Package leaflet: Information for the patient

Ximve, 10 mg, film-coated tablets
Ximve, 20 mg, film-coated tablets
Ximve, 40 mg, film-coated tablets
Simvastatinum
Please read carefully all the information in this leaflet before taking the medicine, as it contains
important information for the patient.

Keep this leaflet, as you may need to read it again.
If you have any further questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents

What Ximve is and what it is used for
Important information before taking Ximve
How to take Ximve
Possible side effects
How to store Ximve
Contents of the pack and other information

1. What Ximve is and what it is used for

Ximve contains the active substance simvastatin. Ximve is a medicine used to lower blood levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and fatty substances called triglycerides. In addition, Ximve increases the level of "good" cholesterol (HDL cholesterol). Ximve belongs to a group of medicines called statins.
Cholesterol is one of several fatty substances present in the blood. Total cholesterol mainly consists 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, 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 in the blood that may contribute to an increased risk of heart disease.
While taking this medicine, you should follow a cholesterol-lowering diet.
Ximve is used as an adjunct to a cholesterol-lowering diet in cases of:

elevated blood cholesterol levels (primary hypercholesterolemia) or elevated blood fat levels (mixed hyperlipidemia);
inherited disorder (homozygous familial hypercholesterolemia), which causes increased blood cholesterol levels. Other treatment methods may also be used;
ischemic heart disease (coronary heart disease) or high risk of ischemic heart disease (due to diabetes, previous stroke, or other blood vessel diseases). Ximve may prolong life by reducing the risk of heart disease, regardless of blood cholesterol levels.

Most people do not experience direct symptoms of high cholesterol. Your doctor can assess cholesterol levels by ordering a simple blood test. You should attend regular check-ups, monitor your blood cholesterol levels, and discuss treatment goals with your doctor.

2. Important information before taking Ximve
Do not take Ximve:

if you are allergic to simvastatin or any of the other ingredients of this medicine (listed in section 6),
if you currently have liver function disorders,
if you are pregnant or breastfeeding,
if you are taking any of the following medicines containing one or more of the listed 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 used in the treatment of HIV infection)
- boceprevir and telaprevir (used to treat hepatitis C virus infection)
- nefazodone (used to treat depression)
- cobicistat
- gemfibrozil (used to lower cholesterol levels)
- cyclosporine (used in patients after organ transplants)
- danazol (a synthetic hormone used to treat endometriosis, a condition in which the tissue lining the uterus grows outside the uterus)
if you are currently taking or have taken within the last 7 days a medicine called fusidic acid (used to treat bacterial infections) orally or by injection. Taking fusidic acid together with Ximve may lead to serious muscle problems (rhabdomyolysis). Do not take Ximve in doses higher than 40 mg if you are taking lomitapide (used to treat severe and rare genetic cholesterol disorder).

If you are unsure whether you are taking any of the medicines listed above, consult your doctor.
Warnings and precautions
Before starting Ximve, discuss this with your doctor or pharmacist.
Inform your doctor:

about all medical conditions, including allergies.
if you consume large amounts of alcohol.
if you have a history of liver disease. Taking Ximve may not be appropriate.
if you are scheduled for surgery. You may need to temporarily stop taking Ximve.
if you are of Asian descent, as a different dose may be suitable 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 eye muscles), as statins may sometimes worsen symptoms of the disease or lead to the development of myasthenia (see section 4).

Your doctor should perform a blood test before starting Ximve and during treatment if you have any liver disorders. The test will assess liver function.
Your doctor may also perform blood tests to evaluate liver function after starting Ximve.
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 blood sugar and fats, overweight, and high blood pressure.
Inform your doctor about serious lung diseases.
Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness. In rare cases, muscle problems may 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 Ximve, especially the 80 mg dose. The risk of muscle tissue breakdown is also higher in certain patients. Inform your doctor if:

you consume large amounts of alcohol
you have kidney problems
you have thyroid problems
you are 65 years of age or older
you are female
you have ever experienced muscle problems during treatment with cholesterol-lowering medicines called "statins" or fibrates
you or a close relative have been diagnosed with inherited muscle disorders.

Inform your doctor or pharmacist if muscle weakness persists. Additional tests and possibly additional medicines may be needed to diagnose and treat this condition.
Children and adolescents
The safety and efficacy of simvastatin have been studied in boys aged 10–17 years and in girls who have had their first menstrual period at least one year earlier (see section 3 "How to take Ximve"). Studies on simvastatin have not been conducted in children under 10 years of age. For additional information, consult your doctor.
Ximve and other medicines
Inform your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take that contain any of the following active substances. Taking Ximve together with any of the following medicines may increase the risk of muscle problems (some of which are listed above under "Do not take Ximve").

