After a comprehensive review of all available data, the FDA is requesting all statin manufacturers to remove the contraindication in the prescribing information against using statins in pregnant patients. Although statin therapy should be discontinued in most pregnant patients, health care providers should consider the ongoing therapeutic needs of the individual patient, especially patients at very high risk of cardiovascular events during pregnancy, such as patients with homozygous familial hypercholesterolemia or those with established cardiovascular disease. Additionally, breastfeeding is still not recommended in patients taking a statin; health care providers should determine whether it is better to temporarily stop statin therapy while breastfeeding or to continue statin therapy and not have the patient breastfeed. If ongoing statin treatment is necessary, infant formula and other alternatives are available. The FDA expects that removing the contraindication will enable health care providers and patients to make individual decisions about benefit and risk, especially for those at very high risk of heart attack or stroke.
Further information is available at https://www.fda.gov/drugs/drug-safety-and-availability/fda-requests-removal-strongest-warning-against-using-cholesterol-lowering-statins-during-pregnancy.
Dosage guidance:
Dosing: Rosuvastatin 20 to 40 mg/day is considered a high-intensity statin (generally reduces low-density lipoprotein cholesterol [LDL-C] by ≥50%). Rosuvastatin 5 to 10 mg/day is considered a moderate-intensity statin (generally reduces LDL-C by ~30% to 49%). Assess response ~1 to 3 months after therapy initiation or dose adjustment and every 3 to 12 months thereafter (Ref). In patients of East Asian descent, exposure can be ~2-fold higher compared to White patients; consider initial dosage reduction and risk versus benefit in East Asian patients not adequately controlled with rosuvastatin 20 mg once daily before increasing dose further (Ref).
Clinical considerations: Use in conjunction with lifestyle modification (eg, diet, exercise). When initiating therapy and selecting dose intensity, consider age, baseline LDL-C, 10-year atherosclerotic cardiovascular disease (ASCVD) risk, risk-enhancing factors, potential adverse effects, and drug interactions.
Heterozygous familial hypercholesterolemia:
Note: Multiple lipid-lowering therapies may be needed if statin monotherapy is not effective. Referral to a lipid specialist should be considered if treatment goals are not met (Ref).
High-intensity therapy: Oral: Initial: 20 or 40 mg once daily; if 20 mg once daily is initiated and tolerated, increase to 40 mg once daily (Ref).
Prevention of atherosclerotic cardiovascular disease :
Note: If LDL-C goal (eg, percent reduction or absolute goal) is not met with the initial dose, may consider up-titration based on estimated 10-year ASCVD risk (see American College of Cardiology ASCVD Risk Estimator Plus online), LDL-C response, and tolerability. If LDL-C goal is not met with maximally tolerated dose, additional lipid-lowering therapy may be warranted (Ref).
Primary prevention:
Patients without diabetes, 40 to 75 years of age, and with LDL-C 70 to 189 mg/dL:
ASCVD 10-year risk 5% to <7.5%:
Note: Depending on baseline LDL-C and presence of risk-enhancing factors, consider statin therapy after shared decision-making with patient. Some experts suggest shared decision-making if ASCVD 10-year risk is 5% to 10%; however, in patients with a baseline LDL-C >160 mg/dL, statin therapy is usually recommended (Ref).
Moderate-intensity therapy: Oral: 5 to 10 mg once daily to reduce LDL-C by 30% to 49% (Ref).
ASCVD 10-year risk ≥7.5% to <20%:
Note: Depending on baseline LDL-C and presence of risk-enhancing factors, consider statin therapy after shared decision-making with patient. Some experts suggest initiating moderate-intensity statin therapy in most patients if ASCVD 10-year risk is >10% to <20% and LDL-C is >100 mg/dL (Ref).
Moderate-intensity therapy: Oral: 5 to 10 mg once daily to reduce LDL-C by 30% to 49%; higher risk patients with multiple risk-enhancing factors may benefit from higher doses to reduce LDL-C by ≥50% (Ref).
ASCVD 10-year risk ≥20%:
High-intensity therapy: Oral: 20 to 40 mg once daily to reduce LDL-C by ≥50%; if unable to tolerate due to adverse effects, may reduce dose to maximum tolerated (Ref).
Patients with diabetes:
40 to 75 years of age without additional ASCVD risk factors :
Moderate-intensity therapy: Oral: 5 to 10 mg once daily to reduce LDL-C by 30% to 49% (Ref).
ASCVD risk ≥7.5% or multiple ASCVD risk factors :
High-intensity therapy: Oral: 20 to 40 mg once daily to reduce LDL-C by ≥50%; if unable to tolerate due to adverse effects, may reduce dose to maximum tolerated (Ref).
Patients with LDL-C ≥190 mg/dL and 20 to 75 years of age:
Note: High-intensity therapy is indicated regardless of ASCVD risk calculation or coexisting diabetes mellitus.
High-intensity therapy: Oral: 20 to 40 mg once daily to reduce LDL-C by ≥50%; if unable to tolerate due to adverse effects, may reduce dose to maximum tolerated (Ref).
Secondary prevention in patients with established ASCVD (eg, coronary heart disease, cerebrovascular disease [ischemic stroke or transient ischemic attack], peripheral arterial disease):
Note: Patients with high-risk ASCVD may require additional therapies to achieve LDL-C goal (eg, <70 mg/dL or <50 mg/dL if very high risk) (Ref).
High-intensity therapy: Oral: 20 to 40 mg once daily to reduce LDL-C by ≥50%; if unable to tolerate due to adverse effects, may reduce dose to maximum tolerated (Ref).
Transplantation:
Note: Certain immunosuppressive drugs can induce or exacerbate hypercholesterolemia. Significant drug interactions between statins and immunosuppressant drugs are frequent; some interactions can increase statin serum concentrations and risk of toxicity (eg, myopathy) (Ref). Consult Drug Interactions Database for more detailed information.
Transplantation, post heart (off-label use): Oral: Initial: 5 to 10 mg once daily starting 1 to 2 weeks after transplant, regardless of baseline cholesterol levels; increase to the maximum tolerated dose within 4 to 8 weeks of transplantation based on response and use of concomitant medications up to 20 mg once daily (Ref).
Transplantation, post kidney (off-label use):
Note: The decision to initiate therapy for primary or secondary prevention is similar to the nontransplant population (see "Dosing: Prevention of Atherosclerotic Cardiovascular Disease"). However, in patients who are 30 to 39 years of age, some experts suggest statin therapy post kidney transplantation for primary prevention of ASCVD. For primary prevention of ASCVD in patients 18 to 29 years of age, use shared decision making while considering risks and benefits (Ref).
Oral: Initial: 5 mg once daily; increase dose based on response, tolerability, and use of concomitant medications up to 10 mg once daily (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult Drug Interactions Database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
CrCl ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
CrCl <30 mL/minute/1.73 m2: 5 to 10 mg once daily.
Hemodialysis, intermittent (thrice weekly): Not dialyzable: Maximum: 10 mg/day. Steady state concentrations are increased ~50% during chronic hemodialysis; however, accumulation is minimal, and rates of adverse effects are similar to placebo with a dose of 10 mg/day (Ref).
Peritoneal dialysis: Maximum: 10 mg/day; accumulation unlikely to occur at a dose of ≤10 mg/day (Ref).
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Close monitoring of response and adverse reactions (eg, rhabdomyolysis) due to drug accumulation is important.
Maximum: 10 mg/day (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and adverse reactions (eg, rhabdomyolysis) due to drug accumulation is important.
Maximum: 10 mg/day (Ref).
The hepatic dosing recommendations are based upon on the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST; Jeong Park, PharmD, MS, BCPS, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.
Hepatic impairment prior to treatment initiation:
Note: Although use is contraindicated in patients with active liver failure or decompensated cirrhosis according to the manufacturer's labeling, baseline elevation in AST/ALT should not preclude use of statins for compelling indications in patients with chronic stable liver disease including compensated cirrhosis (Ref).
Child-Turcotte-Pugh class A: No dosage adjustment necessary (Ref).
Child-Turcotte-Pugh class B: Oral: Initial: 5 mg once daily; may increase to 10 mg once daily based on tolerability and response; maximum recommended dose: 10 mg once daily (Ref).
Child-Turcotte-Pugh class C: Oral: Use generally not recommended. If use deemed necessary (eg, patients with compelling indications): Initial: 5 mg once daily; a maximum dose of 5 mg once daily is recommended (Ref).
Acute hepatoxicity or worsening hepatic function (eg, progression from class A to B) during treatment:
Progression from baseline to Child-Turcotte-Pugh class A through C: Although use is contraindicated in patients with active liver failure or decompensated cirrhosis according to the manufacturer's labeling, if rosuvastatin-induced hepatoxicity has been ruled out, may continue rosuvastatin therapy with no dosage adjustment necessary; monitor closely for signs or symptoms of rhabdomyolysis (Ref).
Severe muscle symptoms or fatigue: Promptly discontinue use; evaluate CPK, creatinine, and urinalysis for myoglobinuria (Ref).
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 (Ref).
Refer to adult dosing.
(For additional information see "Rosuvastatin: Pediatric drug information")
Dosage guidance:
Dosing: 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. A lower, conservative dosing regimen may be necessary in patient populations predisposed to myopathy, including patients of East Asian descent (Ref).
Heterozygous familial hypercholesterolemia:
Children 8 to <10 years: Oral: 5 to 10 mg once daily.
Children ≥10 years and Adolescents: Oral: 5 to 20 mg once daily.
Homozygous familial hypercholesterolemia: Children ≥7 years and Adolescents: Oral: 20 mg once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥7 years and Adolescents:
CrCl ≥30 mL/minute/1.73 m2: No dosage adjustment required.
CrCl <30 mL/minute/1.73 m2 and not receiving hemodialysis: Initial: 5 mg once daily; maximum daily dose: 10 mg/day
Children ≥7 years and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; systemic exposure (increased AUC and Cmax) may be increased in patients with liver disease; monitor closely. Use is contraindicated in patients with active liver disease or decompensated cirrhosis.
