Inegy® (Ezetimibe/Simvastatin)

Inegy® is a combination medication containing ezetimibe (10 mg) and simvastatin (various strengths). It combines two different mechanisms of action: simvastatin inhibits cholesterol production in the liver, while ezetimibe blocks cholesterol absorption in the intestine.

This dual action enables greater LDL lowering than simvastatin alone – typically an additional 15–20% LDL reduction from the ezetimibe component. The IMPROVE-IT study was the first to demonstrate that adding ezetimibe to a statin further reduces cardiovascular risk.

Inegy® is used in patients for whom a statin alone is not sufficient, or when strong LDL lowering is to be achieved without high statin doses.

Inegy® uses two complementary mechanisms of action:

1. Simvastatin (HMG-CoA reductase inhibitor):

• Inhibits cholesterol synthesis in the liver
• Upregulation of LDL receptors
• More LDL cholesterol is taken up from the blood

2. Ezetimibe (cholesterol absorption inhibitor):

• Blocks the NPC1L1 transporter in the small intestine
• Inhibits the absorption of cholesterol from food and bile
• The liver compensates with further upregulation of LDL receptors
• Synergistic effect with statins

Combined effect:

• LDL lowering: 45–60% (stronger than simvastatin alone)
• Triglycerides: reduction of 15–25%
• HDL cholesterol: increase of 8–12%

Clinical benefit: The IMPROVE-IT study showed that ezetimibe/simvastatin reduces cardiovascular events significantly more than simvastatin alone after acute coronary syndrome.

Inegy® is suitable for:

• Patients in whom a statin alone does not achieve the LDL target
• Primary hypercholesterolemia
• Homozygous familial hypercholesterolemia (as add-on therapy)

Especially recommended for:

• High-risk patients who do not reach the LDL target with a statin alone
• When high statin doses are poorly tolerated (muscle problems)
• After acute coronary syndrome (IMPROVE-IT)
• Familial hypercholesterolemia

Not suitable:

• Pregnancy and breastfeeding
• Active liver disease
• Concomitant use of strong CYP3A4 inhibitors (simvastatin component)
• Intolerance to ezetimibe or simvastatin

Available strengths (ezetimibe/simvastatin):

• 10/10 mg
• 10/20 mg (standard dose)
• 10/40 mg (stronger lowering)
• 10/80 mg (continuation only, not for new initiation – see simvastatin)

Recommended dosage:

• Start: 10/20 mg once daily in the evening
• Maximum standard dose: 10/40 mg once daily

LDL lowering (approx.):

• 10/10 mg: approx. 45%
• 10/20 mg: approx. 50%
• 10/40 mg: approx. 55%

Dose adjustment:

• Mildly impaired renal function (GFR ≥ 60 ml/min/1.73 m²): usually no adjustment
• Chronic kidney disease with GFR < 60 ml/min/1.73 m²: recommended dose 10/20 mg, higher doses with caution
• Hepatic impairment: contraindicated in active disease

How to take:

• Take once daily IN THE EVENING (simvastatin component)
• Regardless of meals
• Swallow the tablet whole, without chewing, with water

Important notes:

• Taking it in the evening is important because of the short half-life of simvastatin
• Do not drink grapefruit juice in large quantities (simvastatin interaction)
• First laboratory check after 4–12 weeks
• Regular monitoring: liver function tests, lipid profile, CK
• If you have muscle pain or weakness: inform your doctor immediately

If you miss a dose: Take it if it is still the same evening. Otherwise, the next evening at the regular time.

Bile acid sequestrants: If you are taking cholestyramine at the same time: take Inegy® at least 2 hours before or 4 hours after.

Inegy® must not be taken in case of:

• Active liver disease or unexplained elevation of transaminases
• Pregnancy and breastfeeding
• Hypersensitivity to ezetimibe or simvastatin
• Concomitant use of: itraconazole, ketoconazole, HIV protease inhibitors, erythromycin, clarithromycin, gemfibrozil, cyclosporine, danazol

Caution in case of:

• Hypothyroidism
• Renal impairment
• Muscle disorders
• High alcohol consumption
• Asian ancestry
• Concomitant use of fibrates other than gemfibrozil, including fenofibrate (not recommended)
• Concomitant use of amiodarone, verapamil, diltiazem (simvastatin max. 20 mg)

Pregnancy: Strictly contraindicated. Reliable contraception required.

Common (1–10%):

• Headache
• Myalgia (muscle pain)
• Gastrointestinal complaints (abdominal pain, diarrhea, flatulence)
• Elevated liver enzymes
• Fatigue

Uncommon (0.1–1%):

• Dizziness
• Skin rash
• Itching
• Elevated CK levels
• Elevated blood glucose levels

Rare but serious:

• Myopathy, rhabdomyolysis (caused by simvastatin)
• Hepatitis
• Gallstones (caused by ezetimibe, rare)
• Pancreatitis
• Angioedema

Note on ezetimibe: Ezetimibe has a favorable side effect profile. Most side effects come from the simvastatin component. In rare cases, ezetimibe alone can cause muscle pain.

The interactions mainly concern the simvastatin component:

Contraindicated:

• Strong CYP3A4 inhibitors (itraconazole, ketoconazole, HIV protease inhibitors, erythromycin, clarithromycin)
• Gemfibrozil
• Cyclosporine
• Danazol

Dose limitation (simvastatin component):

• Amiodarone: max. Inegy® 10/20 mg
• Verapamil, diltiazem: max. Inegy® 10/20 mg
• Amlodipine: max. Inegy® 10/20 mg

Ezetimibe-specific:

• Cholestyramine: reduces ezetimibe absorption → keep a time interval between doses
• Other fibrates (including fenofibrate): not recommended due to the risk of gallstones and an increased risk of myopathy (simvastatin component)
• Cyclosporine: increased ezetimibe levels

Grapefruit juice: Avoid large quantities (CYP3A4 inhibition → increased simvastatin levels).