Rosuvastatin is a selective, competitive, HMG-CoA reductase inhibitor. It potently reduces total and LDL cholesterol and lowers plasma triglycerides and apolipoprotein B (Apo-B). Rosuvastatin is indicated 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, and homozygous familial hypercholesterolemia in adults and pediatric patients 7 years and older. Because of its chemical structure binding sites and relatively greater hydrophilicity, rosuvastatin appears to better penetrate the hepatocyte and bind to HMG-CoA reductase with a higher affinity than other statins. In adult patients with primary hypercholesterolemia, dose-related LDL-reduction is 45% with 5 mg, 52% with 10 mg, 55% with 20 mg, and 63% with 40 mg; doses of 5 to 40 mg/day lower triglycerides by 21% to 43%. Similar to other statins, rosuvastatin produces modest increases in HDL (8% to 12%). In a 12-week comparative trial in adult patients, 5 and 10 mg doses reduced LDL by 42% and 49%, compared with 28% for pravastatin and 37% for simvastatin. In another comparative trial, 12 weeks of rosuvastatin 5 and 10 mg reduced LDL by 46% and 50%, compared with 39% for atorvastatin 10 mg. Results from the ECLIPSE study demonstrated that more patients treated with rosuvastatin 40 mg, compared to atorvastatin 80 mg, for 24 weeks achieved the NCEP ATP III LDL-C goal of less than 100 mg/dL (83.6% vs. 74.6%; p less than 0.001). In children with heterozygous familial hypercholesterolemia (n = 176), 12 weeks of rosuvastatin doses of 5 mg, 10 mg, and 20 mg daily reduced LDL by 38%, 45%, and 50%, respectively, and apolipoprotein B by 32%, 38%, and 41%, respectively. Rosuvastatin undergoes minimal hepatic metabolism and is expected to have less potential for hepatic CYP3A4 drug interactions than other statins. Also, relative to other statins, a significant percentage (28%) is excreted renally. Cholesterol-lowering efficacy has been demonstrated in hypercholesterolemic patients with diabetes, peripheral vascular disease, and coronary heart disease. Investigations of intensive lipid-lowering with rosuvastatin 40 mg/day have demonstrated reduced progression of coronary and carotid atherosclerosis and significantly lower LDL-C concentrations (ASTEROID and METEOR trials). The SATURN trial reported no statistically significant difference between atorvastatin 80 mg once daily and rosuvastatin 40 mg once daily on the progression of atherosclerosis in high-risk patients measured by change from baseline in percent atheroma volume in a 40 mm or greater segment of the targeted coronary artery as assessed by intravascular ultrasound. There was, however, a statistically significant difference in total atheroma volume within the targeted coronary artery in favor of rosuvastatin. The Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial, designed to assess rosuvastatin's affects on apparently healthy individuals with normal LDL but elevated C-reactive protein (CRP) concentrations, found that rosuvastatin significantly reduced the composite endpoint of nonfatal MI, nonfatal stroke, hospitalization for unstable angina, revascularization, or confirmed death from cardiovascular causes by 44% compared with individuals treated with placebo. Rosuvastatin also significantly reduced the risk of the secondary endpoint, the first occurrence of symptomatic venous thromboembolism, by 43% compared to placebo. A large retrospective study of adults demonstrated that continuation of statin therapy provides an ongoing reduction in all-cause mortality in patients with and without known coronary heart disease (CHD), with the greatest risk reduction among patients with a baseline LDL-C of 190 mg/dL or greater and patients initiated on higher efficacy statins (i.e., simvastatin, pravastatin, or lovastatin 80 mg/day; atorvastatin 20 mg/day or more; rosuvastatin 10 mg/day or more). Among patients with a proportion of days covered (PDC) of 90% or greater, determined by the number of statin prescriptions dispensed during the time between the first statin prescription and the end of follow up, there was a 45% and 51% lower mortality risk in the primary (patients without known CHD) and secondary (patients with known CHD) prevention groups, respectively, compared to patients with a PDC of 10% or greater. The mean length of follow up was 4 and 5 years in the primary and secondary prevention groups, respectively, with a maximum length of follow up of 9.5 years.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-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.
