Dosing & Uses
Dosage Forms & Strengths
tablet (Crestor)
- 5mg
- 10mg
- 20mg
- 40mg
capsule (Ezallor Sprinkle)
- 5mg
- 10mg
- 20mg
- 40mg
Hypercholesterolemia
Indicated as adjunctive therapy to diet in adults with hypertriglyceridemia, hyperlipidemia, mixed dyslipidemia, or primary dysbetalipoproteinemia
Tablets and capsules: 10-20 mg PO qDay; not to exceed 40 mg/day
After initiation or upon titration, analyze lipid levels within 2-4 weeks and adjust dosage accordingly
Homozygous Familial Hypercholesterolemia
Indicated as adjunctive therapy in adults with homozygous familial hypercholesterolemia
Tablets and capsules: 20 mg PO qDay; not to exceed 40 mg/day
After initiation or upon titration, analyze lipid levels within 2-4 weeks and adjust dosage accordingly
Slowing Progression of Atherosclerosis
Indicated as adjunctive therapy to diet to slow the progression of atherosclerosis in adult patients as part of a treatment strategy to lower total cholesterol and LDL cholesterol to target levels
Tablets and capsules: 10-20 mg PO qDay; not to exceed 40 mg/day
After initiation or upon titration, analyze lipid levels within 2-4 weeks and adjust dosage accordingly
Primary Prevention
Indicated to reduce the risk of stroke, myocardial infarction, and arterial revascularization procedures in individuals without clinically evident coronary heart disease with risk factors
Risk factors
- Age (>50 years in men; >60 years in women), AND
- Elevated high-sensitivity C-reactive protein level (>2 mg/L), AND
- Presence of ≥1 additional cardiovascular risk factor (eg, high blood pressure, low HDL cholesterol, smoking, family history of premature heart disease)
Tablets: 10-20 mg PO qDay; not to exceed 40 mg/day
Dosage range 5-40 mg/day
Dosage Modifications
Dosing in Asian patients
- Consider starting at 5 mg PO qDay, owing to increased rosuvastatin plasma concentrations
- May increase up to 20 mg/day if patients are not adequately controlled
Dosage adjustment for rosuvastatin with concomitant therapy
- Coadministered with cyclosporine: Do not exceed rosuvastatin 5 mg qDay
- Coadministered with gemfibrozil: Avoid use; if use cannot be avoided, initiate rosuvastatin at 5 mg qDay; not to exceed 10mg/day
- Coadministered with atazanavir and ritonavir, lopinavir and ritonavir, or simeprevir: Initiate rosuvastatin at 5 mg qDay; not to exceed 10mg/day
Renal impairment
- Mild or moderate (CrCl ≥30 mL/min/1.73m²): No dosage adjustment necessary
- Severe (CrCl <30 mL/min/1.73m²) and not on hemodialysis: Decrease starting dose to 5 mg PO qDay; not to exceed 10 mg/day
Hepatic impairment
- Active liver disease: Contraindicated
- Chronic alcoholic liver disease: Use with caution; known to increase rosuvastatin exposure
Dosing Considerations
Initiating therapy or switching from another HMG-CoA reductase inhibitor: Start on appropriate dose and then titrate based on patient’s response and individualized goal of therapy
Limitation of use: Not studied in Fredrickson type I and V dyslipidemias
Dosage Forms & Strengths
tablet (Crestor)
- 5mg
- 10mg
- 20mg
- 40mg
Familial Hypercholesterolemia
Heterozygous
- Adjunctive therapy to diet to reduce total cholesterol, LDL cholesterol, and ApoB levels in children and adolescents (8-17 years) with heterozygous familial hypercholesterolemia after an inadequate response to diet therapy
- Inadequate response defined as when the following findings are present: LDL cholesterol >190 mg/dL OR >160 mg/dL with a positive family history of premature cardiovascular disease (CVD) or ≥2 CVD risk factors
- <8 years: Safety and efficacy not established
- 8 to <10 years: 5-10 mg PO qDay
- 10-17 years: 5-20 mg PO qDay; may adjust dose at intervals of at least 4 wk; not to exceed 20 mg/day
Homozygous
- Adjunctive therapy to diet to reduce LDL cholesterol, total cholesterol, non-HDL cholesterol, and ApoB in children and adolescents (7-17 year) with homozygous familial hypercholesterolemia, either alone or with other lipid-lowering treatments (eg, LDL apheresis)
- <7 years: Safety and efficacy not established
- 7-17 years: 20 mg PO qDay
Dosage Modifications
Dosing in Asian patients
