Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
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 (25)
- 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).
- leniolisib
leniolisib will increase the level or effect of ezetimibe by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, an OATP1B1 and OATP1B3 inhibitor, may increase systemic exposure of these substrates
- 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.
- leniolisib
leniolisib will increase the level or effect of rosuvastatin by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, a BCRP, OATP1B1, and OATP1B3 inhibitor, may increase systemic exposure of these substrates
- levoketoconazole
levoketoconazole increases toxicity of rosuvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: OATP1B1 inhibitors may increase risk of myopathy.
- 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 (DSC)
ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) 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.
- trofinetide
trofinetide will increase the level or effect of ezetimibe by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.
trofinetide will increase the level or effect of rosuvastatin by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates. - zavegepant intranasal
ezetimibe will increase the level or effect of zavegepant intranasal by Other (see comment). Avoid or Use Alternate Drug. NTCP inhibitors may result in a significant increase in systemic exposure of zavegepant (a NTCP substrate).
Monitor Closely (63)
- 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.
- encorafenib
encorafenib will increase the level or effect of ezetimibe by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 inhibitor) may increase the concentration and toxicities of OATP1B1 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.
encorafenib will increase the level or effect of rosuvastatin by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1, OATP1B3, and BCRP inhibitor) may increase the concentration and toxicities of OATP1B1, OATP1B3, and BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates. Screen reader support enabled. - erythromycin base
erythromycin base increases toxicity of rosuvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.
- 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.
- 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 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.
- momelotinib
momelotinib increases toxicity of rosuvastatin by plasma protein binding competition. Modify Therapy/Monitor Closely. When coadministered with momelotinib (BCRP inhibitor), initiate rosuvastatin (BCRP substrate) at 5 mg and not to exceed 10 mg once daily.
- nirmatrelvir
nirmatrelvir will increase the level or effect of rosuvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider temporary discontinuation of rosuvastatin during treatment with nirmatrelvir/ritonavir.
- nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will increase the level or effect of rosuvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider temporary discontinuation of rosuvastatin during treatment with nirmatrelvir/ritonavir.
- ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) 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.
- pretomanid
pretomanid will increase the level or effect of rosuvastatin by Other (see comment). Use Caution/Monitor. Increase monitoring for drug-related adverse effects if pretomanid is coadministered with sensitive OATP1B3 or BCRP substrates.
- 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.
- tenapanor
tenapanor decreases levels of rosuvastatin by Other (see comment). Use Caution/Monitor. Comment: Tenapanor (an inhibitor of intestinal uptake transporter, OATP2B1) may reduce the exposure of OATP2B1 substrates.
- 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 anticoagulation. 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.
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
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
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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)
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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
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Antiviral medications
- Avoid coadministration
- Rosuvastatin plasma levels were significantly increased with coadministration of many antiviral drugs, which increases the risk of myopathy and rhabdomyolysis
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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
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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
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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
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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
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.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
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
Images
Formulary
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