Crestor

HMG-CoA Reductase Inhibitors (Statins)

May administer without regard to food at any time of day.
If a dose is missed, resume treatment with the next dose; do not take an extra dose.[27988]

Tablets
Swallow tablets whole.
Capsules
Swallow capsules whole; do not crush or chew.
For those unable to swallow an intact capsule, open the capsule and administer the contents.
Oral:
Open the capsule and sprinkle the contents on a small amount (approximately 5 mL) of soft food, such as applesauce or pudding.
Stir mixture for 10 to 15 seconds.
Swallow the entire mixture within 60 minutes of preparation; do not chew. Do not store for future use.
Nasogastric tube:
Open the capsule and empty the contents into a 60 mL catheter tipped syringe.
Add 40 mL of water. Do not use other types of liquid.
Replace the plunger and shake vigorously for 15 seconds.
Administer the mixture through the NG tube (16 French or more) into the stomach.
Flush the NG tube with 20 mL of water.
Use immediately after preparation. Do not store for future use.

proteinuria / Delayed / 1.3-1.3
immune-mediated necrotizing myopathy / Delayed / 0-1.0
rhabdomyolysis / Delayed / Incidence not known
myoglobinuria / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
myasthenia gravis / Delayed / Incidence not known

constipation / Delayed / 2.1-4.7
diabetes mellitus / Delayed / 2.8-3.0
elevated hepatic enzymes / Delayed / 1.1-2.2
hematuria / Delayed / 1.3-1.3
myasthenia / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
memory impairment / Delayed / Incidence not known
depression / Delayed / Incidence not known
amnesia / Delayed / Incidence not known
confusion / Early / Incidence not known
hyperglycemia / Delayed / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
interstitial lung disease / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known

myalgia / Early / 2.0-12.7
arthralgia / Delayed / 3.8-10.1
headache / Early / 3.1-8.5
nausea / Early / 0-6.3
asthenia / Delayed / 0.9-4.7
dizziness / Early / 4.0-4.0
abdominal pain / Early / 2.4-2.4
malaise / Early / Incidence not known
fever / Early / Incidence not known
nightmares / Early / Incidence not known
insomnia / Early / Incidence not known
lichen planus-like eruption / Delayed / Incidence not known
rash / Early / Incidence not known
urticaria / Rapid / Incidence not known
pruritus / Rapid / Incidence not known
Co-Enzyme Q-10 deficiency / Delayed / Incidence not known

Crestor, Ezallor

Rx

Most potent, oral HMG-CoA reductase inhibitor
Approved for primary hyperlipidemia, including hypercholesterolemia, hyperlipoproteinemia and/or hypertriglyceridemia, and primary prevention of cardiovascular disease events in adults, heterozygous familial hypercholesterolemia in adults and pediatric patients 8 years and older, homozygous familial hypercholesterolemia in adults and pediatric patients 7 years and older
Limited metabolism; less potential for CYP3A4 drug interactions compared to simvastatin or lovastatin

20 or 40 mg PO once daily. Myopathy risk is greater at 40 mg/day compared to lower doses.  

5 or 10 mg PO once daily.

5 to 40 mg PO once daily. Dose depends on LDL-C and individual risk for cardiovascular events. Monitor lipid concentrations as early as 4 weeks after starting therapy and as clinically appropriate and adjust dose if needed. A dosage of 40 mg/day is associated with a higher risk of myopathy. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

5 mg PO once daily, initially. Monitor lipid concentrations as early as 4 weeks after starting therapy and as clinically appropriate and adjust dose if needed. Consider the risks and benefits of rosuvastatin when treating Asian patients not adequately controlled at doses up to 20 mg once daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

5 to 40 mg PO once daily. Dose depends on LDL-C and individual risk for cardiovascular events. Monitor lipid concentrations as early as 4 weeks after starting therapy and as clinically appropriate and adjust dose if needed. A dosage of 40 mg/day is associated with a higher risk of myopathy. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

5 mg PO once daily, initially. Monitor lipid concentrations as early as 4 weeks after starting therapy and as clinically appropriate and adjust dose if needed. Consider the risks and benefits of rosuvastatin when treating Asian patients not adequately controlled at doses up to 20 mg once daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

20 or 40 mg PO once daily. Monitor lipid concentrations as early as 4 weeks after starting therapy and as clinically appropriate and adjust dose if needed. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In persons with clinical atherosclerotic coronary vascular disease (ASCVD), reduction in LDL-C should be targeted with high-intensity or maximally-tolerated statin dosing unless contraindicated.

5 mg PO once daily, initially. Monitor lipid concentrations as early as 4 weeks after starting therapy and as clinically appropriate and adjust dose if needed. Consider the risks and benefits of rosuvastatin when treating Asian patients not adequately controlled at doses up to 20 mg once daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In persons with clinical atherosclerotic coronary vascular disease (ASCVD), reduction in LDL-C should be targeted with high-intensity or maximally-tolerated statin dosing unless contraindicated.

5 to 40 mg PO once daily. Dose depends on LDL-C and individual risk for cardiovascular events. Monitor lipid concentrations as early as 4 weeks after starting therapy and as clinically appropriate and adjust dose if needed. A dosage of 40 mg/day is associated with a higher risk of myopathy. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

5 mg PO once daily, initially. Monitor lipid concentrations as early as 4 weeks after starting therapy and as clinically appropriate and adjust dose if needed. Consider the risks and benefits of rosuvastatin when treating Asian patients not adequately controlled at doses up to 20 mg once daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

5 to 20 mg PO once daily. Monitor lipid concentrations as early as 4 weeks after starting therapy and as clinically appropriate and adjust dose if needed. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

5 to 10 mg PO once daily. Monitor lipid concentrations as early as 4 weeks after starting therapy and as clinically appropriate and adjust dose if needed. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

5 to 40 mg PO once daily. Dose depends on LDL-C and individual risk for cardiovascular events. Monitor lipid concentrations as early as 4 weeks after starting therapy and as clinically appropriate and adjust dose if needed. A dosage of 40 mg/day is associated with a higher risk of myopathy. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

5 mg PO once daily, initially. Monitor lipid concentrations as early as 4 weeks after starting therapy and as clinically appropriate and adjust dose if needed. Consider the risks and benefits of rosuvastatin when treating Asian patients not adequately controlled at doses up to 20 mg once daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

20 mg PO once daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

5 to 40 mg PO once daily. Dose depends on LDL-C and individual risk for cardiovascular events. Monitor lipid concentrations as early as 4 weeks after starting therapy and as clinically appropriate and adjust dose if needed. A dosage of 40 mg/day is associated with a higher risk of myopathy. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

5 mg PO once daily, initially. Monitor lipid concentrations as early as 4 weeks after starting therapy and as clinically appropriate and adjust dose if needed. Consider the risks and benefits of rosuvastatin when treating Asian patients not adequately controlled at doses up to 20 mg once daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Contraindicated in patients with acute hepatic failure or decompensated cirrhosis.

