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Rosuvastatin

Pronunciation

Pronunciation

(roe soo va STAT in)

Index Terms

  • Rosuvastatin Calcium

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Crestor: 5 mg, 10 mg, 20 mg, 40 mg

Generic: 5 mg, 10 mg, 20 mg, 40 mg

Brand Names: U.S.

  • Crestor

Pharmacologic Category

  • Antilipemic Agent, HMG-CoA Reductase Inhibitor

Pharmacology

Inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis (reduces the production of mevalonic acid from HMG-CoA); this then results in a compensatory increase in the expression of LDL receptors on hepatocyte membranes and a stimulation of LDL catabolism. In addition to the ability of HMG-CoA reductase inhibitors to decrease levels of high-sensitivity C-reactive protein (hsCRP), they also possess pleiotropic properties including improved endothelial function, reduced inflammation at the site of the coronary plaque, inhibition of platelet aggregation, and anticoagulant effects (de Denus 2002; Ray 2005).

Distribution

Vd: 134 L

Metabolism

Hepatic (10%), via CYP2C9 (1 active metabolite identified: N-desmethyl rosuvastatin, one-sixth to one-half the HMG-CoA reductase activity of the parent compound)

Excretion

Feces (90%), primarily as unchanged drug

Onset of Action

Within 1 week; maximal at 4 weeks

Time to Peak

Plasma: 3 to 5 hours

Half-Life Elimination

19 hours

Protein Binding

88%

Special Populations: Renal Function Impairment

Plasma concentrations increase about 3-fold in patients with severe renal impairment (CrCl <30 mL/minute/1.73 m2) not requiring hemodialysis. Steady-state plasma concentrations in patients on chronic hemodialysis are ~50% higher compared with patients with normal renal function.

Special Populations: Hepatic Function Impairment

Cmax and AUC are increased in patients with Child-Pugh class A or Child-Pugh class B hepatic impairment.

Special Populations: Race

Asian patients have ~2-fold elevation in exposure (AUC and Cmax).

Use: Labeled Indications

Familial hypercholesterolemia:

Pediatric: Adjunct to diet to reduce total cholesterol, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (apo B) levels in children and adolescents 8 to 17 years of age with heterozygous familial hypercholesteremia (HeFH) if after an adequate trial of diet therapy the following findings are present: LDL-C more than 190 mg/dL or more than 160 mg/dL and there is a positive family history of premature cardiovascular (CV) disease or 2 or more other CV disease risk factors; to reduce LDL-C, total-C, non–high-density lipoprotein cholesterol (non-HDL-C) and apo B in children and adolescents 7 to 17 years of age with homozygous familial hypercholesterolemia (HoFH), either alone or with other lipid-lowering treatments (eg, LDL apheresis).

Adult: To reduce LDL-C, total cholesterol, and apo B in adults with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) or alone if such treatments are unavailable.

Hyperlipidemia and mixed dyslipidemia: Adjunctive therapy to diet to reduce elevated total cholesterol, LDL-C, apo B, non-HDL-C, and triglyceride levels, and to increase HDL-C in adults with primary hyperlipidemia or mixed dyslipidemia.

Hypertriglyceridemia: Adjunct to diet for the treatment of adults with hypertriglyceridemia.

Primary dysbetalipoproteinemia (type III hyperlipoproteinemia): Adjunct to diet for the treatment of adults with primary dysbetalipoproteinemia (type III hyperlipoproteinemia).

Prevention of cardiovascular disease:

Primary prevention: To reduce the risk of stroke, myocardial infarction, or arterial revascularization procedures in patients without clinically evident coronary heart disease but with all of the following: 1) an increased risk of cardiovascular disease based on age ≥50 years old in men and ≥60 years old in women, 2) hsCRP ≥2 mg/L, and 3) the presence of at least one additional cardiovascular disease risk factor such as hypertension, low HDL-C, smoking, or a family history of premature coronary heart disease.

Secondary prevention: Adjunctive therapy to diet to slow the progression of atherosclerosis in adults as part of a treatment strategy to lower total cholesterol and LDL-C to target levels.

Primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) according to the American College of Cardiology/American Heart Association: To reduce the risk of ASCVD in patients with clinical ASCVD (eg, coronary heart disease, stroke/TIA, or peripheral arterial disease presumed to be of atherosclerotic origin); in patients without clinical ASCVD if LDL-C is 190 mg/dL or greater; in patients without clinical ASCVD who have type 1 or type 2 diabetes and are between 40 and 75 years of age; in patients with an estimated 10-year ASCVD risk 7.5% or greater and who are between 40 and 75 years of age (Stone 2013). The American Heart Association (AHA) recommends statin therapy (unless contraindicated) for all coronary artery bypass graft (CABG) surgery patients to help maintain long-term graft patency and help obtain the highest level of physical health and quality of life (AHA [Kulik 2015]). Specific recommendations from the Kidney Disease: Improving Global Outcomes (KDIGO) organization have also been released for patients with chronic kidney disease (KDIGO [Tonelli 2013]).

Contraindications

Hypersensitivity to rosuvastatin or any component of the formulation; active liver disease or unexplained persistent elevations of serum transaminases; pregnancy; breast-feeding.

Canadian labeling: Additional contraindications (not in US labeling): Concomitant administration of cyclosporine; use of 40 mg dose in Asian patients, patients with predisposing risk factors for myopathy/rhabdomyolysis (eg, hereditary muscle disorders, history of myotoxicity with other HMG-CoA reductase inhibitors, concomitant use with fibrates or niacin, severe hepatic impairment, severe renal impairment [CrCl <30 mL/minute/1.73 m2], hypothyroidism, alcohol abuse)

Dosing: Adult

Note: Doses should be individualized according to the baseline LDL-cholesterol levels, the recommended goal of therapy, and patient response; adjustments should be made at intervals of 4 weeks or more.

Hyperlipidemia, mixed dyslipidemia, hypertriglyceridemia, primary dysbetalipoproteinemia, slowing progression of atherosclerosis, primary prevention of cardiovascular disease: Oral:

Initial dose:

General dosing: 10 to 20 mg once daily; 20 mg once daily may be used in patients with severe hyperlipidemia (LDL >190 mg/dL) and aggressive lipid targets (McKenney 2009)

Conservative dosing: Patients requiring less aggressive treatment or predisposed to myopathy (including patients of Asian descent): 5 mg once daily

Titration: After initiation or upon titration, analyze lipid levels within 2 to 4 weeks (peak, steady-state lowering effects usually seen between 4 to 6 weeks [McKenney 2009]) and adjust dose accordingly; usual dosage range: 5 to 40 mg once daily (maximum dose: 40 mg/day)

Note: The 40 mg dose should be reserved for patients who have not achieved goal cholesterol levels on a dose of 20 mg daily, including patients switched from another HMG-CoA reductase inhibitor.

Homozygous familial hypercholesterolemia (HoFH): Oral: Initial: 20 mg once daily; after initiation or upon titration, analyze lipid levels within 2 to 4 weeks (peak, steady-state lowering effects usually seen between 4 to 6 weeks [McKenney 2009]) and adjust dose accordingly; usual dosage range: 5 to 40 mg once daily (maximum dose: 40 mg/day)

Prevention of cardiovascular disease: ACC/AHA Blood Cholesterol Guideline recommendations to reduce the risk of atherosclerotic cardiovascular disease (ASCVD) (Stone 2013): Adults ≥21 years: Oral:

Primary prevention:

LDL-C ≥190 mg/dL: High-intensity therapy: 20 to 40 mg once daily

Type 1 or 2 diabetes and age 40 to 75 years: Moderate-intensity therapy: 5 to 10 mg once daily

Type 1 or 2 diabetes, age 40 to 75 years, and an estimated 10-year ASCVD risk ≥7.5%: High intensity therapy: 20 to 40 mg once daily.