Oral Solid Formulations
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.
Thyroid function abnormalities have been reported during clinical trials of rosuvastatin.
Amyotrophic lateral sclerosis (ALS, Lou Gehrig's Disease) has been reported to the FDA in a higher than expected number of patients taking statins, such as rosuvastatin. ALS is a progressive motor neuron disorder with symptoms such as difficulty walking or standing, difficulty with fine motor skills, atrophy of tongue and hand muscles, dysphagia, dysarthria, and muscle paralysis. Due to the seriousness of ALS and the extensive use of statins, FDA further examined data from 41 long-term controlled clinical trials. The results of the review showed no increased incidence of ALS in patients treated with a statin compared with placebo. Specifically, 9 of approximately 64,000 patients treated with a statin (4.2 cases per 100,000 patient-years) and 10 of approximately 56,000 patients treated with placebo (5 case per 100,000 patient-years) were diagnosed with ALS. FDA is examining the feasibility of performing additional epidemiologic studies to further examine the incidence and clinical course of ALS in patients taking statins.
Rosuvastatin can cause myopathy (muscle pain, muscle tenderness, or muscle weakness (myasthenia) associated with elevated creatine kinase (CK) levels) and rhabdomyolysis. Acute renal failure secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including rosuvastatin. Discontinue rosuvastatin if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Muscle symptoms and CK elevations may resolve if rosuvastatin is discontinued. Temporarily discontinue rosuvastatin in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis (e.g., sepsis, shock, severe hypovolemia, major surgery, trauma, severe metabolic disorders, severe endocrine disease, severe electrolyte imbalance, or uncontrolled seizure disorder). Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain drugs (including other lipid lowering therapies), and higher rosuvastatin dosage. Individuals of Asian descent receiving rosuvastatin may be at higher risk of developing myopathy. Additionally, the risk of myopathy is greater with rosuvastatin 40 mg daily compared with lower rosuvastatin doses. During clinical trials, myalgia occurred in 1.9 to 12.7% of patients taking rosuvastatin. In the METEOR trial, increased serum creatine phosphokinase was observed in 2.6% of patients receiving rosuvastatin 40 mg compared to 0.7% of those receiving placebo. In a pediatric trial of boys and postmenarchal girls, elevations in serum creatine phosphokinase greater than 10 times the upper limit of normal were observed in 3% of children treated with rosuvastatin compared to no children treated with placebo. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. Dipstick-positive proteinuria and microscopic hematuria were reported in rosuvastatin clinical studies. Renal failure (unspecified) has been reported in less than 1% of patients treated with rosuvastatin. In a comparative trial, rosuvastatin 40 mg/day has been associated with a higher frequency (1.3%) of renal-related adverse events (hematuria, proteinuria) versus 40 mg/day of pravastatin (0%), atorvastatin (0.4%), or simvastatin (0.8%). In an observational cohort study evaluating the post-marketing safety of rosuvastatin (5, 10, 20, 30, and 40 mg daily doses) in 11, 680 patients, proteinuria was observed at a rate of less than 0.1% in all patients regardless of dose and 0.4% of patients in the 40 mg/day group. The long-term consequences of these renal-related events are not known. Reduce the rosuvastatin dosage in patients who have unexplained persistent proteinuria or hematuria during routine urinalysis testing.
Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, has occurred rarely (1 to 3 of every 100,000 patients) with HMG-CoA reductase inhibitors, such as rosuvastatin. Recurrence of IMNM has been reported following administration of the same or a different statin. IMNM is characterized by myalgia with symmetrical and proximal muscle weakness and elevated serum creatine phosphokinase, which persist despite discontinuation of HMG-CoA reductase inhibitor treatment. Some cases have occurred months to years after starting HMG-CoA reductase therapy and the myopathy progressed following therapy discontinuation. Other characteristics include positive anti-HMG-CoA reductase antibody, muscle biopsy showing necrotizing myopathy, and improvement with immunosuppressive agents. Dysphagia and respiratory failure have also been reported in patients with IMNM. Reported serum creatine phosphokinase levels have ranged from 576 to 35,000 International Units/L. Patients who develop IMNM may require additional neuromuscular and serologic testing. If IMNM develops, HMG-CoA reductase inhibitor therapy should be discontinued and treatment with immunosuppressants, such as high dose corticosteroids, intravenous immune globulin (IVIG), or other immunosuppressive agents, may be needed.
Adverse GI effects reported during clinical trials of rosuvastatin compared to placebo include nausea (0 to 6.3% vs. 2.3 to 3.1%), constipation (2.1 to 4.7% vs. 2.4 to 3%), and abdominal pain (2.4% vs. 1.8%).
Although rare, severe hepatotoxicity may occur during HMG-CoA reductase inhibitor therapy. Hepatitis, jaundice, pancreatitis, and fatal and non-fatal hepatic failure have been reported with rosuvastatin. Liver function tests (LFTs) should be performed prior to initiation of therapy with rosuvastatin and then repeated as clinically indicated. Elevated hepatic transaminases have been reported in patients receiving HMG-CoA reductase inhibitors; these abnormalities were not associated with cholestasis and did not appear to be associated with treatment duration. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with rosuvastatin, discontinue rosuvastatin. Rosuvastatin therapy has been associated with elevated hepatic enzymes greater than 3 times the upper limit of normal; in pooled analysis of placebo-controlled trials, the incidence was 1.1% in patients taking rosuvastatin compared to 0.5% of patients taking placebo. In the METEOR trial, 2.2% of patients receiving rosuvastatin 40 mg/day experienced an elevation in AST greater than 3 times the upper limit of normal. Elevations in transaminases, glutamyl transpeptidase, alkaline phosphatase, and bilirubin have been reported with rosuvastatin therapy. Additionally, in an observational cohort study evaluating the post-marketing safety of rosuvastatin, abnormalities of liver function tests occurred at a rate 2.5-fold higher for patients taking 40 mg daily compared with those taking 10 mg daily (2.71; 95% CI 1.53, 4.53).
CNS events reported during rosuvastatin therapy compared to placebo have included: asthenia (0.9% to 4.7% vs. 2.6%), headache (3.1 to 8.5% vs. 5 to 5.3%), and dizziness (4% vs. 2.8%). Rare cases of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) have been associated with the use of statins. A review of available data by the FDA did not find an association between the event and a specific statin, statin dose, concomitant medication, or age of the patient. In general, post-marketing reports described patients over the age of 50 years who experienced notable, but ill-defined memory loss or impairment that was reversible upon statin discontinuation. The cases did not appear to be associated with progressive or fixed dementia. The time to symptom onset (1 day to years) and resolution (median 3 weeks) is variable. Depression, memory impairment (memory loss), and sleep disorders, including insomnia and nightmares, have been reported during postmarketing use of rosuvastatin.
Arthralgia has been reported during therapy with rosuvastatin. In clinical trials, arthralgia was reported in 3.8% to 10.1% of rosuvastatin patients vs. 3.2% to 7.1% of placebo-treated patients.
Elevated glycated hemoglobin, hyperglycemia, and new cases of diabetes mellitus have been reported in patients taking rosuvastatin. In the JUPITER trial, elevated glycated hemoglobin occurred more frequently in patients taking rosuvastatin compared to those receiving placebo (5.9% vs. 5.8%, respectively, p=0.001) as did physician-reported diabetes (3% vs. 2.4%, respectively, p=0.01). Increased hemoglobin A1C and fasting serum glucose (hyperglycemia) have been reported during therapy with HMG-CoA reductase inhibitors. A meta-analysis of 13 statin trials with 91,140 participants showed a 9% increase in the likelihood of the development of diabetes (OR 1.09; 95% CI 1.02 to 1.17). The incidence of diabetes was higher in high-risk patients (i.e., age 70 to 82 years with or at high risk of cardiovascular disease, myocardial infarction within the last 6 months, or heart failure) compared to patients with low diabetes risk (i.e., low BMI). Additionally, an analysis of the data from the Women's Health Initiative (WHI) trial found that statin use in postmenopausal women is associated with an increased risk of new-onset diabetes mellitus (multivariate-adjusted HR 1.48; 95% CI 1.38 to 1.59). No difference in the risk for diabetes between statins was detected in either analysis. Because the use of statins has been associated with significant benefit for cardiovascular risk reduction and all-cause mortality at comparable rates in diabetic and non-diabetic patients , no changes to clinical practice guidelines have been recommended in either population. However, the increased risk of diabetes should be considered when initiating rosuvastatin therapy in patients at low risk for cardiovascular events and in patient groups where the cardiovascular benefit of statin therapy has not been established.