CrCl 30 mL/minute/1.73 m2 or greater: No dosage adjustment needed.
CrCl less than 30 mL/minute/1.73 m2: Initially, 5 mg PO once daily for patients not receiving dialysis. Maximum dosage is 10 mg PO once daily.[27988] [63844]
 
Intermittent hemodialysis
Although the FDA-approved product labeling does not provide dosage adjustment recommendations for patients receiving hemodialysis, rosuvastatin serum concentrations are increased by approximately 50% in patients receiving hemodialysis vs. patients with normal renal function. Hemodialysis does not significantly enhance the clearance of rosuvastatin.[27988] [63844]

Acalabrutinib: (Moderate) Coadministration of acalabrutinib and rosuvastatin may increase rosuvastatin exposure and increase the risk of rosuvastatin toxicity. Acalabrutinib is an inhibitor of the breast cancer resistance protein (BCRP) transporter in vitro; it may inhibit intestinal BCRP. Rosuvastatin is a BCRP substrate.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with clarithromycin. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a substrate of the drug transporter OATP1B1/3 and clarithromycin is an OATP1B1/3 inhibitor.
Antacids: (Moderate) Coadministration of rosuvastatin with antacids has reduced rosuvastatin plasma concentrations by 54%. When the antacid is given 2 hours after rosuvastatin, no significant change in rosuvastatin plasma concentrations is observed.
Aprepitant, Fosaprepitant: (Minor) Use caution if rosuvastatin and aprepitant are used concurrently and monitor for a possible decrease in the efficacy of rosuvastatin. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Rosuvastatin is a CYP2C9 substrate and aprepitant is a CYP2C9 inducer. Administration of a CYP2C9 substrate, tolbutamide, on days 1, 4, 8, and 15 with a 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) decreased the tolbutamide AUC by 23% on day 4, 28% on day 8, and 15% on day 15. The AUC of tolbutamide was decreased by 8% on day 2, 16% on day 4, 15% on day 8, and 10% on day 15 when given prior to oral administration of aprepitant 40 mg on day 1, and on days 2, 4, 8, and 15. The effects of aprepitant on tolbutamide were not considered significant. When a 3-day regimen of aprepitant (125 mg/80 mg/80 mg) given to healthy patients on stabilized chronic warfarin therapy (another CYP2C9 substrate), a 34% decrease in S-warfarin trough concentrations was noted, accompanied by a 14% decrease in the INR at five days after completion of aprepitant.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Coadministration of rosuvastatin with antacids has reduced rosuvastatin plasma concentrations by 54%. When the antacid is given 2 hours after rosuvastatin, no significant change in rosuvastatin plasma concentrations is observed.
Atazanavir: (Major) Initiate rosuvastatin at a reduced dosage of 5 mg once daily if coadministered with atazanavir; do not exceed a rosuvastatin dosage of 10 mg once daily. Concurrent use results in elevated rosuvastatin serum concentrations; thereby increasing the risk for myopathy, including rhabdomyolysis. Rosuvastatin is a substrate of the drug transporter organic anion transporting polypeptide (OATP1B1); atazanavir is an OATP1B1 inhibitor. Closely monitor for statin-associated adverse reactions, such as myopathy and rhabdomyolysis.
Atazanavir; Cobicistat: (Major) Avoid concurrent administration of cobicistat and rosuvastatin. Taking these drugs together results in elevated rosuvastatin concentrations. If these drugs must be used together, use the lowest starting dose of rosuvastatin and carefully titrate while monitoring for adverse events (myopathy). Rosuvastatin is taken up into human hepatocytes mainly by organic anion transporting polypeptide (OATP)1B1 and OATP1B3. Cobicistat is an inhibitor of OATP. (Major) Initiate rosuvastatin at a reduced dosage of 5 mg once daily if coadministered with atazanavir; do not exceed a rosuvastatin dosage of 10 mg once daily. Concurrent use results in elevated rosuvastatin serum concentrations; thereby increasing the risk for myopathy, including rhabdomyolysis. Rosuvastatin is a substrate of the drug transporter organic anion transporting polypeptide (OATP1B1); atazanavir is an OATP1B1 inhibitor. Closely monitor for statin-associated adverse reactions, such as myopathy and rhabdomyolysis.
Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like HMG-CoA reductase inhibitors; the risk of peripheral neuropathy may be additive.
Calcium Carbonate: (Moderate) While not specifically reported with calcium carbonate, antacids (aluminum hydroxide; magnesium hydroxide combination) have been shown to reduce rosuvastatin plasma concentrations by 54%. When the antacid is given 2 hours after rosuvastatin, no significant change in rosuvastatin plasma concentrations is observed.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) While not specifically reported with calcium carbonate, antacids (aluminum hydroxide; magnesium hydroxide combination) have been shown to reduce rosuvastatin plasma concentrations by 54%. When the antacid is given 2 hours after rosuvastatin, no significant change in rosuvastatin plasma concentrations is observed.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) While not specifically reported with calcium carbonate, antacids (aluminum hydroxide; magnesium hydroxide combination) have been shown to reduce rosuvastatin plasma concentrations by 54%. When the antacid is given 2 hours after rosuvastatin, no significant change in rosuvastatin plasma concentrations is observed.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) While not specifically reported with calcium carbonate, antacids (aluminum hydroxide; magnesium hydroxide combination) have been shown to reduce rosuvastatin plasma concentrations by 54%. When the antacid is given 2 hours after rosuvastatin, no significant change in rosuvastatin plasma concentrations is observed.
Calcium Carbonate; Simethicone: (Moderate) While not specifically reported with calcium carbonate, antacids (aluminum hydroxide; magnesium hydroxide combination) have been shown to reduce rosuvastatin plasma concentrations by 54%. When the antacid is given 2 hours after rosuvastatin, no significant change in rosuvastatin plasma concentrations is observed.
Calcium; Vitamin D: (Moderate) While not specifically reported with calcium carbonate, antacids (aluminum hydroxide; magnesium hydroxide combination) have been shown to reduce rosuvastatin plasma concentrations by 54%. When the antacid is given 2 hours after rosuvastatin, no significant change in rosuvastatin plasma concentrations is observed.
Capmatinib: (Moderate) Do not exceed a rosuvastatin dose of 10 mg once daily if concomitant use of capmatinib is necessary. Concomitant use may increase rosuvastatin exposure and the risk for rosuvastatin-related adverse reactions, such as myopathy and rhabdomyolysis. Rosuvastatin is a BCRP substrate and capmatinib is a BCRP inhibitor. Coadministration with capmatinib increased rosuvastatin exposure more than 2.1- fold.
Cimetidine: (Moderate) Use HMG-CoA reductase inhibitors with caution with concomitant drugs that may decrease the levels or activity of endogenous steroids, such as cimetidine. Evaluate patients with signs and symptoms of endocrine dysfunction appropriately. HMG-CoA reductase inhibitors interfere with cholesterol synthesis and theoretically might blunt adrenal and/or gonadal steroid production.
Clarithromycin: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with clarithromycin. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a substrate of the drug transporter OATP1B1/3 and clarithromycin is an OATP1B1/3 inhibitor.
Clofarabine: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and rosuvastatin, a substrate of OAT protein (OATP), may result in altered clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g., hand and foot syndrome, rash, pruritus) in patients also receiving OATP substrates.
Clopidogrel: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with clopidogrel. Concurrent use has been observed to increase rosuvastatin overall exposure by 1.4-fold and 2-fold in patients receiving 75 mg and 300 mg of clopidogrel, respectively.
