HMG-CoA reductase inhibitor + cholesterol absorption inhibitor Pregnancy: Contraindicated during pregnancy and lactation (eMC §4.3 and §4.6). Must not be used in women who are pregnant, trying to become pregnant or who suspect they are pregnant; treatment must be suspended for the duration of pregnancy or until it is determined the woman is not pregnant.

Simvastatin with ezetimibe

Brand names: Inegy

A fixed-dose combination tablet pairing simvastatin (an HMG-CoA reductase inhibitor statin) with ezetimibe (a cholesterol-absorption inhibitor), used to lower LDL-cholesterol when a statin alone gives insufficient control.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Ezetimibe/simvastatin 10/20 mg or 10/40 mg once daily (typical dose); dosage range 10/10 mg/day to 10/80 mg/day

Route: Oral

Frequency: Once daily in the evening, as a single dose, with or without food

Max: 10/80 mg/day — only recommended in patients with severe hypercholesterolaemia at high risk of cardiovascular complications who have not reached treatment goals on lower doses and when benefits are expected to outweigh the risks

Product in the fetched SPC is INEGY (ezetimibe/simvastatin). The patient should be on an appropriate lipid-lowering diet before and during treatment. Individualise the dose on LDL-C level, coronary heart disease risk status and response to current cholesterol-lowering therapy; make dose adjustments at intervals of not less than 4 weeks. Tablets must not be split. Coronary heart disease with a history of an ACS event: in the IMPROVE-IT cardiovascular outcomes study the starting dose was 10/40 mg once a day in the evening. Homozygous familial hypercholesterolaemia: recommended starting dose 10/40 mg/day in the evening; may be used as an adjunct to other lipid-lowering treatments (e.g. LDL apheresis) or if such treatments are unavailable. Dose caps with interacting medicines: with amiodarone, amlodipine, verapamil, diltiazem, or products containing elbasvir or grazoprevir, do not exceed 10/20 mg/day; with lipid-lowering doses of niacin (1 g/day or more), do not exceed 10/20 mg/day; with lomitapide (HoFH), do not exceed 10/40 mg/day. Give either at least 2 hours before or at least 4 hours after a bile acid sequestrant. Elderly: no dosage adjustment required. Paediatric: initiation must be under specialist review; in adolescents aged 10 years and over (boys Tanner Stage II and above, girls at least one year post-menarche) the recommended usual starting dose is 10/10 mg once a day in the evening, with a dosing range of 10/10 up to a maximum of 10/40 mg/day — clinical experience in 10–17 year olds is limited; not recommended below 10 years of age due to insufficient safety and efficacy data (no per-kg dose is stated). Hepatic impairment: no adjustment in mild (Child-Pugh 5 to 6); not recommended in moderate (Child-Pugh 7 to 9) or severe liver dysfunction. NOTE: comparator symbols (less-than / greater-than) were stripped when the SPC text was captured — verify numeric thresholds against the source SPC.

Dose adjustments

Renal

No dose modification necessary in mild renal impairment (eGFR 60 mL/min/1.73 m2 or above). In chronic kidney disease with eGFR below 60 mL/min/1.73 m2 the recommended dose is 10/20 mg once a day in the evening (source text reads '60 mL/min/1.73 m2' with the comparator stripped — verify); higher doses should be implemented cautiously.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substances or to any of the excipients
Pregnancy and lactation
Active liver disease or unexplained persistent elevations in serum transaminases
Concomitant administration of potent CYP3A4 inhibitors (agents increasing AUC approximately 5-fold or greater): itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors (e.g. nelfinavir), boceprevir, telaprevir, nefazodone and cobicistat-containing products
Concomitant administration of gemfibrozil, ciclosporin or danazol
In HoFH, concomitant lomitapide with doses above 10/40 mg (comparator stripped in capture — verify)

Side effects

Myalgia (common); myopathy including myositis and rhabdomyolysis with or without acute renal failure (frequency not known)
ALT and/or AST elevations (common); hepatitis/jaundice and hepatic failure reported (frequency not known)
Headache, dizziness, paraesthesia (uncommon)
Gastrointestinal effects — abdominal pain, dyspepsia, flatulence, nausea, vomiting, diarrhoea, dry mouth (uncommon)
Pruritus, rash, urticaria (uncommon); anaphylaxis (very rare) and angioedema (frequency not known)

Interactions

Potent CYP3A4 inhibitors (azole antifungals, macrolides, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, cobicistat) — contraindicated (myopathy/rhabdomyolysis risk)
Gemfibrozil, ciclosporin, danazol — contraindicated
Amiodarone, amlodipine, verapamil, diltiazem, elbasvir or grazoprevir — cap dose at 10/20 mg/day
Niacin at lipid-lowering doses (1 g/day or more) — cap dose at 10/20 mg/day
Lomitapide — cap dose at 10/40 mg/day (contraindicated above this in HoFH)
Bile acid sequestrants — dose at least 2 hours before or at least 4 hours after

Clinical monograph

How it works

Simvastatin inhibits hepatic HMG-CoA reductase to reduce cholesterol synthesis and upregulate LDL receptors, while ezetimibe blocks the intestinal NPC1L1 transporter to cut dietary and biliary cholesterol uptake, giving complementary LDL lowering.

Prescribing in practice

Simvastatin has more clinically significant drug interactions than other statins via CYP3A4 — it is contraindicated with potent CYP3A4 inhibitors (including certain azole antifungals, macrolides and HIV protease inhibitors) and high doses carry an increased myopathy/rhabdomyolysis risk, so combination with fibrates, amiodarone, diltiazem, verapamil or amlodipine requires dose limits per the SPC.
Avoid large quantities of grapefruit juice, which raises simvastatin exposure and myopathy risk.
Both components are contraindicated in active liver disease and in pregnancy and breastfeeding.

Monitoring

Check a lipid profile and liver transaminases before starting and periodically thereafter, and measure creatine kinase if the patient reports unexplained muscle pain, tenderness or weakness.

Counselling the patient

Report any unexplained muscle pain, tenderness or weakness promptly.
Take the dose in the evening and avoid grapefruit juice.
Continue lifestyle and dietary measures alongside the tablet.

Evidence & guidelines

The IMPROVE-IT trial showed adding ezetimibe to a statin further reduced cardiovascular events after acute coronary syndrome, supporting combined therapy when statin monotherapy is insufficient.

Reference: NICE NG181; MHRA; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways