Introduction
Crestor (rosuvastatin calcium) is a synthetic, selective HMG-CoA reductase inhibitor belonging to the statin class of medications. It is primarily indicated for the management of dyslipidemia to reduce the risk of cardiovascular events. First approved by the FDA in 2003, Crestor has become a widely prescribed medication for cholesterol management due to its potent LDL-cholesterol lowering effects.
Mechanism of Action
Rosuvastatin competitively inhibits HMG-CoA reductase, the rate-limiting enzyme in the hepatic cholesterol biosynthesis pathway. This inhibition reduces intracellular cholesterol production, leading to upregulation of hepatic LDL receptors and increased clearance of LDL-cholesterol from the bloodstream. Additionally, rosuvastatin modestly increases HDL-cholesterol and reduces triglycerides through mechanisms that include reduced VLDL production.
Indications
- Hyperlipidemia and mixed dyslipidemia (Fredrickson type IIa and IIb)
- Primary hypercholesterolemia (heterozygous familial and non-familial)
- Homozygous familial hypercholesterolemia
- Primary dysbetalipoproteinemia (Fredrickson type III)
- Hypertriglyceridemia
- Primary prevention of cardiovascular disease in adults without clinically evident coronary heart disease but with multiple risk factors
- Slowing the progression of atherosclerosis
- Cardiovascular risk reduction in patients with established cardiovascular disease
Dosage and Administration
Standard dosing: 5-40 mg orally once daily- Initial dose: 10-20 mg daily
- Maximum dose: 40 mg daily (reserved for patients not achieving LDL-C goal with 20 mg)
- Asian patients: Consider 5 mg starting dose
- Renal impairment (CrCl <30 mL/min): Initial dose 5 mg, not to exceed 10 mg daily
- Severe hepatic impairment (Child-Pugh C): Contraindicated
- Elderly: No dosage adjustment necessary
- Cyclosporine coadministration: Limit rosuvastatin to 5 mg daily
Pharmacokinetics
Absorption: Absolute bioavailability approximately 20%. Peak plasma concentrations reached 3-5 hours post-dose. Food decreases rate but not extent of absorption. Distribution: Volume of distribution approximately 134 L. Approximately 90% protein bound, primarily to albumin. Metabolism: Minimal hepatic metabolism (approximately 10%) primarily via CYP2C9 isoenzyme. N-desmethyl and lactone metabolites are pharmacologically inactive. Elimination: Primarily excreted unchanged in feces (90%). Renal excretion accounts for approximately 10% of elimination. Half-life approximately 19 hours.Contraindications
- Active liver disease or unexplained persistent elevations of serum transaminases
- Pregnancy and breastfeeding
- Hypersensitivity to rosuvastatin or any component of the formulation
- Concomitant use with cyclosporine
Warnings and Precautions
Skeletal Muscle Effects: Risk of myopathy and rhabdomyolysis, particularly with higher doses, advanced age, renal impairment, and hypothyroidism. Monitor for unexplained muscle pain, tenderness, or weakness. Hepatotoxicity: Elevated liver enzymes reported. Obtain liver enzyme tests before initiation and as clinically indicated thereafter. Renal Effects: Proteinuria reported, particularly at higher doses. Generally transient and not associated with worsening renal function. Diabetes: Increased risk of HbA1c and fasting serum glucose levels. Cognitive Impairment: Rare reports of memory loss and confusion.Drug Interactions
Strong inhibitors of CYP2C9: May increase rosuvastatin exposure (e.g., fluconazole) Gemfibrozil: Avoid combination due to increased risk of myopathy Other fibrates: Increased risk of myopathy (use with caution) Warfarin: May enhance anticoagulant effect (monitor INR) Protease inhibitors: May increase rosuvastatin exposure (use with caution) Niacin: Increased risk of myopathy Colchicine: Increased risk of myopathyAdverse Effects
Common (≥2%): Headache, myalgia, constipation, nausea, abdominal pain, asthenia Serious:- Rhabdomyolysis with renal failure
- Hepatotoxicity
- Myopathy
- Hemorrhagic stroke (particularly in patients with advanced cerebrovascular disease)
- Diabetes mellitus
- Cognitive impairment
Monitoring Parameters
- Lipid panel at baseline, 4-12 weeks after initiation or dose change, and periodically thereafter
- Liver enzymes at baseline and as clinically indicated
- CPK in patients with muscle symptoms
- Renal function at baseline and periodically
- HbA1c or fasting glucose in patients with diabetes risk factors
- Signs and symptoms of muscle pain, tenderness, or weakness
Patient Education
- Take medication as prescribed, typically once daily
- Report unexplained muscle pain, tenderness, or weakness immediately
- Report any symptoms of liver problems (unusual fatigue, loss of appetite, abdominal pain, dark urine, jaundice)
- Maintain regular follow-up appointments for monitoring
- Adhere to cholesterol-lowering diet and exercise regimen
- Avoid excessive alcohol consumption
- Inform all healthcare providers about Crestor use, especially before new medications
- Use effective contraception if of childbearing potential
- Notify physician if planning pregnancy or becoming pregnant
References
1. FDA Prescribing Information: Crestor (rosuvastatin calcium) tablets. 2023 2. Cholesterol Treatment Trialists' Collaboration. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet. 2015;385(9976):1397-1405 3. Rosenson RS, et al. Statin safety: an update. Curr Atheroscler Rep. 2022;24(11):855-870 4. Mach F, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2020;41(1):111-188 5. Sirtori CR. The pharmacology of statins. Pharmacol Res. 2014;88:3-11 6. Stroes ES, et al. Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J. 2015;36(17):1012-1022