Pravastatin 💊
Always check the BNF link here before prescribing or adjusting doses.
Pravastatin is a lipid-lowering agent that primarily reduces LDL cholesterol, thereby lowering cardiovascular morbidity and mortality.
- ⬇️ Reduces LDL-C and total cholesterol, modestly increases HDL-C.
- 📉 Lowers risk of coronary heart disease (CHD) death, non-fatal MI, and stroke.
- 🩺 Reduces need for revascularisation procedures (both coronary and peripheral).
⚙️ Mechanism of Action
- Competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase - the rate-limiting enzyme in hepatic cholesterol synthesis.
- 🧬 Decreased intracellular cholesterol → upregulation of hepatic LDL receptors → increased plasma LDL clearance.
- Overall effect: ↓ LDL, ↓ total cholesterol, ↓ triglycerides, ↑ HDL.
- Pravastatin is hydrophilic and undergoes minimal CYP450 metabolism → lower risk of drug–drug interactions compared with other statins.
📋 Indications
- Primary hypercholesterolaemia (familial or non-familial).
- Mixed hyperlipidaemia (when diet alone is insufficient).
- Secondary prevention of cardiovascular events in patients with established atherosclerotic disease.
💊 Dose and Administration
- Use alongside a lipid-lowering diet and lifestyle modification.
- Typical dose: Pravastatin 20–40 mg once nightly.
- LFT monitoring: Check before initiation, at 3 months, then annually.
Stop or review if ALT/AST >3× upper limit of normal.
- CK monitoring: Stop immediately if myalgia develops and check CK.
- Adjust dose in renal impairment - start low and titrate cautiously.
⚠️ Contraindications
- Active liver disease or unexplained persistent transaminase elevation.
- Pregnancy and breastfeeding (teratogenic in animal studies).
- Acute porphyria.
🔄 Drug Interactions
- Fibrates → ↑ risk of myopathy and rhabdomyolysis → avoid combination.
- Ciclosporin → ~4-fold ↑ pravastatin levels; use lowest possible dose.
- Macrolides (erythromycin, clarithromycin) → temporarily stop pravastatin during therapy.
- Azoles (itraconazole, ketoconazole) → increase myopathy risk.
- Cholestyramine/Colestipol → ↓ pravastatin bioavailability by 40–50%; dose pravastatin ≥4 h after resin.
- Warfarin: No clinically significant interaction demonstrated.
- CYP450 system: Pravastatin is not metabolised by CYP3A4 or 2C9, so interactions are fewer than with simvastatin or atorvastatin.
💥 Adverse Effects
- 💪 Myalgia, muscle cramps, aches, weakness - monitor CK if severe.
- 🫀 Myositis or rhabdomyolysis (rare, reversible on withdrawal).
- 😣 GI disturbance - abdominal pain, diarrhoea, flatulence, nausea.
- 🧠 Headache, dizziness, fatigue.
- 🩸 Hepatotoxicity: Elevated transaminases, rarely hepatitis or pancreatitis.
- 💇♂️ Alopecia and rash occasionally reported.
📊 Pharmacology Summary
| Property | Details |
|---|
| Class | HMG-CoA reductase inhibitor (Statin) |
| Onset | 2–4 weeks for measurable lipid lowering |
| Half-life | 1.5–2 hours (shorter than atorvastatin or rosuvastatin) |
| Metabolism | Hepatic, minimal CYP450 involvement |
| Elimination | Renal and biliary routes |
| Hydrophilicity | Yes - reduces central nervous system penetration and muscle toxicity risk |
🧠 Clinical Pearls
- 🔹 In the WOSCOPS trial, pravastatin reduced first MI and cardiovascular death by ~31% in hyperlipidaemic men.
- 🔹 Hydrophilic nature = lower muscle toxicity risk → useful in statin-intolerant patients.
- 🔹 Dose at night to coincide with peak hepatic cholesterol synthesis.
- 🔹 Avoid high alcohol intake and review for reversible secondary causes of dyslipidaemia (e.g., hypothyroidism, nephrotic syndrome).
- 🔹 If intolerance develops, consider alternate statin (rosuvastatin, fluvastatin) or non-statin therapy (ezetimibe, PCSK9 inhibitors).
📚 References
- BNF: Pravastatin Sodium
- MHRA Drug Safety Update (Aug 2012): Statins and risk of myopathy.
- WOSCOPS Study Group. NEJM 1995;333:1301–1307.
- Stone NJ et al. 2018 AHA/ACC Cholesterol Guideline.