Statins are associated with increased serum transaminases and hepatotoxicity (Ref). Asymptomatic transient or persistent increases both <3 or >3 times the ULN in serum transaminases may occur with all statins; the increased serum alanine aminotransferase (ALT) is typically greater than the increase in aspartate aminotransferase (AST) (Ref). One case report of increased liver function tests has also been reported as part of drug rash eosinophilia with systemic symptoms (Ref). Acute hepatotoxicity, often presenting as a drug-induced autoimmune hepatitis, has been documented (Ref).
Upon dose reduction or discontinuation, transaminase levels return to or near pretreatment levels; although, mild elevations resolve with continued use in some cases (Ref). Chronic liver injury (defined as liver biochemical or histological abnormalities that persisted for 6 months or more after onset) have been reported (Ref).
Mechanism: Unknown; rosuvastatin undergoes minimal hepatic metabolism. Acute liver injury may be caused by immune-mediated mechanisms (Ref). Changes in the lipid components of the hepatocyte membrane may lead to increased permeability and leakage of liver enzymes (Ref).
Onset: Varied; most cases occur within the first 3 months of initiation or dose escalation (Ref). Duration of rosuvastatin prior to development of hepatotoxicity has been reported from approximately 2 months to 2 years (Ref).
Risk factors:
• Higher doses may increase the risk of liver injury (Ref)
• Concurrent medications with statin drug-drug interactions or hepatotoxic properties (Ref)
• Hepatotoxicity is more commonly associated with atorvastatin than pravastatin, rosuvastatin, and simvastatin (Ref). Fluvastatin is associated with the greatest risk of developing hepatotoxicity (Ref).
• Cross-reactivity between different statins and the susceptibility to hepatotoxicity is unknown, as data have shown conflicting results (Ref).
• Chronic hepatitis B and alcohol consumption are independent risk factors for hepatic aminotransferase elevation associated with statins in patients 80 years of age or older (Ref).
Statins are associated with several muscle-related effects, including:
• Myalgia (muscle symptoms without significant creatine kinase [CK] elevations; also known as statin-associated muscle symptoms) (Ref)
• Myopathy (defined as unexplained muscle pain or weakness accompanied by a CK concentration >10 times the ULN) (Ref)
• Rhabdomyolysis (CK >40 times the ULN) (Ref) often with acute renal failure secondary to myoglobinuria (Ref)
• Immune-mediated necrotizing myopathy (IMNM) (elevated CK plus the presence of antibodies against HMG-CoA) (Ref)
Mechanism: Uncertain; alterations in the mevalonate pathway and changes in the electrical and structural characteristics of the sarcolemma related to calcium ion flux possibly contribute (Ref). Decreased ubiquinone, which is essential for energy production in skeletal muscle, may also contribute (Ref). Myopathy/rhabdomyolysis risk is related to circulating active drug concentrations (Ref). IMNM is considered an immune-mediated process; autoantibodies against HMG-CoA reductase (anti-HMG-CoA) have been identified (Ref).
Onset: Delayed; often presents within a few months after starting therapy (highest risk within first year of use), when the dose of the statin is increased, or when introducing an interacting drug (Ref). Muscle symptoms often appear more promptly when patients are reexposed to the same statin (Ref). Duration of statin use prior to development of IMNM is ~2 to 3 years (Ref).
Risk factors:
• First year of therapy (Ref)
• Dose increase (for myopathy and rhabdomyolysis, but not IMNM) (Ref)
• Addition of an interacting drug (eg, concurrent use of medications associated with myopathy [eg, gemfibrozil]) (Ref); since there is minimal metabolism of rosuvastatin by CYP3A4, low risk for clinically significant drug interactions with CYP3A4 inhibitors (Ref)
• Older patients (Ref)
• Hypothyroidism (Ref)
• Preexisting muscle disease (Ref)
• Kidney impairment (Ref)
• Females (Ref)
• Low body mass index (Ref)
• Heavy exercise (Ref)
• Surgery (Ref)
• Higher HMG-COA reductase inhibitory activity (Ref), rosuvastatin > atorvastatin > simvastatin > pravastatin ≈ lovastatin (Ref)
• East Asian population: Increased plasma concentrations (up to ≈ twofold with rosuvastatin) may result in increased risk of myopathy (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Neuromuscular & skeletal: Myalgia (2% to 13%) (table 1)
Drug (Rosuvastatin) |
Placebo |
Dose |
Number of Patients (Rosuvastatin) |
Number of Patients (Placebo) |
---|---|---|---|---|
13% |
12% |
40 mg once daily |
700 |
281 |
8% |
7% |
20 mg once daily |
8,901 |
8,901 |
6% |
1% |
20 mg once daily |
64 |
382 |
3% |
1% |
5 mg once daily |
291 |
382 |
2% |
1% |
10 mg once daily |
283 |
382 |
2% |
1% |
40 mg once daily |
106 |
382 |
1% to 10%:
Endocrine & metabolic: Diabetes mellitus (new onset: 3%)
Gastrointestinal: Constipation (3% to 5%), nausea (4% to 6%)
Hepatic: Increased serum transaminases (>3 × ULN; including increased serum alanine aminotransferase [2%] (table 2) , increased serum alkaline phosphatase, increased serum bilirubin)
Drug (Rosuvastatin) |
Placebo |
Dose |
Number of Patients (Rosuvastatin) |
Number of Patients (Placebo) |
Comments |
---|---|---|---|---|---|
2% |
0.7% |
40 mg once daily |
700 |
281 |
>3 x ULN |
Nervous system: Asthenia (5%) (table 3) , dizziness (4%), headache (6% to 9%)
Drug (Rosuvastatin) |
Placebo |
Dose |
Number of Patients (Rosuvastatin) |
Number of Patients (Placebo) |
---|---|---|---|---|
5% |
3% |
20 mg once daily |
64 |
382 |
3% |
3% |
10 mg once daily |
283 |
382 |
2% |
3% |
5 mg once daily |
291 |
382 |
0.9% |
3% |
40 mg once daily |
106 |
382 |
Neuromuscular & skeletal: Arthralgia (4% to 10%) (table 4) , increased creatine phosphokinase in blood specimen (3%) (table 5)
Drug (Rosuvastatin) |
Placebo |
Dose |
Number of Patients (Rosuvastatin) |
Number of Patients (Placebo) |
---|---|---|---|---|
10% |
7% |
40 mg once daily |
700 |
281 |
4% |
3% |
20 mg once daily |
8,901 |
8,901 |
Drug (Rosuvastatin) |
Placebo |
Population |
Dose |
Number of Patients (Rosuvastatin) |
Number of Patients (Placebo) |
Comments |
---|---|---|---|---|---|---|
3% |
0% |
Children and adolescents |
10 mg to 20 mg once daily |
130 |
46 |
>10 x ULN |
3% |
0.7% |
Adults |
40 mg once daily |
700 |
281 |
N/A |
Frequency not defined:
Endocrine & metabolic: Abnormal thyroid function test, elevated glycosylated hemoglobin, increased serum glucose
Gastrointestinal: Abdominal pain
Hepatic: Increased gamma-glutamyl transferase
Hypersensitivity: Hypersensitivity reaction
Postmarketing:
Dermatologic: Lichenoid eruption (Vesza 2018), maculopapular rash (Mancano 2018), pemphigoid (Murad 2012), pruritus (Malik 2022), purpuric rash (photolocalized) (Thabouti 2022)
Endocrine & metabolic: Gynecomastia (Roberto 2012)
Gastrointestinal: Oral mucosa ulcer (Algeffari 2022), pancreatitis (Chintanabonia 2012)
Genitourinary: Cystitis (interstitial) (Huang 2015), microscopic hematuria (Shin 2022), proteinuria (Shin 2022)
Hematologic & oncologic: Thrombocytopenia (Vrettos 2010)
Hepatic: Autoimmune hepatitis (Russo 2014), hepatic failure, hepatitis (Oteri 2008), jaundice (Oteri 2008)
Hypersensitivity: Angioedema (Shahbaz 2018), drug reaction with eosinophilia and systemic symptoms (Mustafa 2020)
Nervous system: Cognitive dysfunction (reversible; includes amnesia, confusion, memory impairment) (Tuccori 2014), depression, myasthenia (myonecrosis) (Hassan 2022), myasthenia gravis (including exacerbation of myasthenia gravis and ocular myasthenia gravis) (Purvin 2006), peripheral neuropathy (Özdemir 2019), sleep disorder (including insomnia, nightmares)
Neuromuscular & skeletal: Immune-mediated necrotizing myopathy (Essers 2019), myoglobinuria (Hilton-Jones 2018), myopathy (Newman 2019), myositis, rhabdomyolysis (Kariyanna 2019)
Renal: Acute interstitial nephritis (Londrino 2013), acute kidney injury (Wagner 2021), kidney failure (Hilton-Jones 2018)
Respiratory: Interstitial lung disease (including interstitial pneumonitis) (Kim 2015)
Hypersensitivity (eg, angioedema, pruritus, rash, urticaria) to rosuvastatin or any component of the formulation; active liver failure or decompensated cirrhosis.
Canadian labeling: Additional contraindications (not in US labeling): Concomitant administration of cyclosporine or sofosbuvir/velpatasvir/voxilaprevir; patients with active liver disease or unexplained persistent elevations of serum transaminases (>3 times ULN); pregnancy; breastfeeding; use of 40 mg dose in East Asian patients or patients with predisposing risk factors for myopathy/rhabdomyolysis.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients who consume large amounts of ethanol and/or have a history of liver disease; may require dosage adjustment in some patients with hepatic impairment.
• Myasthenia gravis: May rarely worsen or precipitate myasthenia gravis (MG); monitor for worsening MG if treatment is initiated (AAN [Narayanaswami 2021]).
• Renal impairment: Dosage adjustment may be required in patients with renal impairment.
Special populations:
• East Asian population: Dosage adjustment should be considered for patients of East Asian descent.
