Inegy (Ezetimibe/Simvastatin)
Combination cholesterol-lowering tablet for reducing LDL cholesterol and cardiovascular risk
Inegy is a prescription combination medicine containing ezetimibe and simvastatin. It works through a dual mechanism to lower LDL ("bad") cholesterol: ezetimibe blocks cholesterol absorption in the intestine, while simvastatin reduces cholesterol production in the liver. Together, they can reduce LDL cholesterol by up to 60%. Inegy is used alongside diet and exercise for patients with primary hypercholesterolaemia, homozygous familial hypercholesterolaemia, or homozygous sitosterolaemia.
Quick Facts
Key Takeaways
- Inegy combines two cholesterol-lowering mechanisms in a single tablet, reducing LDL cholesterol by up to 60% when combined with lifestyle changes.
- Take Inegy once daily in the evening, with or without food. Evening dosing is preferred because cholesterol synthesis peaks at night.
- Report any unexplained muscle pain, tenderness or weakness to your doctor immediately, as this may be a sign of rhabdomyolysis, a rare but serious condition.
- Inegy is strictly contraindicated during pregnancy and breastfeeding. Women of childbearing potential must use effective contraception.
- Avoid grapefruit and grapefruit juice while taking Inegy, as they can dangerously increase simvastatin levels in the blood.
What Is Inegy and What Is It Used For?
Inegy belongs to a class of medicines known as lipid-modifying agents. It contains two active substances that work through complementary mechanisms to lower cholesterol levels in the blood. Ezetimibe acts at the brush border of the small intestine, where it selectively inhibits the Niemann-Pick C1-Like 1 (NPC1L1) protein, which is responsible for the absorption of cholesterol from the intestinal lumen into enterocytes. By blocking this transporter, ezetimibe reduces the amount of dietary and biliary cholesterol that enters the bloodstream by approximately 50%.
Simvastatin belongs to the statin class of drugs. It works by competitively inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in hepatic cholesterol biosynthesis. By reducing intracellular cholesterol synthesis in the liver, simvastatin triggers an upregulation of LDL receptors on hepatocyte surfaces, which in turn increases the clearance of LDL cholesterol from the circulation. Simvastatin also modestly raises HDL ("good") cholesterol and lowers triglycerides.
The combination of these two mechanisms provides a more comprehensive approach to cholesterol lowering than either agent alone. Clinical trials have demonstrated that the ezetimibe/simvastatin combination can reduce LDL cholesterol by up to 60%, compared with approximately 35-45% with simvastatin monotherapy. The landmark IMPROVE-IT trial, published in the New England Journal of Medicine in 2015, demonstrated that adding ezetimibe to simvastatin therapy significantly reduced cardiovascular events in patients who had recently experienced an acute coronary syndrome, providing robust evidence for the clinical benefit of dual-mechanism cholesterol lowering.
Approved Indications
Inegy is approved by the European Medicines Agency (EMA) and equivalent regulatory authorities worldwide for the following indications:
- Primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet, in patients who are already controlled on the individual components given concurrently at the same dose level, or in patients inadequately controlled with a statin alone.
- Homozygous familial hypercholesterolaemia (HoFH), as an adjunct to diet and other lipid-lowering treatments (such as LDL apheresis) or when such treatments are unavailable.
- Cardiovascular disease prevention, to reduce the risk of cardiovascular events in patients with coronary heart disease and a history of acute coronary syndrome, as an adjunct to ongoing statin therapy or when statin therapy is being initiated.
According to the ESC/EAS Guidelines for the Management of Dyslipidaemia (2019), combination therapy with ezetimibe and a statin is recommended when the LDL cholesterol goal is not achieved with the maximum tolerated dose of a statin alone. This is a Class I recommendation with Level B evidence, reflecting the strong clinical data supporting the use of this combination approach.
What Should You Know Before Taking Inegy?
Contraindications
Inegy must not be taken in the following situations, as the risks significantly outweigh any potential benefits:
- Hypersensitivity to ezetimibe, simvastatin, or any of the excipients in the formulation.