- Consider starting at 5 mg PO qDay, owing to increased rosuvastatin plasma concentrations
- May increase up to 20 mg/day if patients are not adequately controlled
Dosage adjustment for rosuvastatin with concomitant therapy
- Coadministered with cyclosporine: Do not exceed rosuvastatin 5 mg qDay
- Coadministered with gemfibrozil: Avoid use; if use cannot be avoided, initiate rosuvastatin at 5 mg qDay; not to exceed 10mg/day
- Coadministered with atazanavir and ritonavir, lopinavir and ritonavir, or simeprevir: Initiate rosuvastatin at 5 mg qDay; not to exceed 10mg/day
Renal impairment
- Mild or moderate (CrCl ≥30 mL/min/1.73m²): No dosage adjustment necessary
- Severe (CrCl <30 mL/min/1.73m²) and not on hemodialysis: Decrease starting dose to 5 mg PO qDay; not to exceed 10 mg/day
Hepatic impairment
- Active liver disease: Contraindicated
- Chronic alcoholic liver disease: Use with caution; known to increase rosuvastatin exposure
Dosing Considerations
Initiating therapy or switching from another HMG-CoA reductase inhibitor: Start on appropriate dose and then titrate based on patient’s response and individualized goal of therapy
Limitation of use: Not studied in Fredrickson type I and V dyslipidemias
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Myalgia (3-13%)
1-10%
Arthralgia (10%)
Pharyngitis (9%)
Headache (3.1-8.5%)
Myalgia (7.6%)
Nausea (2.4-6.3%)
Asthenia (0.9-6.3%)
Constipation (2.1-4.7%)
Dizziness (4%)
Arthralgia (3.8%)
CPK increased (3%)
Diabetes mellitus (2.8%)
Abdominal pain (2%)
ALT increased (2%)
Flulike illness (2%)
UTI (2%)
<1%
Jaundice
Myopathy
Rhabdomyolysis
Postmarketing Reports
Arthralgia
Peripheral neuropathy
Depression and sleep disorders (including insomnia and nightmares)
Fatal and nonfatal hepatic failure, hepatitis, jaundice
Thrombocytopenia
Gynecomastia
Interstitial lung disease
Immune-mediated necrotizing myopathy
Cognitive impairment (eg, memory loss, forgetfulness, amnesia, memory impairment, confusion)
Warnings
Contraindications
Hypersensitivity
Active liver disease (including unexplained persistent elevations of LFTs)
Pregnancy, lactation
Cautions
Nonserious and reversible cognitive adverse effects may occur
Increased blood glucose and glycosylated hemoglobin (HbA1c) levels reported with statin intake; in some instances, these increases may exceed the threshold for the diagnosis of diabetes mellitus
Use caution in patients who consume large amounts of ethanol or have a history of liver disease
Interrupt therapy if serious hepatotoxicity with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment
Increases in AST or ALT reported with HMG-CoA reductase inhibitors; monitor liver enzymes before initiating and if signs or symptoms of liver injury occur
Cases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria reported with HMG-CoA reductase inhibitors; may occur at any dose level, but are increased at the highest dose (40 mg); caution in patients with predisposing factors for myopathy (eg, age ≥65 years, inadequately treated hypothyroidism, renal impairment)
Discontinue treatment if markedly elevated creatine kinase levels occur or myopathy is diagnosed or suspected; temporarily withhold in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (eg, sepsis; hypotension; dehydration; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; uncontrolled seizures)
Pharmacokinetic studies demonstrated an ~2-fold elevation in median exposure (AUC and peak plasma concentrations) in Asian subjects when compared with a white control group
Rare reports of immune-mediated necrotizing myopathy, characterized by increased serum creatine kinase that persists despite discontinuing statin
Hematuria and proteinuria reported without decrease in renal function; consider dosage reduction if unexplained hematuria and proteinuria persists
Rule out secondary causes of hyperlipidemia prior to initiating therapy
Drug interactions overview
- Exercise caution when anticoagulants coadministered with rosuvastatin because of its potentiation of effect of coumarin-type anticoagulants in prolonging the prothrombin time/INR; monitor INR at baseline and frequently during concomitant therapy