Hypersensitivity reactions, including rash, pruritus, urticaria, and angioedema have been reported with rosuvastatin therapy. Drug reaction with eosinophilia and systemic symptoms (DRESS) and lichen planus-like eruption (lichenoid drug eruption) have been reported in post-marketing surveillance with rosuvastatin.
An association between HMG-CoA reductase inhibitors (statins), including rosuvastatin, and peripheral neuropathy has been reported in the literature (case series, case-control studies, cohort studies). In a nested case-control study of a Danish population, the odds ratio for idiopathic peripheral neuropathy in 166 patients that ever or were currently taking a statin, was 3.7 (95% CI 1.8 to 7.6); similar results have been found in other population-based studies, although the number of patients studied was significantly smaller. Case reports and series indicate that the onset of neuropathy is typically greater than 1 year after drug initiation and is reversible with drug discontinuation. However, cases describing irreversible neuropathy are also reported. The adverse effect appears to be a class effect because in all cases when a patient is either rechallenged or treated with a different statin, the symptoms of neuropathy return. While the data appear to support an association between HMG-CoA reductase inhibitors and peripheral neuropathy, the incidence is rare and estimated to be approximately 1 per 14,000 person-years. Furthermore, a causal relationship cannot be definitively established based on the observational nature of the available data. The benefits of statin therapy far outweigh any risk of peripheral neuropathy; however, until more information is available, health care providers should be aware of this adverse effect. Peripheral neuropathy has been reported with post-marketing use of rosuvastatin.
HMG-CoA reductase inhibitors (statins), such as rosuvastatin, inhibit the synthesis of mevalonate and decrease Co-Enzyme Q-10 concentrations, which may lead to Co-Enzyme Q-10 deficiency. Supplementation with Co-Enzyme Q-10 may limit potential adverse reactions.
Interstitial lung disease has been reported with postmarketing use of rosuvastatin.
Rosuvastatin has been associated with rare reports of new-onset or exacerbation of myasthenia gravis (including ocular myasthenia) and reports of recurrence when the same or different statin was administered. In a review of adult patients enrolled at a neuromuscular disease clinic over a 4-year time period, 6 of 54 myasthenia gravis patients (11%) receiving statin therapy experienced worsening myasthenia gravis. In a disproportionality analysis of the World Health Organization's VigiBase pharmacovigilance database, 169 of 3,967 (4.2%) of adverse reactions with the term 'myasthenia gravis and related conditions' were related to statin therapy. The reporting odds ratio (ROR) of myasthenia gravis relative to all other adverse reactions was 2.66 [95% CI: 2.28, 3.1] for statin therapy. In addition, the ROR was greater than 1 and statistically significant for all individual statins except lovastatin. The onset of symptoms following initiation of statin therapy has ranged from 1 week to 4 months for exacerbation and 6 months to 6 years for induction of myasthenia gravis. Partial or complete recovery has been reported following discontinuation of statin therapy; however, some patients have required treatment with pyridostigmine or immunosuppressive agents. Though this appears to be a rare adverse reaction, clinicians should closely monitor patients with myasthenia gravis for disease exacerbation and encourage them to report any muscle-related symptoms.
Thrombocytopenia has been reported with postmarketing use of rosuvastatin.
Rosuvastatin is contraindicated in patients with a known hypersensitivity to rosuvastatin or any component of the products. Hypersensitivity reactions including rash, pruritus, urticaria, and angioedema have been reported with rosuvastatin.
