ZEVISTAT 10 mg/10 mg Coated Tablet

Зміст інструкції

1. Zevistat 10 mg/10 mg tablets, 10 mg/20 mg tablets, 10 mg/40 mg tablets
   1. What is Zevistat and what it is used for
   2. What you need to know before taking Zevistat
   3. How to take Zevistat
   4. Possible side effects
   5. How to store Zevistat
   6. Package contents and other information

Zevistat 10 mg/10 mg tablets, 10 mg/20 mg tablets, 10 mg/40 mg tablets

Ezetimibe and simvastatin
Generic medicine

Read this leaflet carefully before you start to take 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 pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Zevistat is and what it is used for
• 2. What you need to know before you take Zevistat
• 3. How to take Zevistat
• 4. Possible side effects
• 5. How to store Zevistat
• 6. Contents of the pack and other information

1. What is Zevistat and what it is used for

Zevistat contains the active ingredients ezetimibe and simvastatin. Zevistat is a medicine used to lower total cholesterol levels, “bad” cholesterol (LDL cholesterol) and fatty substances called triglycerides in the blood. In addition, Zevistat increases levels of “good” cholesterol (HDL cholesterol).
Zevistat reduces cholesterol in two ways. The active ingredient ezetimibe reduces cholesterol absorbed in the digestive system. The active ingredient simvastatin, belonging to the class of “statins”, inhibits the production of cholesterol by the body itself.
Cholesterol is one of the various fatty substances present in the bloodstream. Total cholesterol is predominantly formed by LDL and HDL cholesterol.
LDL cholesterol is often called “bad” cholesterol, because it can accumulate on the walls of the arteries forming plaques. Over time, this accumulation in the form of plaque can lead to a narrowing of the arteries. This narrowing can slow down or block blood flow to vital organs, such as the heart and brain. Obstruction of blood flow can thus cause a heart attack or stroke.
HDL cholesterol is often called “good” cholesterol, because it helps prevent the accumulation of bad cholesterol in the arteries and protects against heart disease.
Triglycerides are another form of fat present in the blood that can increase the risk of heart disease.
Zevistat is intended for patients who are unable to control their cholesterol levels with diet alone.
During therapy with this medicine, it is necessary to follow a low-fat diet.
Zevistat must be used in addition to diet to lower cholesterol, if you have:

• high cholesterol levels in the blood (primary hypercholesterolemia [familial heterozygous and non-familial]) or high levels of fats in the blood (mixed hyperlipidemia):
• not adequately controlled with a statin alone
• for which you have used a statin and ezetimibe in the form of separate tablets
• an inherited disease (homozygous familial hypercholesterolemia) that increases cholesterol levels in the blood. You may also receive other therapies.
• a heart disease; Zevistat reduces the risk of heart attack, stroke, surgery to improve blood flow to the heart, or hospitalization for chest pain.

Zevistat does not help with weight loss.

2. What you need to know before taking Zevistat

Do not takeZevistat:

• if you are allergic to ezetimibe, simvastatin or any of the other ingredients of this medicine (listed in section 6),
• if you currently have liver problems,
• if you are pregnant or breastfeeding,
• if you are taking medicines that contain 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 infection)
• boceprevir or telaprevir (used to treat hepatitis C virus infections)
• nefazodone (used to treat depression)
• cobicistat
• gemfibrozil (used to lower cholesterol)
• cyclosporine (often used in patients who have had an organ transplant)
• danazol (a synthetic hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside of it).

Do not take more than 10 mg/40 mg of Zevistat if you are taking lomitapide (used to treat a serious and rare genetic disorder of cholesterol).
Ask your doctor for advice if you are not sure whether the medicine you are taking is among those listed above.

