Introduction
Rosuvastatin is a widely prescribed lipid-lowering agent belonging to the statin class. It is primarily used to improve lipid profiles by lowering low-density lipoprotein cholesterol (LDL-C), increasing high-density lipoprotein cholesterol (HDL-C), and reducing triglycerides, thereby reducing cardiovascular risk.
Pharmacological Mechanism
Rosuvastatin functions as a competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in hepatic cholesterol biosynthesis. By inhibiting this enzyme, rosuvastatin decreases intrahepatic cholesterol synthesis, leading to:
- Upregulation of LDL receptors on hepatocytes
- Enhanced clearance of LDL particles from plasma
- Suppression of very low-density lipoprotein (VLDL) synthesis
These effects collectively reduce circulating LDL-C and triglycerides, improving lipid profiles and reducing atherosclerotic risk.
Indications and Dosage
Indications:
- Primary hypercholesterolemia and mixed dyslipidemia
- Familial hypercholesterolemia (heterozygous and homozygous forms)
- Prevention of atherosclerotic cardiovascular disease (ASCVD)
Dosage:
- Adults: Initial dose usually 10-20 mg daily, titratable to a maximum of 40 mg/day.
- Familial hypercholesterolemia homozygotes: Start at 20 mg, up to 40 mg/day.
- Pediatric patients (8-17 years): For HeFH, 5-20 mg daily depending on age and response; safety below 8 years not established.
Administration is oral, with or without food, at any time of day.
Clinical Efficacy
Multiple randomized controlled trials and meta-analyses have demonstrated that rosuvastatin effectively:
- Lowers LDL-C by approximately 45-63%, dose-dependent
- Increases HDL-C modestly by 5-10%
- Reduces triglycerides by 15-30%
These lipid modifications are associated with significant reductions in cardiovascular events including myocardial infarction, stroke, and cardiovascular mortality.
Safety Profile and Adverse Effects
Common Adverse Effects (occurring in ~1% of patients):
- Gastrointestinal symptoms: nausea, abdominal pain, constipation
- Headache
- Dizziness and weakness
Serious Adverse Effects:
- Rhabdomyolysis and myopathy: Though rare, muscle breakdown can lead to acute renal failure; risk increased at higher doses (40 mg). Patients should report muscle pain, weakness, or dark urine immediately.
- Hepatotoxicity: Signs include jaundice, elevated liver enzymes, and symptoms like dark urine or pale stools.
- Proteinuria: Particularly monitored at high doses, though typically asymptomatic.
Drug Interactions
Rosuvastatin may interact pharmacokinetically with:
- Vitamin K antagonists (e.g., warfarin)
- Cyclosporine
- Gemfibrozil
- Certain antiretroviral agents
Such interactions may increase rosuvastatin plasma levels and risk of toxicity, necessitating careful monitoring.
Precautions and Contraindications
Contraindications include:
- Active liver disease or unexplained persistent elevations of hepatic transaminases
- Untreated hypothyroidism
- History of rhabdomyolysis or muscle disorders
- Pregnancy and lactation (category X): rosuvastatin is teratogenic and contraindicated during pregnancy
- Recent major surgery or severe renal impairment may require caution
Precautions:
- Regular monitoring of liver function tests and creatine kinase is recommended.
- Patients should avoid excessive alcohol consumption and report any muscle symptoms promptly.
- Dose adjustments and discontinuation decisions should only be made by a healthcare provider.
Storage and Administration Notes
- Store at room temperature away from moisture and heat sources.
- Oral tablets should be swallowed whole and can be taken with or without food.
Conclusion
Rosuvastatin remains a cornerstone in lipid management with a robust evidence base supporting its efficacy in reducing LDL cholesterol and preventing cardiovascular events. While generally well tolerated, awareness of serious adverse effects, potential drug interactions, and contraindications is essential for safe use. Its role extends across adult and pediatric populations with specific dosing guidelines tailored to disease severity and patient characteristics.