If oral fusidic acid must be taken to treat a bacterial infection, temporary discontinuation of this medicine will be necessary. Your doctor will inform you when it is safe to restart taking Ximve. Taking Ximve together with fusidic acid may in rare cases lead to muscle weakness, tenderness, or pain (rhabdomyolysis). Additional information on rhabdomyolysis can be found in section 4.
cyclosporine (commonly used in patients after organ transplants)
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 lower cholesterol levels)
erythromycin, clarithromycin, telithromycin (used to treat bacterial infections)
HIV protease inhibitors such as indinavir, nelfinavir, ritonavir, and saquinavir (used to treat AIDS)
antiviral medicines used to treat hepatitis C virus infection, 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 heart rhythm disorders)
verapamil, diltiazem, or amlodipine (used to treat high blood pressure, chest pain related to heart disease, or other heart conditions)
lomitapide (used to treat severe and rare genetic cholesterol disorder)
daptomycin (a medicine used to treat complicated skin and soft tissue infections and bacteremia). Muscle-related adverse effects may be increased when this medicine is taken during simvastatin treatment (e.g., Ximve). Your doctor may decide to temporarily discontinue Ximve,
colchicine (used to treat gout)
ticagrelor (an antiplatelet medicine).

Similarly, inform your doctor or pharmacist about all medicines you are currently taking, including those available without a prescription. In particular, inform your doctor about taking medicines containing any of the following active substances:

medicines containing active substances that prevent blood clot formation, such as warfarin, phenprocoumon, or acenocoumarol (anticoagulants)
fenofibrate (also used to lower cholesterol levels)
niacin (also used to lower cholesterol levels)
rifampicin (used to treat tuberculosis).

Inform any doctor prescribing a new medicine that you are taking Ximve.
Taking Ximve with food and drink
Grapefruit juice contains one or more compounds that affect the action of certain medicines in the body, including Ximve. Avoid drinking beverages containing grapefruit juice.
Pregnancy and breastfeeding
Do not take Ximve if you are pregnant, planning to become pregnant, or suspect you may be pregnant. If you become pregnant while taking Ximve, stop treatment immediately and contact your doctor. Do not take Ximve during breastfeeding, as it is unknown whether the medicine is excreted in breast milk.
Before taking any medicine, consult your doctor or pharmacist.
Driving and operating machinery
Ximve does not affect the ability to drive or operate machinery. However, consider that dizziness may occur in some people after taking Ximve.
Ximve contains anhydrous lactose
Ximve tablets contain a sugar called lactose. If you have previously been diagnosed with intolerance to certain sugars, consult your doctor before taking this medicine.
3. How to take Ximve
Your doctor will determine the appropriate dose of the medicine for you, depending on your current treatment and individual risk.
Always take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.
While taking Ximve, follow a low-cholesterol diet.
Dosage:
The recommended dose is 10 mg, 20 mg, 40 mg, or 80 mg taken orally once daily.
Adults:
The starting dose is 10 mg, 20 mg, or in some cases 40 mg per day. Your doctor may adjust the dose after at least 4 weeks of treatment to a maximum of 80 mg per day. Do not take more than 80 mg per day.
Your doctor may recommend lower doses, especially if you are taking certain medicines listed above or have certain kidney-related conditions.
The 80 mg dose is recommended only for adult patients with very high blood cholesterol levels and a high risk of heart disease, in whom the target cholesterol level has not been achieved with a lower dose.
Use in children and adolescents
For children (aged 10–17 years), the usual starting dose is 10 mg once daily in the evening. The maximum recommended dose is 40 mg per day.
Administration method:
Ximve should be taken in the evening. It can be taken with or without food. Ximve should be taken continuously until your doctor advises stopping.
If your doctor has prescribed Ximve together with another cholesterol-lowering medicine containing a bile acid sequestrant, take Ximve at least 2 hours before or 4 hours after taking the bile acid sequestrant.
Taking more Ximve than recommended
Contact your doctor or pharmacist.
Missing a dose of Ximve
Do not take a double dose to make up for a missed dose. Take the next dose of Ximve the next day at the usual time.
Stopping Ximve
Consult your doctor or pharmacist, as cholesterol levels may increase again.
If you have any further questions about using this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.
The following terms are used to describe how often the adverse effects have been reported:

rare (may affect 1 in 1,000 patients)
very rare (may affect 1 in 10,000 patients)
unknown (frequency cannot be estimated from the available data).

