interruption in therapy
            • Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury
            • Consider liver enzyme testing before initiation and thereafter, when clinically indicated.
            • Contraindicated in patients with acute liver failure or decompensated cirrhosis
            • If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue treatment

            Drug interaction overview

            • Rosuvastatin a substrate of CYP2C9 and transporters (eg, OATP1B1, BCRP)
            • Cyclosporine or gemfibrozil
              • Avoid coadministration
              • Cyclosporine increased rosuvastatin exposure 7-fold
              • In addition, ezetimibe and cyclosporine used concomitantly can increase exposure to both ezetimibe and cyclosporine
              • Gemfibrozil significantly increased rosuvastatin exposure and gemfibrozil may cause myopathy when given alone
              • Concurrent use with cyclosporine or gemfibrozil may increase the risk of myopathy and rhabdomyolysis
            • Antiviral medications
              • Avoid coadministration
              • Rosuvastatin plasma levels were significantly increased with coadministration of many antiviral drugs, which increases the risk of myopathy and rhabdomyolysis
            • Darolutamide and regorafenib
              • Reduce rosuvastatin/ezetimibe dose
              • Darolutamide increased rosuvastatin exposure more than 5-fold and increasing the risk of myopathy and rhabdomyolysis
              • Regorafenib increased rosuvastatin exposure and may increase the risk of myopathy
            • Fenofibrates and niacin
              • Consider benefits outweigh increased risk of myopathy and rhabdomyolysis; monitor for signs and symptoms of myopathy during initiation and during uptitration of either fenofibrates, niacin, or rosuvastatin/ezetimibe
              • Cases of myopathy and rhabdomyolysis have occurred with concomitant use of niacin with rosuvastatin
              • Fibrates may cause myopathy when given alone; and may increase the risk of myopathy and rhabdomyolysis when coadministered with rosuvastatin/ezetimibe use
            • Antacids and bile acid sequestrants
              • Administer rosuvastatin/ezetimibe at least 2 hr before or at least 4 hr after bile acid sequestrant
              • Administer at least 2 hr before an aluminum and magnesium hydroxide combination antacid
              • Cholestyramine administration decreased the mean exposure of total ezetimibe ~55%
              • Aluminum and magnesium hydroxide combination antacid administration decreased the mean exposure of rosuvastatin 50% and total ezetimibe 4%
              • Incremental LDL-C reduction due to adding ezetimibe may be attenuated by coadministration with cholestyramine or antacid combination
            • Warfarin
              • Obtain an INR before starting and frequently after initiation, dose titration or discontinuation to ensure that no significant alteration in INR occurs; once INR is stable, monitor INR at regularly recommended intervals
              • Rosuvastatin significantly increased INR in patients receiving vitamin K depleting anticoagulants
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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

            Rosuvastatin

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

            Ezetimibe

            • Blocks GI cholesterol absorption via NPC1L1 (Niemann-Pick C1-Like 1) inhibition, reducing cholesterol deliver to the liver
            • This action reduces hepatic cholesterol stores and increases LDL receptors, resulting in clearance of cholesterol from the blood
            • NPC1L1 is a sterol transporter that mediates intestinal cholesterol absorption

            Absorption

            Rosuvastatin

            • Bioavailability: 20%
            • Peak plasma time: 3-5 hr

            Ezetimibe

            • Bioavailability: Variable
            • Peak plasma time: 4-12 hr (parent drug); 1-2 hr (metabolite)
            • Peak plasma concentration: 3.4-5.5 ng/mL (parent drug); 45-71 ng/mL (metabolite)

            Distribution

            Rosuvastatin

            • Vd: 134 L
            • Protein bound: 88%

            Ezetimibe

            • Protein bound: >90%

            Metabolism

            Rosuvastatin

            • Metabolism: ~10% by hepatic CYP2C9
            • Metabolites: N-desmethyl, lactone

            Ezetimibe

            • Metabolized by glucuronide conjugation
            • Metabolites: Ezetimibe-glucuronide (80-90%)

            Elimination

            Rosuvastatin

            • Half-life: 19 hr
            • Excretion: Feces (90%)

            Ezetimibe

            • Half-life: 22 hr
            • Excretion: Feces (78% [69% ezetimibe]), urine (11% [9% ezetimibe-glucuronide])

            Pharmacogenomics

            Hepatic influx and efflux transporters (single-nucleotide polymorphisms [SNPs] within the solute carrier organic anion transporter 1B1 (SLCO1B1) gene, encoding the organic anion transporter polypeptide 1B1 (OATP1B1) influx transporter)

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

            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, pravastatin, simvastatin)

            SLCO1B1 CC genotype is most common in Caucasians and Asians (15%); decrease dose by 50% in people of Asian descent

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

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            Administration

            Oral Administration

            Take with or without food

            Swallow tablets whole at any time of day

            Do NOT crush, dissolve, or chew tablets

            Administer at least 2 hr before or 4 hr after bile acid sequestrant

            Administer at least 2 hr before aluminum/magnesium hydroxide combination antacid

            Missed dose: Do not take an extra dose; resume at next schedule

            Storage

            Store at controlled room temperature (20-25ºC (68-77ºF)

            Store in original container to protect from light; protect from moisture

            Dispense in original container to protect from moisture

            Opened bottles: Use within 30 days

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            Images

            No images available for this drug.
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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            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
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            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the 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.