Inegy

Package leaflet: Information for the patient

INEGY 10 mg/10 mg, 10 mg/20 mg, 10 mg/40 mg or 10 mg/80 mg tablets

ezetimibe and simvastatin
Please read all of this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist (see section 4).

Contents of this leaflet:

1. What INEGY is and what it is used for
2. What you need to know 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 lower levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and fatty substances called triglycerides in the blood. In addition, INEGY increases levels of "good" cholesterol (HDL cholesterol).
INEGY works in two ways to lower cholesterol. The active substance ezetimibe reduces the amount of cholesterol absorbed in the digestive tract. The active substance simvastatin, which belongs to the class of drugs known as "statins", inhibits the body's production of cholesterol.
Cholesterol is one of several fatty substances present in the bloodstream. Total cholesterol is made up mainly of LDL cholesterol and HDL cholesterol.
LDL cholesterol is often called "bad" cholesterol because it can accumulate in the walls of arteries, forming plaques. Over time, this plaque buildup can lead to narrowing of the arteries. This narrowing can slow down or block blood flow to vital organs such as the heart and brain. Such blockage of blood flow may cause a heart attack or stroke.
HDL cholesterol is often called "good" cholesterol because it helps prevent "bad" cholesterol from building up in the arteries and protects against heart disease.
Triglycerides are another type of fat in the blood that may increase the risk of heart disease.
INEGY is used for patients who cannot control their cholesterol levels through diet alone. While taking this medicine, you must still follow a cholesterol-lowering diet.
INEGY is used as an additional therapy to diet to lower cholesterol if you have:

• elevated cholesterol levels in the blood (primary hypercholesterolemia [heterozygous familial and non-familial]) or elevated levels of fats in the blood (mixed hyperlipidemia):
• that are not well controlled by a statin alone,
• for which you have previously been treated with a statin and ezetimibe as separate tablets,
• a hereditary condition (homozygous familial hypercholesterolemia) that increases your blood cholesterol levels. You may also be receiving other treatments,
• heart disease; INEGY reduces the risk of heart attack, stroke, surgery to improve blood flow to the heart, or hospitalization due to chest pain.

INEGY does not help with weight loss.

2. What you need to know before taking INEGY

Do not take INEGY if:

• you are allergic (hypersensitive) to ezetimibe, simvastatin, or any of the other ingredients of this medicine (listed in section 6: Contents of the pack and other information),
• you currently have liver problems,
• you are pregnant or breastfeeding,
• you are taking a medicine(s) 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),
  ○ HIV protease inhibitors such as indinavir, nelfinavir, ritonavir, and saquinavir (HIV protease inhibitors are used to treat HIV infections),
  ○ boceprevir or telaprevir (used to treat hepatitis C virus infection),
  ○ nefazodone (used to treat depression),
  ○ cobicistat,
  ○ gemfibrozil (used to lower cholesterol),
  ○ cyclosporine (often used in patients who have had an organ transplant),
  ○ danazol (an artificial hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside the uterus).
• you are taking or have taken within the last 7 days an oral or injectable medicine called fusidic acid (a medicine used to treat bacterial infection). The combination of fusidic acid and INEGY can lead to serious muscle problems (rhabdomyolysis). Do not take more than 10 mg/40 mg of INEGY if you are taking lomitapide (used to treat a rare, genetic, severe cholesterol condition).

Ask your doctor for advice if you are unsure whether the medicine you are taking is one of those listed above.

Warnings and precautions

Tell your doctor:

• about all your medical conditions, including allergies,
• if you consume large amounts of alcohol or have ever had liver disease. In this case, INEGY may not be suitable for you,
• if you are scheduled for surgery. You may need to temporarily stop taking INEGY tablets,
• if you are of Asian origin, as a different dose may be appropriate for you,
• if you have or have had myasthenia (a disease characterized by generalized muscle weakness, which in some cases may include muscles used for breathing) or ocular myasthenia (a disease causing weakness of the eye muscles), since statins may sometimes worsen myasthenia or trigger its onset (see section 4).

