Class: HMG-CoA Reductase Inhibitors
- Statins
VA Class: CV350
Chemical Name: 7-[4-(4-fluorophenyl)-6-(1-methylethyl)-2-[methylsulfonyl)amino]-5-pyrimi-dinyl]-3,5-dihydroxy-6-heptenoic acid calcium
Molecular Formula: 2C22H27FN3O6S • Ca
CAS Number: 147098-20-2
Brands: Crestor, Ezallor
Medically reviewed by Drugs.com. Last updated on June 16, 2020.
Introduction
Antilipemic agent; hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (i.e., statin).1
Uses for Rosuvastatin
Prevention of Cardiovascular Events
ACC/AHA cholesterol management guideline recommends statins as first-line therapy for prevention of atherosclerotic cardiovascular disease (ASCVD) in adults; extensive evidence demonstrates that statins can substantially reduce ASCVD risk when used for secondary prevention or primary prevention (in high-risk patients).336 337 338 350 Relative reduction in ASCVD risk is correlated with degree of LDL-cholesterol lowering; therefore, use maximum tolerated statin intensity to achieve optimum ASCVD benefits.350 According to ACC/AHA, rosuvastatin may be used for primary or secondary† prevention in adults when moderate- or high-intensity statin therapy is indicated.350 (See Prevention of Cardiovascular Events under Dosage and Administration.)
Adjunct to nondrug therapies (i.e., lifestyle modifications) in patients without clinical evidence of CHD who have multiple risk factors (e.g., age, smoking, hypertension, low HDL-cholesterol concentrations, family history of early CHD) to reduce the risk of MI, stroke, or angina and the risk of undergoing revascularization procedures.1 350 Consider benefits, adverse effects, drug interactions, and patient preferences before initiating statin therapy for primary prevention.350
Adjunct to dietary therapy to slow the progression of atherosclerosis as part of a treatment strategy to lower total and LDL-cholesterol concentrations to target levels.1
Current recommendations from ACC/AHA regarding prevention of ASCVD and lifestyle modifications to reduce cardiovascular risk are available at [Web] or [Web]).352
Dyslipidemias
Adjunct to nondrug therapies (e.g., dietary management) in adults to decrease elevated serum total cholesterol, LDL-cholesterol, apolipoprotein B (apo B), non-HDL-cholesterol, and triglyceride concentrations, and to increase HDL-cholesterol concentrations in the management of primary hyperlipidemia or mixed dyslipidemia.1 Also used in combination with fenofibrate to decrease triglyceride concentrations and increase HDL-cholesterol concentrations in patients with mixed dyslipidemia and CHD (or CHD risk equivalents) who are on optimal statin therapy; however, no incremental benefit on cardiovascular morbidity and mortality beyond that provided by statin monotherapy.18 353
Adjunct to nondrug therapies (e.g., dietary management) to decrease elevated serum total cholesterol, LDL-cholesterol, and apo B concentrations in the management of heterozygous familial hypercholesterolemia in children and adolescents 8–17 years of age who, despite an adequate trial of dietary management, have a serum LDL-cholesterol concentration >190 mg/dL or a serum LDL-cholesterol concentration >160 mg/dL and either a family history of premature cardiovascular disease or ≥2 other cardiovascular risk factors.1 375
Reduction of elevated serum total cholesterol, LDL-cholesterol, and apo B concentrations in adults with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering therapies (e.g., plasma LDL-apheresis) or when such therapies are not available.1
Adjunct to nondrug therapies (e.g., dietary management) to decrease elevated serum LDL-cholesterol, total cholesterol, non-HDL-cholesterol, and apo B concentrations in children and adolescents 7–17 years of age with homozygous familial hypercholesterolemia; used alone or in conjunction with other lipid-lowering therapies (e.g., LDL apheresis).1 376
Adjunct to nondrug therapies (e.g., dietary management) for the management of hypertriglyceridemia.1 However, fibric acid derivatives provide greater benefit in patients with elevated triglyceride concentrations compared with statins.356
Adjunct to nondrug therapies (e.g., dietary management) for the management of primary dysbetalipoproteinemia (Fredrickson type III).1 14
Produces greater reductions in LDL-cholesterol concentrations than atorvastatin, pravastatin, or simvastatin on a mg-for-mg basis.1
Rosuvastatin Dosage and Administration
General
-
Patients should be placed on a standard lipid-lowering diet before initiation of rosuvastatin therapy and should remain on this diet during treatment with the drug.1 7
Monitoring during Antilipemic Therapy
-
Manufacturer recommends obtaining lipoprotein concentrations within 2–4 weeks following initiation and/or titration of rosuvastatin and adjusting dosage accordingly.1 ACC/AHA cholesterol management guideline recommends obtaining lipoprotein concentrations within 4–12 weeks following initiation of statin therapy (to assess response and adherence) and monitoring every 3–12 months thereafter as clinically indicated.350
-
