Inegy

Patient Information Leaflet

INEGY, 10 mg + 10 mg, tablets
INEGY, 10 mg + 20 mg, tablets
INEGY, 10 mg + 40 mg, tablets
INEGY, 10 mg + 80 mg, tablets
Ezetimibe + Simvastatin
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet so that you can read it again if necessary.
• If you have any further questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm someone else, even if their symptoms are the same as yours.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of Contents

1. What INEGY is and what it is used for
2. Important information before taking INEGY
3. How to take INEGY
4. Possible side effects
5. How to store INEGY
6. Contents of the pack and other information

1. What INEGY is and what it is used for

INEGY contains the active substances ezetimibe and simvastatin. INEGY is a medicine used to reduce blood levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and fatty substances called triglycerides. In addition, INEGY increases the level of "good" cholesterol (HDL cholesterol).

INEGY works through two mechanisms to reduce cholesterol levels. The active ingredient ezetimibe reduces the absorption of cholesterol in the gastrointestinal tract. The active ingredient simvastatin, which belongs to a class of medicines known as "statins", inhibits the production of cholesterol in the body.

Cholesterol is one of several fatty substances present in the blood. Total cholesterol consists mainly of LDL cholesterol and HDL cholesterol fractions.

LDL cholesterol is often called "bad" cholesterol because it can deposit on the walls of arteries, forming atherosclerotic plaques. Eventually, these plaques can narrow the arteries, thereby restricting or blocking blood flow to vital organs such as the heart and brain. Blocked blood flow may lead to heart attack or stroke.

HDL cholesterol is often called "good" cholesterol because it helps prevent the buildup of bad cholesterol in the arteries and protects against heart disease.

Triglycerides are another type of fat present in the blood that may contribute to an increased risk of heart disease.

INEGY is used in patients in whom diet alone is not sufficient to control cholesterol levels. You should continue to follow a cholesterol-lowering diet while taking this medicine.

INEGY is used as an addition to a cholesterol-lowering diet in the following cases:

• Elevated blood cholesterol levels (primary hypercholesterolemia [heterozygous familial or non-familial]) or elevated blood fat levels (mixed hyperlipidemia):
• When adequate response has not been achieved with statin therapy alone,
• When treatment with a statin and ezetimibe has previously been administered as separate tablets.
• Inherited disorders (homozygous familial hypercholesterolemia) that cause elevated blood cholesterol levels. Other treatment methods may also be used in such cases.
• Heart disease. INEGY reduces the risk of heart attack, stroke, the need for surgical procedures to improve blood flow to the heart, or hospitalization due to chest pain.

INEGY does not affect body weight reduction.

2. Important information before taking INEGY

When not to use INEGY:

• if the patient is allergic to ezetimibe, simvastatin, or any of the other ingredients of this medicine (listed in section 6),
• if the patient currently has liver problems,
• during pregnancy or breastfeeding,
• if the patient is currently taking any medicine containing one or more of the following active substances:
  • itraconazole, ketoconazole, posaconazole, or voriconazole (used to treat fungal infections),
  • erythromycin, clarithromycin, or telithromycin (used to treat infections),
  • protease inhibitors of HIV virus, such as indinavir, nelfinavir, ritonavir, and saquinavir (HIV protease inhibitors used in the treatment of HIV infection),
  • boceprevir or telaprevir (used in the treatment of hepatitis C),
  • nefazodone (used to treat depression),
  • cobicistat,
  • gemfibrozil (used to lower cholesterol levels),
  • cyclosporine (commonly used in patients who have undergone organ transplantation),
  • danazol (a synthetic hormone used to treat endometriosis, a condition in which the tissue lining the uterus grows outside the uterus).
• if the patient is currently taking or has taken within the last 7 days a medicine called fusidic acid (a medicine used to treat bacterial infections) by mouth or injection. Taking fusidic acid together with INEGY may lead to serious muscle problems (rhabdomyolysis). Do not take INEGY at a dose higher than 10 mg + 40 mg if the patient is taking lomitapide (used to treat a severe and rare genetic disorder affecting cholesterol levels).