Cobicistat: (Major) Avoid concurrent administration of cobicistat and rosuvastatin. Taking these drugs together results in elevated rosuvastatin concentrations. If these drugs must be used together, use the lowest starting dose of rosuvastatin and carefully titrate while monitoring for adverse events (myopathy). Rosuvastatin is taken up into human hepatocytes mainly by organic anion transporting polypeptide (OATP)1B1 and OATP1B3. Cobicistat is an inhibitor of OATP.
Colchicine: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
Cyclosporine: (Major) Do not exceed a rosuvastatin dose of 5 mg once daily when coadministered with cyclosporine. Concurrent use results in elevated rosuvastatin serum concentrations; thereby increasing the risk for myopathy, including rhabdomyolysis. Rosuvastatin is a substrate of the drug transporter organic anion transporting polypeptide (OATP1B1) and breast cancer resistance protein (BCRP) and cyclosporine is an inhibitor of these transporters. Closely monitor for statin-associated adverse reactions, such as myopathy and rhabdomyolysis. The rosuvastatin AUC was increased 7-fold in the presence of cyclosporine.
Daclatasvir: (Moderate) Caution and close monitoring is advised if daclatasvir is administered with HMG-CoA reductase inhibitors (Statins). Use of these drugs together may result in elevated Statin serum concentrations, potentially resulting in adverse effects such as myopathy and rhabdomyolysis.
Daptomycin: (Major) Temporarily suspend HMG-CoA reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. Both agents can cause myopathy and rhabdomyolysis when given alone and the risk may be increased when given together.
Darolutamide: (Major) Do not exceed a rosuvastatin dose of 5 mg once daily when coadministered with doralutamide. Concurrent use results in elevated rosuvastatin serum concentrations; thereby increasing the risk for myopathy, including rhabdomyolysis. Rosuvastatin is a substrate of the drug transporter breast cancer resistance protein (BCRP) and OATP1B1/3; darolutamide is a BCRP and OATP1B1/3 inhibitor. Closely monitor for statin-associated adverse reactions, such as myopathy and rhabdomyolysis.
Darunavir: (Major) The risk of myopathy, including rhabdomyolysis, may be increased when darunavir is given in combination with most HMG-CoA reductase inhibitors. When coadministered with darunavir (in the FDA approved dosage regimen), increased rosuvastatin concentrations are seen, although the drugs can be coadministered with careful monitoring when rosuvastatin is started at the lowest possible dose; gradual dose increases may be considered based on clinical response. The dose of rosuvastatin should not exceed 20 mg/day when given with darunavir boosted with cobicistat.
Darunavir; Cobicistat: (Major) Avoid concurrent administration of cobicistat and rosuvastatin. Taking these drugs together results in elevated rosuvastatin concentrations. If these drugs must be used together, use the lowest starting dose of rosuvastatin and carefully titrate while monitoring for adverse events (myopathy). Rosuvastatin is taken up into human hepatocytes mainly by organic anion transporting polypeptide (OATP)1B1 and OATP1B3. Cobicistat is an inhibitor of OATP. (Major) The risk of myopathy, including rhabdomyolysis, may be increased when darunavir is given in combination with most HMG-CoA reductase inhibitors. When coadministered with darunavir (in the FDA approved dosage regimen), increased rosuvastatin concentrations are seen, although the drugs can be coadministered with careful monitoring when rosuvastatin is started at the lowest possible dose; gradual dose increases may be considered based on clinical response. The dose of rosuvastatin should not exceed 20 mg/day when given with darunavir boosted with cobicistat.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concurrent administration of cobicistat and rosuvastatin. Taking these drugs together results in elevated rosuvastatin concentrations. If these drugs must be used together, use the lowest starting dose of rosuvastatin and carefully titrate while monitoring for adverse events (myopathy). Rosuvastatin is taken up into human hepatocytes mainly by organic anion transporting polypeptide (OATP)1B1 and OATP1B3. Cobicistat is an inhibitor of OATP. (Major) The risk of myopathy, including rhabdomyolysis, may be increased when darunavir is given in combination with most HMG-CoA reductase inhibitors. When coadministered with darunavir (in the FDA approved dosage regimen), increased rosuvastatin concentrations are seen, although the drugs can be coadministered with careful monitoring when rosuvastatin is started at the lowest possible dose; gradual dose increases may be considered based on clinical response. The dose of rosuvastatin should not exceed 20 mg/day when given with darunavir boosted with cobicistat.
Desogestrel; Ethinyl Estradiol: (Minor) When coadministered with oral contraceptives during drug interaction studies, rosuvastatin produced an approximately 1.3-fold increase in the AUC and maximal concentrations of ethinyl estradiol. The changes are not likely to be of clinical consequence for most patients; some patients may experience increases in common side effects of hormonal contraceptives, such as breast tenderness, nausea, headache, or fluid retention.
Drospirenone; Ethinyl Estradiol: (Minor) When coadministered with oral contraceptives during drug interaction studies, rosuvastatin produced an approximately 1.3-fold increase in the AUC and maximal concentrations of ethinyl estradiol. The changes are not likely to be of clinical consequence for most patients; some patients may experience increases in common side effects of hormonal contraceptives, such as breast tenderness, nausea, headache, or fluid retention.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) When coadministered with oral contraceptives during drug interaction studies, rosuvastatin produced an approximately 1.3-fold increase in the AUC and maximal concentrations of ethinyl estradiol. The changes are not likely to be of clinical consequence for most patients; some patients may experience increases in common side effects of hormonal contraceptives, such as breast tenderness, nausea, headache, or fluid retention.
Elacestrant: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with elacestrant. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP substrate and elacestrant is a BCRP inhibitor. Concomitant administration increased overall exposure of rosuvastatin by 1.2 fold.
Elagolix: (Moderate) Monitor for a decrease in rosuvastatin efficacy during concomitant use with elagolix and adjust the rosuvastatin dose as appropriate. Concomitant use has been observed to decrease rosuvastatin overall exposure by 40%.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Monitor for a decrease in rosuvastatin efficacy during concomitant use with elagolix and adjust the rosuvastatin dose as appropriate. Concomitant use has been observed to decrease rosuvastatin overall exposure by 40%.
Elbasvir; Grazoprevir: (Major) Initiate rosuvastatin at a reduced dosage of 5 mg once daily if coadministered with elbasvir; grazoprevir; do not exceed a rosuvastatin dosage of 10 mg once daily. Concurrent use results in elevated rosuvastatin serum concentrations; thereby increasing the risk for myopathy, including rhabdomyolysis. Closely monitor for statin-associated adverse reactions, such as myopathy and rhabdomyolysis. Rosuvastatin is a substrate for the breast cancer resistance protein (BCRP); both elbasvir and grazoprevir are BCRP inhibitors.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with elexacaftor. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a substrate of the drug transporter OATP1B1/3 and elexacaftor is an OATP1B1/3 inhibitor.
Eltrombopag: (Moderate) Use caution and monitor for signs of rosuvastatin toxicity if this drug is coadministered with eltrombopag. In clinical trials, a 50% dose reduction of rosuvastatin was recommended. Eltrombopag is an inhibitor of OATP1B1 and BCRP, and rosuvastatin is a substrate of both of these transporters. In a clinical study, administration of a single dose of rosuvastatin with eltrombopag increased plasma rosuvastatin AUC by 55% and the Cmax by 103%.