• Older adult: Use with caution in patients with advanced age; these patients are more predisposed to myopathy.
• Surgical patients: Based on current research and clinical guidelines, HMG-CoA reductase inhibitors should be continued in the perioperative period for noncardiac and cardiac surgery (ACC/AHA [Fleisher 2014]; ACC/AHA [Hillis 2011]). Perioperative discontinuation of statin therapy is associated with an increased risk of cardiac morbidity and mortality.
Other warnings/precautions:
• Appropriate use: Rosuvastatin has not been studied when the primary lipid abnormality is chylomicron elevation (Fredrickson types I and V).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule Sprinkle, Oral:
Ezallor Sprinkle: 5 mg [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye)]
Ezallor Sprinkle: 10 mg, 20 mg [contains fd&c blue #1 (brilliant blue)]
Ezallor Sprinkle: 40 mg
Tablet, Oral:
Crestor: 5 mg, 10 mg, 20 mg, 40 mg
Generic: 5 mg, 10 mg, 20 mg, 40 mg
May be product dependent
Capsule, sprinkles (Ezallor Sprinkle Oral)
5 mg (per each): $3.97
10 mg (per each): $3.97
20 mg (per each): $3.97
40 mg (per each): $3.97
Tablets (Crestor Oral)
5 mg (per each): $11.06
10 mg (per each): $11.06
20 mg (per each): $11.06
40 mg (per each): $11.06
Tablets (Rosuvastatin Calcium Oral)
5 mg (per each): $0.19 - $8.95
10 mg (per each): $0.19 - $8.95
20 mg (per each): $8.61 - $8.95
40 mg (per each): $8.61 - $8.95
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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
Capsule:
Oral: Administer with or without food. May be taken at any time of the day. Swallow capsule whole; do not crush or chew. Capsule may be opened and contents sprinkled over a small amount (teaspoonful) of soft food (eg, applesauce, chocolate/vanilla flavored pudding); stir mixture for 10 to 15 seconds. Swallow mixture within 60 minutes without chewing.
Nasogastric tube: Capsule may be opened and contents emptied into a 60 mL catheter tipped syringe. Add 40 mL of water (do not use other liquids), then replace plunger and shake syringe vigorously for 15 seconds. Attach syringe to a ≥16-French NG tube and administer contents; flush NG tube with additional 20 mL of water. Mixture must be used immediately after preparation.
Tablet: Administer with or without food. May be taken at any time of the day; swallow tablet whole.
Oral: May be taken with or without food; may be taken at any time of the day; swallow tablet whole.
Missed dose: Do not take an extra dose; resume treatment with next scheduled dose.
Familial hypercholesterolemia:
Pediatric: Adjunct to diet to reduce total cholesterol, LDL-C, and apoB levels in children and adolescents 8 to 17 years of age with heterozygous familial hypercholesterolemia (HeFH) if after an adequate trial of diet therapy the following findings are present: LDL-C greater than 190 mg/dL or greater than 160 mg/dL and there is a positive family history of premature cardiovascular disease or 2 or more other cardiovascular disease risk factors; adjunct to diet to reduce LDL-C, total cholesterol, nonHDL-C, and apoB 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 apoB in adults with familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) or alone if such treatments are unavailable.
Prevention of cardiovascular disease:
Primary prevention of atherosclerotic cardiovascular disease: To reduce the risk of myocardial infarction (MI), stroke, revascularization procedures, and angina in adults without a history of coronary heart disease (CHD) but who have multiple CHD risk factors.
Secondary prevention in patients with established atherosclerotic cardiovascular disease (Crestor only): To reduce the risk of MI, stroke, revascularization procedures, and angina in adults with a history of CHD.
Transplantation, post heart; Transplantation, post kidney
HMG-CoA reductase inhibitors (when referred to as "statins") may be confused with nystatin.
