Zevistat: detailed information

Package leaflet: Information for the user

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

Ezetimibe and simvastatin
Generic medicine
Please read 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 their symptoms are the same as yours, as it could be harmful.
If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

What Zevistat is and what it is used for
What you need to know before taking Zevistat
How to take Zevistat
Possible side effects
How to store Zevistat
Contents of the pack and other information

1. What Zevistat is and what it is used for

Zevistat contains the active substances ezetimibe and simvastatin. Zevistat is a medicine used to lower levels of total cholesterol, "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 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 own production of cholesterol.
Cholesterol is one of several fatty substances present in the bloodstream. Total cholesterol consists mainly of LDL and HDL cholesterol.
LDL cholesterol is often called "bad" cholesterol because it can accumulate on 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. Blockage of blood flow may thus cause a 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 form of fat in the blood that can increase the risk of heart disease.
Zevistat is intended for patients who cannot control their cholesterol levels with diet alone.
While taking this medicine, you must follow a low-fat diet.
Zevistat should be used in addition to diet to lower cholesterol if you have:

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

Zevistat does not help with weight loss.

2. What you should know before taking Zevistat

Do not take Zevistat:

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 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 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 undergone organ transplantation)
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 severe, rare genetic cholesterol disorder).
Ask your doctor for advice if you are unsure whether the medicine you are taking is one of those listed above.

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

about all 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 scheduled for surgery. You may need to temporarily stop taking Zevistat tablets.
if you are of Asian origin, as you may require a different dose.
if you are taking or have taken within the last 7 days an oral or injectable medicine called fusidic acid (for bacterial infections). 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 well your liver is functioning.
Your doctor may also order blood tests to monitor liver function after you start taking Zevistat.
While taking this medicine, your doctor will closely monitor whether you have diabetes or are at risk of developing it. Risk factors for developing diabetes include high levels of sugar and fats in the blood, being overweight, and having high blood pressure.
Inform your doctor if you have a severe lung disease.
The use of Zevistat with fibrates (certain medicines used to lower cholesterol) should be avoided, as the combination of Zevistat with fibrates has not been studied.
Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness. In rare cases, muscle problems can be severe and lead to muscle damage causing kidney injury; very rarely, deaths have occurred.
The risk of muscle damage is higher at higher doses of Zevistat, especially with the 10 mg/80 mg dose. The risk of muscle damage is also increased in certain patients. Inform your doctor if:

you have kidney problems,
you have thyroid problems,
you are 65 years of age or older,
you are female,
you have previously experienced muscle problems while being treated with cholesterol-lowering medicines called "statins" (such as simvastatin, atorvastatin, and rosuvastatin) or fibrates (such as gemfibrozil and bezafibrate),
you or a close relative has a hereditary muscle disease.

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

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

Other medicines and Zevistat
Inform 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 may increase the risk of muscle problems (some of which are already listed above under "Do not take Zevistat"):

cyclosporine (often used in patients who have undergone organ transplantation),
danazol (a synthetic hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside of it),
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, 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 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 severe, rare genetic cholesterol disorder),
large quantities (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 oral fusidic acid to treat a bacterial infection, you will need to temporarily stop taking this medicine. Your doctor will tell you when it is safe to restart Zevistat. Taking Zevistat with fusidic acid may, in rare cases, cause muscle weakness, tenderness, or pain (rhabdomyolysis). For more information about rhabdomyolysis, see section 4.
In addition to the medicines listed above, inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including those not requiring a prescription. In particular, inform your doctor if you are taking:

medicines containing an active substance to prevent blood clots, such as warfarin, fluindione, phenprocoumon, or acenocoumarol (anticoagulants),
colestyramine (also used to lower cholesterol), as it may interfere with 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 certain medicines, including Zevistat. Consumption of grapefruit juice should be avoided, as it may 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 inform your doctor. Do not take Zevistat if you are breastfeeding, as it is unknown whether the medicine passes into breast milk.
Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
Zevistat is not expected to affect 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 informed you that you have an intolerance to certain sugars, inform them before taking this medicinal product.

3. How to take Zevistat

Take this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Your doctor will determine the appropriate tablet dosage for you, depending on your ongoing therapy and
your individual risk.

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

Adults: the dose is 1 Zevistat tablet by mouth once daily.
Use in adolescents (aged 10 to 17 years): the dose is 1 Zevistat tablet by mouth once daily (do not exceed the maximum dose of 10 mg/40 mg once daily).
The 10 mg/80 mg dose is recommended only for adult patients with very high cholesterol levels and high risk of heart problems, who have not achieved their target cholesterol levels with lower doses.
Not all recommended doses are available with this product; however, other products with different dosages (10 mg/80 mg) are available.
Take Zevistat in the evening. You may take the medicine with meals or on an empty stomach.
If your doctor has prescribed Zevistat together with another cholesterol-lowering medicine containing the active substance cholestyramine 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 the missed tablet. Take your next normal dose of Zevistat at the usual time the following day.

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

4. Possible side effects

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

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

Contact your doctor immediately if you experience unexplained pain, tenderness or muscle weakness.
In rare cases, muscle problems may be serious and include muscle breakdown leading to
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 laboratory blood test values for liver function (transaminases) and/or muscle function (CK)

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

elevated blood test values for liver function; increased blood uric acid levels; prolonged blood clotting time; protein in urine; weight reduction
dizziness; headache; tingling sensation
abdominal pain; indigestion; flatulence; nausea; vomiting; abdominal distension; diarrhoea; dry mouth; heartburn
rash; itching; urticaria
joint pain; muscle pain, tenderness, weakness or spasms; neck pain; pain in arms and legs; back pain
unusual fatigue or weakness; feeling of tiredness; 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 substances ezetimibe or simvastatin:

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

Other side effects reported with some statins:

sleep disorders, including nightmares
sexual difficulties
diabetes. The risk of diabetes is higher if you have high levels of sugar and fats in your blood, are overweight and have high blood pressure. While you are taking this medicine, your doctor will monitor you closely.
persistent muscle pain, tenderness or weakness which may continue despite stopping Zevistat (frequency not known)

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 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 stated on the packaging after "Exp.". The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature.
Store in the original packaging to protect the medicine from light and moisture.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Zevistat contains

The active substances 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 monohydrate lactose, 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 contents of the pack
The 10 mg/10 mg tablets are slightly biconvex round tablets, white to off-white in colour, with bevelled edges. Tablet diameter: 6 mm.
The 10 mg/20 mg tablets are biconvex oval tablets, white to pinkish in colour. Tablet dimensions: 10 x 5 mm.
The 10 mg/40 mg tablets are biconvex capsule-shaped tablets, white or almost white. 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 European Economic Area countries under the following names:
Italy Zevistat