- Pregnancy and breastfeeding — Simvastatin is classified as FDA Pregnancy Category X. Cholesterol and other products of cholesterol biosynthesis are essential for foetal development, and inhibiting cholesterol synthesis may cause foetal harm. Women of childbearing potential must use effective contraception during treatment. If pregnancy occurs, Inegy must be discontinued immediately.
- Active liver disease or unexplained persistent elevations of serum transaminases (ALT or AST greater than three times the upper limit of normal).
- Concurrent use of potent CYP3A4 inhibitors including itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors (such as nelfinavir), boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, and cobicistat-containing products.
- Concurrent use of gemfibrozil, ciclosporin, or danazol.
Warnings and Precautions
Simvastatin, like other statins, can rarely cause myopathy, which manifests as muscle pain, tenderness or weakness associated with elevated creatine kinase (CK) levels. In very rare cases, myopathy can progress to rhabdomyolysis, a serious condition involving the breakdown of skeletal muscle tissue that can lead to acute kidney failure and death. The risk of myopathy and rhabdomyolysis increases with higher doses of simvastatin and with concurrent use of certain interacting drugs. Report any unexplained muscle symptoms to your doctor immediately.
Before starting Inegy, your doctor should perform liver function tests (LFTs) and may check creatine kinase levels. These tests should be repeated periodically during treatment, especially if the dose is increased. Conditions that predispose patients to myopathy include advanced age (over 65 years), female sex, uncontrolled hypothyroidism, renal impairment, and high alcohol consumption.
Patients of Chinese ancestry may be at increased risk for myopathy when taking simvastatin with lipid-modifying doses of niacin. Caution is warranted, and lower doses of simvastatin should be considered in this population. Additionally, the 80 mg dose of simvastatin is associated with a significantly higher risk of myopathy compared to lower doses, and its use should be restricted to patients who have been taking this dose chronically without evidence of muscle toxicity.
If you develop interstitial lung disease (progressive dyspnoea, non-productive cough, and general health deterioration including fatigue, weight loss and fever), discontinue Inegy and consult your doctor. Rare cases of immune-mediated necrotising myopathy (IMNM) have been reported with statin therapy. IMNM is characterised by proximal muscle weakness and elevated CK that persist despite statin discontinuation, and it requires immunosuppressive treatment.
Pregnancy and Breastfeeding
Inegy is absolutely contraindicated during pregnancy. Simvastatin may cause congenital abnormalities when administered to pregnant women. Cholesterol and other products of cholesterol biosynthesis are essential components for foetal development, including the synthesis of steroids and cell membranes. The potential risk to the foetus outweighs any possible benefit of treating hypercholesterolaemia during pregnancy.
Women of childbearing potential must use reliable contraception during treatment with Inegy. If a patient becomes pregnant while taking Inegy, the drug must be discontinued immediately and the patient informed of the potential hazard to the foetus. It is not known whether ezetimibe or simvastatin is excreted in human breast milk; therefore, breastfeeding women should not take Inegy.
Effects on Driving and Operating Machinery
Inegy has no or negligible influence on the ability to drive and use machines. However, dizziness has been reported as an uncommon side effect. If you experience dizziness while taking Inegy, avoid driving or operating machinery until the symptoms resolve.
How Does Inegy Interact with Other Drugs?
Drug interactions with Inegy are primarily driven by the simvastatin component. Simvastatin is metabolised by cytochrome P450 3A4 (CYP3A4) in the liver. Drugs that inhibit CYP3A4 can increase plasma concentrations of simvastatin acid, the active metabolite, thereby increasing the risk of myopathy and rhabdomyolysis. The ezetimibe component has fewer clinically significant drug interactions but does interact with ciclosporin and some bile acid sequestrants.
Understanding these interactions is critical for safe prescribing. The following table summarises the most important drug interactions. Your doctor or pharmacist should always check for potential interactions when prescribing Inegy alongside other medications.