Periodically reinforce adherence to lifestyle modifications.350
Administration
Oral Administration
Administer orally at any time of day without regard to meals.1 Swallow tablets whole.1
Do not take 2 doses within 12 hours of each other.1
Dosage
Available as rosuvastatin calcium; dosage expressed in terms of rosuvastatin.1
When initiating statin therapy or switching from another statin, select appropriate initial dosage, then carefully adjust dosage according to individual requirements and response.1
Pediatric Patients
Dyslipidemias
Heterozygous Familial Hypercholesterolemia
OralChildren 8 to <10 years of age: Recommended dosage range is 5–10 mg once daily.1
Children and adolescents 10–17 years of age: Recommended dosage range is 5–20 mg once daily.1
Adjust dosage at intervals of ≥4 weeks.1
Homozygous Familial Hypercholesterolemia
OralChildren and adolescents 7–17 years of age: Recommended dosage is 20 mg once daily.1
Adults
Prevention of Cardiovascular Events
Select appropriate statin intensity to achieve optimal ASCVD risk reduction.350 Giving maximally tolerated statin intensity is preferred over giving lower statin dosages in combination with nonstatin drugs, a strategy not yet shown to reduce ASCVD risk.350
Although dosages of 5 and 40 mg once daily are FDA-labeled dosages, these dosages were not evaluated in randomized controlled studies reviewed by the ACC/AHA expert panel.350
Primary Prevention in Patients with LDL-cholesterol Concentrations ≥190 mg/dL (≥21 years of age)
OralACC/AHA cholesterol management guideline recommends initiating high-intensity statin therapy (e.g., rosuvastatin 20–40 mg once daily); if not well tolerated, use maximum tolerated statin intensity.350
Intensify statin therapy to achieve ≥50% reduction in LDL-cholesterol concentrations.350
In patients currently receiving maximum intensity of statin therapy, consider adding a nonstatin drug to further reduce LDL-cholesterol concentrations; however, consider potential benefits, adverse effects, drug interactions, and patient preferences.350
Primary Prevention in Patients with Type 1 or 2 Diabetes Mellitus† (40–75 years of age)
OralACC/AHA cholesterol management guideline recommends moderate-intensity statin therapy (e.g., rosuvastatin 5–10 mg once daily).350
If estimated 10-year ASCVD risk ≥7.5%, consider high-intensity statin therapy (e.g., rosuvastatin 20–40 mg once daily).350
In patients <40 or >75 years of age, consider potential benefits, adverse effects, drug interactions, and patient preferences when deciding to initiate, continue, or intensify statin therapy.350
Primary Prevention in Patients with LDL-cholesterol Concentrations 70–189 mg/dL and Elevated ASCVD Risk (40–75 years of age)
OralEstimated 10-year ASCVD risk ≥7.5%: ACC/AHA cholesterol management guideline recommends moderate- (e.g., rosuvastatin 5–10 mg once daily) to high-intensity statin therapy (e.g., rosuvastatin 20–40 mg once daily).350
Estimated 10-year ASCVD risk of 5 to <7.5%: ACC/AHA cholesterol management guideline recommends moderate-intensity statin therapy.350
Consider potential benefits, adverse effects, drug interactions, and patient preferences before initiating statin therapy.350
Secondary Prevention† in Patients with Clinical ASCVD (i.e., acute coronary syndromes; history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of atherosclerotic origin) (21–75 years of age)
OralACC/AHA cholesterol management guideline recommends high-intensity statin therapy (e.g., rosuvastatin 20–40 mg once daily) unless contraindicated.350
In patients at increased risk for developing statin-associated adverse effects or in whom high-intensity statin therapy is inappropriate or contraindicated, consider moderate-intensity statin therapy (e.g., rosuvastatin 5–10 mg once daily) if tolerated.350
Patients >75 years of age: Individualize therapy based on potential benefits, adverse effects, drug interactions, and patient preferences; may consider moderate-intensity statin therapy if tolerated.350
Dyslipidemias
General Dosage
OralUsual initial dosage is 10–20 mg once daily.1
Dosage range is 5–40 mg once daily.1 Reserve maximum 40-mg daily dosage for patients who have not achieved adequate response with the 20-mg daily dosage.1
Homozygous Familial Hypercholesterolemia
OralUsual initial dosage is 20 mg once daily.1
Dosage Modification
Oral
ACC/AHA cholesterol management guideline states may consider decreasing statin dosage when LDL-cholesterol concentrations are <40 mg/dL on 2 consecutive measurements; however, no data to suggest that LDL-cholesterol concentrations <40 mg/dL increase risk of adverse effects.350
Dosage modifications may be necessary when used concomitantly with certain drugs (see Specific Drugs under Interactions).1
Prescribing Limits
Pediatric Patients
Dyslipidemias
Oral
Maximum 20 mg once daily.1
Adults
Prevention of Cardiovascular Events or Management of Dyslipidemias
Oral
Maximum 40 mg once daily.1
Special Populations
Hepatic Impairment
No specific dosage recommendations at this time.1 (See Hepatic Impairment under Cautions.)