Eluxadoline: (Moderate) Close monitoring for adverse effects, such as rhabdomyolysis and myopathy, is advised when eluxadoline is administered concurrently with rosuvastatin. Eluxadoline is an inhibitor of the organic anion-transporting peptide (OATP1B1) and the breast cancer resistance protein (BCRP); rosuvastatin is a substrate of both transporters. Use of these drugs together results in a 40% increase in the exposure (AUC) and a 18% increase in the maximum plasma concentration (Cmax) of rosuvastatin. Administer the lowest effect rosuvastatin dose and monitor for adverse effects.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concurrent administration of cobicistat and rosuvastatin. Taking these drugs together results in elevated rosuvastatin concentrations. If these drugs must be used together, use the lowest starting dose of rosuvastatin and carefully titrate while monitoring for adverse events (myopathy). Rosuvastatin is taken up into human hepatocytes mainly by organic anion transporting polypeptide (OATP)1B1 and OATP1B3. Cobicistat is an inhibitor of OATP. (Moderate) Caution is warranted when elvitegravir is administered with rosuvastatin as there is a potential for decreased rosuvastatin concentrations. Alternatively, when elvitegravir is boosted with cobicistat, the concentration of rosuvastatin may be increased due to inhibition of OATP by cobicistat. In one pharmacokinetic study, the Cmax and AUC of rosuvastatin were increased by 89% and 38%, respectively, when given concurrently with cobicistat and elvitegravir. Patients may experience a decreased antilipemic effect elvitegravir and rosuvastatin are coadministered. If elvitegravir is boosted with cobicistat, patients may be at increased risk for side effects of rosuvastatin. Rosuvastatin is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concurrent administration of cobicistat and rosuvastatin. Taking these drugs together results in elevated rosuvastatin concentrations. If these drugs must be used together, use the lowest starting dose of rosuvastatin and carefully titrate while monitoring for adverse events (myopathy). Rosuvastatin is taken up into human hepatocytes mainly by organic anion transporting polypeptide (OATP)1B1 and OATP1B3. Cobicistat is an inhibitor of OATP. (Moderate) Caution is warranted when elvitegravir is administered with rosuvastatin as there is a potential for decreased rosuvastatin concentrations. Alternatively, when elvitegravir is boosted with cobicistat, the concentration of rosuvastatin may be increased due to inhibition of OATP by cobicistat. In one pharmacokinetic study, the Cmax and AUC of rosuvastatin were increased by 89% and 38%, respectively, when given concurrently with cobicistat and elvitegravir. Patients may experience a decreased antilipemic effect elvitegravir and rosuvastatin are coadministered. If elvitegravir is boosted with cobicistat, patients may be at increased risk for side effects of rosuvastatin. Rosuvastatin is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer.
Enasidenib: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with enasidenib is necessary. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a substrate of the drug transporters OATP1B1/3 and BCRP and enasidenib is an OATP1B1/3 and BCRP inhibitor. Coadministration of rosuvastatin after multiple doses of enasidenib increased rosuvastatin Cmax by 366% and AUC by 244%.
Encorafenib: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with encorafenib. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a substrate of OATP1B1/3 and BCRP; encorafenib is an OATP1B1/3 and BCRP inhibitor.
Erythromycin: (Minor) Erythromycin is generally associated with an increased risk of myopathy with HMG-CoA reductase inhibitors. This interaction is likely due to CYP3A4 inhibition of statins which are CYP3A4 substrates; however, rosuvastatin is not substantially metabolized, and is less likely to be significantly affected by CYP3A4 inhibitors such as erythromycin. However, other mechanisms, such as an effect on OATP1B1, may be involved. Rosuvastatin is an OATP1B1 substrate. Coadministration of a single dose of rosuvastatin (80 mg) with erythromycin results in 31% and 20% decrease in Cmax and AUC of rosuvastatin, respectively. The clinical significance of this interaction has not been established, monitor for effectiveness of rosuvastatin and for myopathy and adjust treatment as clinically indicated.
Ethinyl Estradiol; Norelgestromin: (Minor) When coadministered with oral contraceptives during drug interaction studies, rosuvastatin produced an approximately 1.3-fold increase in the AUC and maximal concentrations of ethinyl estradiol. The changes are not likely to be of clinical consequence for most patients; some patients may experience increases in common side effects of hormonal contraceptives, such as breast tenderness, nausea, headache, or fluid retention.
Ethinyl Estradiol; Norethindrone Acetate: (Minor) When coadministered with oral contraceptives during drug interaction studies, rosuvastatin produced an approximately 1.3-fold increase in the AUC and maximal concentrations of ethinyl estradiol. The changes are not likely to be of clinical consequence for most patients; some patients may experience increases in common side effects of hormonal contraceptives, such as breast tenderness, nausea, headache, or fluid retention.
Ethinyl Estradiol; Norgestrel: (Minor) When coadministered with oral contraceptives during drug interaction studies, rosuvastatin produced an approximately 1.1 to 1.3-fold increase in the AUC and maximal concentrations of norgestrel. The changes are not likely to be of clinical consequence for most patients; some patients may experience increases in common side effects of norgestrel, such as breast tenderness, nausea, headache, or fluid retention. (Minor) When coadministered with oral contraceptives during drug interaction studies, rosuvastatin produced an approximately 1.3-fold increase in the AUC and maximal concentrations of ethinyl estradiol. The changes are not likely to be of clinical consequence for most patients; some patients may experience increases in common side effects of hormonal contraceptives, such as breast tenderness, nausea, headache, or fluid retention.
Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) When coadministered with oral contraceptives during drug interaction studies, rosuvastatin produced an approximately 1.3-fold increase in the AUC and maximal concentrations of ethinyl estradiol. The changes are not likely to be of clinical consequence for most patients; some patients may experience increases in common side effects of hormonal contraceptives, such as breast tenderness, nausea, headache, or fluid retention.
Etonogestrel; Ethinyl Estradiol: (Minor) When coadministered with oral contraceptives during drug interaction studies, rosuvastatin produced an approximately 1.3-fold increase in the AUC and maximal concentrations of ethinyl estradiol. The changes are not likely to be of clinical consequence for most patients; some patients may experience increases in common side effects of hormonal contraceptives, such as breast tenderness, nausea, headache, or fluid retention.
Etravirine: (Moderate) Concomitant use of etravirine and rosuvastatin has no effect on the serum concentration of rosuvastatin; however, the risk of myopathy, including rhabdomyolysis, may be increased when antiretrovirals are given in combination with HMG-CoA reductase inhibitors.
Febuxostat: (Moderate) Do not exceed a rosuvastatin dose of 20 mg once daily if concomitant use of febuxostat is necessary. Concomitant use may increase rosuvastatin exposure and the risk for rosuvastatin-related adverse reactions, such as myopathy and rhabdomyolysis. Coadministration with febuxostat increased rosuvastatin exposure more than 1.9-fold.
Fenofibrate: (Moderate) Clinical practice guidelines state the concurrent use of fenofibrate and rosuvastatin is reasonable and preferred over gemfibrozil if statin/fibrate combination therapy is indicated. However, because combination therapy increases the risk of myopathy, caution is advised.
