Simvastatin is a moderate-intensity statin that inhibits HMG-CoA reductase, reducing hepatic cholesterol synthesis. It is a prodrug requiring hepatic activation.
Also known as: Zocor
Statin + antiarrhythmic: increased risk of myopathy.
Amiodarone may increase simvastatin levels. Maximum simvastatin dose: 20 mg/day with amiodarone.
DailyMed/FDA (NIH/NLM) — approved Simvastatin (Zocor) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8f55d5de-5a4f-4a39-8c84-c53976dd6af9
Statin + azole antifungal: CONTRAINDICATED — simvastatin levels increased >10-fold.
Ketoconazole is a potent CYP3A4 inhibitor. Simvastatin is a prodrug extensively metabolised by CYP3A4. CYP3A4 inhibition by ketoconazole increases simvastatin and active metabolite levels more than 10-fold. Such elevated levels cause massive muscle destruction — rhabdomyolysis with myoglobinuria, hyperkalaemia, and potentially fatal acute renal failure. CONTRAINDICATED — no safe dose exists. Use statins not metabolised by CYP3A4 (rosuvastatin, pravastatin).
Statin + azole antifungal: CONTRAINDICATED. Ketoconazole inhibits CYP3A4, increasing simvastatin levels >10-fold. Extreme risk of rhabdomyolysis.
Ketoconazole potently inhibits CYP3A4, increasing simvastatin levels more than 10-fold. CONTRAINDICATED — extreme risk of rhabdomyolysis.
DailyMed/FDA (NIH/NLM) — approved Simvastatin (Zocor) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8f55d5de-5a4f-4a39-8c84-c53976dd6af9
Statin + macrolide: CONTRAINDICATED — simvastatin levels significantly increased.
Erythromycin is a moderate CYP3A4 inhibitor. Combination with simvastatin increases simvastatin levels 2-4 fold. Although the increase is less than with ketoconazole, the risk of myopathy and rhabdomyolysis remains significant. The FDA withdrew the 80 mg simvastatin dose precisely due to rhabdomyolysis risk with CYP3A4 inhibitors. CONTRAINDICATED — use azithromycin (does not inhibit CYP3A4) as macrolide alternative.
Statin + macrolide: CONTRAINDICATED. Erythromycin inhibits CYP3A4, significantly increasing simvastatin levels. Risk of myopathy and rhabdomyolysis.
Erythromycin inhibits CYP3A4, increasing simvastatin levels and the risk of myopathy and rhabdomyolysis. CONTRAINDICATED.
DailyMed/FDA (NIH/NLM) — approved Simvastatin (Zocor) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8f55d5de-5a4f-4a39-8c84-c53976dd6af9
Ketolide + statin: severe risk of myopathy/rhabdomyolysis. Telithromycin inhibits CYP3A4, increasing simvastatin levels ~10-fold.
Telithromycin moderately inhibits CYP3A4, the main metabolic pathway for simvastatin. Increased simvastatin levels can cause severe myopathy with rhabdomyolysis. The combination is clinically significant and should be avoided.
Creatine kinase (CK), myopathy symptoms (muscle pain, weakness, dark urine).
Avoid coadministration. If unavoidable, discontinue simvastatin during telithromycin treatment. Alternative: pravastatin (not CYP3A4-metabolised).
DailyMed/FDA (NIH/NLM) — approved Telithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ba1cca98-f350-4655-88e3-6ef990779fb9
Significantly increases simvastatin levels (inhibits intestinal CYP3A4).
Avoid grapefruit juice. May substitute with other statins (rosuvastatin, pravastatin).
DailyMed/FDA (NIH/NLM) — approved Simvastatin (Zocor) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8f55d5de-5a4f-4a39-8c84-c53976dd6af9
No documented disease interactions.
CONTRAINDICATED in pregnancy and breastfeeding. Risk of fetal malformations.
CONTRAINDICATED in all trimesters.
Do not use during breastfeeding.
Discontinue at least 3 months before conception.
DailyMed/FDA (NIH/NLM) — approved Simvastatin (Zocor) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8f55d5de-5a4f-4a39-8c84-c53976dd6af9
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Moderate-intensity HMG-CoA reductase inhibitor. It is a prodrug requiring hepatic hydrolysis to the active metabolite (simvastatin acid).
Prodrug that undergoes hepatic hydrolysis by esterases to simvastatin acid (active metabolite), which inhibits HMG-CoA reductase.
Oral bioavailability: ~5%. Food slightly increases absorption. Tmax: 1.3-2.4 hours.
Metabolised by CYP3A4. Numerous interactions: strong inhibitors (ketoconazole, itraconazole, erythromycin, clarithromycin) CONTRAINDICATED. Induced by rifampicin, phenytoin, carbamazepine.
~2 hours (active metabolite). Elimination: ~60% faeces, ~13% urine. Extensive first-pass metabolism.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
