Ezetimibe and simvastatin Krka

Patient Information Leaflet

Ezetimibe and Simvastatin Krka 10 mg/10 mg tablets, mg/20 mg tablets, mg/40 mg tablets

Equivalent medicine
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 you, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Ezetimibe and Simvastatin Krka is and what it is used for

Ezetimibe and Simvastatin Krka contains the active substances ezetimibe and simvastatin. Ezetimibe and Simvastatin Krka is a medicine used to lower levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and fats known as triglycerides in the blood. In addition, Ezetimibe and Simvastatin Krka increases levels of "good" cholesterol (HDL cholesterol).
Ezetimibe and Simvastatin Krka works by reducing 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 medicines called "statins", inhibits the body's own production of cholesterol.
Cholesterol is one of several types of fat 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. This blockage of blood flow can 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.
Ezetimibe and Simvastatin Krka is intended for patients who cannot control their cholesterol levels through diet alone. While taking this medicine, you must follow a low-fat diet.
Ezetimibe and Simvastatin Krka should be used in addition to diet to lower cholesterol when you have:

• high levels of cholesterol 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 disease (homozygous familial hypercholesterolemia) that increases cholesterol levels in the blood. You may also be receiving other treatments.
• heart disease, Ezetimibe and Simvastatin Krka reduces the risk of heart attack, stroke, surgery to improve blood flow to the heart, or hospitalization due to chest pain. Ezetimibe and Simvastatin Krka does not help with weight loss.

2. What you need to know before taking Ezetimibe and Simvastatin Krka

Do not take Ezetimibe and Simvastatin Krka:

• 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 a(n) 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 infections)
• nefazodone (used to treat depression)
• cobicistat
• gemfibrozil (used to lower cholesterol)
• cyclosporine (often used in organ transplant patients)
• danazol (a hormone produced in the body, used to treat endometriosis, a condition in which the lining of the uterus grows outside the uterus).

Do not take more than 10 mg/40 mg of Ezetimibe and Simvastatin Krka if you are taking lomitapide (used to
treat a rare, serious genetic disorder affecting cholesterol).
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 Ezetimibe and Simvastatin Krka.
Inform your doctor:

• about all your medical conditions, including allergies
• if you consume large amounts of alcohol or have ever had liver disease. In such cases, Ezetimibe and Simvastatin Krka may not be suitable for you.
• if you are scheduled for surgery. You may need to temporarily stop taking Ezetimibe and Simvastatin Krka tablets.
• if you are of Asian descent, as you may require a different dose
• if you are taking, have taken within the last 7 days, or have been administered a medicine called fusidic acid (used to treat bacterial infections) orally or by injection. The combination of fusidic acid and Ezetimibe and Simvastatin Krka can lead to serious muscle problems (rhabdomyolysis).

Your doctor should perform a blood test before you start taking Ezetimibe and Simvastatin Krka and if you
develop symptoms of liver problems while taking Ezetimibe and Simvastatin Krka. This test is performed to
determine whether your liver is functioning properly.
Your doctor may also order blood tests to monitor liver function after you start treatment with Ezetimibe and
Simvastatin Krka.
During treatment with this medicine, your doctor will closely monitor whether you have diabetes or are at
risk of developing diabetes. You are at risk of developing diabetes if you have high levels of sugar and
fats in your blood, are overweight, and have high blood pressure.
Inform your doctor if you suffer from a serious lung disease.
The use of Ezetimibe and Simvastatin Krka together with fibrates (certain types of cholesterol-lowering
medicines) should be avoided, as the combination of Ezetimibe and Simvastatin Krka with fibrates has
not been studied.
Contact your doctor immediately if you experience muscle pain, tenderness, or weakness of unknown
cause, as muscle problems can, rarely, be serious and lead to muscle tissue damage causing kidney
damage; very rare cases of death have occurred.
The risk of muscle injury is higher at higher doses of Ezetimibe and Simvastatin Krka, particularly with the
10/80 mg dose. The risk of muscle damage is also higher 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 65 years of age 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 experience persistent muscle weakness. Further tests
and treatment may be required to diagnose and manage this condition.
Children and adolescents
Ezetimibe and Simvastatin Krka is not recommended for children under 10 years of age.
Other medicines and Ezetimibe and Simvastatin Krka
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine. Taking Ezetimibe and Simvastatin Krka with any of these medicines may increase the risk of muscle problems (some of which have already been listed in the section above “Do not take Ezetimibe and Simvastatin Krka”).