Fenofibric Acid: (Moderate) Clinical practice guidelines state the concurrent use of fenofibric acid and rosuvastatin is reasonable and preferred over gemfibrozil if statin/fibrate combination therapy is indicated. However, because combination therapy increases the risk of myopathy, caution is advised.
Fosamprenavir: (Major) Fosamprenavir increases rosuvastatin plasma concentrations. If these drugs are to be coadministered, use the lowest possible dose of rosuvastatin, or consider treatment with an alternative HMG-CoA reductase inhibitor such as fluvastatin or pravastatin.
Fostamatinib: (Moderate) Do not exceed a rosuvastatin dose of 20 mg once daily if concomitant use of fostamatinib is necessary. Concomitant use may increase rosuvastatin exposure and the risk for rosuvastatin-related adverse reactions, such as myopathy and rhabdomyolysis. Rosuvastatin is a BCRP substrate and fostamatinib is a BCRP inhibitor. Coadministration with fostamatinib increased rosuvastatin exposure more than 2-fold.
Fostemsavir: (Moderate) Use the lowest possible starting dose for rosuvastatin when administered concurrently with fostemsavir and monitor for signs of rosuvastatin-associated adverse events, such as rhabdomyolysis. Use of these drugs together increases the systemic exposure of rosuvastatin. Rosuvastatin is a substrate for the transporters OATP1B1/3 and fostemsavir is an inhibitor of OATP1B1/3.
Futibatinib: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with futibatinib. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP substrate and futibatinib is a BCRP inhibitor.
Gemfibrozil: (Major) Avoid concomitant use of gemfibrozil and rosuvastatin due to the increased risk of myopathy and rhabdomyolysis. If coadministration cannot be avoided, initiate rosuvastatin at a reduced dosage of 5 mg once daily; do not exceed a rosuvastatin dosage of 10 mg once daily. Clinical practice guidelines state the concurrent use of gemfibrozil and rosuvastatin is acceptable to use if clinically indicated and fenofibrate or fenofibric acid is not an option. The risk of myopathy/rhabdomyolysis increases when HMG-CoA reductase inhibitors are administered concurrently with gemfibrozil. The serious risk of myopathy or rhabdomyolysis should be weighed carefully against the benefits of combined statin and gemfibrozil therapy; there is no assurance that periodic monitoring of CK will prevent the occurrence of severe myopathy and renal damage.
Gilteritinib: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with gilteritinib. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP substrate and gilteritinib is a BCRP inhibitor.
Glecaprevir; Pibrentasvir: (Major) Initiate rosuvastatin at a reduced dosage of 5 mg once daily if coadministered with glecaprevir; do not exceed a rosuvastatin dosage of 10 mg once daily. Concurrent use results in elevated rosuvastatin serum concentrations; thereby increasing the risk for myopathy, including rhabdomyolysis. Closely monitor for statin-associated adverse reactions, such as myopathy and rhabdomyolysis. Rosuvastatin is a substrate of the drug transporters OATP1B1, OATP1B3, and BRCP; glecaprevir is an inhibitor of these transporters. In drug interaction studies, coadministration of rosuvastatin with glecaprevir; pibrentasvir resulted in more than a 2-fold increase in the AUC of rosuvastatin. (Major) Initiate rosuvastatin at a reduced dosage of 5 mg once daily if coadministered with pibrentasvir; do not exceed a rosuvastatin dosage of 10 mg once daily. Concurrent use results in elevated rosuvastatin serum concentrations; thereby increasing the risk for myopathy, including rhabdomyolysis. Closely monitor for statin-associated adverse reactions, such as myopathy and rhabdomyolysis. Rosuvastatin is a substrate of the drug transporters OATP1B1, OATP1B3, and BRCP; pibrentasvir is an inhibitor of these transporters. In drug interaction studies, coadministration of rosuvastatin with glecaprevir; pibrentasvir resulted in more than a 2-fold increase in the AUC of rosuvastatin.
Itraconazole: (Moderate) Itraconazole modestly increases the AUC of rosuvastatin by 28% and 39% in healthy volunteers receiving 80 mg and 10 mg rosuvastatin, respectively. A potential mechanism for this interaction is inhibition of the breast cancer resistance protein (BCRP) by itraconazole; rosuvastatin is a BCRP substrate.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with clarithromycin. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a substrate of the drug transporter OATP1B1/3 and clarithromycin is an OATP1B1/3 inhibitor.
Lanthanum Carbonate: (Major) To limit absorption problems, HMG-CoA reductase inhibitors ("statins") should not be taken within 2 hours of dosing with lanthanum carbonate. Oral drugs known to interact with cationic antacids, like statin cholesterol treatments, may also be bound by lanthanum carbonate. Separate the times of administration appropriately. Monitor the patient's lipid profile to ensure the appropriate response to statin therapy is obtained.
Ledipasvir; Sofosbuvir: (Major) Avoid coadministration of ledipasvir with rosuvastatin. Taking these drugs together may significantly increase rosuvastatin plasma concentrations, potentially resulting in myopathy and rhabdomyolysis. Rosuvastatin is a substrate of the breast cancer resistance protein (BCRP); ledipasvir is a BCRP inhibitor.
Leflunomide: (Major) Consider reducing the dose of HMG-CoA reductase inhibitors ("Statins" including atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin) during use of leflunomide and monitor patients closely for signs and symptoms of myopathy. For a patient taking leflunomide, the dose of rosuvastatin should not exceed 10 mg once daily. Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Teriflunomide is an inhibitor of the organic anion transporting polypeptide OATP1B1, and some statins are substrates for the OATP transporters. Teriflunomide may increase the exposure (AUC) of these statins. Increased concentrations of the statins increases the risk for myopathy and other statin-related side effects.
Leniolisib: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with leniolisib. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a substrate of BCRP and OATP1B1/3; leniolisib is an inhibitor of BCRP and OATP1B1/3.
Letermovir: (Moderate) Closely monitor for rosuvastatin-related adverse events (myopathy, rhabdomyolysis) and consider a rosuvastatin dose reduction if administered with letermovir. Do not exceed a rosuvastatin dose of 5 mg daily if the patient is also receiving cyclosporine. The magnitude of this interaction may be increased if letermovir is given with cyclosporine. Concurrent administration of letermovir, an organic anion-transporting polypeptide (OATP1B1/3) inhibitor, with rosuvastatin, an OATP1B1/3 substrate, may result in a clinically relevant increase in rosuvastatin plasma concentration.
Levonorgestrel; Ethinyl Estradiol: (Minor) When coadministered with oral contraceptives during drug interaction studies, rosuvastatin produced an approximately 1.3-fold increase in the AUC and maximal concentrations of ethinyl estradiol. The changes are not likely to be of clinical consequence for most patients; some patients may experience increases in common side effects of hormonal contraceptives, such as breast tenderness, nausea, headache, or fluid retention.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) When coadministered with oral contraceptives during drug interaction studies, rosuvastatin produced an approximately 1.3-fold increase in the AUC and maximal concentrations of ethinyl estradiol. The changes are not likely to be of clinical consequence for most patients; some patients may experience increases in common side effects of hormonal contraceptives, such as breast tenderness, nausea, headache, or fluid retention.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Minor) When coadministered with oral contraceptives during drug interaction studies, rosuvastatin produced an approximately 1.3-fold increase in the AUC and maximal concentrations of ethinyl estradiol. The changes are not likely to be of clinical consequence for most patients; some patients may experience increases in common side effects of hormonal contraceptives, such as breast tenderness, nausea, headache, or fluid retention.