If in doubt whether any of the above-mentioned medicines are being taken, consult a doctor.
Warnings and precautions
Inform your doctor:

• about all medical conditions, including allergies,
• if you consume large amounts of alcohol or have a history of liver disease. Use of INEGY may not be appropriate,
• if you are scheduled for surgery. It may be necessary to temporarily stop taking INEGY tablets,
• if you are of Asian descent, as a different dose may be appropriate for you,
• if you have or have had myasthenia (a disease causing general muscle weakness, including in some cases the muscles used for breathing) or ocular myasthenia (a disease causing weakness of the eye muscles), because statins may sometimes worsen the condition or lead to the development of myasthenia (see section 4).

Your doctor should perform a blood test before starting treatment with INEGY and during treatment if you have any liver disorders. The purpose of this test is to assess liver function.
Your doctor may also perform blood tests to assess liver function after starting treatment with INEGY.
During treatment, your doctor will closely monitor your health if you have diabetes or are at risk of developing diabetes. The risk of developing diabetes exists in people who have high levels of sugar and fats in the blood, overweight, and high blood pressure.
Inform your doctor about serious lung diseases.
Avoid taking INEGY together with fibrates (certain medicines that reduce cholesterol levels), as no studies have been conducted on the concomitant use of INEGY and fibrates.
Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness. In rare cases, muscle-related side effects can be serious, including muscle breakdown leading to kidney damage, and in very rare cases, death.
The risk of muscle damage is higher when taking higher doses of INEGY, especially the 10 mg + 80 mg dose. The risk of muscle tissue breakdown is also higher in certain patients. Talk to your doctor:

• if you have kidney problems,
• if you have thyroid problems,
• if you are 65 years of age or older,
• if the patient is a girl or woman,
• if you have ever experienced muscle problems during treatment with cholesterol-lowering medicines called "statins" (such as simvastatin, atorvastatin, and rosuvastatin) or fibrates (such as gemfibrozil and bezafibrate),
• if you or a close family member has a hereditary muscle disorder.

Inform your doctor or pharmacist if muscle weakness persists. Additional tests and treatment with other medicines may be necessary to diagnose and treat this condition.
Children and adolescents

• INEGY is not recommended for children under 10 years of age.

INEGY and other medicines
Tell your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take, containing any of the following active substances. Taking INEGY together with any of the following medicines may increase the risk of muscle-related side effects (some of these are listed above under "When not to use INEGY").

• If oral fusidic acid is required to treat a bacterial infection, temporary discontinuation of INEGY will be necessary. Your doctor will advise when it is safe to restart taking INEGY. Taking INEGY together with fusidic acid may rarely lead to muscle weakness, tenderness, or pain (rhabdomyolysis). Additional information on rhabdomyolysis is provided in section 4.
• cyclosporine (commonly used in patients after organ transplantation),
• danazol (a synthetic hormone used to treat endometriosis, a condition in which the tissue lining the uterus grows outside the uterus),
• medicines containing active substances such as itraconazole, ketoconazole, fluconazole, posaconazole, or voriconazole (used to treat fungal infections),
• fibrates containing active substances such as gemfibrozil and bezafibrate (used to reduce cholesterol levels),
• erythromycin, clarithromycin, or telithromycin (used to treat bacterial infections),
• HIV protease inhibitors such as indinavir, nelfinavir, ritonavir, and saquinavir (used in the treatment of AIDS),
• antiviral medicines used to treat hepatitis C, such as boceprevir, telaprevir, elbasvir, or grazoprevir (used to treat hepatitis C),
• nefazodone (used to treat depression),
• medicines containing the active substance cobicistat,
• amiodarone (used to treat heart rhythm disorders),
• verapamil, diltiazem, or amlodipine (used to treat high blood pressure, angina related to heart disease, or other heart conditions),
• lomitapide (used to treat a severe and rare genetic disorder affecting cholesterol levels),
• daptomycin (a medicine used to treat complicated skin and soft tissue infections and bacteremia). Muscle-related side effects may be increased when this medicine is taken during treatment with simvastatin (e.g., INEGY). Your doctor may decide to temporarily stop taking INEGY,
• high doses (1 g or more daily) of niacin or nicotinic acid (also used to reduce cholesterol levels),
• colchicine (used to treat gout).

Similarly, inform your doctor or pharmacist about all medicines you have recently taken, including those available without a prescription. In particular, inform your doctor if you are taking any of the following:

• medicines containing active substances that prevent blood clots, such as warfarin, fluindione, phenprocoumon, or acenocoumarol (anticoagulants),
• cholestyramine (also used to reduce cholesterol levels), as it affects the action of INEGY,
• fenofibrate (also used to lower cholesterol levels),
• rifampicin (used to treat tuberculosis),
• ticagrelor (an antiplatelet medicine).