Renal Impairment
Patients with severe renal impairment (Clcr <30 mL/minute) not undergoing hemodialysis: Initially, 5 mg once daily; do not exceed 10 mg once daily.1
Asian Patients
Consider initiating therapy at 5 mg once daily.1 (See Special Populations under Pharmacokinetics.)
Consider increased systemic exposure when treating Asian patients not adequately controlled at dosages up to 20 mg daily.1
Geriatric Patients
No specific dosage recommendations at this time; however, use with caution.1 (See Geriatric Use under Cautions.)
Cautions for Rosuvastatin
Contraindications
-
Active liver disease, including unexplained, persistent elevations of hepatic aminotransferases.1
-
Pregnancy.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
-
Lactation.1
-
Known hypersensitivity to rosuvastatin or any ingredient in the formulation.1
Warnings/Precautions
Fetal/Neonatal Morbidity and Mortality
Suppression of cholesterol biosynthesis could cause fetal harm.1
Increased risk of major congenital malformations or miscarriage not identified with rosuvastatin; however, congenital anomalies reported rarely with other statins.1 In animal studies, no adverse developmental effects, but decreased pup survival observed.1 (See Pregnancy under Cautions.)
Musculoskeletal Effects
Myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria reported.1 Can occur at any dosage, but risk is increased with highest dosage (40 mg daily).1
Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, reported rarely in patients receiving statins.1 Characterized by proximal muscle weakness and elevated CK concentrations that persist despite discontinuance of statin therapy, necrotizing myopathy without substantial inflammation, and improvement following therapy with immunosuppressive agents.1
Certain drug interactions also may increase risk of myopathy and/or rhabdomyolysis.1 (See Interactions.)
Use with caution in patients with predisposing factors for myopathy (e.g., age ≥65 years, renal impairment, inadequately treated hypothyroidism).1 11
ACC/AHA cholesterol management guideline does not recommend routine monitoring of CK concentrations in adults; however, may obtain CK concentrations before initiating therapy in adults at increased risk of developing adverse musculoskeletal effects (e.g., patients with personal or family history of statin intolerance or muscle disease, patients receiving concomitant therapy with myotoxic drugs).350 During statin therapy, may measure CK concentrations in adults with muscle symptoms (e.g., pain, tenderness, stiffness, cramping, weakness, generalized fatigue).350
National Heart, Lung, and Blood (NHLBI) expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents recommends obtaining CK concentrations in pediatric patients before initiating statin therapy and routinely monitoring for muscle toxicity during therapy.357
Discontinue therapy if serum CK concentrations increase markedly or if myopathy is diagnosed or suspected.1
Temporarily withhold or discontinue therapy in any patient experiencing an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., sepsis; hypotension; dehydration; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; uncontrolled seizures).1 (See Advice to Patients.)
