Pravastatin
Pravastatin
Generic Name
Pravastatin
Mechanism
- Inhibits the HMG‑CoA reductase enzyme, the rate‑limiting step in cholesterol biosynthesis.
- Reduces hepatic intracellular cholesterol, upregulating LDL‑receptor expression and enhancing clearance of LDL‑cholesterol from plasma.
- Exerts pleiotropic effects: anti‑inflammatory, improved endothelial function, and plaque stabilization.
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Pharmacokinetics
- Absorption: Rapid, peak plasma concentration (Cmax) 1–2 h post‑dose; oral bioavailability ≈ 35 %.
- Distribution: Low plasma protein binding (~ 10 %); limited tissue penetration due to hydrophilicity.
- Metabolism: Minimal; primarily via glucuronidation (UGT1A9, UGT1A10); negligible CYP3A4 involvement.
- Excretion: Renal (≈ 55 %) and biliary (≈ 45 %).
- Half‑life: 1–2 h; steady state reached in ~ 4 days.
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Indications
- Primary prevention of atherosclerotic cardiovascular disease (ASCVD) in adults ≥ 40 y with LDL‑C ≥ 70 mg/dL.
- Secondary prevention post‑myocardial infarction, ischemic stroke, or established peripheral arterial disease.
- Heterozygous familial hypercholesterolemia (HDL‑C < 100 mg/dL or LDL‑C ≥ 190 mg/dL).
- Pre‑operative LDL lowering in high‑risk cardiac surgery patients.
- Reduction of LDL‑C in statin‑tolerant patients requiring low‑dose therapy.
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Contraindications
- Contraindicated: Pregnancy, lactation, active liver disease (ALT/AST > 3× ULN), suspected or confirmed statin intolerance.
- Warnings:
- Myopathy/rhabdomyolysis: rare but possible, especially with high doses or concomitant nephrotoxic agents.
- Hepatotoxicity: monitor liver enzymes; discontinue if ALT/AST > 3× ULN.
- Renal impairment: dose adjustment NOT required for mild–moderate CKD; safety data limited in end‑stage renal disease.
- Drug interactions: minimal CYP interactions, but caution with potent P-gp inhibitors (e.g., ivermectin) and strong renal tubular secretagogues.
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Dosing
| Population | Dose | Duration | Notes |
| Adults (primary/secondary) | 10 mg once daily | 4–12 weeks | Start low, titrate ↑10 mg weekly to 40 mg if LDL‑C goal unmet. |
| Heterozygous FH | 20–80 mg daily | 4–12 weeks | 20 mg may be sufficient; titrate to 40–80 mg per response. |
| Elderly or renal impairment | 10 mg daily | 4–12 weeks | No dose adjustment required for CKD < 60 mL/min/1.73 m². |
| Children (≥ 10 y) | 5 mg daily | 4–12 weeks | Limited data; use only in clinical trials or research settings. |
• Take with or without food; no significant food‑drug interaction.
• Avoid concurrent use with high‑dose chloramphenicol or zoxacrine.
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Adverse Effects
Common (≤ 2 % incidence)
• Headache, abdominal pain, diarrhea, mild myalgia.
Serious (≤ 0.3 % incidence)
• Myopathy/rhabdomyolysis: CK > 10× ULN, dark urine, muscle weakness.
• Hepatotoxicity: ALT/AST > 3× ULN, jaundice, fatigue.
• Allergic reactions: rash, pruritus, angioedema.
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Monitoring
| Test | Frequency | Reason |
| Serum lipids | Baseline, 4–6 wks, then 3–6 mo | Assess therapeutic response, adjust dose. |
| LFTs (ALT, AST) | Baseline, 4–6 wks, then annually | Detect hepatotoxicity early. |
| CK (if symptoms) | As clinically indicated | Identify myopathy/rhabdomyolysis. |
| Glucose/HbA1c | Baseline, annually | Monitor for new‑onset diabetes. |
| Renal function | Baseline, 6 mo, then annually | Not dose‑adjusting, but used for safety. |
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Clinical Pearls
- Low drug‑drug interaction profile: Because pravastatin has negligible CYP metabolism, it’s ideal for polypharmacy patients (e.g., on antiretrovirals or beta‑blockers).
- Milder side‑effect burden: Clinical trials show the lowest incidence of myalgia compared to other statins.
- No dose adjustment in mild–moderate CKD: Unlike simvastatin or atorvastatin, it can be safely used in up to stage 3 CKD.
- Efficacy in the elderly: Maintains lipid‑lowering potency and safety; useful when muscle toxicity risks are higher.
- Pregnancy warning: Though generally contraindicated, evidence suggests lower placental transfer owing to hydrophilicity; still avoid unless absolutely needed.
- Real‑world effectiveness: Registries report consistent LDL‑C reductions (~ 35–45 %) with high adherence rates due to tolerability.
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