Age 40 to 75 years and an estimated 10-year ASCVD risk ≥7.5%: Moderate- to high-intensity therapy: 5 to 40 mg once daily.

Secondary prevention:

Patient has clinical ASCVD (eg, coronary heart disease, stroke/TIA, or peripheral arterial disease presumed to be of atherosclerotic origin) or is post-CABG (AHA [Kulik 2015]) and:

Age ≤75 years: High-intensity therapy: 20 to 40 mg once daily

Age >75 years or not a candidate for high-intensity therapy: Moderate-intensity therapy: 5 to 10 mg once daily

Dosage adjustment for rosuvastatin with concomitant medications: Oral:

US labeling:

Cyclosporine: Rosuvastatin dose should not exceed 5 mg once daily

Gemfibrozil: Avoid concurrent use; if unable to avoid concurrent use, initiate rosuvastatin at 5 mg once daily (maximum: 10 mg/day)

Atazanavir/ritonavir, lopinavir/ritonavir, or simeprevir: Initiate rosuvastatin at 5 mg once daily (maximum: 10 mg/day).

Canadian labeling:

Cyclosporine: Concomitant use is contraindicated.

Gemfibrozil: Rosuvastatin dose should not exceed 20 mg daily

Dosage adjustment for hematuria and/or persistent, unexplained proteinuria while on 40 mg daily: Reduce dose and evaluate causes.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Doses should be individualized according to the baseline LDL-cholesterol levels, the recommended goal of therapy, and patient response; adjustments should be made at intervals of 4 weeks or more.

Heterozygous familial hypercholesterolemia (HeFH):

US labeling: Oral:

Children 8 to <10 years: 5 to 10 mg once daily (maximum: 10 mg/day)

Children ≥10 years and Adolescents: 5 to 20 mg once daily (maximum: 20 mg/day)

Dosage adjustment for rosuvastatin with concomitant cyclosporine, gemfibrozil, atazanavir/ritonavir, lopinavir/ritonavir, or simeprevir: Refer to adult dosing.

Canadian labeling: Children and Adolescents 10 to 17 years (females >1 year postmenarche): Oral: 5 to 10 mg once daily; maximum: 10 mg/day

Homozygous familial hypercholesterolemia (HoFH):

Manufacturer's labeling: Children ≥7 years and Adolescents: Oral: 20 once daily (maximum: 20 mg/day)

Alternate recommendations: Limited data available: Children and Adolescents (≥8 years and ≥32 kg): Oral: Initial dose: 20 mg once daily; titrate at 6-week intervals to 40 mg once daily. Although higher doses have been used (ie, 80 mg/day), additional benefit has not been reported. Dosing based on an open-label, forced-titration study of 44 patients (n=8 pediatric patients ≥8 years) which reported 72% of patients responded to rosuvastatin treatment (Marias 2008).

Dosing: Renal Impairment

CrCl ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.

CrCl <30 mL/minute/1.73 m2: Initial: 5 mg once daily (maximum: 10 mg/day).

Dosing: Hepatic Impairment

US labeling: There are no specific dosage adjustments provided in the manufacturer's labeling; however, systemic exposure may be increased in patients with liver disease (increased AUC and Cmax); use is contraindicated in active liver disease or unexplained transaminase elevations.

Canadian labeling:

Active hepatic disease or unexplained persistent transaminase >3 x ULN: Use is contraindicated.

Mild-to-moderate impairment: No dosage adjustment necessary.

Severe impairment: Initial: 5 mg daily. Maximum: 20 mg once daily.

Dosing: Adjustment for Toxicity

Severe muscle symptoms or fatigue: Promptly discontinue use; evaluate CPK, creatinine, and urinalysis for myoglobinuria (Stone 2013).