Rosuvastatin may be confused with atorvastatin, nystatin, pitavastatin
Substrate of BCRP/ABCG2, CYP2C9 (minor), CYP3A4 (minor), OATP1B1/1B3 (SLCO1B1/1B3); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abiraterone Acetate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Acipimox: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Antacids: May decrease the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Apalutamide: May decrease the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Asciminib: May increase the serum concentration of Rosuvastatin. Risk X: Avoid combination
Asunaprevir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Atazanavir: May increase the serum concentration of Rosuvastatin. Rosuvastatin may increase the serum concentration of Atazanavir. Management: Initiate rosuvastatin at 5 mg daily and do not exceed rosuvastatin 10 mg daily if coadministered with atazanavir/ritonavir. If combined, monitor for signs and symptoms of myopathy and rhabdomyolysis and for increased atazanavir toxicities. Risk D: Consider therapy modification
BCRP/ABCG2 Inhibitors: May increase the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Bezafibrate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Bezafibrate may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). More specifically, bezafibrate may increase the serum concentration of fluvastatin Management: Avoid use of bezafibrate and HMG-CoA reductase inhibitors (statins) unless strictly indicated due to the increased of muscle toxicity (including rhabdomyolysis). In patients who may be predisposed to myopathy, concomitant use is contraindicated. Risk D: Consider therapy modification
Capmatinib: May increase the serum concentration of Rosuvastatin. Management: Limit the dose of rosuvastatin to 10 mg daily when combined with capmatinib. Monitor closely for increased rosuvastatin effects/toxicities (eg, myalgias, rhabdomyolysis) when these agents are combined. Risk D: Consider therapy modification
CarBAMazepine: May decrease the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Ciprofibrate: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). 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. Risk D: Consider therapy modification
Cobicistat: May increase the serum concentration of Rosuvastatin. Management: If coadministeed with cobicistat/atazanavir or cobicistat/darunavir, initiate rosuvastatin at the lowest dose. Do not exceed rosuvastatin 10 mg/day with concurrent use of atazanavir/cobicistat or 20 mg/day with concurrent use of darunavir/cobicistat. Risk D: Consider therapy modification
Colchicine: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). HMG-CoA Reductase Inhibitors (Statins) may increase the serum concentration of Colchicine. Risk C: Monitor therapy
CycloSPORINE (Systemic): May increase the serum concentration of Rosuvastatin. Management: Limit rosuvastatin to 5 mg daily in patients who are also receiving cyclosporine, and monitor patients for increased rosuvastatin toxicities. Canadian labeling contraindicates concomitant use of rosuvastatin with cyclosporine. Risk D: Consider therapy modification
Daclatasvir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
DAPTOmycin: HMG-CoA Reductase Inhibitors (Statins) may enhance the adverse/toxic effect of DAPTOmycin. Specifically, the risk of skeletal muscle toxicity may be increased. Management: Consider temporarily stopping statin (HMG-CoA reductase inhibitor) therapy prior to daptomycin. If daptomycin is used with a statin, creatine phosphokinase (CPK) monitoring could be considered. Risk D: Consider therapy modification
Darolutamide: May increase the serum concentration of Rosuvastatin. Management: Limit the dose of rosuvastatin to 5 mg daily when combined with darolutamide. Monitor closely for increased rosuvastatin effects/toxicities (eg, myalgias, rhabdomyolysis) when these agents are combined. Risk D: Consider therapy modification
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. Labeling outside of the US recommends limiting the rosuvastatin dose to 5 mg per day. Risk D: Consider therapy modification
Dronedarone: May increase the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Elacestrant: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Elagolix: May decrease the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Elagolix, Estradiol, and Norethindrone: May decrease the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Elbasvir and Grazoprevir: May increase the serum concentration of Rosuvastatin. Management: Initiate rosuvastatin at 5 mg daily and limit the rosuvastatin dose to a maximum of 10 mg per day during coadministration with elbasvir/grazoprevir. Monitor closely for evidence of rosuvastatin toxicities (eg, myopathy, rhabdomyolysis). Risk D: 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. Risk D: Consider therapy modification
Enasidenib: May increase the serum concentration of Rosuvastatin. Management: Limit the dose of rosuvastatin to 10 mg once daily when combined with enasidenib. Risk D: Consider therapy modification
Eslicarbazepine: May decrease the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Febuxostat: May increase the serum concentration of Rosuvastatin. Management: Limit the dose of rosuvastatin to 20 mg daily when combined with febuxostat. Monitor closely for increased rosuvastatin effects/toxicities (eg, myalgias, rhabdomyolysis) when these agents are combined. Risk D: Consider therapy modification
Fenofibrate and Derivatives: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Fostamatinib: May increase the serum concentration of Rosuvastatin. Management: Limit the dose of rosuvastatin to 20 mg daily when combined with fostamatinib. Monitor closely for increased rosuvastatin effects/toxicities (eg, myalgias, rhabdomyolysis) when these agents are combined. Risk D: Consider therapy modification
Fostemsavir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Use the lowest possible starting statin dose and monitor patients closely for statin-related adverse effects (eg, muscle aches and pains) during coadministration with fostemsavir. Risk D: Consider therapy modification
Fusidic Acid (Systemic): May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). 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. Risk X: Avoid combination
Futibatinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Gemfibrozil: May enhance the myopathic (rhabdomyolysis) effect of Rosuvastatin. Gemfibrozil may increase the serum concentration of Rosuvastatin. Management: Avoid combination if possible. If combination cannot be avoided, initiate rosuvastatin at 5 mg/day and limit rosuvastatin to 10 mg/day. Monitor for signs/symptoms of rhabdomyolysis. Risk D: Consider therapy modification
Gilteritinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Glecaprevir and Pibrentasvir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Use the lowest statin dose possible if combined with glecaprevir/pibrentasvir and monitor for increased statin effects/toxicities. Avoid concomitant use with atorva-, simva-, or lovastatin. Limit rosuvastatin to 10 mg daily and reduce pravastatin dose 50% Risk D: Consider therapy modification
Itraconazole: May increase the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Lanthanum: May decrease the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Administer HMG-CoA reductase inhibitors (eg, statins) at least two hours before or after lanthanum. Risk D: Consider therapy modification
Ledipasvir: May increase the serum concentration of Rosuvastatin. Risk X: Avoid combination
Leflunomide: May increase the serum concentration of Rosuvastatin. Management: Limit the maximum adult rosuvastatin dose to 10 mg/day in patients receiving leflunomide, and monitor for evidence of rosuvastatin toxicity (eg, muscle toxicity, elevated transaminase concentrations). Risk D: Consider therapy modification
Leniolisib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Letermovir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Lopinavir: May increase the serum concentration of Rosuvastatin. Management: Initiate rosuvastatin at 5 mg daily and limit the rosuvastatin dose to a maximum of 10 mg per day when used with lopinavir/ritonavir. Monitor patients closely for evidence of rosuvastatin toxicities (eg, myopathy, rhabdomyolysis). Risk D: Consider therapy modification
Maribavir: May increase the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Momelotinib: May increase the serum concentration of Rosuvastatin. Management: In patients who are receiving momelotinib, initiate rosuvastatin at a dose of 5 mg once daily and limit the rosuvastatin dose to a maximum of 10 mg once daily. Risk D: Consider therapy modification
Niacin: May enhance the myopathic (rhabdomyolysis) effect of Rosuvastatin. Risk C: Monitor therapy
Nirmatrelvir and Ritonavir: May increase the serum concentration of Rosuvastatin. Management: Consider temporarily discontinuing rosuvastatin during treatment with nirmatrelvir/ritonavir. It is not necessary to hold rosuvastatin either prior to or after completion of nirmatrelvir/ritonavir treatment. Risk D: Consider therapy modification
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May increase the serum concentration of Rosuvastatin. Management: Initiate rosuvastatin at 5 mg daily and limit the rosuvastatin dose to a maximum of 10 mg per day when used with the ombitasvir/paritaprevir/ritonavir/dasabuvir combination product. Monitor for rosuvastatin toxicities (eg, myopathy, rhabdomyolysis). Risk D: Consider therapy modification
Pacritinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Pretomanid: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Protease Inhibitors: May increase the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Raltegravir: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Red Yeast Rice: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Risk X: Avoid combination
Regorafenib: May increase the serum concentration of Rosuvastatin. Management: Limit the dose of rosuvastatin to 10 mg daily when combined with regorafenib. Monitor closely for increased rosuvastatin effects/toxicities (eg, myalgias, rhabdomyolysis) when these agents are combined. Risk D: Consider therapy modification
Repaglinide: HMG-CoA Reductase Inhibitors (Statins) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy
RifAMPin: May decrease the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Rupatadine: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Specifically, the risk for increased CPK and/or other muscle toxicities may be increased. Risk C: 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. Risk D: Consider therapy modification
Sparsentan: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Tafamidis: May enhance the myopathic (rhabdomyolysis) effect of Rosuvastatin. Tafamidis may increase the serum concentration of Rosuvastatin. Management: Avoid this combination if possible. If combined, initiate rosuvastatin at a dose of 5 mg once daily and do not exceed a dose of rosuvastatin 20 mg daily. Monitor for signs of myopathy and rhabdomyolysis. Risk D: Consider therapy modification
Taurursodiol: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Tedizolid: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: 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). Risk D: Consider therapy modification
Ticagrelor: May enhance the myopathic (rhabdomyolysis) effect of Rosuvastatin. Ticagrelor may increase the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Trabectedin: HMG-CoA Reductase Inhibitors (Statins) may enhance the myopathic (rhabdomyolysis) effect of Trabectedin. Risk C: Monitor therapy
Trofinetide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid concurrent use with OATP1B1/1B3 substrates for which small changes in exposure may be associated with serious toxicities. Monitor for evidence of an altered response to any OATP1B1/1B3 substrate if used together with trofinetide. Risk D: Consider therapy modification
Velpatasvir: May increase the serum concentration of Rosuvastatin. Management: Initiate rosuvastatin at 5 mg daily and limit the rosuvastatin dose to a maximum of 10 mg per day during coadministration with sofosbuvir/velpatasvir. Monitor closely for evidence of rosuvastatin toxicities (eg, myopathy, rhabdomyolysis). Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): HMG-CoA Reductase Inhibitors (Statins) may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Voclosporin: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Voxilaprevir: May increase the serum concentration of Rosuvastatin. Risk X: Avoid combination
Adequate contraception is recommended if an HMG-CoA reductase inhibitor (statin) is required in patients who may become pregnant (AHA/ACC [Grundy 2019]; CCS [Pearson 2021]). Patients planning to become pregnant should discuss their lifetime risk of cardiovascular disease, as well as risks and benefits of statin therapy with their health care team (CCS [Pearson 2021]). When appropriate, statins can be discontinued 1 to 2 months prior to conception (AHA/ACC [Grundy 2019]).
When a statin is needed in a patient of reproductive potential, a more hydrophilic option (eg, pravastatin, rosuvastatin) may be preferred to limit placental transfer (CCS [Pearson 2021]).