Major Interactions (Contraindicated or Avoid)
| Interacting Drug | Effect | Recommendation |
|---|---|---|
| Itraconazole, Ketoconazole, Posaconazole | Potent CYP3A4 inhibition; markedly increases simvastatin levels | Contraindicated — do not use together |
| HIV Protease Inhibitors (e.g. ritonavir, nelfinavir) | Strong CYP3A4 inhibition; large increase in simvastatin exposure | Contraindicated — do not use together |
| Erythromycin, Clarithromycin, Telithromycin | Moderate-strong CYP3A4 inhibition; increases myopathy risk | Contraindicated — do not use together |
| Gemfibrozil | Increases simvastatin levels via glucuronidation inhibition; high myopathy risk | Contraindicated — do not use together |
| Ciclosporin | Increases both ezetimibe and simvastatin exposure; high myopathy risk | Contraindicated — do not use together |
| Danazol | Increases simvastatin levels; increased myopathy risk | Contraindicated — do not use together |
| Grapefruit juice (large quantities) | CYP3A4 inhibition; increases simvastatin exposure | Avoid grapefruit and grapefruit juice entirely |
Moderate Interactions (Dose Adjustment Required)
| Interacting Drug | Effect | Simvastatin Dose Limit |
|---|---|---|
| Amiodarone | Moderate CYP3A4 inhibition; increased myopathy risk | Max 20 mg/day |
| Verapamil, Diltiazem | Moderate CYP3A4 inhibition; increased myopathy risk | Max 20 mg/day |
| Amlodipine | Mild CYP3A4 inhibition; modestly increases simvastatin levels | Max 20 mg/day |
| Lomitapide | Increases simvastatin exposure | Max 40 mg/day (or 20 mg for HoFH patients on lomitapide) |
| Niacin (nicotinic acid) ≥1 g/day | Increased myopathy risk, particularly in patients of Chinese ancestry | Caution — weigh risks and benefits |
| Fusidic acid | May increase simvastatin levels; isolated myopathy reports | Temporarily suspend Inegy during fusidic acid course |
Other Notable Interactions
Warfarin and other coumarin anticoagulants: Simvastatin may modestly potentiate the effect of coumarin anticoagulants. If Inegy is started or the dose is changed in patients taking warfarin, the INR should be monitored more frequently until it has stabilised.
Bile acid sequestrants (cholestyramine, colestipol): Administration of ezetimibe at the same time as cholestyramine reduces the bioavailability of ezetimibe by approximately 55%. Inegy should be taken at least 2 hours before or 4 hours after a bile acid sequestrant.
Fibrates (other than gemfibrozil): While fenofibrate, bezafibrate and other fibrates (except gemfibrozil) may be used cautiously with lower doses of simvastatin, the combination increases the risk of myopathy. Clinical monitoring for muscle symptoms is essential. The combination of ezetimibe with fibrates has not been extensively studied and cannot be recommended as a standard approach.
Colchicine: Cases of myopathy, including rhabdomyolysis, have been reported with simvastatin co-administered with colchicine, and caution should be exercised when prescribing these drugs together.
What Is the Correct Dosage of Inegy?
Inegy should always be taken as prescribed by your doctor. The dose is individualised based on the patient's baseline LDL cholesterol level, cardiovascular risk profile, treatment goals defined by current guidelines (such as ESC/EAS 2019), and potential drug interactions. Before starting Inegy, patients should be placed on a standard cholesterol-lowering diet and should continue this diet throughout treatment.
Adults
Standard Adult Dosing
The recommended dose range is Inegy 10/10 mg to 10/40 mg, taken once daily in the evening. The choice of simvastatin dose should be based on the patient's cardiovascular risk and the LDL cholesterol reduction needed to reach target levels.
- Inegy 10/10 mg: Suitable for patients requiring modest LDL reduction or those at risk of drug interactions limiting simvastatin dose.