Your doctor will perform a blood test before you start taking INEGY and if you develop symptoms of liver problems while taking INEGY. This test is to check whether your liver is functioning properly.

Your doctor may also prescribe blood tests to monitor liver function after starting treatment with INEGY.

During treatment with this medicine, your doctor will carefully monitor whether you have diabetes or are at risk of developing diabetes. Risk factors for developing diabetes include high blood sugar and fat levels, being overweight, and having high blood pressure.

Inform your doctor if you have a serious lung disease.

The use of INEGY together with fibrates (certain types of cholesterol-lowering medicines) should be avoided, as the combination of INEGY with fibrates has not been studied.

Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness, as muscle problems can rarely be serious and lead to muscle tissue damage causing kidney damage, and very rare cases of death have occurred.

The risk of muscle damage is higher at higher doses of INEGY, particularly with the 10 mg/80 mg dose. The risk of muscle damage is also increased in certain patients. Inform your doctor if any of the following conditions apply to you:

• you have kidney problems,
• you have thyroid problems,
• you are aged 65 years or older,
• you are female,
• you have previously experienced muscle problems during treatment with cholesterol-lowering medicines known as "statins" (such as simvastatin, atorvastatin, and rosuvastatin) or fibrates (such as gemfibrozil and bezafibrate),
• you or your close family members have a hereditary muscle disease.

Additionally, inform your doctor or pharmacist if you have persistent muscle weakness. Further tests and treatments may be needed to diagnose and manage this condition.

Children and adolescents

• The use of INEGY is not recommended in children under 10 years of age.

Other medicines and INEGY

Inform your doctor if you are taking, have recently taken, or might take any other medicine containing any of the following active substances. Taking INEGY with any of the following medicines may increase the risk of muscle problems (some of these have already been mentioned in the section "Do not take INEGY if").

• If you need to take oral fusidic acid to treat a bacterial infection, you must temporarily stop taking this medicine. Your doctor will tell you when it is safe to restart INEGY. Taking INEGY with fusidic acid can rarely lead to muscle weakness, tenderness, or pain (rhabdomyolysis). See further information on rhabdomyolysis in section 4.
• cyclosporine (often used in patients who have received an organ transplant),
• danazol (an artificial hormone used to treat endometriosis, a condition in which the lining of 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 lower cholesterol),
• erythromycin, clarithromycin, or telithromycin (used to treat bacterial infections),
• HIV protease inhibitors such as indinavir, nelfinavir, ritonavir, and saquinavir (used to treat AIDS),
• antiviral agents for hepatitis C such as boceprevir, telaprevir, elbasvir, or grazoprevir (used to treat hepatitis C virus infection),
• nefazodone (used to treat depression),
• medicines containing the active substance cobicistat,
• amiodarone (used to treat irregular heartbeat),
• verapamil, diltiazem, or amlodipine (used to treat high blood pressure, chest pain associated with heart disease, or other heart conditions),
• lomitapide (used to treat a rare, genetic, severe cholesterol condition),
• daptomycin (a medicine used to treat complicated skin and soft tissue infections and bacteremia). The risk of muscle-related side effects may be increased when this medicine is taken during treatment with simvastatin (e.g., INEGY). Your doctor may decide that you should temporarily stop taking INEGY,
• high doses (1 gram or more per day) of niacin or nicotinic acid (also used to lower cholesterol),
• colchicine (used to treat gout).

In addition to the medicines listed above, inform your doctor or pharmacist if you are taking or have recently taken any other medicine, including those without a prescription. In particular, tell your doctor if you are taking any of the following:

• medicines containing active substances to prevent blood clotting, such as warfarin, fluindione, phenprocoumon, or acenocoumarol (anticoagulants),
• colestyramine (also used to lower cholesterol), as it affects how INEGY works,
• fenofibrate (also used to lower cholesterol),
• rifampicin (used to treat tuberculosis),
• ticagrelor (an antiplatelet medicine).

