Rosuvastatin is a competitive inhibitor of HMG-CoA reductase, the enzyme responsible for converting HMG-CoA to mevalonate in cholesterol biosynthesis. By blocking this step, it:

1. Reduces Hepatic Cholesterol Synthesis: Depletes intracellular cholesterol, prompting upregulation of LDL receptors.
2. Enhances LDL Clearance: Increases hepatic uptake of LDL particles from the bloodstream.
3. Improves Lipid Profile:
   • Lowers LDL cholesterol by 45–63% (high-intensity statin effect).
   • Reduces triglycerides by 10–28%.
   • Raises HDL cholesterol by 8–14% (Lippincott Textbook of Pharmacology).

1. Primary Hyperlipidemia:
   • Management of elevated LDL cholesterol, mixed dyslipidemia, and familial hypercholesterolemia.
2. Atherosclerotic Cardiovascular Disease (ASCVD) Prevention:
   • Primary Prevention: For patients with a 10-year CVD risk ≥7.5% or diabetes.
   • Secondary Prevention: Reduces recurrent events post-MI, stroke, or revascularization (BNF).
3. Pediatric Use:
   • Familial hypercholesterolemia in children ≥10 years (dose: 5–20 mg daily).

• Adults:
  • Starting Dose: 5–10 mg once daily.
  • Maintenance Dose: 5–40 mg daily (max 40 mg/day for severe hyperlipidemia).
• Special Populations:
  • Asian Patients: Start at 5 mg due to higher systemic exposure.
  • Renal Impairment: Avoid 40 mg dose if eGFR <30 mL/min/1.73m².
  • Hepatic Impairment: Contraindicated in active liver disease or persistent transaminase elevation (BNF).
• Administration:
  • Take any time of day, with or without food.

• Common (≥1%):
  • Myalgia (muscle pain), headache, gastrointestinal disturbances (nausea, constipation).
  • Asymptomatic transaminase elevation (1–3% of patients).
• Serious (Rare):
  • Rhabdomyolysis: Severe muscle breakdown (risk <0.1%).
  • Hepatotoxicity: ALT/AST >3× ULN (discontinue if persistent).
  • New-Onset Diabetes: Slight increased risk with long-term use (Lange Basic & Clinical Pharmacology).

• Contraindications:
  • Active liver disease or unexplained transaminase elevation.
  • Pregnancy and lactation (risk of fetal harm).
• Monitoring:
  • Baseline liver function tests (LFTs) and lipid profile.
  • Repeat LFTs at 12 weeks, then annually.
  • Check creatine kinase (CK) if myalgia develops.
• Patient Counseling:
  • Avoid excessive grapefruit juice (>1 L/day) and alcohol.
  • Report unexplained muscle pain, tenderness, or dark urine promptly.

Rosuvastatin is minimally metabolized by CYP2C9 and relies on hepatic uptake via OATP1B1 transporters. Key interactions include:

1. OATP1B1 Inhibitors:
   • Cyclosporine: ↑ Rosuvastatin exposure 7–10× (max dose: 5 mg/day).
   • Gemfibrozil: ↑ Risk of myopathy (avoid combination).
2. Antacids: Separate administration by 2 hours (reduces absorption).
3. Warfarin: Monitor INR (rosuvastatin may ↑ anticoagulant effect).

• Generic Name: Rosuvastatin calcium.
• Brand Names: Crestor (original), Rozavel, Rovasta, and generics.