Hepatic Effects
Increases in serum aminotransferase (AST, ALT) concentrations reported.1 Usually transient and resolve or improve with continued therapy or after temporary interruption of therapy.1
Jaundice reported in ≥2 patients in clinical studies but resolved following discontinuance of therapy; causal relationship to rosuvastatin not established.1
Liver failure or irreversible liver disease not reported in clinical studies; however, fatal and nonfatal hepatic failure reported rarely.1
Perform liver function tests before initiation of therapy and as clinically indicated (e.g., presence of manifestations suggestive of liver damage201 ).1 Although manufacturer previously recommended more frequent monitoring,13 FDA concluded that serious statin-related liver injury is rare and unpredictable, and that routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury.200 ACC/AHA cholesterol management guideline recommends obtaining liver function tests in adults with symptoms of hepatotoxicity (e.g., unusual fatigue or weakness, loss of appetite, abdominal pain, dark colored urine, yellowing of skin or sclera).350 However, NHLBI expert panel on cardiovascular health and risk reduction in children and adolescents strongly recommends routine monitoring of hepatic function in children and adolescents receiving statins.357
If serious liver injury with clinical manifestations and/or hyperbilirubinemia or jaundice occurs, promptly interrupt rosuvastatin therapy.1 If an alternate etiology is not found, do not restart rosuvastatin.1
Also see Hepatic Impairment under Cautions.
Interactions with Coumarin-derivative Anticoagulants
Because of possible potentiation of anticoagulant effects, caution when used concomitantly with coumarin-derivative anticoagulants.1 (See Specific Drugs under Interactions.)
Proteinuria and Hematuria
Transient dipstick-positive proteinuria and microscopic hematuria (not associated with worsening renal function) reported; occurred more frequently with rosuvastatin 40 mg compared with lower doses of rosuvastatin or comparator statins.1 Clinical importance not known; however, consider reducing dosage in patients who have unexplained persistent proteinuria and/or hematuria during routine urinalysis testing.1
Hyperglycemic Effects
Increases in HbA1c and fasting serum glucose concentrations reported.1 200 Possible increased risk of developing diabetes.1 200 May need to monitor glucose concentrations following initiation of statin therapy.201
FDA states that cardiovascular benefits of statins outweigh these small increased risks.200
ACC/AHA cholesterol management guideline recommends evaluating patients for new-onset diabetes mellitus according to current diabetes screening guidelines.350
If diabetes mellitus develops during statin therapy, encourage patients to adhere to a heart-healthy diet, engage in physical activity, achieve and maintain a healthy body weight, cease tobacco use, and continue statin therapy to reduce the risk of ASCVD.350
Endogenous Steroid Production
No effects on basal plasma cortisol concentration or adrenal reserve observed with rosuvastatin.1
Caution advised if used concomitantly with drugs that may decrease concentrations or activity of endogenous steroid hormones (e.g. ketoconazole, spironolactone, cimetidine).1
Hypersensitivity Reactions
Hypersensitivity reactions, including rash, pruritus, urticaria, and angioedema, reported.1
Cognitive Impairment
Cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) reported rarely.1
Generally nonserious and reversible, with variable times to symptom onset (1 day to years) and resolution (median of 3 weeks following discontinuance of therapy).1 200 Not associated with fixed or progressive dementia (e.g., Alzheimer’s disease) or clinically important cognitive decline.200 Not associated with any specific statin, patient's age, statin dosage, or concomitant drug therapy.200
FDA states that cardiovascular benefits of statins outweigh the small increased risk of cognitive impairment.200
If manifestations consistent with cognitive impairment occur, National Lipid Association (NLA) statin safety assessment task force recommends evaluating and managing patients appropriately.202
If patients present with confusion or memory impairment, ACC/AHA cholesterol management guideline recommends evaluating patient for statin as well as nonstatin causes (e.g., other drugs, systemic or neuropsychiatric causes).350
Role as Adjunct Therapy
Prior to institution of antilipemic therapy, vigorously attempt to control serum cholesterol by appropriate dietary regimens, weight reduction, exercise, and treatment of any underlying disorder that might be the cause of lipid abnormality.1
Specific Populations
Pregnancy
Safety in pregnant women not established; no known benefits with use during pregnancy.1 (See Contraindications and also see Fetal/Neonatal Morbidity and Mortality under Cautions.)
Discontinue immediately if pregnancy is known or suspected.1 Women of childbearing potential should use effective contraception during therapy.1 (See Advice to Patients.)