- Inegy 10/20 mg: Common starting dose for many patients with primary hypercholesterolaemia.
- Inegy 10/40 mg: For patients requiring more aggressive LDL lowering; provides approximately 55% LDL reduction.
- Inegy 10/80 mg: Restricted to patients who have been taking this dose for 12 months or more without evidence of muscle toxicity. Not recommended for new patients or dose escalation due to increased myopathy risk.
Children and Adolescents
Paediatric Dosing (Age 10-17 years)
In adolescents aged 10 to 17 years with heterozygous familial hypercholesterolaemia, the recommended starting dose is Inegy 10/10 mg once daily in the evening. The dose may be titrated up to Inegy 10/40 mg based on the individual response and tolerability. The 10/80 mg dose is not recommended in paediatric patients.
Inegy is not recommended for children under 10 years of age, as data on safety and efficacy in this age group are insufficient.
Elderly
Dosing in Elderly Patients
No dose adjustment is necessary based on age alone. However, elderly patients (over 65 years) are at increased risk of myopathy with statins, particularly at higher doses. Careful dose selection is recommended, starting at the lower end of the dosing range. Clinical monitoring for muscle symptoms is particularly important in this population.
Patients with Renal Impairment
Renal Impairment Dosing
No dose adjustment is needed for patients with mild renal impairment (eGFR ≥60 mL/min). For patients with moderate to severe renal impairment (eGFR <60 mL/min), doses exceeding Inegy 10/20 mg should be carefully considered and implemented with caution, as simvastatin exposure may be increased.
Patients with Hepatic Impairment
Hepatic Impairment
Inegy is contraindicated in patients with active liver disease or unexplained persistent elevations of serum transaminases. For patients with mild hepatic impairment (Child-Pugh score 5-6), no dose adjustment is generally needed, but close monitoring of liver function is recommended.
Missed Dose
If you miss a dose of Inegy, take it as soon as you remember on the same day. If you do not remember until the next day, skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for the missed one. Missing a single dose will not significantly affect your overall cholesterol control, as the effects of Inegy are maintained over time with consistent daily dosing.
Overdose
In the event of an overdose, contact your local poison control centre or seek emergency medical attention immediately. There is no specific antidote for Inegy overdose. Treatment is supportive and symptomatic. General measures include monitoring of liver function and CK levels, along with standard supportive care. Due to the extensive protein binding of both ezetimibe and simvastatin, haemodialysis is not expected to significantly enhance drug clearance.
What Are the Side Effects of Inegy?
Like all medicines, Inegy can cause side effects, although not everybody gets them. The side effect profile of the combination is consistent with the known safety profiles of the individual components. The following side effects have been reported in clinical trials and post-marketing surveillance. They are grouped by frequency according to the MedDRA convention used by the European Medicines Agency.
Common
- Headache
- Muscle pain (myalgia)
- Abdominal pain
- Flatulence
- Diarrhoea
- Nausea
- Constipation
- Fatigue and asthenia
- Elevated liver enzymes (ALT and/or AST)
- Upper respiratory tract infection
Uncommon
- Dizziness
- Elevated creatine kinase (CK)
- Muscle cramps or spasms
- Rash or pruritus (itching)
- Dyspepsia (indigestion)
- Dry mouth
- Insomnia
- Paraesthesia (tingling or numbness)
- Peripheral neuropathy
- Gallstones (cholelithiasis)
Rare
- Myopathy (muscle disease with CK elevation)
- Rhabdomyolysis (muscle breakdown; potentially life-threatening)
- Hepatitis (liver inflammation)
- Jaundice
- Pancreatitis
- Thrombocytopenia (low platelet count)
- Angioedema
- Erythema multiforme
Very Rare
- Immune-mediated necrotising myopathy (IMNM)
- Interstitial lung disease
- Stevens-Johnson syndrome
- Lupus-like syndrome
- Dermatomyositis
- Acute kidney failure (secondary to rhabdomyolysis)
Contact your doctor immediately if you experience any of the following: unexplained muscle pain, tenderness, weakness or cramps (especially if accompanied by fever or malaise); dark-coloured urine (which may indicate rhabdomyolysis); yellowing of the skin or eyes (jaundice); unusual fatigue; severe abdominal pain; or any signs of an allergic reaction (rash, swelling of the face or throat, difficulty breathing).