Rosuvastatin is contraindicated in patients with acute hepatic failure or decompensated cirrhosis (hepatic decompensation). Increases in hepatic transaminases have been reported with rosuvastatin. In most cases, increases in hepatic transaminases occurred soon after initiation, were transient, were not associated with symptoms, and resolved or improved on continued therapy or after temporary discontinuation of therapy. Marked persistent increases in hepatic transaminases have also occurred with rosuvastatin. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including rosuvastatin. Patients with alcoholism or those who consume substantial quantities of alcohol and/or have a history of hepatic disease (i.e., hepatitis) may be at increased risk for hepatic injury. Assess liver enzymes prior to treatment initiation and repeat as clinically indicated if signs or symptoms of hepatic injury occur. Promptly discontinue rosuvastatin if hepatic injury with clinical symptoms, hyperbilirubinemia, or jaundice occurs.
Rosuvastatin can cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK) levels) and rhabdomyolysis. Acute renal failure secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including rosuvastatin. Discontinue rosuvastatin if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Muscle symptoms and CK elevations may resolve if rosuvastatin is discontinued. Temporarily discontinue rosuvastatin in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis (e.g., sepsis, shock, severe hypovolemia, major surgery, trauma, severe metabolic disorders, severe endocrine disease, severe electrolyte imbalance, or uncontrolled seizure disorder). Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain drugs (including other lipid lowering therapies), and higher rosuvastatin dosage (i.e., higher risk with 40 mg daily compared to lower doses). Additionally, individuals of Asian descent receiving rosuvastatin may be at higher risk of developing myopathy. Since rosuvastatin undergoes minimal hepatic metabolism, the potential for drug interactions is expected to be less than with 'statins' metabolized by CYP3A4 isoenzymes such as atorvastatin, cerivastatin, lovastatin, and simvastatin. Rosuvastatin should be used with caution in patients with pre-existing significant renal impairment who are generally at a higher risk of developing rhabdomyolysis during therapy with HMG-CoA reductase inhibitors. Patients receiving the highest rosuvastatin dosage of 40 mg/day were found to have an increased frequency of hematuria and proteinuria (1.3%) compared to those on lower dosages or other HMG CoA-reductase inhibitors. In patients who have unexplained persistent proteinuria or hematuria during routine urinalysis testing, reduce the rosuvastatin dosage. Relative to other statins, a significant percentage (28%) of rosuvastatin is excreted renally. Rosuvastatin serum concentrations are increased approximately 3-fold in patients with severe renal impairment (i.e., creatinine clearance or CrCl less than 30 mL/minute not on hemodialysis) and thus a lower rosuvastatin daily dosage is recommended for these patients. Hemodialysis does not appreciably remove the drug. Inform patients of the increased risk of myopathy and rhabdomyolysis when starting or increasing the dosage of rosuvastatin. Instruct patients to promptly report unexplained muscle pain, tenderness or weakness, especially if accompanied by malaise or fever.
Use caution in prescribing rosuvastatin to Asian patients. Pharmacokinetic studies show an approximate 2-fold elevation in median exposure in Japanese subjects residing in Japan and in Chinese subjects residing in Singapore compared with White patients residing in North America and Europe. The contribution of environmental and genetic factors to the difference observed has not been determined. However, these increases should be considered when making rosuvastatin dosing decisions for Asian patients of Japanese and Chinese ancestry and consider lower starting and maximum doses.
Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, has occurred rarely (1 to 3 of every 100,000 patients) with HMG-CoA reductase inhibitors, such as rosuvastatin. Recurrence of IMNM has been reported following administration of the same or a different statin. IMNM is characterized by myalgia with symmetrical and proximal muscle weakness and elevated serum creatine phosphokinase, which persist despite discontinuation of HMG-CoA reductase inhibitor treatment. Some cases have occurred months to years after starting HMG-CoA reductase therapy and the myopathy progressed following therapy discontinuation. Other characteristics include positive anti-HMG-CoA reductase antibody, muscle biopsy showing necrotizing myopathy, and improvement with immunosuppressive agents. Dysphagia and respiratory failure have also been reported in patients with IMNM. Reported serum creatine phosphokinase levels have ranged from 576 to 35,000 International Units/L. Patients who develop IMNM may require additional neuromuscular and serologic testing. If IMNM develops, HMG-CoA reductase inhibitor therapy should be discontinued and treatment with immunosuppressants, such as high dose corticosteroids, intravenous immune globulin (IVIG), or other immunosuppressive agents, may be needed.