- Cyclosporine and gemfibrozil increased rosuvastatin exposure and may result in increased risk of myopathy
- Coadministration of rosuvastatin with certain protease inhibitors has differing effects on rosuvastatin exposure and may increase risk of myopathy
- Risk of skeletal muscle effects may be enhanced when used in combination with lipid-modifying doses (≥1 g/day) of niacin; use with caution when administered with rosuvastatin
- Because the risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with concomitant use of fenofibrates, use with caution
- Cases of myopathy, including rhabdomyolysis, reported with HMG-CoA reductase inhibitors when coadministered with colchicine
- Also see Dosage Modifications
Pregnancy & Lactation
Pregnancy
Contraindicated
Because HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly synthesis of other biologically active substances derived from cholesterol (eg, cell membranes), rosuvastatin may cause fetal harm when administered to pregnant women
Lactation
Contraindicated
Limited data indicate that rosuvastatin is present in human milk; because statins have the potential for serious adverse reactions in nursing infants, women who require rosuvastatin treatment should not breastfeed their infants
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
HMG-CoA reductase inhibitor; inhibits the rate-limiting step in cholesterol biosynthesis by competitively inhibiting HMG-CoA reductase
Absorption
Bioavailability: 20%
Peak plasma time: 3-5 hr
Distribution
Vd: 134 L
Protein bound: 88%
Metabolism
Metabolism: ~10% by hepatic CYP2C9
Metabolites: N-desmethyl, lactone
Elimination
Half-Life, Elimination: 19 hr
Excretion: Feces (90%)
Pharmacogenomics
Hepatic influx and efflux transporters (single-nucleotide polymorphisms [SNPs] within the solute carrier organic anion transporter 1B1 (SLCO1B1) gene, encoding the organic anion transporter polypeptide 1B1 (OATP1B1) influx transporter)
SLCO1B1 (OATP1B1) CC genotype significantly increases AUCs of parent drug and metabolites compared with the CT or TT genotypes
This polymorphism is proposed to reduced transport into the liver, the main site of statin metabolism and elimination, resulting in elevated plasma concentrations
SLCO1B1 polymorphism is thought to have a lesser effect on the more hydrophilic statins (eg, rosuvastatin, fluvastatin) compared with those that are more lipophilic (eg, atorvastatin, pravastatin, simvastatin)
Other genetic polymorphisms of elimination (eg, CYP450, P-glycoprotein) for each individual drug must also be considered, to explain variability for statin clearance among patients that exhibit SCLO1B1 polymorphism
SLCO1B1 CC genotype is most common in Caucasians and Asians (15%); decrease dose by 50% in people of Asian descent
Risk of myopathy is 2.6- to 4.3-fold higher if the C allele is present and 16.9-fold higher in CC homozygotes than in TT homozygotes
Genetic testing laboratories
- Optivia Biotechnology, Inc (http://optiviabio.com)
Administration
Oral Administration
Take with or without food
Tablets: Swallow whole
Capsules
- Swallow whole; do not crush or chew
For patients who have difficulty swallowing capsules
- May open capsule and carefully empty granules onto 1 tsp of applesauce; swallow immediately, without chewing
- Do not store mixture for future use
- If not used in its entirety, discard remaining contents immediately
Nasogastric Tube Administration
Open capsule and empty granules into a 60-mL catheter-tipped syringe and add 40 mL of water
Shake syringe vigorously for 15 seconds; granules may start dissolving which is acceptable
Attach syringe to a nasogastric tube (≥16-French) and deliver contents of syringe through nasogastric tube
After administering granules, flush nasogastric tube with 20 mL of additional water
Use immediately after preparation and do not store for future use
If not used in its entirety, discard remaining contents immediately
Use with any other liquids is not recommended
Storage
Capsules and tablets: Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)
Protect from moisture
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Patient Handout
Formulary
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