Makindo Medical Notes

💊 About

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

🧠 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.