You should also inform any doctor who prescribes you a new medicine that you are taking INEGY.

INEGY with food and drink

Grapefruit juice contains one or more substances that alter the metabolism of certain medicines, including INEGY. Consumption of grapefruit juice should be avoided, as it may increase the risk of muscle problems.

Pregnancy and breastfeeding

Do not use INEGY if you are pregnant, planning to become pregnant, or suspect you may be pregnant. If you become pregnant while taking INEGY, stop treatment immediately and contact your doctor. INEGY must not be used during breastfeeding, as it is not known whether the medicine passes into human milk.

Consult your doctor or pharmacist before taking any medicine.

Driving and using machines

INEGY is not expected to affect your ability to drive or operate machinery. However, you should be aware that some people have experienced dizziness after taking INEGY.

INEGY contains lactose

INEGY tablets contain a sugar called lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact him or her before taking this medicine.

INEGY contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially "sodium-free".

3. How to take INEGY

Your doctor will determine the appropriate tablet dosage for you, based on your current treatment and your individual risk profile.
The tablets do not have a score line and must not be divided.
Always take this medicine exactly as your doctor or pharmacist has instructed you. If you are unsure, consult your doctor or pharmacist.

• Before starting treatment with INEGY, you must already be following a cholesterol-lowering diet.
• While taking INEGY, you must continue to follow this cholesterol-lowering diet.
  Adults: The dose is 1 tablet of INEGY taken orally once daily.

Use in adolescents (aged 10 to 17 years): The dose is 1 tablet of INEGY taken orally once daily (a maximum dose of 10 mg/40 mg once daily must not be exceeded).
The INEGY dose of 10 mg/80 mg is recommended only for adult patients with very high cholesterol levels and high risk of heart disease who have not reached their target cholesterol level with lower doses.
Take INEGY in the evening. You may take it with or without food.
If your doctor has prescribed INEGY together with another cholesterol-lowering medicine containing the active substance cholestyramine or any other bile acid sequestrant, you must take INEGY at least 2 hours before or 4 hours after taking the bile acid sequestrant.

If you take more INEGY than you should:

• Contact your doctor or pharmacist.

If you forget to take INEGY:

• Do not take a double dose to make up for the missed tablet. Take only your usual dose of INEGY at the next scheduled time.

If you stop taking INEGY:

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

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, INEGY can cause side effects, although not everybody gets them (see section 2, What you should know before taking INEGY).

The following common side effects have been reported (may affect up to 1 in 10 people):

• muscle pain,
• increases in blood laboratory test values related to liver function (transaminases) and/or muscle (CK).

The following uncommon side effects have been reported (may affect up to 1 in 100 people):

• increases in blood test values related to liver function; increases in blood uric acid levels; prolonged blood clotting time; presence of protein in urine; decrease in body weight,
• dizziness; headache; tingling sensation,
• abdominal pain; indigestion; flatulence; nausea; vomiting; abdominal swelling; diarrhoea; dry mouth; heartburn,
• skin rash; itching; urticaria,
• joint pain; pain, tenderness, weakness or muscle spasms; neck pain; arm or leg pain; back pain,
• unusual tiredness or weakness; feeling of fatigue; chest pain; swelling, especially of the hands and feet,
• sleep disorders; difficulty falling asleep.

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

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

Contact your doctor if you experience worsening weakness in the arms or legs after periods of activity, double vision or drooping eyelids, difficulty swallowing or shortness of breath.