If rosuvastatin is initiated in a patient with diabetes, increased monitoring of blood glucose control may be warranted. Increased hemoglobin A1C, hyperglycemia, and worsening glycemic control have been reported during therapy with HMG-CoA reductase inhibitors. Optimization of lifestyle measures, including regular exercise, maintaining a healthy body weight and making healthy food choices are recommended. Because the use of statins has been associated with significant benefit for cardiovascular risk reduction and all-cause mortality at comparable rates in diabetic and non-diabetic patients , no changes to clinical practice guidelines have been recommended in either population. However, the increased risk of diabetes mellitus should be considered when initiating rosuvastatin therapy in patients at low risk for cardiovascular events and in patient groups where the cardiovascular benefit of statin therapy has not been established. Although an analysis of participants from the JUPITER trial found an increased incidence of developing diabetes in patients allocated to rosuvastatin compared to placebo (270 reports of diabetes vs. 216 in the placebo group; HR 1.25, 95% CI 1.05 to 1.49, p = 0.01), the cardiovascular and mortality benefits of statin therapy exceeded the diabetes hazard even in patients at high risk for developing diabetes (i.e., patients with 1 or more major diabetes risk factor: metabolic syndrome, impaired fasting glucose, BMI 30 kg/m2 or more, or A1C greater than 6%). In patients at high risk for developing diabetes, treatment with rosuvastatin was associated with a 39% reduction in the primary endpoint (composite of non-fatal myocardial infarction, non-fatal stroke, unstable angina or revascularization, and cardiovascular death) (HR 0.61, 95% CI 0.47 to 0.79, p = 0.0001), nonsignificant reductions in venous thromboembolism (VTE) (HR 0.64, CI 0.39 to 1.06, p = 0.08) and total mortality (HR 0.83, CI 0.64 to 1.07, p = 0.15), and a 28% increase in diabetes (HR 1.28, CI 1.07 to 1.54, p = 0.01). In patients with no major diabetes risk factor, treatment with rosuvastatin was associated with a 52% reduction in the primary endpoint (HR 0.48, 95% CI 0.33 to 0.68, p = 0.0001), nonsignificant reductions in VTE (HR 0.47, CI 0.21 to 1.03, p = 0.05) and total mortality (HR 0.78, CI 0.59 to 1.03, p = 0.08), and no increase in diabetes (HR 0.99, CI 0.45 to 2.21, p = 0.99). For those at high risk for developing diabetes, 134 total cardiovascular events or deaths were avoided for every 54 new cases of diabetes diagnosed. In those without major risk factors, 86 total cardiovascular events or deaths were avoided with no excess new cases of diabetes diagnosed.
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.
Since advanced age (65 years or more) is a predisposing risk factor for myopathy and rhabdomyolysis, rosuvastatin should be prescribed with caution in the geriatric adult. Use cautious dose selection for older adults due to greater frequency of decreased hepatic, renal, or cardiac function. During clinical trials, no significant differences in rosuvastatin safety or efficacy between older and younger adult patients were identified.
Safety and efficacy of rosuvastatin have not been established in infants and children younger than 8 years of age with heterozygous familial hypercholesterolemia (HeFH), children younger than 7 years of age with homozygous hypercholesterolemia, or in pediatric patients with other types of hyperlipidemia. During clinical trials, there was no detectable effect of rosuvastatin on growth, body mass index, or sexual maturation in children and adolescents older than 10 years. Because cholesterol plays a crucial role in growth and development, the clinical implications of using pharmacologic therapy to alter the normal production of cholesterol in young children are not clear. Because of these potential safety concerns and lack of safety data, most experts generally recommend delaying cholesterol-lowering medications until the child is at least 8 to 10 years old. In some cases of severe familial hypercholesterolemia, however, HMG-CoA reductase inhibitors have been used in younger children with careful monitoring of growth and development.