Lopinavir; Ritonavir: (Major) Initiate rosuvastatin at a reduced dosage of 5 mg once daily if coadministered with lopinavir; do not exceed a rosuvastatin dosage of 10 mg once daily. When rosuvastatin was coadministered with lopinavir in healthy volunteers, the Cmax and AUC of rosuvastatin was increased 5-fold and 2-fold, respectively. Rosuvastatin is a substrate of the drug transporter organic anion transporting polypeptide (OATP1B1); lopinavir is OATP1B1 inhibitor. Closely monitor for statin-associated adverse reactions, such as myopathy and rhabdomyolysis.
Maralixibat: (Minor) Maralixibat may reduce the oral absorption of HMG-CoA reductase inhibitors, also known as statins, which may reduce their efficacy. This risk is greatest with maralixibat doses greater than 4.75 mg. Monitor statin therapy and adjust the dose as needed based on clinical response. Maralixibat is a OATP2B1 inhibitor and statins are OATP2B1 substrates.
Maribavir: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with maribavir. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP substrate and maribavir is a BCRP inhibitor.
Midostaurin: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with midostaurin. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP and OATP1B1/3 substrate and midostaurin is a BCRP and OATP1B1 inhibitor.
Niacin, Niacinamide: (Major) There is no clear indication for routine use of niacin in combination with rosuvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with rosuvastatin. If coadministered, consider lower starting and maintenance does of rosuvastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue rosuvastatin immediately if myopathy is diagnosed or suspected.
Niacin; Simvastatin: (Major) There is no clear indication for routine use of niacin in combination with rosuvastatin. The addition of niacin to a statin has not been shown to reduce cardiovascular morbidity or mortality. In addition, lipid-modifying doses (1 g/day or more) of niacin increase the risk of myopathy and rhabdomyolysis when combined with rosuvastatin. If coadministered, consider lower starting and maintenance does of rosuvastatin. Monitor patients closely for myopathy or rhabdomyolysis, particularly in the early months of treatment or after upward dose titration of either drug. Consider monitoring serum creatinine phosphokinase (CPK) and potassium periodically in such situations. Discontinue rosuvastatin immediately if myopathy is diagnosed or suspected.
Nirmatrelvir; Ritonavir: (Major) Consider temporary discontinuation of rosuvastatin during treatment with ritonavir-boosted nirmatrelvir; if this is not feasible, consider an alternative COVID-19 therapy. Rosuvastatin does not need to be held prior to or after completing ritonavir-boosted nirmatrelvir. Coadministration may increase rosuvastatin exposure resulting in increased toxicity. Rosuvastatin is a CYP3A substrate and nirmatrelvir is a CYP3A inhibitor.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) When coadministered with oral contraceptives during drug interaction studies, rosuvastatin produced an approximately 1.3-fold increase in the AUC and maximal concentrations of ethinyl estradiol. The changes are not likely to be of clinical consequence for most patients; some patients may experience increases in common side effects of hormonal contraceptives, such as breast tenderness, nausea, headache, or fluid retention.
Norethindrone; Ethinyl Estradiol: (Minor) When coadministered with oral contraceptives during drug interaction studies, rosuvastatin produced an approximately 1.3-fold increase in the AUC and maximal concentrations of ethinyl estradiol. The changes are not likely to be of clinical consequence for most patients; some patients may experience increases in common side effects of hormonal contraceptives, such as breast tenderness, nausea, headache, or fluid retention.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) When coadministered with oral contraceptives during drug interaction studies, rosuvastatin produced an approximately 1.3-fold increase in the AUC and maximal concentrations of ethinyl estradiol. The changes are not likely to be of clinical consequence for most patients; some patients may experience increases in common side effects of hormonal contraceptives, such as breast tenderness, nausea, headache, or fluid retention.
Norgestimate; Ethinyl Estradiol: (Minor) When coadministered with oral contraceptives during drug interaction studies, rosuvastatin produced an approximately 1.3-fold increase in the AUC and maximal concentrations of ethinyl estradiol. The changes are not likely to be of clinical consequence for most patients; some patients may experience increases in common side effects of hormonal contraceptives, such as breast tenderness, nausea, headache, or fluid retention.
Norgestrel: (Minor) When coadministered with oral contraceptives during drug interaction studies, rosuvastatin produced an approximately 1.1 to 1.3-fold increase in the AUC and maximal concentrations of norgestrel. The changes are not likely to be of clinical consequence for most patients; some patients may experience increases in common side effects of norgestrel, such as breast tenderness, nausea, headache, or fluid retention.
Omeprazole; Sodium Bicarbonate: (Major) Coadministration of rosuvastatin with antacids has reduced rosuvastatin plasma concentrations by 54%. When the antacid is given 2 hours after rosuvastatin, no significant change in rosuvastatin plasma concentrations is observed.
Oritavancin: (Moderate) Rosuvastatin is metabolized by CYP2C9; oritavancin is a weak CYP2C9 inhibitor. Coadministration may result in elevated rosuvastatin plasma concentrations. If these drugs are administered concurrently, monitor patients for signs of rosuvastatin toxicity, such as muscle aches, muscle pain or tenderness, general weakness or fatigue, side or back pain, or decreased urination.
Osimertinib: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including rhabdomyolysis and myopathy, if coadministration with osimertinib is necessary. Rosuvastatin is a BCRP substrate and osimertinib is a BCRP inhibitor. Concomitant use increased the AUC of rosuvastatin by 35% and the Cmax by 72%.
Oteseconazole: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with oteseconazole. Oteseconazole increased rosuvastatin exposure by 114%. Rosuvastatin is a BCRP substrate and oteseconazole is a BCRP inhibitor.
Pacritinib: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with pacritinib. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP substrate and pacritinib is a BCRP inhibitor.
Pirtobrutinib: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with pirtobrutinib. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP substrate and pirtobrutinib is a BCRP inhibitor. Concomitant use was observed to increase rosuvastatin overall exposure by 140%.
Pretomanid: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with pretomanid. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP substrate and pretomanid is a BCRP inhibitor.
Probenecid; Colchicine: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
Raltegravir: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Red Yeast Rice: (Contraindicated) Since compounds in red yeast rice claim to have HMG-CoA reductase inhibitor activity, red yeast rice should not be used in combination with HMG-CoA reductase inhibitors. The administration of more than one HMG-CoA reductase inhibitor at one time would be duplicative therapy and perhaps increase the risk of drug-related toxicity including myopathy and rhabdomyolysis.
Regorafenib: (Major) Do not exceed a rosuvastatin dose of 10 mg once daily when coadministered with regorafenib. Concurrent use results in elevated rosuvastatin serum concentrations; thereby increasing the risk for myopathy, including rhabdomyolysis. Rosuvastatin is a substrate of the drug transporter breast cancer resistance protein (BCRP) and regorafenib is a BCRP inhibitor. Coadministration with regorafenib increased the mean AUC and Cmax of rosuvastatin by 3.8-fold and 4.6-fold, respectively. Closely monitor for statin-associated adverse reactions, such as myopathy and rhabdomyolysis.