Lactation
Distributed into human milk; effects on breast-fed infants or milk production not known.1 Use is contraindicated in nursing women; women who require rosuvastatin therapy should not breast-feed their infants.1
Pediatric Use
Safety and efficacy not established in children <8 years of age.1
Safety and efficacy in pediatric patients 8–17 years of age with heterozygous familial hypercholesterolemia generally similar to those observed in the adult population.1 Pharmacokinetic studies indicated rosuvastatin exposure similar to or less than that observed in adults.1 377
Safety profile in children and adolescents 7–15 years of age with homozygous familial hypercholesterolemia similar to that observed in adults.1
No detectable adverse effects on growth, weight, body mass index (BMI), or sexual maturation in children and adolescents.1 375
Advise adolescent girls to use effective and appropriate contraceptive methods during therapy to reduce the likelihood of unintended pregnancy.1
Geriatric Use
No substantial differences in safety and efficacy relative to younger adults; however, increased sensitivity cannot be ruled out.1
Use with caution, since age ≥65 is a predisposing risk factor for myopathy.1 In patients >75 years of age, consider benefits, adverse effects, drug interactions, and patient preferences before initiating statin therapy.350
Hepatic Impairment
Use with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease (e.g., chronic alcoholic liver disease).1 (See Contraindications under Cautions.)
Contraindicated in patients with active liver disease, including unexplained, persistent elevations in hepatic aminotransferase concentrations.1
Renal Impairment
Dosage adjustments necessary in patients with severe renal impairment.1 (See Renal Impairment under Dosage and Administration.)
Common Adverse Effects
Headache, nausea, myalgia, asthenia, constipation, abdominal pain.1
Interactions for Rosuvastatin
Minimally (approximately 10%) metabolized by CYP2C9.1 Clearance not dependent on metabolism by CYP3A4 to a clinically important extent.1
Drugs Affecting Transport Systems
Substrate for organic anion transport protein (OATP) 1B1 and breast cancer resistance protein (BCRP).1 Concomitant use with drugs that inhibit these transport proteins potentially may increase plasma concentrations of rosuvastatin and increase risk of myopathy.1 Consult relevant prescribing information of such drugs when considering concomitant use.1
Specific Drugs
Drug |
Interaction |
Comments |
---|---|---|
Antacids (aluminum hydroxide- and magnesium hydroxide-containing) |
Substantially decreased rosuvastatin peak plasma concentration and AUC following simultaneous administration; less substantial decreases when antacid administered 2 hours after rosuvastatin1 |
Administer antacid ≥2 hours after rosuvastatin1 |
Antifungals, azoles |
Fluconazole or itraconazole: Increased rosuvastatin concentrations1 Ketoconazole: Rosuvastatin peak plasma concentration and AUC unaffected1 |
|
Colchicine |
Myopathy, including rhabdomyolysis, reported1 |
Use concomitantly with caution1 |
Cyclosporine |
Increased rosuvastatin peak plasma concentration and AUC1 339 Increased risk of myopathy1 |
If used concomitantly, do not exceed rosuvastatin dosage of 5 mg daily1 |
Digoxin |
Slight increases in digoxin peak plasma concentration and AUC1 |
|
Dronedarone |
Increased rosuvastatin AUC1 |
|
Eltrombopag |
Increased rosuvastatin peak plasma concentration and AUC1 |
|
Erythromycin |
Decreased rosuvastatin concentrations1 |
|
Ezetimibe |
Increased rosuvastatin peak plasma concentration and AUC1 |
|
Fibric acid derivatives (fenofibrate, gemfibrozil) |
Increased risk of myopathy and/or rhabdomyolysis1 Fenofibrate: Modest increase in rosuvastatin peak plasma concentration, rosuvastatin AUC unaffected; not considered clinically important1 Gemfibrozil: Increased rosuvastatin peak plasma concentration and AUC1 |
Fenofibrate: Use concomitantly with caution1 Gemfibrozil: Avoid concomitant use; if concomitant use cannot be avoided, initiate rosuvastatin at 5 mg once daily and do not exceed 10 mg daily1 |
HCV protease inhibitors |
Simeprevir: Increased risk of myopathy; increased rosuvastatin peak plasma concentration and AUC1 |
Use concomitantly with caution1 Simeprevir: Initiate rosuvastatin at 5 mg once daily and do not exceed 10 mg once daily1 |
HIV protease inhibitors |
