Simvastatin
📖 About
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- ⬇️ Reduces LDL & total cholesterol; ⬆️ increases HDL.
- ❤️ Reduces CHD mortality, non-fatal MI, and stroke.
- 💉 Lowers need for revascularisation (CABG/PCI).
⚙️ Action
- 🔒 HMG-CoA reductase inhibitor acting on hepatocytes.
- 🛑 Blocks rate-limiting step in cholesterol synthesis.
- ⬆️ Upregulates hepatic LDL receptors → clears plasma LDL.
- ⬇️ Plasma LDL, TGs, and total cholesterol.
💉 Indications
- Hypercholesterolaemia.
- Mixed hyperlipidaemia.
- Secondary prevention of cardiovascular disease.
🔄 Interactions
- ⬆️ Myositis/myopathy risk with: ciclosporin, erythromycin, clarithromycin, fibrates, itraconazole, ketoconazole.
- ⚠️ Simvastatin may increase INR with warfarin → monitor.
- Amiodarone/verapamil: do not exceed 20 mg simvastatin daily.
🧬 Pharmacology
- Metabolised via CYP3A4 → very sensitive to CYP3A4 inhibitors.
⚠️ Simvastatin & Amlodipine
- Max dose with amlodipine = 20 mg (higher is off-label).
- Simvastatin 40 mg + amlodipine ≈ equivalent to simvastatin 80 mg → ↑ myopathy risk.
- Options if already on 40 mg:
- Reduce to 20 mg.
- Switch to pravastatin, fluvastatin, rosuvastatin, or atorvastatin (20–40 mg daily).
- Switch to alternative calcium channel blocker (but note: verapamil & diltiazem also max 20 mg).
⛔ Drugs Contraindicated with Simvastatin
- Azole antifungals: itraconazole, ketoconazole, posaconazole.
- Macrolides: erythromycin, clarithromycin, telithromycin.
- HIV protease inhibitors (e.g. nelfinavir).
- Nefazodone, ciclosporin, danazol, gemfibrozil.
⚠️ Dose Restrictions
- Do not exceed 10 mg with other fibrates (except fenofibrate).
- Do not exceed 20 mg with amiodarone, amlodipine, verapamil, diltiazem.
⚖️ Cautions
- Renal or liver disease.
- Heavy alcohol intake (check baseline risk).
⛔ Contraindications
- Active liver disease.
- Pregnancy & breastfeeding.
- Acute porphyria.
💥 Side Effects
- 🦵 Myalgia, cramps, muscle aches.
- 🧪 Myositis (reversible), rare myopathy/rhabdomyolysis (<1/1000).
- 🧠 Headache, GI upset (flatulence, abdominal pain, diarrhoea).
- 🩺 Hepatitis, ↑ LFTs, pancreatitis.
- Dermatological: rash, alopecia.
📊 Dose & Monitoring
- 💊 Usually: 10–40 mg nocte PO.
Max: 80 mg nocte (restricted use due to myopathy risk).
- ⚠️ Check LFTs before, at 3 months, then annually.
Stop if >3× ULN or persistent elevation.
- 💉 Stop statin and check CK if significant myalgia develops.
📚 References