Rolapitant: (Moderate) Avoid the concurrent use of rosuvastatin and rolapitant if possible; if coadministration is necessary, use the lowest effective dose of rosuvastatin and monitor for rosuvastatin-related adverse effects. Rosuvastatin is a substrate of the Breast Cancer Resistance Protein (BCRP), where an increase in exposure may significantly increase adverse effects; rolapitant is a BCRP inhibitor. The Cmax and AUC of another BCRP substrate, sulfasalazine, were increased by 140% and 130%, respectively, on day 1 with rolapitant, and by 17% and 32%, respectively, on day 8 after rolapitant administration.
Safinamide: (Moderate) Safinamide at the 100 mg dose and its major metabolite may inhibit intestinal breast cancer resistance protein (BCRP), which could increase plasma concentrations of BCRP substrates such as rosuvastatin. Monitor patients for increased pharmacologic or adverse effects of BCRP substrates during concurrent use of safinamide, particularly the 100 mg dose.
Saquinavir: (Major) The concurrent use of saquinavir boosted with ritonavir and rosuvastatin should be avoided if possible due to the potential for myopathies, including rhabdomyolysis. Coadministration of saquinavir boosted with ritonavir and rosuvastatin results in an increased plasma concentration of rosuvastatin. The combination saquinavir/ritonavir is a potent inhibitor of CYP3A and may significantly increase the exposure of drugs primarily metabolized by CYP3A. If coadministered, use the lowest possible dose of rosuvastatin with careful clinical monitoring,
Segesterone Acetate; Ethinyl Estradiol: (Minor) When coadministered with oral contraceptives during drug interaction studies, rosuvastatin produced an approximately 1.3-fold increase in the AUC and maximal concentrations of ethinyl estradiol. The changes are not likely to be of clinical consequence for most patients; some patients may experience increases in common side effects of hormonal contraceptives, such as breast tenderness, nausea, headache, or fluid retention.
Sodium Bicarbonate: (Major) Coadministration of rosuvastatin with antacids has reduced rosuvastatin plasma concentrations by 54%. When the antacid is given 2 hours after rosuvastatin, no significant change in rosuvastatin plasma concentrations is observed.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with taurursodiol. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP substrate and taurursodiol is a BCRP inhibitor.
Sofosbuvir; Velpatasvir: (Major) Initiate rosuvastatin at a reduced dosage of 5 mg once daily if coadministered with velpatasvir; do not exceed a rosuvastatin dosage of 10 mg once daily. Concurrent use results in elevated rosuvastatin serum concentrations; thereby increasing the risk for myopathy, including rhabdomyolysis. Closely monitor for statin-associated adverse reactions, such as myopathy and rhabdomyolysis. Rosuvastatin is a substrate of the breast cancer resistance protein (BCRP) and OATP1B1 transporters, while velpatasvir inhibits both BCRP and OATP1B1.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid concurrent administration of voxilaprevir with rosuvastatin. Taking these drugs may significantly increase systemic exposure to rosuvastatin, which may increase the risk of myopathy and rhabdomyolysis. Rosuvastatin is a substrate of the Breast Cancer Resistance Protein (BCRP) and Organic Anion Transporting Polypeptides (OATP1B1/1B3) transporters, while voxilaprevir inhibits both BCRP and OATP1B1/1B3. (Major) Initiate rosuvastatin at a reduced dosage of 5 mg once daily if coadministered with velpatasvir; do not exceed a rosuvastatin dosage of 10 mg once daily. Concurrent use results in elevated rosuvastatin serum concentrations; thereby increasing the risk for myopathy, including rhabdomyolysis. Closely monitor for statin-associated adverse reactions, such as myopathy and rhabdomyolysis. Rosuvastatin is a substrate of the breast cancer resistance protein (BCRP) and OATP1B1 transporters, while velpatasvir inhibits both BCRP and OATP1B1.
Sotorasib: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with sotorasib. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP substrate and sotorasib is a BCRP inhibitor.
Sparsentan: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with sparsentan. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP substrate and sparsentan is a BCRP inhibitor.
Tacrolimus: (Moderate) Carefully weigh the benefits of combined use of tacrolimus and rosuvastatin against the potential risk of statin-induced myopathy/rhabdomyolysis. Guidelines recommend lower doses of statins in combination with tacrolimus. A maximum dose of rosuvastatin of 5 mg/day is recommended.
Tafamidis: (Major) Avoid concomitant use of rosuvastatin and tafamidis. Concomitant use may increase rosuvastatin exposure and the risk for rosuvastatin-related adverse reactions, such as myopathy and rhabdomyolysis. If concomitant use is necessary, initiate rosuvastatin at 5 mg once daily and do not exceed a rosuvastatin dose of 20 mg once daily; monitor for adverse effects. Rosuvastatin is a BCRP substrate and tafamidis is a BCRP inhibitor. Coadministration with tafamidis increased rosuvastatin exposure by almost 2-fold.
Tedizolid: (Moderate) If possible, stop use of rosuvastatin temporarily during treatment with oral tedizolid. If coadministration cannot be avoided, closely monitor for rosuvastatin-associated adverse events. In clinical trials involving healthy adults, multiple doses of oral tedizolid (200 mg PO once daily) increased the Cmax and AUC of rosuvastatin (10 mg single PO dose) by approximately 55% and 70%, respectively. Rosuvastatin is a substrate of the Breast Cancer Resistance Protein (BCRP); oral tedizolid inhibits BCRP in the intestine.
Teriflunomide: (Major) Consider reducing the dose of HMG-CoA reductase inhibitors ("Statins" including atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin) during use of teriflunomide and monitor patients closely for signs and symptoms of myopathy. For a patient taking teriflunomide, the dose of rosuvastatin should not exceed 10 mg once daily. Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Teriflunomide is an inhibitor of the organic anion transporting polypeptide OATP1B1, and some statins are substrates for the OATP transporters. Teriflunomide may increase the exposure (AUC) of these statins. Increased concentrations of the statins increases the risk for myopathy and other statin-related side effects.
Tipranavir: (Major) The risk of myopathy, including rhabdomyolysis, may be increased when tipranavir is given in combination with most HMG-CoA reductase inhibitors. If rosuvastatin is to be used concomitantly with tipranavir (in the FDA approved dosage regimen), use the lowest possible dose with careful monitoring, or consider an alternative HMG-CoA reductase inhibitor that is less significantly metabolized by CYP3A4 (i.e., fluvastatin, pravastatin).
Trofinetide: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with trofinetide. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a substrate of the drug transporter OATP1B1/3 and trofinetide is an OATP1B1/3 inhibitor.
Voclosporin: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with voclosporin. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a substrate of the drug transporter OATP1B1/3 and voclosporin is an OATP1B1/3 inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with clarithromycin. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a substrate of the drug transporter OATP1B1/3 and clarithromycin is an OATP1B1/3 inhibitor.
Warfarin: (Moderate) Addition of rosuvastatin to warfarin therapy has resulted in significant increases in the INR (> 4, baseline 2 to 3), without a change in warfarin plasma concentrations. INR should be monitored at baseline prior to rosuvastatin initiation, and frequently following initiation of rosuvastatin therapy and subsequent dosage changes. Adjust warfarin dosage based on INR and clinical response. Once a stable INR is documented, INR can be monitored at the intervals otherwise recommended based on the indication for anticoagulation and co-existing conditions. Rosuvastatin has not been associated with bleeding or with changes in INR in patients not taking oral anticoagulants.