Use rosuvastatin with caution in persons with myasthenia gravis. Closely monitor for myasthenia gravis exacerbation and encourage reporting of any muscle-related symptoms. Exacerbation of myasthenia gravis, including ocular myasthenia gravis, has been reported during treatment with statins, including rosuvastatin. Reports of recurrence have been noted when the same or a different statin was administered. The onset of symptom exacerbation following initiation of statin therapy has ranged from 1 week to 4 months. Partial or complete recovery has been reported following discontinuation of statin therapy; however, some patients have required treatment with pyridostigmine or immunosuppressive agents.
General Dosing Information
-Rosuvastatin 20 or 40 mg once daily is considered to be a high-intensity statin (expected to lower low-density lipoprotein cholesterol (LDL-C) by 50% or more), while rosuvastatin 5 or 10 mg once daily is considered to be a moderate-intensity statin (expected to lower LDL-C by 30% to 49%).
-Choice of high- or moderate-intensity statin therapy is dependent on patient age, baseline LDL-C, ASCVD risk factors, and concomitant diseases. High-intensity therapy provides the greatest LDL-C reductions and is associated with a significantly greater reduction in ASCVD events vs. moderate-intensity therapy.
-Monitor lipid concentrations at 4 to 12 weeks after initiation or dose adjustment, and then every 3 to 12 months as necessary.
For general dosing information in persons requiring high-intensity statin therapy:
Oral dosage:
Adults: 20 or 40 mg PO once daily. Myopathy risk is greater at 40 mg/day compared to lower doses.
For general dosing information in persons requiring moderate-intensity statin therapy:
Oral dosage:
Adults: 5 or 10 mg PO once daily.
For the treatment of primary hyperlipidemia, including hypercholesterolemia, hyperlipoproteinemia, and/or hypertriglyceridemia, as an adjunct to dietary control:
Oral dosage:
Adults: 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.
Asian Adults: 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.
For reduction of cardiovascular mortality and events, including myocardial infarction prophylaxis and stroke prophylaxis, in high-risk persons:
-for primary prevention to reduce the risk of stroke, myocardial infarction, and arterial revascularization procedures in persons without established coronary heart disease who are at increased risk of cardiovascular (CV) disease:
NOTE: Increased risk of CV disease is based on age, elevated C-reactive protein concentrations (greater than or equal to 2 mg/L), and the presence of at least 1 additional cardiovascular disease risk factor.
Oral dosage:
Adults: 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.
Asian Adults: 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.
-for secondary prevention in persons with clinical atherosclerotic cardiovascular disease (ASCVD)*:
NOTE: Clinical ASCVD consists of acute coronary syndromes (ACS), those with history of MI, stable or unstable angina or coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral artery disease (PAD), including aortic aneurysm.
Oral dosage:
Adults: 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.
Asian Adults: 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.
For the treatment of heterozygous familial hypercholesterolemia (HeFH) as an adjunct to dietary control:
Oral dosage:
Adults: 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.
Asian Adults: 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.
Children and Adolescents 10 to 17 years: 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.
Children 8 to 9 years: 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.
For the treatment of homozygous familial hypercholesterolemia (HoFH) as an adjunct to other LDL-C-lowering therapies, or alone if such therapies are unavailable:
Oral dosage:
Adults: 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.
Asian Adults: 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.
Children and Adolescents 7 to 17 years: 20 mg PO once daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
For slowing the progression of atherosclerosis (i.e., carotid, coronary):
Oral dosage:
Adults: 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.
Asian Adults: 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.
Maximum Dosage Limits:
-Adults
40 mg/day PO.
-Geriatric
40 mg/day PO.
-Adolescents
20 mg/day PO.
-Children
7 to 12 years: 20 mg/day PO.
1 to 6 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Contraindicated in patients with acute hepatic failure or decompensated cirrhosis.
Patients with Renal Impairment Dosing
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.
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.
*non-FDA-approved indication
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.
Aluminum Hydroxide: (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.
Aluminum Hydroxide; Magnesium Carbonate: (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.
Aluminum Hydroxide; Magnesium Hydroxide: (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.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (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.