It is important to note that statin therapy, including the simvastatin component of Inegy, has been associated in large observational studies with a small increase in the risk of new-onset type 2 diabetes mellitus, particularly in patients with pre-existing risk factors such as impaired fasting glucose, obesity, elevated triglycerides, or a history of hypertension. However, the cardiovascular benefits of statin therapy generally far outweigh this modest increase in diabetes risk. The ESC/EAS guidelines affirm that the net clinical benefit of statins remains strongly positive across all patient groups for whom they are indicated.
Some patients report cognitive effects such as memory loss or confusion while taking statins. Regulatory agencies, including the FDA and EMA, have reviewed available evidence and concluded that while these reports exist, a causal relationship has not been established. The symptoms appear to be reversible upon discontinuation and are not associated with fixed cognitive impairment or dementia. If you experience cognitive symptoms, discuss them with your doctor.
How Should You Store Inegy?
Proper storage of Inegy is important to ensure the medication remains effective and safe throughout its shelf life. The tablets should be stored at a temperature not exceeding 30°C (86°F). Do not freeze the medication. Keep the tablets in the original blister packaging to protect them from moisture and light, as both ezetimibe and simvastatin can degrade when exposed to excessive humidity or ultraviolet radiation.
Do not use Inegy after the expiry date stated on the carton and blister packaging. The expiry date refers to the last day of that month. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment and prevent accidental ingestion by children or pets.
Keep this and all medicines out of the sight and reach of children. If you notice any visible changes in the appearance of the tablets (discolouration, crumbling, or an unusual odour), do not use them and return them to your pharmacy for safe disposal.
What Does Inegy Contain?
Active Ingredients
The active substances in Inegy are:
- Ezetimibe 10 mg — A selective cholesterol absorption inhibitor that blocks the NPC1L1 transporter in the small intestine.
- Simvastatin 10 mg, 20 mg, 40 mg or 80 mg — An HMG-CoA reductase inhibitor (statin) that reduces cholesterol synthesis in the liver. Simvastatin is a prodrug administered as an inactive lactone that is hydrolysed to the active beta-hydroxyacid form in the liver.
Inactive Ingredients (Excipients)
The tablets contain the following inactive ingredients, which serve various pharmaceutical functions:
- Butylated hydroxyanisole (BHA) — Antioxidant to prevent degradation of the active substances.
- Citric acid monohydrate — pH buffer.
- Croscarmellose sodium — Disintegrant to facilitate tablet dissolution.
- Hydroxypropyl cellulose — Binder.
- Lactose monohydrate — Filler. Note: Patients with lactose intolerance should be aware of this excipient.
- Magnesium stearate — Lubricant for tablet manufacturing.
- Microcrystalline cellulose — Filler and binder.
- Hypromellose — Film coating agent.
- Iron oxide (yellow, red, or black depending on strength) — Colouring agent to distinguish different strengths.
- Titanium dioxide — Opacifier in the film coating.
Tablet Appearance
Inegy tablets are film-coated and vary in colour by strength to facilitate identification:
- 10/10 mg: White to off-white, capsule-shaped tablet marked "311" on one side.
- 10/20 mg: Beige, capsule-shaped tablet marked "312" on one side.
- 10/40 mg: Red-brown, capsule-shaped tablet marked "313" on one side.
- 10/80 mg: Dark brown, capsule-shaped tablet marked "315" on one side.
Frequently Asked Questions About Inegy
Inegy is used to lower high cholesterol (primary hypercholesterolaemia) and to reduce the risk of cardiovascular events such as heart attacks and strokes. It combines two active ingredients — ezetimibe, which blocks cholesterol absorption in the intestine, and simvastatin, which reduces cholesterol production in the liver. This dual mechanism can lower LDL ("bad") cholesterol by up to 60%. It is always prescribed alongside a healthy diet and lifestyle changes.