Crestor/Rosuvastatin/Rosuvastatin Calcium Oral Tab: 5mg, 10mg, 20mg, 40mg
Rosuvastatin Oral Cap Coated Pellets: 5mg, 10mg, 20mg, 40mg

40 mg/day PO.

40 mg/day PO.

20 mg/day PO.

7 to 12 years: 20 mg/day PO.
1 to 6 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Rosuvastatin is a selective, competitive inhibitor of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase is the rate-limiting hepatic enzyme responsible for converting HMG-CoA to mevalonate, a precursor of sterols including cholesterol. Inhibition of HMG-CoA reductase lowers the amount of mevalonate and subsequently reduces cholesterol levels in hepatic cells. This, in turn, results in upregulation of LDL-receptors and increased hepatic uptake of LDL-cholesterol from the circulation. Due to its unique structural binding sites and relative hydrophilicity, rosuvastatin has a high affinity for HMG-CoA reductase and is selective for hepatic cells with minimal uptake by nonhepatic tissues. In a rat hepatocyte model, rosuvastatin was found to be 7-fold more potent than atorvastatin; in a model using human HMG-CoA reductase, rosuvastatin was 8-fold more potent than pravastatin.[27110] Rosuvastatin decreases total cholesterol, LDL cholesterol, triglycerides, and apolipoprotein B while increasing HDL. During a Phase II study, rosuvastatin doses of 1 to 80 mg lowered LDL cholesterol by 34 to 65%.[27113] Evening or morning administration does not affect rosuvastatin pharmacokinetics or antilipemic effects.[27113]
 
HMG-CoA reductase inhibitors have been reported to decrease endogenous CoQ10 serum concentrations; the clinical significance of these effects is unknown.

Rosuvastatin is administered orally. Unlike prodrugs, such as lovastatin or simvastatin, the majority of HMG-CoA reductase inhibitory activity (more than 90%) in plasma is associated with the parent compound. Evening or morning dosing does not affect pharmacokinetic parameters or cholesterol-lowering effects. The mean Vd of rosuvastatin at steady-state is approximately 134 L. Rosuvastatin is about 88% bound to plasma proteins, mostly albumin. Studies with human hepatic CYP450 microsomes and human hepatocytes have suggested little or no metabolism of rosuvastatin via the CYP3A4 isoenzyme; hepatic metabolism of the drug via CYP450 is limited. Rosuvastatin appears to be metabolized to a limited extent to an N-desmethyl metabolite (one-sixth to one-half less potent than rosuvastatin) and a 5S-lactone product. In human hepatocytes, the in vitro formation of the N-desmethyl metabolite is inhibited by sulphaphenazole, and to a lower extent by omeprazole, which suggests some metabolism by CYP2C9 and CYP2C19 isoenzymes.[27115] [63844] Rosuvastatin is eliminated primarily unchanged via the fecal route (90%, including unabsorbed drug), and approximately 10% of the dose is eliminated renally. Approximately 72% of an absorbed dose is excreted via the bile and about 28% is excreted renally. Rosuvastatin has a plasma half-life of about 19 hours.[27113] [27114] [63844]
 
Affected cytochrome P450 isoenzymes and drug transporters: OATP1B1, BCRP
Rosuvastatin is a substrate for certain transporter proteins including the hepatic uptake transporter organic anion-transporting polyprotein 1B1 (OATP1B1) and efflux transporter breast cancer resistance protein (BCRP). Concomitant administration of medications that are inhibitors of these transporter proteins may result in increased rosuvastatin plasma concentrations. CYP3A4 is not involved in rosuvastatin metabolism to a clinically relevant extent.[27113] [27114] [27988] Since hepatic metabolism is a minor pathway for elimination, clinically significant drug interactions with rosuvastatin via CYP450 are limited. In vivo studies have demonstrated that azole antifungals (e.g., itraconazole, ketoconazole, fluconazole) and erythromycin have minimal or no effects on the pharmacokinetics of rosuvastatin.[27113]

The bioavailability of rosuvastatin is approximately 20%, with peak rosuvastatin plasma concentrations reached within 3 to 5 hours after oral dosing. Food does not affect the absorption of rosuvastatin.

Rosuvastatin therapy should be discontinued once pregnancy is identified in most patients. Alternatively, consider the ongoing therapeutic needs of the individual patient. Based on the mechanism of action, rosuvastatin may cause fetal harm when administered to pregnant patients due to decreases in the synthesis of cholesterol and possibly other biologically active substances derived from cholesterol. Cholesterol and other products of cholesterol biosynthesis are important for fetal development including synthesis of steroids and cell membranes. Treatment of hyperlipidemia during pregnancy is not generally necessary as atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have minimal impact on the outcome of long-term therapy of primary hypercholesterolemia. The U.S. Food and Drug Administration (FDA) completed a review of data from case series, prospective and retrospective observational cohort studies over decades of statin use in pregnant patients and concluded that these studies have not identified a drug-associated risk of major congenital malformations associated with statin use during pregnancy. In a Medicaid cohort linkage study of 1,152 statin-exposed pregnant women, no significant teratogenic effects were observed following maternal statin use during the first trimester of pregnancy after adjusting for potential confounders (i.e., maternal age, diabetes mellitus, hypertension, obesity, alcohol use, and tobacco use); the relative risk (RR) of congenital malformations was 1.07 (95% confidence interval (CI), 0.85 to 1.37). In addition, after accounting for confounders, there were no statistically significant increases in organ-specific malformations. In the study, statin treatment was started prior to pregnancy and was discontinued within the first trimester after pregnancy was detected in a majority of patients. In another cohort study of 469 patients who were dispensed statins during pregnancy, it was determined that there was no increase in congenital anomalies after adjustment for maternal age and comorbidities; however, statin use was associated with an increased risk of preterm labor (RR, 1.99 [95% CI, 1.46 to 2.71]) and low birth weight (RR, 1.51 [95% CI, 1.05 to 2.16]). In a published, retrospective cohort study of 281 statin-exposed pregnant women, patients on statin therapy had a miscarriage rate of 25% compared to 21% for pregnant women not on statin therapy (n = 2,643); adjusted hazard ratio was 1.64 (95% CI, 1.1 to 2.46). The FDA also re-reviewed non-clinical, animal data statin development programs and concluded that statins have a limited potential to cause malformations or embryofetal lethality, and limited potential to affect nervous system development during embryofetal development during the pre- and post-natal period. Decreased fetal body weight, delayed ossification, and decreased pup survival were observed in pregnant rats administered rosuvastatin doses 10 to 12 times the maximum recommended human dose (MRHD). In pregnant rabbits administered rosuvastatin doses equivalent to the MRHD of 40 mg/day, a decrease in fetal viability and maternal mortality was observed. Rosuvastatin has been shown to cross the placenta in both rats and rabbits. Overall, available data have not identified a drug-associated risk of major congenital malformations, but published data are insufficient to determine if there is a drug-associated risk of miscarriage. Advise pregnant patients and patients of child-bearing potential of the potential risk of statin therapy to the fetus and the importance of informing their health care provider of known or suspected pregnancy.

Rosuvastatin is not recommended for use during breast-feeding. Limited data from case reports in published literature indicate that rosuvastatin is present in human milk. There is no information on the effects of rosuvastatin on the breastfed infant or the effects of the drug on milk production. Cholesterol and other products of the cholesterol biosynthesis pathway are essential components for infant growth and development, including synthesis of steroids and cell membranes. HMG-CoA reductase inhibitors decrease the synthesis of cholesterol and possibly other products of the cholesterol biosynthesis pathway. Based on the mechanism of action of rosuvastatin, there is potential for development of serious adverse reactions in a breastfed infant. Advise patients that breastfeeding is not recommended during treatment with rosuvastatin. If pharmacotherapy for hypercholesterolemia is necessary in the nursing mother, an alternative agent such as a nonabsorbable resin (cholestyramine, colesevelam, or colestipol) may be considered. These agents do not enter the bloodstream and will not be excreted during lactation. However, resins bind fat-soluble vitamins and prolonged use may result in deficiencies of these vitamins in the mother and her nursing infant.