Increased risk of myopathy1 Ritonavir-boosted atazanavir or lopinavir/ritonavir: Increased rosuvastatin peak plasma concentration and AUC1 Ritonavir-boosted darunavir, ritonavir-boosted fosamprenavir, or ritonavir-boosted tipranavir: Minimal to no change in exposure to rosuvastatin1 |
Use concomitantly with caution1 Ritonavir-boosted atazanavir or lopinavir/ritonavir: Initiate rosuvastatin at 5 mg once daily and do not exceed 10 mg once daily1 |
Lomitapide |
Slight increases in peak plasma concentration and AUC of rosuvastatin374 |
Dosage adjustment of rosuvastatin not required374 |
Niacin (antilipemic dosages [≥1 g daily]) |
Increased risk of severe adverse effects (disturbances in glycemic control requiring hospitalization, development of diabetes mellitus, adverse GI effects, myopathy, gout, rash, skin ulceration, infection, bleeding) with concomitant use of niacin (1.5–2 g daily) and simvastatin (40–80 mg daily, with or without ezetimibe)369 371 |
Use concomitantly with caution1 |
Omega-3-acid ethyl esters |
No effect on rate or extent of exposure to rosuvastatin at steady state373 |
|
Oral contraceptives |
Increased concentrations of ethinyl estradiol and norgestrel1 |
|
Rifampin |
Rosuvastatin AUC unaffected1 |
|
Warfarin |
Potentiation of anticoagulant effects (e.g., increased INR)1 |
Use concomitantly with caution; ensure INR is stable before initiating rosuvastatin; monitor INR frequently enough during early therapy (or following rosuvastatin dosage adjustment) to ensure that no substantial alteration in INR occurs1 339 |
Rosuvastatin Pharmacokinetics
Absorption
Bioavailability
Absolute bioavailability is approximately 20%.1
Peak plasma concentrations attained within 3–5 hours.1
AUC does not differ following evening or morning administration.1
Onset
Maximal response occurs within 4 weeks.13
Duration
Response maintained during continued therapy.1
Food
Food does not affect AUC.1
Special Populations
Pediatric patients: Exposure in children and adolescents (8–17 years of age) is similar to or less than that observed in adults.1 377
Geriatric patients: Plasma concentrations are similar between geriatric (≥65 years of age) and younger patients.1
Race: Clinically important differences in pharmacokinetics among white, Hispanic, African American, or Afro-Caribbean groups not demonstrated.1 Compared with Caucasian patients residing in the US, median rosuvastatin exposure (peak plasma concentration and AUC) is approximately twofold higher in Asian patients.1 (See Asian Patients under Dosage and Administration.)
Mild to moderate renal impairment (Clcr ≥30 mL/minute): Plasma concentrations not altered.1
Severe renal impairment (Clcr <30 mL/minute not requiring hemodialysis): Plasma concentrations increased about threefold.1
Chronic hemodialysis: Steady-state plasma concentrations approximately 50% higher than in healthy individuals with normal renal function.1
Hepatic impairment (Child-Pugh class A or B or chronic alcoholic liver disease): Increased plasma concentrations.1
Genetic polymorphism of the OATP1B1 gene may affect rosuvastatin exposure.1 Higher plasma concentrations reported in a limited number of patients with 2 reduced-function variant OATP1B1 alleles.1 Frequency of this genotype is <5% in most populations; effect on efficacy and safety not established.1
Distribution
Extent
Crosses the placenta.1 Distributed into milk in rats; not known whether distributed into human milk.1
Plasma Protein Binding
88% (mainly albumin).1
Elimination
Metabolism
Not extensively metabolized; only 10% of dose is recovered as metabolite.1
Metabolized by CYP2C9 to active metabolite.1
Elimination Route
Excreted principally in feces (90%) as unchanged drug and metabolites.1
Half-life
Approximately 19 hours.1
Stability
Storage
Oral
Tablets
20–25°C.1 Protect from moisture.1
Actions
-
Selectively and competitively inhibits HMG-CoA reductase, causing subsequent reduction in hepatic cholesterol synthesis.1 2 Reduces serum concentrations of total cholesterol, LDL-cholesterol, VLDL-cholesterol, non-HDL-cholesterol, apo B, and triglycerides; increases HDL-cholesterol concentrations.1
-
Statins may slow progression of and/or induce regression of atherosclerosis in coronary and/or carotid arteries,113 114 115 116 117 118 119 120 121 122 123 modulate BP in hypercholesterolemic patients with hypertension,124 125 and possess anti-inflammatory activity.126 127