Inform any doctor prescribing a new medicine that you are taking INEGY.
INEGY with food and drink
Grapefruit juice contains one or more components that increase the metabolism of certain medicines, including INEGY. Avoid drinking grapefruit juice, as it may increase the risk of muscle-related side effects.
Pregnancy and breastfeeding
Do not take INEGY if you are pregnant, planning to become pregnant, or suspect you may be pregnant. If you become pregnant while taking INEGY, stop taking the medicine immediately and contact your doctor. Do not take INEGY during breastfeeding, as it is not known whether the medicine passes into breast milk.
Before taking any medicine, consult your doctor or pharmacist.
Driving and using machines
INEGY is not expected to affect the ability to drive or operate machinery. However, consider that dizziness may occur in some people after taking INEGY.
INEGY contains lactose
INEGY tablets contain the sugar lactose. If you have been previously diagnosed with intolerance to certain sugars, consult your doctor before taking this medicine.
INEGY contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., considered "sodium-free".

3. How to use INEGY

Your doctor will determine the appropriate dose of the medicine for you, depending on your current
treatment and individual risk factors.
The tablets do not have a score line and should not be divided.
This medicine should always be taken exactly as prescribed by your doctor or pharmacist. If in
doubt, consult your doctor or pharmacist.

• Before starting treatment with INEGY, a cholesterol-lowering diet should be initiated.
• During treatment with INEGY, a cholesterol-lowering diet should be maintained. Adults: the recommended dose is 1 tablet of INEGY taken orally once daily.

Use in adolescents (aged 10 to 17 years): the recommended dose is 1 tablet of INEGY taken orally once daily (the maximum dose of 10 mg + 40 mg once daily must not be exceeded).
The INEGY 10 mg + 80 mg dose is recommended only for adult patients with very high cholesterol levels and a high risk of heart disease, in whom the target cholesterol level has not been achieved with a lower dose.
INEGY should be taken in the evening. It can be taken with or without food.
If your doctor has prescribed INEGY and another cholesterol-lowering medicine containing the active substance cholestyramine or another bile acid sequestrant, INEGY should be taken at least 2 hours before or 4 hours after taking the bile acid sequestrant.

Taking more INEGY than prescribed:

• Contact your doctor or pharmacist.

If you forget to take INEGY:

• Do not take a double dose to make up for the missed dose; take the usual dose at the usual time the next day.

Stopping INEGY:

• Consult your doctor or pharmacist, as cholesterol levels may rise again.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them
(see section 2: Important information before taking INEGY).

The following adverse effects occurred frequently (may affect up to 1 in 10 people):

• muscle pain,
• increased liver function parameters (aminotransferase activity) and (or) muscle parameters (creatine kinase, CK activity) in blood.

The following adverse effects occurred uncommonly (may affect up to 1 in 100 people):

• increased liver function parameters in blood; elevated uric acid levels in blood; prolonged blood clotting time; presence of protein in urine; decreased body weight,
• dizziness; headache; tingling sensation,
• abdominal pain; indigestion; bloating; nausea; vomiting; abdominal distension; diarrhoea; dryness of oral mucous membranes; heartburn,
• rash; itching; urticaria,
• joint pain; muscle pain, tenderness, weakness or cramps; neck pain; pain in hands and feet; back pain,
• unusual tiredness or weakness; feeling of fatigue; chest pain; swelling, especially of hands and feet,
• sleep disorders; problems with sleeping.

The following adverse effects have been reported with unknown frequency (frequency cannot be estimated from the available data):

• myasthenia gravis (a disease causing general muscle weakness, including in some cases muscles used during breathing),
• ocular myasthenia (a disease causing weakness of eye muscles).

You should contact a doctor if the patient experiences weakness in arms or legs that worsens with activity, double vision or drooping eyelids, difficulty swallowing or shortness of breath.