Aluminum Hydroxide; Magnesium Trisilicate: (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.
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.
Asciminib: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with asciminib. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP and OATP1B1/3 substrate and asciminib is a BCRP and OATP1B1/3 inhibitor.
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: (Moderate) Concomitant use of colchicine and HMG-CoA reductase inhibitors (statins) may increase the risk for myopathy and rhabdomyolysis. If concomitant use is necessary, monitor for signs and symptoms of muscle pain, tenderness, or weakness especially following therapy initiation and upward dose titration. The use of low dose colchicine may further reduce the risk for myopathy.
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.
Danicopan: (Major) Limit the dose of rosuvastatin to 10 mg once daily and monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with danicopan. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP substrate and danicopan is a BCRP inhibitor. Coadministration with danicopan increased the overall exposure of rosuvastatin by approximately 2-fold.
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.
Magnesium Hydroxide: (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.
Magnesium Salts: (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.
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.
Momelotinib: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with momelotinib. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP substrate and momelotinib is a BCRP 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.
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: (Moderate) Concomitant use of colchicine and HMG-CoA reductase inhibitors (statins) may increase the risk for myopathy and rhabdomyolysis. If concomitant use is necessary, monitor for signs and symptoms of muscle pain, tenderness, or weakness especially following therapy initiation and upward dose titration. The use of low dose colchicine may further reduce the risk for myopathy.
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.
Resmetirom: (Major) Limit the dose of rosuvastatin to 20 mg once daily during concomitant use with resmetirom. Concomitant use was observed to increase rosuvastatin overall exposure by 1.8-fold which may increase the risk for rosuvastatin-related adverse effects.
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.
Sulfacetamide; Sulfur: (Moderate) HMG-CoA reductase inhibitors have been administered safely with niacin (nicotinic acid) in some patients; however the risk of potential myopathy should be considered. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in lipid-altering doses (i.e., >=1 g/day) and HMG-CoA reductase inhibitors (Statins) concurrently. The serious risk of myopathy or rhabdomyolysis should be carefully weighed against the potential risks. Patients undergoing combined therapy should be carefully monitored for myopathy or rhabdomyolysis, particularly in the early months of treatment or during periods of upward dose titration of either drug. Chinese patients receiving concomitant lipid-altering doses of niacin-containing products should not receive the 80 mg dose of simvastatin due to increased risk of myopathy.
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.
Vitamin B Complex Supplements: (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.
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.
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. 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%. Evening or morning administration does not affect rosuvastatin pharmacokinetics or antilipemic effects.
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. 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.
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. 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.
-Route-Specific Pharmacokinetics
Oral Route
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.
-Special Populations
Hepatic Impairment
In patients with chronic alcohol hepatic disease, the AUC of rosuvastatin was increased by 5% and 21% in patients with Child-Pugh class A and B disease, respectively.
Renal Impairment
Rosuvastatin serum concentrations were increased approximately 3-fold in patients with severe renal impairment not receiving hemodialysis (CrCl less than 30 mL/minute/1.73 m2) vs. patients with normal renal function. Mild to moderate renal impairment did not impact rosuvastatin plasma concentrations. Hemodialysis does not significantly enhance the clearance of rosuvastatin. Rosuvastatin serum concentrations are increased approximately 50% in hemodialysis vs. patients with normal renal function.
Pediatrics
In a population pharmacokinetic analysis of 2 pediatric trials involving patients 10 to 17 years of age and 8 to 17 years of age, respectively, rosuvastatin exposure appeared comparable to or lower than rosuvastatin exposure in adult patients.
Geriatric
There were no differences in plasma concentrations of rosuvastatin between younger adult and older adult subjects.
Gender Differences
There were no differences in plasma concentrations of rosuvastatin between male and female subjects.
Ethnic Differences
A population pharmacokinetic analysis revealed no clinically relevant differences in rosuvastatin pharmacokinetics among White, Hispanic, and Black or Afro-Caribbean subjects. However, pharmacokinetic studies have demonstrated an approximate 2-fold increase in median exposure (AUC and Cmax) in Asian subjects compared with White subjects.