Common side effects include headache, muscle pain (myalgia), abdominal pain, flatulence, diarrhoea, nausea, constipation, fatigue, and mildly elevated liver enzymes. Most of these are mild and transient. The most important side effect to watch for is unexplained muscle pain or weakness, which could indicate a rare but serious condition called rhabdomyolysis. Report any unusual muscle symptoms to your doctor immediately.
No. Inegy is absolutely contraindicated during pregnancy and breastfeeding. Simvastatin is classified as FDA Pregnancy Category X, meaning it can cause birth defects. Cholesterol is essential for normal foetal development, and blocking its synthesis may cause harm. Women of childbearing potential must use reliable contraception while taking Inegy. If you become pregnant, stop taking Inegy immediately and contact your doctor.
You should avoid grapefruit and grapefruit juice while taking Inegy. Grapefruit contains compounds called furanocoumarins that inhibit the CYP3A4 enzyme in the gut and liver, which is responsible for breaking down simvastatin. This can lead to significantly elevated simvastatin levels in the blood, increasing the risk of serious side effects including rhabdomyolysis. Even small amounts of grapefruit juice can have this effect.
Inegy should be taken once daily in the evening. The evening timing is important because cholesterol synthesis in the liver follows a circadian rhythm and is most active during the night. By taking simvastatin in the evening, peak drug activity coincides with peak cholesterol production, maximising its effectiveness. The tablet can be taken with or without food. Consistency in timing is more important than the exact hour — aim to take it at approximately the same time each evening.
Inegy and Vytorin contain the exact same active ingredients (ezetimibe and simvastatin) in the same strengths. The difference is purely in the brand name: Inegy is the name used in Europe and many other countries, while Vytorin is the brand name used in the United States. Both are manufactured by the same pharmaceutical company (Organon, formerly part of Merck/MSD) and have identical formulations and clinical effects.
References
All information in this article is based on peer-reviewed medical literature, regulatory documents, and international clinical guidelines. No pharmaceutical company has funded or influenced this content.
- Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes (IMPROVE-IT). New England Journal of Medicine. 2015;372(25):2387-2397. doi:10.1056/NEJMoa1410489
- Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. European Heart Journal. 2020;41(1):111-188. doi:10.1093/eurheartj/ehz455
- European Medicines Agency. Inegy Summary of Product Characteristics (SmPC). Available at: www.ema.europa.eu. Accessed December 2025.
- U.S. Food and Drug Administration. Vytorin (ezetimibe/simvastatin) Prescribing Information. Reference ID: 5046456.
- National Institute for Health and Care Excellence (NICE). Cardiovascular disease: risk assessment and reduction, including lipid modification (CG181). Updated September 2023.
- Baigent C, Blackwell L, Emberson J, et al. (Cholesterol Treatment Trialists' Collaboration). Efficacy and safety of more intensive lowering of LDL cholesterol. Lancet. 2010;376(9753):1670-1681. doi:10.1016/S0140-6736(10)61350-5
- World Health Organization. WHO Model List of Essential Medicines. 23rd List, 2023.
- Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. Journal of the American College of Cardiology. 2019;73(24):e285-e350.
- British National Formulary (BNF). Ezetimibe with simvastatin. National Institute for Health and Care Excellence. Updated 2025.
Editorial Team
This article was medically reviewed by the iMedic Medical Review Board, a panel of board-certified physicians with expertise in cardiology, clinical pharmacology, and evidence-based medicine. All clinical claims have been verified against current ESC/EAS, NICE, and AHA/ACC guidelines.
iMedic follows the GRADE evidence framework for assessing the quality of medical evidence. This article is rated Evidence Level 1A, based on systematic reviews of randomised controlled trials. We maintain strict independence with no commercial funding or pharmaceutical sponsorship.