Additionally, the following adverse effects have been observed in patients treated with INEGY or medicines containing ezetimibe or simvastatin as active substances:

• decreased number of red blood cells (anaemia); decreased number of platelets, which may lead to bruising/bleeding (thrombocytopenia),
• numbness or weakness of arms and legs; memory impairment, memory loss, confusion,
• breathing problems, including persistent cough and (or) shortness of breath or fever,
• constipation,
• pancreatitis, often with severe abdominal pain,
• hepatitis with the following symptoms: yellowing of the skin and eyes; itching, dark urine or pale stools, fatigue or weakness, loss of appetite; liver failure; gallstones or cholecystitis (which may cause abdominal pain, nausea, vomiting),
• hair loss; red, raised rash, sometimes with lesions shaped like a disc (erythema multiforme),
• blurred vision and visual disturbances (each of these symptoms may affect up to 1 in 1000 people),
• skin rash possibly occurring on the skin or oral mucosal ulcers (lichenoid mucosal lesions) (each of these symptoms may affect up to 1 in 10,000 people),
• hypersensitivity reactions, including: allergic reactions, such as swelling of the face, lips, tongue and (or) throat, which may cause difficulty breathing or swallowing and require immediate treatment (angioedema), joint pain or arthritis, vasculitis, unusual bruising, skin damage and swelling, urticaria, photosensitivity, fever, hot flushes, shortness of breath and malaise, clinical symptoms of lupus-like syndrome (including rash, joint disorders and effects on white blood cells). A severe, very rare allergic reaction may occur (may affect up to 1 in 10,000 people), causing difficulty breathing or dizziness and requiring immediate treatment (anaphylaxis),
• muscle pain, tenderness, weakness or cramps; muscle breakdown; muscle damage (may affect up to 1 in 10,000 people); tendon disorders, sometimes complicated by tendon rupture,
• gynaecomastia (enlargement of breasts in men) (may affect up to 1 in 10,000 people),
• decreased appetite,
• hot flushes with facial redness; high blood pressure,
• pain,
• erectile dysfunction,
• depression,
• changes in parameters of certain laboratory tests assessing liver function.

Additional possible adverse effects reported in patients taking certain statins:

• sleep disorders, including nightmares,
• reduced sexual function,
• diabetes. The likelihood of developing diabetes is higher if the patient has high levels of blood sugar and fat, overweight and high blood pressure. The doctor will monitor the patient's condition during treatment with this medicine,
• muscle pain, tenderness or persistent muscle weakness, which may not resolve after discontinuation of INEGY (frequency not known).

You should contact a doctor immediately if unexplained muscle pain, tenderness or weakness occurs. In rare cases, muscle-related symptoms may be serious, including rhabdomyolysis leading to kidney damage; in very rare cases, death has occurred.

Reporting of adverse effects

If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist.

Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309,
Website: https://smz.ezdrowie.gov.pl .

Adverse effects can also be reported to the marketing authorisation holder.

Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store the medicine INEGY

• Keep the medicine out of sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton or container following: EXP.
• Do not store the INEGY medicine above 30 °C.

Blister packs: store in the original packaging to protect from moisture and light.
Bottles: keep tightly closed to protect from moisture and light.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What INEGY contains
The active substances are ezetimibe and simvastatin. Each tablet contains 10 mg of ezetimibe
and 10 mg, 20 mg, 40 mg, or 80 mg of simvastatin.
Other ingredients are: butylated hydroxyanisole, citric acid monohydrate, sodium croscarmellose,
hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, propyl gallate.
What INEGY looks like and contents of the pack
INEGY tablets are white or almost white, capsule-shaped, with the imprint "311", "312", "313", or "315"
on one side. The tablets do not have a break line and should not be divided.
Pack sizes:
14 tablets, 28 tablets, and a multipack containing 98 tablets (2 boxes of 49 tablets each).
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Organon Polska Sp. z o.o.
ul. Marszałkowska 126/134
00-008 Warszawa
Tel.: +48 22 105 50 01
[email protected]
Manufacturer
Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands
Organon Heist bv
Industriepark 30
2220 Heist-op-den-Berg
Belgium
This medicinal product is authorised for sale in the European Economic Area under the following names:
INEGY in Austria, Belgium, Cyprus, the Czech Republic, Denmark, Finland, France, Germany, Greece,
Hungary, Iceland, Ireland, Italy, Luxembourg, the Netherlands, Norway, Poland, Portugal, the Slovak Republic,
Slovenia, Spain, Sweden, and the United Kingdom.
Vytorin in Germany, Italy, Portugal, and Spain.
Goltor in Germany and Italy.