Advice to Patients
-
Importance of advising patients to read the manufacturer's patient information.1
-
Importance of adhering to nondrug therapies and measures, including adherence to a heart-healthy diet, regular exercise, avoidance of tobacco products, and maintenance of a healthy weight.1 350
-
Importance of informing patients that 2 doses of rosuvastatin should not be taken within 12 hours of each other.1
-
Risk of myopathy and/or rhabdomyolysis; risk is increased with higher dosages (i.e., 40 mg daily) or when used concomitantly with certain drugs.1 Importance of promptly reporting any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever, or if manifestations persist after discontinuance of therapy.1
-
Risk of adverse hepatic effects.1 Importance of promptly reporting any symptoms suggestive of liver injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice).1
-
Risk of nonserious, reversible cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion).1 200
-
Risk of increased glucose concentrations and development of type 2 diabetes;1 200 may need to monitor glucose concentrations following initiation of statin therapy.201
-
Importance of advising women and adolescent girls to avoid pregnancy (i.e., using effective and appropriate contraceptive methods) during therapy; if the patient becomes pregnant, importance of discontinuing rosuvastatin and contacting a clinician.1
-
Importance of avoiding breast-feeding during therapy.1
-
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1
-
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Capsules |
5 mg (of rosuvastatin) |
Ezallor |
Sun |
10 mg (of rosuvastatin) |
Ezallor |
Sun |
||
20 mg (of rosuvastatin) |
Ezallor |
Sun |
||
40 mg (of rosuvastatin) |
Ezallor |
Sun |
||
Tablets |
5 mg (of rosuvastatin)* |
Crestor |
AstraZeneca |
|
Rosuvastatin Tablets |
||||
10 mg (of rosuvastatin)* |
Crestor |
AstraZeneca |
||
Rosuvastatin Tablets |
||||
20 mg (of rosuvastatin)* |
Crestor |
AstraZeneca |
||
Rosuvastatin Tablets |
||||
40 mg (of rosuvastatin)* |
Crestor |
AstraZeneca |
||
Rosuvastatin Tablets |
AHFS DI Essentials™. © Copyright 2021, Selected Revisions June 26, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
1. AstraZeneca Pharmaceuticals. Crestor (rosuvastatin calcium) tablets prescribing information. Wilmington, DE. 2016 May.
2. Davidson M, Ma P, Stein EA. Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia. Am J Cardiol. 2003; 89:268-75.
3. Jones PH, Davidson MH, Stein EA et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR trial). Am J Cardiol. 2003; 92:152-60. http://www.ncbi.nlm.nih.gov/pubmed/12860216?dopt=AbstractPlus
4. Schneck DW, Knopp RH, Ballantyne CM. Comparative effects of rosuvastatin and atorvastatin across their dose ranges in patients with hypercholesterolemia and without active arterial disease. Am J Cardiol. 2003; 91:33-41. http://www.ncbi.nlm.nih.gov/pubmed/12505568?dopt=AbstractPlus
5. Capuzzi DM, Morgan JM, Weiss RJ. Beneficial effects of rosuvastatin alone and in combination with extended-release niacin in patients with combined hyperlipidemia and low high-density lipoprotein cholesterol levels. Am J Cardiol. 2003; 91:1304-10. http://www.ncbi.nlm.nih.gov/pubmed/12767421?dopt=AbstractPlus
6. Carswell CI, Plosker GL, Jarvis B. Rosuvastatin. Drugs. 2002; 62:2075-85.
7. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Adult Treatment Panel III Report. From AHA web site. http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3_rpt.htm
8. Pasternak RC, Smith SC Jr, Bairey-Merz CN et al. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. American College of Cardiology/American Heart Association/National Heart, Lung and Blood Institute. Circulation. 2002;106:1024-8.
9. Anon. Bayer voluntarily withdraws Baycol. FDA Talk Paper. Rockville, MD: Food and Drug Administration; 2001 Aug 8.
10. Pasternak RC, Smith SC Jr, Bairey-Merz CN et al. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. American College of Cardiology/American Heart Association/National Heart, Lung and Blood Institute. Circulation. 2002;106:1024-8.
11. AstraZeneca, Wilmington, DE: Personal communication.
12. Anon. Rosuvastatin (marketed as Crestor). FDA Alert for Healthcare Professionals. Rockville, MD. From FDA website; accessed 2005 Mar 2. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm200102.htm
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