Warnings and precautions
Talk to your doctor or pharmacist before taking Zevistat.
Tell your doctor:

• about all of your medical conditions, including allergies.
• if you drink large amounts of alcohol or have had liver disease. Zevistat may not be suitable for you.
• if you are going to have surgery. You may need to stop taking Zevistat tablets for a short period.
• if you are of Asian origin, because in this case a different dose may be needed.
• if you are taking or have taken in the last 7 days a medicine called fusidic acid (against bacterial infections) by mouth or by injection. The combination of fusidic acid and Zevistat can cause serious muscle problems (rhabdomyolysis).

Your doctor should perform a blood test before you start taking Zevistat and if you develop
symptoms of liver problems during treatment with Zevistat. This will check how your liver is working.
Your doctor may prescribe blood tests to check your liver function after starting
treatment with Zevistat.
While taking this medicine, your doctor will carefully monitor if you have diabetes or are at risk of
developing it. You are at risk of developing diabetes if you have high levels of sugars and fats in your blood, if you are overweight and have high blood pressure.
Tell your doctor if you have a serious lung disease.
The administration of Zevistat with fibrates (some medicines to lower cholesterol) should be
avoided, as the use of Zevistat with fibrates has not been studied.

Contact your doctor immediately if you experience pain, tenderness or weakness in your muscles for
unexplained reasons. In rare cases, muscle problems can be severe and lead to muscle damage causing kidney damage; and in very rare cases deaths have occurred.
The risk of muscle damage is greater at higher doses of Zevistat, especially with the 10 mg/80 mg dose.
The risk of muscle damage is also greater in certain patients. Tell your doctor if:

• you have kidney problems,
• you have thyroid problems,
• you are 65 years of age or older,
• you are a woman,
• you have previously had muscle problems during treatment with cholesterol-lowering medicines called “statins” (such as simvastatin, atorvastatin and rosuvastatin) or fibrates (such as gemfibrozil and bezafibrato),
• you or a close family member has a hereditary muscle disease.

Also, tell your doctor or pharmacist if you experience persistent muscle weakness. Further tests and medications may be needed to diagnose and
treat this problem.

Children and adolescents
Zevistat is not recommended in children under 10 years of age.

Other medicines and Zevistat
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other
medicines. Taking Zevistat with any of the following medicines can increase the risk of
muscle problems (some of which are already listed in the previous section, “Do not take Zevistat”).

• cyclosporine (often used in patients who have had an organ transplant),
• danazol (a synthetic hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside of the uterus itself),
• medicines with an active ingredient such as itraconazole, ketoconazole, fluconazole, posaconazole or voriconazole (used to treat fungal infections),
• fibrates with active ingredients such as gemfibrozil and bezafibrato (used to lower cholesterol),
• erythromycin, clarithromycin, telithromycin or fusidic acid (used to treat bacterial infections),
• HIV protease inhibitors such as indinavir, nelfinavir, ritonavir and saquinavir (used to treat AIDS),
• boceprevir or telaprevir (used to treat hepatitis C virus infections),
• nefazodone (used to treat depression),
• medicines with the active ingredient 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 serious and rare genetic disorder of cholesterol),
• large amounts (1 gram or more per day) of niacin or nicotinic acid (also used to lower cholesterol),
• colchicine (used to treat gout).

If you need to take fusidic acid orally to treat a bacterial infection, you will need to temporarily stop
using this medicine. Your doctor will tell you when it is safe to restart therapy with
Zevistat. Taking Zevistat with fusidic acid can cause, in rare cases, weakness, tenderness or muscle pain (rhabdomyolysis). For more information regarding rhabdomyolysis see section 4.
In addition to the medicines listed above, tell your doctor or pharmacist if you are taking or have recently
taken any other medicines, including those available without a prescription. In particular, tell your doctor if you are taking:

• medicines containing an active ingredient to prevent blood clots from forming, such as warfarin, fluindione, phenprocoumone or acenocoumarol (anticoagulants),
• cholestyramine (also used to lower cholesterol), because it affects the mechanism of action of Zevistat,
• fenofibrate (also used to lower cholesterol),
• rifampicin (used in the treatment of tuberculosis).