Mild to moderate muscle symptoms: Discontinue use until symptoms can be evaluated; evaluate patient for conditions that may increase the risk for muscle symptoms (eg, hypothyroidism, reduced renal or hepatic function, rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases). Upon resolution, resume the original or lower dose of rosuvastatin. If muscle symptoms recur, discontinue rosuvastatin use. After muscle symptom resolution, may then use a low dose of a different statin; gradually increase if tolerated. In the absence of continued statin use, if muscle symptoms or elevated CPK continues after 2 months, consider other causes of muscle symptoms. If determined to be due to another condition aside from statin use, may resume statin therapy at the original dose (Stone 2013).

Administration

Administer with or without food. May be taken at any time of the day; swallow tablet whole.

Dietary Considerations

Red yeast rice contains variable amounts of several compounds that are structurally similar to HMG-CoA reductase inhibitors, primarily monacolin K (or mevinolin) which is structurally identical to lovastatin; concurrent use of red yeast rice with HMG-CoA reductase inhibitors may increase the incidence of adverse and toxic effects (Lapi 2008; Smith 2003).

Storage

Store between 20°C and 25°C (68°F to 77°F). Protect from moisture.

Drug Interactions

Acipimox: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Monitor therapy

Amiodarone: May decrease the metabolism of HMG-CoA Reductase Inhibitors. Management: Dose of HMG-CoA reductase inhibitor may need to be reduced (limit simvastatin adult maximum dose to 20 mg/day, limit lovastatin adult maximum dose to 40 mg/day). Consider therapy modification

Antacids: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy

Asunaprevir: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy

Bezafibrate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Bezafibrate may increase the serum concentration of HMG-CoA Reductase Inhibitors. More specifically, bezafibrate may increase the serum concentration of fluvastatin Management: Monitor patients closely for myopathy with concomitant use of bezafibrate and HMG-CoA reductase inhibitors. Concomitant use is contraindicated in patients predisposed to myopathy and alternative therapy should be considered. Consider therapy modification

Boceprevir: May increase the serum concentration of Rosuvastatin. Monitor therapy

Ciprofibrate: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Management: Avoid the use of HMG-CoA reductase inhibitors and ciprofibrate if possible. If concomitant therapy is considered, benefits should be carefully weighed against the risks, and patients should be monitored closely for signs/symptoms of muscle toxicity. Consider therapy modification

Clopidogrel: May increase the serum concentration of Rosuvastatin. Monitor therapy

Colchicine: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification

CycloSPORINE (Systemic): May increase the serum concentration of Rosuvastatin. Management: Limit rosuvastatin to 5 mg/day in patients who are also receiving cyclosporine. Canadian labeling contraindicates concomitant use of rosuvastatin with cyclosporine. Consider therapy modification

Daclatasvir: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy

DAPTOmycin: HMG-CoA Reductase Inhibitors may enhance the adverse/toxic effect of DAPTOmycin. Specifically, the risk of skeletal muscle toxicity may be increased. Management: Consider temporarily stopping HMG-CoA reductase inhibitor therapy prior to daptomycin. If used together, regular (i.e., at least weekly) monitoring of CPK concentrations is recommended. Consider therapy modification

Dronedarone: May increase the serum concentration of Rosuvastatin. Monitor therapy

Elbasvir: May increase the serum concentration of Rosuvastatin. Management: Limit the dose of rosuvastatin to a maximum of 10 mg/day when used together with elbasvir and grazoprevir. Monitor closely for evidence of statin-related toxicities such as myalgia or myopathy. Consider therapy modification

Eltrombopag: May increase the serum concentration of Rosuvastatin. Management: Consideration a preventive 50% reduction in rosuvastatin adult dose when starting this combination; Canadian labeling recommends limiting rosuvastatin to a maximum of 20 mg/day. Consider therapy modification

Eluxadoline: May increase the serum concentration of Rosuvastatin. Management: Use the lowest effective dose of rosuvastatin if combined with eluxadoline. Consider therapy modification

Eslicarbazepine: May decrease the serum concentration of Rosuvastatin. Monitor therapy

Fenofibrate and Derivatives: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy

Fusidic Acid (Systemic): May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Specifically, the risk for muscle toxicities, including rhabdomyolysis may be significantly increased. Management: Avoid concurrent use whenever possible. Use is listed as contraindicated in product characteristic summaries in several countries, although UK labeling suggests that use could be considered under exceptional circumstances and with close supervision. Avoid combination

Gemfibrozil: May enhance the myopathic (rhabdomyolysis) effect of Rosuvastatin. Gemfibrozil may increase the serum concentration of Rosuvastatin. Management: If possible, avoid concomitant use of rosuvastatin with gemfibrozil. If concomitant can not be avoided, limit rosuvastatin to 10 mg/day (US recommendation) or 20 mg/day (Canadian recommendation). Monitor for signs/symptoms of rhabdomyolysis. Avoid combination

Grazoprevir: May increase the serum concentration of Rosuvastatin. Management: Limit the dose of rosuvastatin to a maximum of 10 mg/day when used together with elbasvir and grazoprevir. Monitor closely for evidence of statin-related toxicities such as myalgia or myopathy. Consider therapy modification

Itraconazole: May increase the serum concentration of Rosuvastatin. Monitor therapy

Lanthanum: HMG-CoA Reductase Inhibitors may decrease the serum concentration of Lanthanum. Management: Administer HMG-CoA reductase inhibitors at least two hours before or after lanthanum. Consider therapy modification

Ledipasvir: May increase the serum concentration of Rosuvastatin. Avoid combination

Niacin: May enhance the myopathic (rhabdomyolysis) effect of Rosuvastatin. Monitor therapy

Niacinamide: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May increase the serum concentration of Rosuvastatin. Management: Limit the rosuvastatin dose to a maximum of 10 mg per day when used with the ombitasvir/paritaprevir/ritonavir/dasabuvir combination product. Canadian labeling recommends limiting the rosuvastatin dose to 5 mg per day. Consider therapy modification

Osimertinib: May increase the serum concentration of BCRP/ABCG2 Substrates. Monitor therapy

PAZOPanib: HMG-CoA Reductase Inhibitors may enhance the hepatotoxic effect of PAZOPanib. Specifically, the risk for increased serum transaminase concentrations may be increased. Management: Simvastatin is specifically implicated in the interaction. There is a lack of data regarding risk with other statins, but caution appears warranted with any statins. Atorvastatin should be avoided due to P-gp inhibition. Monitor therapy

Protease Inhibitors: May increase the serum concentration of Rosuvastatin. Management: Start at the lowest rosuvastatin dose and monitor for toxicity. See full drug interaction monograph for details. Consider therapy modification

Raltegravir: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Monitor therapy

Red Yeast Rice: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Avoid combination

Regorafenib: May increase the serum concentration of BCRP/ABCG2 Substrates. Monitor therapy

Rolapitant: May increase the serum concentration of BCRP/ABCG2 Substrates. Management: Monitor patients receiving rolapitant for increased exposure to and/or effects of BCRP/ABCG2 substrates. Use the lowest effective rosuvastatin dose when used in combination with rolapitant. Monitor therapy

Simeprevir: May increase the serum concentration of Rosuvastatin. Management: Limit initial rosuvastatin dose to 5 mg/day when being started in a patient who is also being treated with simeprevir. The maximum rosuvastatin dose should not exceed 10 mg/day with concurrent use of simeprevir. Consider therapy modification

Telaprevir: May increase the serum concentration of Rosuvastatin. Monitor therapy

Teriflunomide: May increase the serum concentration of Rosuvastatin. Management: Limit the maximum adult rosuvastatin dose to 10 mg/day in patients receiving teriflunomide, and monitor for evidence of rosuvastatin toxicity (eg, muscle toxicity, elevated transaminase concentrations). Consider therapy modification

Trabectedin: HMG-CoA Reductase Inhibitors may enhance the myopathic (rhabdomyolysis) effect of Trabectedin. Monitor therapy

