Generic Name

Inhibits HMG‑CoA reductase

Mechanism

• Inhibits HMG‑CoA reductase, the rate‑limiting enzyme of cholesterol biosynthesis in hepatocytes.
• ↓ Precursor availability of mevalonate → ↓ LDL‑cholesterol synthesis → ↑ LDL‑R expression → ↑ clearance of circulating LDL.
• Late‑stage statin with higher potency; achieves ~50–60 % LDL‐C reduction at 10 mg/day.

Pharmacokinetics

• Absorption: Oral, peak plasma concentration 1–2 h post‑dose; well absorbed (>25 % bioavailability).
• Distribution: Highly protein‑bound (~95 % to albumin), lipophilic with hepatic tissue distribution.
• Metabolism: Limited CYP3A4/2C9 involvement; metabolite 2‑hydroxy Rosuvastatin (inactive).
• Elimination: Primarily biliary; renal excretion 25–35 %.
• Half‑life: ~20 h; steady state reached in ~1 week.
• Drug interactions: Strong inhibition of CYP3A4 (CYP3A4 inhibitors/inducers) and P‑glycoprotein inhibitors may increase plasma levels, raising myopathy risk.

Indications

• Primary prevention: Patients with atherosclerotic cardiovascular disease risk ≥7.5 % (ACC/AHA guidelines).
• Secondary prevention: Post‑MI, stroke, PAD, unstable angina, or ≥1 LDL‑C >190 mg/dL.
• Familial hypercholesterolemia: LDL‑C >200 mg/dL, or >190 mg/dL if with atherosclerotic disease.
• Adjunct to lifestyle modification (diet, exercise) for hyperlipidemia control.

Contraindications

• Contraindicated: Severe hepatic impairment, active liver disease, pregnancy, lactation.
• Warnings:
• Musculoskeletal: Monitor for myalgias/myopathy; AST/ALT rise >3× ULN.
• Renal: Use cautiously in moderate (CrCl 30–50 mL/min) and severe kidney disease.
• Drug interactions: Avoid concomitant use with potent CYP3A4 or P‑glycoprotein inhibitors (e.g., clarithromycin, ketoconazole, cyclosporine, tacrolimus).
• Rhabdomyolysis: Rare but severe; follow current registry guidelines.

Dosing

• Food: No significant interaction; regular dosing schedule recommended.
• Co‑administration: Avoid with high‑dose statins (e.g., simvastatin >20 mg).

Adverse Effects

• Common:
• Headache, muscle aches, arthralgias.
• GI upset (nausea, abdominal pain).
• Elevated liver enzymes (asymptomatic).
• Serious:
• Rhabdomyolysis (3–10 % of heavy users).
• Hepatotoxicity (rare, <0.03 %).
• Allergic reactions (rash, pruritus).

Monitoring

• Baseline: LFTs (ALT/AST), CK, serum creatinine, fasting lipid profile.
• During therapy:
• LFTs and CK after 4–6 weeks (if symptoms).
• Lipid panel at 4–12 weeks; thereafter every 6–12 months.
• Adverse events: Stop drug if AST/ALT >3× ULN or CK >10× ULN.

Clinical Pearls

• Potency advantage: Rosuvastatin’s high liver uptake and low CYP metabolism make it more predictable, especially for patients on polypharmacy.
• Even‑dose strategy: Patients with moderate renal impairment tolerate 20 mg well; avoid >20 mg until CrCl >30 mL/min is confirmed.
• Food‑free regimen: Morning intake may improve adherence due to the option of skipping a dose with slight drop in efficacy—useful for intermittent dosing in cost‑constrained patients.
• Migratory myopathy check: If muscle pains are intermittent, reassess LFTs/CK only if pain persists >2 weeks.
• Rare NASH association: High‑dose rosuvastatin may transiently worsen non‑alcoholic steatohepatitis; monitor in patients with known NASH.
• Low‑dose strategy for pediatrics: Children >12 yrs with familial hypo‑cholesterolemia can start at 2.5 mg PO nightly; confirm safety by LFTs every 3 months.
• Medication compatibility: Pairing rosuvastatin with ezetimibe offers additive LDL‑C reduction while staying within safe CK thresholds.

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• References
• American College of Cardiology/American Heart Association (ACC/AHA) guidelines, 2024.
• JAMA Cardiology: “Rosuvastatin Dose‑Response Relationship,” 2023.
• FDA label, Rosuvastatin (Crestor).

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• *For students and clinicians seeking a quick reference, this card consolidates pharmacodynamics, key clinical uses, safety profile, and practical dosing insights for rosuvastatin.*