In addition, the following side effects have been reported in people taking INEGY or medicines containing the active substances ezetimibe or simvastatin:

• reduction in red blood cell count (anaemia); decrease in blood cells, which may lead to bruising/bleeding (thrombocytopenia),
• loss of sensation or weakness in arms and legs; poor memory; memory loss; confusion,
• breathing problems including persistent cough and/or shortness of breath or fever,
• constipation,
• inflammation of the pancreas, often with severe abdominal pain,
• inflammation of the liver with the following symptoms: yellowing of the skin and eyes; itching; dark urine or pale stools; feeling of tiredness or weakness; loss of appetite; liver failure; gallstones or inflammation of the gallbladder (which may cause abdominal pain, nausea and vomiting),
• hair loss; red, raised skin rash, sometimes with target-like lesions (erythema multiforme),
• blurred vision and impaired vision (may affect up to 1 in 1,000 people),
• skin rash which may occur on the skin or mouth ulcers (drug-induced lichenoid eruptions) (may affect up to 1 in 10,000 people),
• hypersensitivity reactions including some of the following: allergic reactions including swelling of the face, lips, tongue and/or throat which may cause difficulty breathing or swallowing and require immediate treatment (angioedema), joint pain or inflammation, inflammation of blood vessels, abnormal bruising, skin rashes and swelling, urticaria, skin sensitivity to sunlight, fever, hot flushes, shortness of breath and feeling unwell, lupus-like symptoms (including skin rash, joint problems and effects on white blood cells). A very rare severe allergic reaction (may affect up to 1 in 10,000 people) causing difficulty breathing or dizziness, requiring immediate treatment (anaphylaxis), may occur,
• muscle pain, tenderness, weakness or cramps; muscle injury; muscle breakdown (may affect up to 1 in 10,000 people); tendon problems, sometimes complicated by tendon rupture,
• gynaecomastia (enlargement of breast tissue in men) (may affect up to 1 in 10,000 people),
• decreased appetite,
• hot flushes; high blood pressure,
• pain,
• erectile dysfunction,
• depression,
• changes in certain blood test values related to liver function.

Additional possible side effects reported with some statins:

• sleep disorders, including nightmares,
• sexual difficulties,
• diabetes. This is more likely if you have high levels of sugar and fats in the blood, are overweight and have high blood pressure. Your doctor will monitor you during treatment with this medicine,
• persistent muscle pain, tenderness or weakness that may not resolve after stopping treatment with INEGY (frequency not known).

Contact your doctor immediately if you experience unexplained muscle pain, tenderness or weakness, as muscle problems can, rarely, be serious and lead to muscle tissue damage causing kidney injury, and very rare cases of death have occurred.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the Italian Medicines Agency (Agenzia Italiana del Farmaco) at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store INEGY

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton or container after the word "Exp".
• Do not store INEGY tablets at temperatures above 30°C.

Blister packs: store in the original packaging to protect the medicine from moisture and light.
Bottles: keep bottles tightly closed to protect the medicine from moisture and light.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What INEGY contains
The active substances in INEGY are ezetimibe and simvastatin. Each tablet contains 10 mg of
ezetimibe and either 10 mg, 20 mg, 40 mg, or 80 mg of simvastatin.
The other components are: butylated hydroxyanisole, citric acid monohydrate, croscarmellose sodium,
hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, propyl gallate.
Description of the appearance of INEGY and package contents
INEGY tablets are white to off-white capsule-shaped tablets with the code “311”, “312”, “313”, or “315” on one side. The tablets do not have a break line and must not be divided.
Pack sizes:
7, 10, 14, 28, 30, 50, 56, 84, 90, 98, multiple pack containing 98 (2 boxes of 49), 100 or 300 tablets.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Organon Italia S.r.l.
Piazza Carlo Magno, 21
00162 Rome
Italy
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 in the Member States of the European Economic Area under the
following names:
INEGY in Austria, Belgium, Cyprus, Czech Republic, Denmark, Finland, France, Germany, Greece,
Hungary, Iceland, Ireland, Italy, Luxembourg, The Netherlands, Norway, Poland, Portugal, Slovakia,
Slovenia, Spain, Sweden and the United Kingdom.
VYTORIN in Germany, Italy, Portugal and Spain.
GOLTOR in Germany and Italy.