If any of these serious adverse effects occur, stop taking the medicine immediately and
contact your doctor or go to the nearest hospital emergency department without delay.
The following rare but serious adverse effects have been reported:

muscle pain, tenderness, weakness, muscle damage or cramps. In rare cases, these symptoms may be severe and associated with muscle breakdown leading to kidney damage; very rare cases of death have been reported
hypersensitivity (allergic) reactions including:
- swelling of the face, tongue and throat, which may cause difficulty in breathing (angioedema)
- severe muscle pain, usually in the shoulder and hip joints
- rash with muscle weakness in the limbs and neck
- rash occurring on the skin or ulceration of the oral mucosa (lupus-like skin lesions)
- pain or inflammation of joints (polymyalgia rheumatica)
- inflammation of blood vessels (vasculitis)
- unusual bruising, skin rashes and swelling (dermatomyositis), urticaria, photosensitivity, fever, hot flushes
- shortness of breath (dyspnoea) and malaise
- symptoms of lupus-like illness (including rash, joint problems and blood cell changes)
hepatitis with symptoms of yellowing of the skin and eyes, itching, dark-coloured urine or pale-coloured stools, fatigue or weakness, loss of appetite, liver failure (very rare)
pancreatitis, often with severe abdominal pain.

The following very rare but serious adverse effects have been reported:

severe allergic reaction causing difficulty in breathing or dizziness (anaphylaxis)
gynaecomastia (enlargement of breasts in men)
rash occurring on the skin or ulceration of the oral mucosa (lupus-like skin lesions)
muscle damage.

The following adverse effects have also been reported rarely:

decrease in the number of red blood cells (anaemia)
numbness or weakness in the hands and feet
headache, tingling sensation, dizziness
gastrointestinal disturbances (abdominal pain, constipation, bloating, indigestion, diarrhoea, nausea, vomiting)
rash, itching, hair loss
fatigue
sleep disorders (very rare)
mild memory impairment (very rare), memory loss, confusion
blurred vision and visual disturbances.

The following adverse effects have also been reported, but their frequency cannot be estimated
from the available data (frequency unknown):

erectile dysfunction
depression
lung inflammation causing breathing problems, including persistent cough and/or dyspnoea or fever
tendon disorders, sometimes complicated by tendon rupture
myasthenia (a disease causing generalised muscle weakness, including in some cases muscles involved in breathing)
ocular myasthenia (a disease causing weakness of the eye muscles). You should contact your doctor if the patient experiences weakness in the arms or legs that worsens after periods of activity, double vision or drooping eyelids, difficulty swallowing or shortness of breath.

Additional possible adverse effects reported during the use of certain statins:

sleep disorders, including nightmares
sexual dysfunction
diabetes. The occurrence of diabetes is more likely in people with high levels of blood sugar and fats, overweight and high blood pressure. Your doctor will monitor your health during treatment with this medicine
pain, tenderness or persistent muscle weakness, which may not resolve after discontinuation of Ximve (frequency unknown).

Laboratory test results
Elevated levels of muscle enzymes (creatine kinase) in the blood and abnormal liver function tests have been observed.
Reporting of adverse effects
If you experience any adverse effects, including any not listed in this leaflet, tell your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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 provide more information on the safety of the medicine.

5. How to store the medicine Ximve

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard box/blister labeled "EXP". The expiry date refers to the last day of the stated month.
Store below 25°C.
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 Ximve contains

The active substance is simvastatin. Each coated tablet contains 10 mg, 20 mg, or 40 mg of simvastatin, respectively.
The other ingredients are: Anhydrous lactose, microcrystalline cellulose, pregelatinized maize starch, butylhydroxyanisole, magnesium stearate, talc. Coating: hydroxypropylcellulose, hypromellose, talc, titanium dioxide (E 171).

What Ximve looks like and contents of the pack
Ximve is a white, elongated, biconvex coated tablet with a central breakline on one side.
Ximve 10 mg – tablets are marked with "SVT" on the side without the breakline and "10" on the other side.
Ximve 20 mg – tablets are marked with "SVT" on the side without the breakline and "20" on the other side.
Ximve 40 mg – tablets are marked with "SVT" on the side without the breakline and "40" on the other side.
The tablets are packed in blisters contained in cardboard boxes. The boxes contain 28 or 30 coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Recordati Polska sp. z o.o.
al. Armii Ludowej 26
00-609 Warsaw
Tel. +48 22 206 84 50

Manufacturer:
Synthon Hispania S.L.
Castelló 1
08830 Sant Boi de Llobregat
Spain
Rottendorf Pharma GmbH
Ostenfelder Strasse 51-61
59320 Ennigerloh
Germany