Fixed-dose combination: statin plus intestinal cholesterol absorption inhibitor
Updated · Methodology
Second line
Primary hypercholesterolemia and mixed dyslipidemia when -C goal is not met on the maximum tolerated simvastatin dose. Per 2019 and SEA 2023 – second-line. Dose: 10/10, 10/20, 10/40 mg once daily in the evening. 80 mg simvastatin is not recommended due to rhabdomyolysis ( Safety Communication 2011). If 10/40 fails, switch to atorvastatin + ezetimibe or rosuvastatin + ezetimibe.
Sources
ICD-10: E78 · ICD-11: 5C80
Simvastatin inhibits HMG-CoA reductase after hepatic activation (prodrug); ezetimibe blocks the intestinal NPC1L1 protein. Combined -C reduction of 40–55%. Historical pair – the IMPROVE-IT trial (NEJM 2015) showed a 6.4% MACE reduction over 7 years in post-ACS patients, which is why ezetimibe entered the guidelines.
Contraindicated. Effective contraception in women of reproductive age; stop 1–2 months before conception.
Contraindicated. Defer therapy until breastfeeding ends.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
The simvastatin in this combination interacts with grapefruit just as simvastatin alone does: the juice blocks intestinal CYP3A4 and lets more drug into the blood. According to the Inegy SmPC, more than a litre of juice a day raised simvastatin acid exposure 7-fold, and one 240 ml glass in the morning raised it 1.9-fold. The excess damages muscle: pain, weakness, dark urine, raised creatine kinase. The SmPC says to avoid grapefruit juice during treatment. For people who want to keep drinking it, ezetimibe also comes combined with rosuvastatin.
Source: AEMPS: Ficha técnica de Inegy 10 mg/20 mg comprimidos (ezetimiba y simvastatina) (2026)
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Simvastatin + Ezetimibe is evaluated for the following indications with varying evidence strength: Dyslipidemia (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of Simvastatin + Ezetimibe (≥ 1 in 100): Myalgia, GI upset, Transaminase elevation, Headache. See the Safety section for uncommon and serious reactions.
Contraindicated. Effective contraception in women of reproductive age; stop 1–2 months before conception.
Contraindicated. Defer therapy until breastfeeding ends.
Simvastatin + Ezetimibe is contraindicated in: Hypersensitivity; Active liver disease; Pregnancy and breastfeeding; Concomitant strong CYP3A4 inhibitors (macrolides, azoles), gemfibrozil, cyclosporine, danazol. Full list in the Safety section.
Atorvastatin, Atorvastatin + Ezetimibe, Cod liver oil, Ezetimibe, Gemfibrozil, Omega-3 triglycerides (EPA and DHA), Rosuvastatin, Fluvastatin