Velpatasvir: May increase the serum concentration of Rosuvastatin. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): HMG-CoA Reductase Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Adverse Reactions

>10%: Neuromuscular & skeletal: Myalgia (2% to 13%)

1% to 10%:

Central nervous system: Headache (6% to 9%), dizziness (4%)

Endocrine & metabolic: Diabetes mellitus (new onset: 3%)

Gastrointestinal: Nausea (4% to 6%), constipation (3% to 5%)

Genitourinary: Cystitis (interstitial; Huang 2015)

Hepatic: Increased serum ALT (2%; >3 times ULN)

Neuromuscular & skeletal: Arthralgia (4% to 10%), increased creatine phosphokinase (3%; >10 x ULN: Children 3%), weakness (5%)

<1% (Limited to important or life-threatening): Abnormal thyroid function test, cognitive dysfunction (reversible; includes amnesia, confusion, memory impairment), depression, elevated glycosylated hemoglobin (HbA1c), gynecomastia, hematuria (microscopic), hepatic failure, hepatitis, hypersensitivity reaction (including angioedema, pruritus, skin rash, urticaria), immune-mediated necrotizing myopathy, increased gamma-glutamyl transferase, increased serum alkaline phosphatase, increased serum bilirubin, increased serum glucose, increased serum transaminases, jaundice, myoglobinuria, myopathy, myositis, pancreatitis, peripheral neuropathy, proteinuria (dose related), renal failure, rhabdomyolysis, sleep disorder (including insomnia and nightmares), thrombocytopenia

Warnings/Precautions

Concerns related to adverse effects:

• Diabetes mellitus: Small increases in HbA1c (mean: ~0.1%) and fasting blood glucose have been reported with rosuvastatin; however, the benefits of statin therapy far outweigh the risk of dysglycemia.

• Hematuria/proteinuria: Hematuria (microscopic) and proteinuria have been observed; more commonly reported in adults receiving rosuvastatin 40 mg daily. Typically, transient and not associated with a decrease in renal function. Consider dosage reduction if unexplained hematuria and proteinuria persists.

• Hepatotoxicity: Postmarketing reports of fatal and nonfatal hepatic failure are rare. If serious hepatotoxicity with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, interrupt therapy. If an alternate etiology is not identified, do not restart rosuvastatin. Liver enzyme tests should be obtained at baseline and as clinically indicated; routine periodic monitoring of liver enzymes is not necessary.

• Hypersensitivity: Hypersensitivity reactions, including rash, pruritus, urticaria, and angioedema, have been reported.

• Immune-mediated necrotizing myopathy (IMNM): IMNM, an autoimmune-mediated myopathy, has been reported (rarely) with HMG-CoA reductase inhibitor therapy. IMNM presents as proximal muscle weakness with elevated CPK levels, which persists despite discontinuation of HMG-CoA reductase inhibitor therapy; additionally, muscle biopsy may show necrotizing myopathy with limited inflammation. Immunosuppressive therapy (eg, corticosteroids, azathioprine) may be useful for treatment.

• Myopathy/rhabdomyolysis: Patients receiving HMG-CoA reductase inhibitors have developed rhabdomyolysis with acute renal failure and/or myopathy; patients should be monitored closely. This risk is dose-related and is increased with concurrent use of other lipid-lowering medications (fibric acid derivatives or niacin doses ≥1 g/day), other interacting drugs, other drugs associated with myopathy (eg, colchicine), age ≥65 years, female gender, uncontrolled hypothyroidism, and renal dysfunction. Use caution in patients with renal impairment, inadequately treated hypothyroidism, and those taking other drugs associated with myopathy (eg, colchicine); these patients are predisposed to myopathy. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or dark urine.

Disease-related concerns:

• Hepatic impairment and/or ethanol use: Use with caution in patients who consume large amounts of ethanol or have a history of liver disease. Use is contraindicated with active liver disease or unexplained transaminase elevations.