In healthy pregnancies, changes in lipid synthesis occur that are required for normal placental and fetal growth. Low-density lipoprotein cholesterol and triglycerides increase as pregnancy progresses and decline postpartum. HMG-CoA reductase inhibitors (statins) decrease the synthesis of cholesterol and substances derived from cholesterol. Therefore, based on the mechanism of action, in utero exposure may cause fetal harm (Lecarpentier 2012); however, data from available studies have not shown an increased risk of major congenital anomalies following first trimester exposure (Bateman 2015; Chang 2021; Vahedian-Azimi 2021a). Additional data are needed to evaluate other pregnancy outcomes, such as miscarriage (Vahedian-Azimi 2021b).
Because there is potential for fetal harm, statins should be discontinued once pregnancy is recognized (AHA/ACC [Grundy 2019]; Brunham 2018). If lipid-lowering therapy during pregnancy is required, it should be individualized based on the therapeutic needs of the patient, considering the lifetime risk of untreated disease, use of nonstatin therapies, as well as the known risks and benefits of statins. Based on limited data, when a statin is needed in a pregnant patient, a more hydrophilic option (eg, pravastatin, rosuvastatin) may be preferred. Lipophilic statins (eg, atorvastatin, fluvastatin, lovastatin, simvastatin, pitavastatin) may be more likely to cross the placenta and increase the risk of congenital malformations (AHA/ACC [Grundy 2019]; CCS [Pearson 2021]; Lecarpentier 2012).
Additional data are needed to clarify the role of statins for the prevention of atherosclerotic cardiovascular disease in at-risk pregnant patients (AHA/ACC [Grundy 2019]; CCS [Pearson 2021]; Parikh 2021).
Rosuvastatin is present in breast milk.
Data related to the presence of rosuvastatin in breast milk are available from case reports (Lwin 2018; Schutte 2013).
• Rosuvastatin 40 mg daily was re-initiated in a lactating patient 33 days postpartum. Rosuvastatin breast milk concentrations were 15.2 ng/mL (1 hour after the oral dose) and increased to 29.4 ng/mL (7 hours after the dose). Additional breast milk concentrations of rosuvastatin were between 21.9 ng/mL and 22.8 ng/mL (3 samples obtained at random times between 4 and 80 days of treatment). Maternal serum concentrations of rosuvastatin on day 25 of therapy were 18 ng/mL, 23 hours after the dose (Schutte 2013).
• Rosuvastatin 20 mg once daily was initiated in a lactating patient 13 months postpartum. Breast milk samples were obtained over 24 hours after the patient had received at least 5 doses. Rosuvastatin breast milk concentrations ranged from 16.58 ng/mL to 58.59 ng/mL with the highest concentration occurring ~17 hours after the dose. Maternal plasma concentrations of rosuvastatin were 2.47 ng/mL (~14 hours after the dose). Authors of the study calculated the estimated exposure of rosuvastatin to a breastfeeding infant to be 4.63 mcg/kg/day (relative infant dose [RID] 1.5% based on the weight adjusted maternal dose). The infant was not breastfed in this study (Lwin 2018).
• In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000); however, authors of one study suggest monitoring growth and development of infants exposed to rosuvastatin via breast milk until additional data are available (Lwin 2018).
HMG-CoA reductase inhibitors (statins) decrease the synthesis of cholesterol and substances derived from cholesterol. Normal concentrations of cholesterol in breast milk are required for infant development (Holmsen 2017; Lecarpentier 2012). Due to the potential for adverse events in the breastfed infant, breastfeeding is not recommended by the manufacturer. Available guidelines recommend resuming statin therapy once breastfeeding is completed (AHA/ACC [Grundy 2019]; CCS [Pearson 2021]).
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).
ACC/AHA Blood Cholesterol Guideline recommendations (ACC/AHA [Grundy 2019 ]):
Lipid panel (total cholesterol, HDL, LDL, triglycerides): Lipid profile (fasting or nonfasting) before initiating treatment. Fasting lipid profile should be rechecked 4 to 12 weeks after starting therapy and every 3 to 12 months thereafter. If 2 consecutive LDL levels are <40 mg/dL, consider decreasing the dose.
Hepatic transaminase levels: Baseline measurement of hepatic transaminase levels (ie, AST and ALT); measure AST, ALT, total bilirubin, and alkaline phosphatase if symptoms suggest rosuvastatin-induced 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. Monitor for signs and symptoms of myopathy or rhabdomyolysis.
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: Consider neuromuscular and serologic testing if immune-mediated necrotizing myopathy is suspected.
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).
Note: In pediatric patients (10 to 17 years of age), maximum serum concentration and AUC have been shown to be similar to adult values
Onset of action: Within 1 week; maximal at 4 weeks
Distribution: Vd: 134 L
Protein binding: 88%
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)
Bioavailability: 20% (high first-pass extraction by liver)
Half-life elimination: 19 hours
Time to peak, plasma: 3 to 5 hours
Excretion: Feces (90%), primarily as unchanged drug
Altered kidney function: 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.
Hepatic function impairment: Cmax and AUC are increased in patients with Child-Pugh class A or Child-Pugh class B hepatic impairment.
Race/ethnicity: East Asian patients have ~2-fold elevation in exposure (AUC and Cmax).
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