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

Zevistat with food and drink
Grapefruit juice contains one or more substances that alter the metabolism of some medicines, including
Zevistat. Consumption of grapefruit juice should be avoided, as it can increase the risk of muscle
problems.

Pregnancy and breastfeeding
Do not take Zevistat if you are pregnant, suspect you may be pregnant or are planning a pregnancy. If you become
pregnant while taking Zevistat, stop taking it immediately and tell your doctor. Do not
take Zevistat if you are breastfeeding, because we do not know if the medicine passes into breast milk.
Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
It is not expected that Zevistat will interfere with your ability to drive or use machines. However,
you should be aware that some people have experienced dizziness after taking Zevistat.

Zevistat contains lactose
If your doctor has told you that you have an intolerance to some sugars, tell your doctor before you take
this product.

3. How to take Zevistat

Take this medicine following exactly the instructions of your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The doctor will determine the appropriate dosage of tablets for you, depending on the ongoing therapy and your
personal risk.

• Before starting to take Zevistat, you must follow a diet to lower cholesterol.
• While taking Zevistat, you must continue to follow this diet to lower cholesterol.

Adults: the dose is 1 Zevistat tablet by mouth once a day.
Use in adolescents (10 to 17 years of age): the dose is 1 Zevistat tablet by mouth once a day
(do not exceed the maximum dose of 10 mg/40 mg once a day).
The 10 mg/80 mg dose is recommended only in adult patients with very high cholesterol levels and a high
risk of heart problems, who have not reached their ideal cholesterol levels with lower doses.
Not all recommended doses are possible with this product; however, other products with different dosages (10 mg/80 mg) are also available.
Take Zevistat in the evening. You can take the medicine with or without food.
If your doctor has prescribed Zevistat together with another medicine to lower cholesterol containing
the active ingredient colestyramine or another bile acid sequestrant, you must take Zevistat at least 2
hours before or 4 hours after taking the bile acid sequestrant.

If you take more Zevistat than you should
Contact your doctor or pharmacist.

If you forget to take Zevistat
Do not take a double dose to make up for a missed tablet. Take the normal dose of
Zevistat the next day at the usual time.

If you stop taking Zevistat
Inform your doctor or pharmacist before stopping treatment with this medicine, as your
cholesterol may increase again.
If you have any questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience any of the following side effects, stop taking the medicine immediately and inform your
doctor immediately:

• muscle pain (common: may affect up to 1 in 10 people)
• signs of blood disorders, e.g. fatigue, unexplained bruises/bleeding, mouth ulcers (not known: frequency cannot be estimated from the available data)
• pancreatitis which can cause severe abdominal and back pain accompanied by a feeling of severe illness (not known: frequency cannot be estimated from the available data)
• signs of problems with the liver, gallstones or inflammation of the gallbladder, e.g. yellowing of the skin, nausea, stomach pain, itching, dark urine and pale stools (not known: frequency cannot be estimated from the available data)
• angioedema (immediately stop using Zevistat and contact a doctor if you experience any of the following symptoms: swelling of the face, tongue or throat, difficulty swallowing, hives and difficulty breathing)

Contact your doctor immediately if you experience muscle pain, tenderness or weakness for no reason.
In rare cases, muscle problems can be serious and include muscle breakdown causing kidney damage; in very rare cases, deaths have occurred.
The following common side effects have been reported (may affect up to 1 in 10 people):

• elevated values in laboratory blood tests related to liver function (transaminases) and/or muscles (CK)

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

• elevated values in blood tests related to liver function; increases in uric acid in the blood; increases in the time it takes for blood to clot; protein in the urine; weight loss
• dizziness; headache; tingling sensation
• abdominal pain; indigestion; flatulence; nausea; vomiting; abdominal bloating; diarrhea; dry mouth; heartburn
• rash; itching; hives
• joint pain, pain, tenderness, weakness or muscle spasms; neck pain; pain in arms and legs; back pain
• unusual fatigue or weakness; feeling tired; chest pain; swelling, especially of hands and feet
• sleep disorders; difficulty falling asleep