• Renal impairment: Dosage adjustment required in patients with a CrCl <30 mL/minute/1.73 m2 and not receiving hemodialysis (contraindicated in the Canadian labeling).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Asian population: Increased risk of rosuvastatin-associated myopathy in certain subgroups; dosage adjustment should be considered for patients of Asian descent. Use of rosuvastatin at a dose of 40 mg/day in Asian patients is contraindicated in the Canadian labeling.

• Elderly: Use with caution in patients with advanced age; these patients are more predisposed to myopathy.

• Surgical patients: The manufacturer recommends temporary discontinuation for elective major surgery, acute medical or surgical conditions, or in any patient experiencing an acute or serious condition predisposing to renal failure (eg, sepsis, hypotension, trauma, uncontrolled seizures). Based on current research and clinical guidelines (Fleisher 2009), HMG-CoA reductase inhibitors should be continued in the perioperative period. Postoperative discontinuation of statin therapy is associated with an increased risk of cardiac morbidity and mortality.

Other warnings/precautions:

• Appropriate use: Secondary causes of hyperlipidemia should be ruled out prior to therapy. Rosuvastatin has not been studied when the primary lipid abnormality is chylomicron elevation (Fredrickson types I and V).

Monitoring Parameters

2013 ACC/AHA Blood Cholesterol Guideline recommendations (Stone 2013):

Lipid panel (total cholesterol, HDL, LDL, triglycerides): Baseline lipid panel; fasting lipid profile within 4-12 weeks after initiation or dose adjustment and every 3-12 months (as clinically indicated) thereafter. If 2 consecutive LDL levels are <40 mg/dL, consider decreasing the dose.

Hepatic transaminase levels: Baseline measurement of hepatic transaminase levels (ie, ALT); measure hepatic function if symptoms suggest hepatotoxicity (eg, unusual fatigue or weakness, loss of appetite, abdominal pain, dark-colored urine or yellowing of skin or sclera) during therapy.

CPK: CPK should not be routinely measured. Baseline CPK measurement is reasonable for some individuals (eg, family history of statin intolerance or muscle disease, clinical presentation, concomitant drug therapy that may increase risk of myopathy). May measure CPK in any patient with symptoms suggestive of myopathy (pain, tenderness, stiffness, cramping, weakness, or generalized fatigue).

Evaluate for new-onset diabetes mellitus during therapy; if diabetes develops, continue statin therapy and encourage adherence to a heart-healthy diet, physical activity, a healthy body weight, and tobacco cessation.

If patient develops a confusional state or memory impairment, may evaluate patient for nonstatin causes (eg, exposure to other drugs), systemic and neuropsychiatric causes, and the possibility of adverse effects associated with statin therapy.

Manufacturer's labeling: Liver enzyme tests at baseline and repeated when clinically indicated. Upon initiation or titration, lipid panel should be analyzed within 2 to 4 weeks.

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. There are reports of congenital anomalies following maternal use of HMG-CoA reductase inhibitors in pregnancy; however, maternal disease, differences in specific agents used, and the low rates of exposure limit the interpretation of the available data (Godfrey 2012; Lecarpentier 2012). Cholesterol biosynthesis may be important in fetal development; serum cholesterol and triglycerides increase normally during pregnancy. The discontinuation of lipid lowering medications temporarily during pregnancy is not expected to have significant impact on the long term outcomes of primary hypercholesterolemia treatment.

Use of rosuvastatin is contraindicated in pregnancy. HMG-CoA reductase inhibitors should be discontinued prior to pregnancy (ADA 2013). If treatment of dyslipidemias is needed in pregnant women or in women of reproductive age, other agents are preferred (Berglund 2012; Stone 2013). The manufacturer recommends administration to women of childbearing potential only when conception is highly unlikely and patients have been informed of potential hazards.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, abdominal pain, nausea, or joint pain. Have patient report immediately to prescriber signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), hematuria, urinary retention, change in amount of urine passed, muscle pain, muscle tenderness, or muscle weakness (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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