• cyclosporine (often used in organ transplant patients),
• danazol (a synthetic hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside the uterus),
• medicines with an active substance such as itraconazole, ketoconazole, fluconazole, posaconazole, or voriconazole (used to treat fungal infections),
• fibrates with 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 rare, serious genetic cholesterol condition),
• large quantities (1 gram or more daily) 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 must temporarily stop taking this
medicine. Your doctor will tell you when it is safe to restart treatment with Ezetimibe and Simvastatin Krka.
Taking Ezetimibe and Simvastatin Krka with fusidic acid may rarely lead to muscle weakness, tenderness, or
pain (rhabdomyolysis). For more information on 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 medicine, including those without a prescription. In particular, inform your doctor if you are
taking any of the following medicines:

• 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 affects the mechanism of action of Ezetimibe and Simvastatin Krka,
• fenofibrate (also used to lower cholesterol),
• rifampicin (used to treat tuberculosis).

You should also inform any doctor who prescribes you a new medicine that you are taking Ezetimibe and
Simvastatin Krka.
Ezetimibe and Simvastatin Krka with food and drink
Grapefruit juice contains one or more substances that alter the metabolism of certain medicines, including
Ezetimibe and Simvastatin Krka. Consumption of grapefruit juice should be avoided, as it may increase
the risk of muscle problems.
Pregnancy and breastfeeding
Do not take Ezetimibe and Simvastatin Krka if you are pregnant, planning to become pregnant, or suspect you
are pregnant. If you become pregnant while taking Ezetimibe and Simvastatin Krka, stop taking it immediately
and contact your doctor. Do not take Ezetimibe and Simvastatin Krka if you are breastfeeding, as it is not known
whether the medicine passes into human milk.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
Ezetimibe and Simvastatin Krka is not expected to affect your ability to drive or use machines. However,
please note that some people have experienced dizziness after taking Ezetimibe and Simvastatin Krka.
Ezetimibe and Simvastatin Krka contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this
medicine.

3. How to take Ezetimibe and Simvastatin Krka

Take this medicine exactly as instructed 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, based on your current treatment and your
individual risk profile.

• Before starting treatment with Ezetimibe and Simvastatin Krka, you must already have been following a cholesterol-lowering diet.
• You must continue this cholesterol-lowering diet throughout your treatment with Ezetimibe and Simvastatin Krka.

Adults: The dose is 1 tablet of Ezetimibe and Simvastatin Krka once daily by mouth.
Use in adolescents (aged 10 to 17 years): The dose is 1 tablet of Ezetimibe and Simvastatin Krka by mouth once daily (the maximum dose should not exceed 10 mg/40 mg once daily).
The 10 mg/80 mg dose is recommended only for adult patients with very high cholesterol levels and at high risk of heart problems who have not achieved their target cholesterol levels with lower doses.
Not all recommended doses are available with these products; however, other products with different dosages (10 mg/80 mg) are also available.
Take Ezetimibe and Simvastatin Krka in the evening. You may take it with or without food.
If your doctor has prescribed Ezetimibe and Simvastatin Krka together with another cholesterol-lowering medicine containing the active substance colestyramine or any other bile acid sequestrant, you must take Ezetimibe and Simvastatin Krka at least 2 hours before or 4 hours after taking these medicines.

If you take more Ezetimibe and Simvastatin Krka than you should
Contact your doctor or pharmacist.