The following side effects have also been reported in people taking Zevistat or medicines
containing the active ingredients ezetimibe or simvastatin:

• numbness or weakness of arms and legs; difficulty remembering, memory loss, confusion
• breathing problems, including persistent cough and/or shortness of breath or fever
• constipation
• hair loss; raised, red rash, sometimes target-shaped (erythema multiforme)
• blurred vision and impaired vision (may affect up to 1 in 1,000 people)
• rash that can occur on the skin or ulcers in the mouth (drug-induced lichenoid eruptions) (may affect up to 1 in 10,000 people)
• hypersensitivity reaction including some of the following symptoms: hypersensitivity (allergic reactions, joint pain or inflammation, inflammation of blood vessels, unusual bruising, skin rashes and swelling, skin sensitivity to the sun, fever, flushing and feeling unwell, clinical picture of lupus-like syndrome (including rash, joint disorders and effects on white blood cells))
• pain, tenderness, weakness or cramps in muscles; muscle injury; muscle rupture (may affect up to 1 in 10,000 people); tendon problems, sometimes complicated by tendon rupture
• gynecomastia (breast enlargement in men) (may affect up to 1 in
• 10,000)
• reduced appetite
• hot flushes; high blood pressure
• pain
• erectile dysfunction
• depression
• changes in some blood test values related to liver function

Other side effects reported with some statins:

• sleep disturbances, including nightmares
• sexual difficulties
• diabetes. Diabetes is more likely if you have high levels of sugars and fats in your blood, if you are overweight and have high blood pressure. While taking this medicine, your doctor will monitor you carefully
• constant muscle pain, tenderness or weakness that may persist despite stopping Zevistat (frequency not known)

Reporting of side effects
If you get any side effect, talk to your doctor or pharmacist. You can also report side effects directly through the
national reporting system 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 Zevistat

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the packaging after “Exp.”. The expiry
date refers to the last day of that month.
This medicine does not require any particular storage temperature.
Store in the original packaging to protect the medicine from light and moisture.
Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to eliminate the
medicines that you no longer use. This will help protect the environment.

6. Package contents and other information

What Zevistat contains

• The active ingredients are ezetimibe and simvastatin. Each tablet contains 10 mg of ezetimibe and 10 mg of simvastatin. Each tablet contains 10 mg of ezetimibe and 20 mg of simvastatin. Each tablet contains 10 mg of ezetimibe and 40 mg of simvastatin.
• The other excipients are lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, magnesium stearate, hypromellose 2910, yellow iron oxide (E172) - only for the 10 mg/10 mg tablets and red iron oxide (E172) - only for the 10 mg/20 mg tablets. See section 2 “Zevistat contains lactose”.

Description of the appearance of Zevistat and package contents
The 10 mg/10 mg tablets appear as round, slightly biconvex tablets, of a
whitish-yellow color, with beveled edges. Tablet diameter 6 mm.
The 10 mg/20 mg tablets appear as biconvex oval tablets, of a white-pink color.
Tablet dimensions 10 x 5 mm.
The 10 mg/40 mg tablets appear as biconvex capsule-shaped tablets, of a white or
almost white color. Tablet dimensions 14 x 6 mm.
Zevistat is available in boxes containing 28 and 30 tablets in blisters.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
LABORATORIO FARMACEUTICO CT S.r.l. - Via Dante Alighieri, 71 - 18038 Sanremo (IM) Italy

Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
TAD Pharma GmbH, Heinz-Lohmann-Straße 5 , 27472 Cuxhaven, Germany

This medicinal product is authorised in the Member States of the European Economic Area under the following
names:
Italy Zevistat