If you forget to take Ezetimibe and Simvastatin Krka
Do not take a double dose to make up for the missed tablet. Take your next dose at the usual time the following day.

If you stop taking Ezetimibe and Simvastatin Krka
Inform your doctor or pharmacist before stopping treatment with this medicine, 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, this medicine can cause side effects, although not everyone gets them.
If you experience any of the following side effects, stop taking this medicine and inform your doctor immediately:

• muscle pain (common: may affect up to 1 in 10 people)
• signs indicating blood disorders, e.g. fatigue, bleeding, unexplained bruising, mouth ulcers (not known: frequency cannot be determined from available data)
• inflammation of the pancreas which may cause severe abdominal and back pain accompanied by feeling unwell (not known: frequency cannot be determined from 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 or pale-coloured stools (not known: frequency cannot be determined from available data)
• angioedema (stop taking Ezetimibe and Simvastatin Krka and contact your doctor immediately 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 unexplained muscle pain, tenderness or weakness. This is because, in rare cases, muscle problems can be serious, including muscle breakdown leading to kidney damage; very rare cases of death have occurred.

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

• increases in blood laboratory test values related to liver function (transaminases) and/or muscle function (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
• rash; itching; hives
• joint pain; muscle pain; tenderness; weakness or 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

In addition, the following side effects have been reported in patients taking Ezetimibe and Simvastatin Krka or medicines containing the active substances ezetimibe or simvastatin:

• numbness or weakness in arms and legs; poor memory, memory loss, confusion
• breathing problems, including persistent cough and/or shortness of breath or fever
• constipation
• hair loss; red rash, sometimes with target-shaped lesions (erythema multiforme)
• hypersensitivity reactions including: hypersensitivity (allergic reactions, joint pain or inflammation, inflammation of blood vessels, bruising, skin rashes and swelling, hives, skin sensitivity to sunlight, fever, hot flushes, shortness of breath and feeling unwell, lupus-like illness (including skin rash, joint disorders, and effects on white blood cells))
• muscle pain, tenderness, weakness or cramps; muscle injury; tendon problems, sometimes complicated by tendon rupture
• decreased appetite
• hot flushes; high blood pressure
• pain
• erectile dysfunction
• depression
• changes in certain blood test values related to liver function

Additional 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 fat in your blood, are overweight, and have high blood pressure. Your doctor will monitor you while you are taking this medicine.
• persistent muscle pain, tenderness or weakness that may not resolve after stopping Ezetimibe and Simvastatin Krka (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 www.agenziafarmaco.gov.it/it/responsabili.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ezetimibe and Simvastatin Krka

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack 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 you no longer use. This will help protect the environment.

6. Package contents and other information

What Ezetimibe and Simvastatin Krka 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 10 mg/10 mg tablets, and red iron oxide (E172) – only for 10 mg/20 mg tablets. See section 2 "Ezetimibe and Simvastatin Krka contains lactose".

Description of the appearance of Ezetimibe and Simvastatin Krka and contents of the pack
The 10 mg/10 mg tablets are white to slightly yellowish, round, slightly biconvex with bevelled edges. Tablet diameter 6 mm.
The 10 mg/20 mg tablets are white to pinkish, oval-shaped, biconvex. Tablet dimensions 10 x 5 mm.
The 10 mg/40 mg tablets are white or almost white, biconvex, capsule-shaped. Tablet dimensions 14 x 6 mm.
Ezetimibe and Simvastatin Krka is available in packs containing:

• 14, 28, 30, 56, 60, 90, 98 or 100 tablets in blisters,
• 14 x 1, 28 x 1, 30 x 1, 56 x 1, 60 x 1, 90 x 1, 98 x 1 or 100 x 1 tablets in unit dose divisible blister packs.

Not all pack sizes may be marketed.
Marketing Authorization Holder
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
Local representative for Italy
Krka Farmaceutici Milano S.r.l. – 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 authorized in the European Economic Area Member States under the following names: