Vasilip

Package leaflet: Information for the patient

Vasilip, 10 mg, film-coated tablets
Vasilip, 20 mg, film-coated tablets
Vasilip, 40 mg, film-coated tablets
Simvastatinum
Please read this leaflet carefully before using this medicine, as it contains
important information for you.

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

Leaflet contents

1. What Vasilip is and what it is used for
2. Important information before taking Vasilip
3. How to take Vasilip
4. Possible side effects
5. How to store Vasilip
6. Contents of the pack and other information

1. What Vasilip is and what it is used for

Vasilip contains the active substance simvastatin. Vasilip is a medicine used to
reduce blood levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and
fatty substances called triglycerides. In addition, Vasilip increases the level of "good"
cholesterol (HDL cholesterol). Vasilip belongs to a group of medicines called statins.
Cholesterol is one of several fatty substances present in the blood. Total cholesterol
consists mainly 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, thereby 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 deposition of bad cholesterol in the arteries and protects against heart disease.
Triglycerides are another type of fat present in the blood that may contribute to an increased
risk of heart disease.
While taking this medicine, you should follow a cholesterol-lowering diet.
Vasilip is used as an adjunct to a cholesterol-lowering diet in the following conditions:

• Elevated blood cholesterol levels (primary hypercholesterolemia) or elevated blood fat levels (mixed hyperlipidemia);
• Inherited disorder (homozygous familial hypercholesterolemia) causing high blood cholesterol levels. Other treatment methods may also be used;
• Ischemic heart disease (coronary artery disease) or high risk of ischemic heart disease (due to diabetes, previous stroke, or other vascular diseases). Vasilip may prolong life by reducing the risk of heart disease, regardless of blood cholesterol levels. Most people do not experience direct symptoms from high cholesterol levels. Your doctor can assess your 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 using Vasilip

When not to use Vasilip

• if the patient is allergic to simvastatin or to any of the other ingredients of this medicine (listed in section 6),
• if the patient currently has impaired liver function,
• if the patient is pregnant or breastfeeding,
• if the patient is concurrently taking medicine(s) containing any 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 used in the treatment of HIV infection),
  • boceprevir or telaprevir (used in the treatment of hepatitis C),
  • nefazodone (used to treat depression),
  • cobicistat (used in the treatment of HIV infection),
  • gemfibrozil (used to reduce cholesterol levels),
  • cyclosporine (used in organ transplant patients),
  • danazol (a synthetic hormone used in the treatment of endometriosis, a condition in which the tissue lining the uterus grows outside the uterus),
• if the patient is taking or has taken within the last 7 days an oral or injectable medicine containing fusidic acid (used to treat bacterial infections). Taking Vasilip with fusidic acid may lead to severe muscle problems (rhabdomyolysis). Do not use Vasilip at a dose higher than 40 mg if the patient is taking lomitapide (used to treat a severe and rare genetic disorder affecting cholesterol levels). If in doubt whether any of the above medicines are being used, consult a doctor.

Warnings and precautions

Before starting treatment with Vasilip, consult a doctor or pharmacist. Inform the doctor:

• about all medical conditions, including allergies,
• if consuming large amounts of alcohol,
• if there is a history of liver disease. Use of Vasilip may not be appropriate,
• if undergoing surgery. Temporary discontinuation of Vasilip may be necessary,
• if the patient is of Asian origin, as a different dose may be suitable for this patient,
• if the patient has or has had myasthenia (a disease causing general muscle weakness, including in some cases muscles involved in breathing) or ocular myasthenia (a disease causing weakness of eye muscles), because statins may sometimes worsen symptoms or lead to the development of myasthenia (see section 4).

The doctor should perform a blood test before starting Vasilip and during treatment if the patient has any liver disorders, to assess liver function. The doctor may also perform blood tests to evaluate liver function after starting Vasilip. During therapy, the doctor will closely monitor the patient's health if the patient has diabetes or is at risk of developing diabetes. The risk of developing diabetes exists in individuals with high blood sugar and fat levels, overweight, and high blood pressure.

Inform the doctor about serious lung diseases.

Contact a doctor immediately if unexplained muscle pain, tenderness to touch, or muscle weakness occur. 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 greater when higher doses of Vasilip are used, especially the 80 mg dose. The risk of muscle breakdown is also higher in patients:

• who consume large amounts of alcohol,
• with kidney problems,
• with thyroid disorders,
• aged 65 years or older,
• female gender,
• who have previously experienced muscle problems during treatment with cholesterol-lowering medicines called "statins" or fibrates,
• who have or whose close relatives have had inherited muscle disorders.

If any of the above conditions apply, inform the doctor. Also notify the doctor or pharmacist if muscle weakness persists. Additional tests and additional medications may be necessary for diagnosis and treatment of this condition.

Children and adolescents

The safety and efficacy of simvastatin have been studied in boys aged 10–17 years and in girls who started menstruation at least one year earlier (see section 3 "How to use Vasilip"). Studies with simvastatin have not been conducted in children under 10 years of age. For additional information, consult a doctor.

Vasilip and other medicines

Tell the doctor about all medicines currently or recently used, and about any medicines the patient plans to use, containing any of the following active substances. Concurrent use of Vasilip with any of the following medicines may increase the risk of muscle problems (some of which are listed above under "When not to use Vasilip"):

• if oral fusidic acid is required for the treatment of a bacterial infection, temporary discontinuation of this medicine will be necessary. The doctor will advise when it is safe to restart Vasilip. Concurrent use of Vasilip with fusidic acid may in rare cases lead to muscle weakness, tenderness or pain (rhabdomyolysis). Additional information regarding rhabdomyolysis is provided in section 4,

• cyclosporine (commonly used in organ transplant patients),

• danazol (a synthetic hormone used in the treatment of 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 reduce cholesterol levels),

• erythromycin, clarithromycin or telithromycin (used to treat bacterial infections),

• HIV protease inhibitors such as indinavir, nelfinavir, ritonavir and saquinavir (used in the treatment of AIDS),

• antiviral medicines used in the treatment of hepatitis C, such as boceprevir, telaprevir, elbasvir or grazoprevir (used in the treatment of hepatitis C),

• nefazodone (used to treat depression),

• cobicistat (used in the treatment of HIV infection),

• 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 a severe and rare genetic disorder affecting cholesterol levels),

• daptomycin (a medicine used to treat complicated skin and soft tissue infections and bacteremia). Muscle-related adverse effects may be greater when this medicine is taken during treatment with simvastatin (e.g., Vasilip). The doctor may decide to temporarily discontinue Vasilip,

• colchicine (used to treat gout),

• ticagrelor (an antiplatelet medicine),

• ribociclib (used to treat breast cancer),

• palbociclib (used to treat breast cancer).

Similarly, inform the doctor or pharmacist about all medicines currently or recently used, and about any medicines the patient plans to use, including over-the-counter medicines. In particular, inform the doctor about using medicines containing any of the following active substances:

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

Inform any doctor prescribing a new medicine that the patient is taking Vasilip.

Vasilip with food and drink

Grapefruit juice contains one or more compounds that affect the action of certain medicines in the body, including Vasilip. Avoid drinking beverages containing grapefruit juice.

Pregnancy and breastfeeding

Do not use Vasilip in women who are pregnant, planning pregnancy, or suspect they may be pregnant. If pregnancy occurs during treatment with Vasilip, stop treatment immediately and contact a doctor. Do not use Vasilip during breastfeeding, as it is not known whether the medicine is excreted in breast milk. If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult a doctor or pharmacist before using this medicine.

Driving and operating machinery
Vasilip does not affect the ability to drive or operate machinery. However, consider that dizziness may occur in some individuals after taking Vasilip.

Vasilip contains lactose
If the patient has previously been diagnosed with intolerance to certain sugars, consult a doctor before taking this medicine.

3. How to take Vasilip

The doctor will determine the appropriate dose of the medicine for each patient, depending on the current treatment and individual risk factors.
This medicine should always be taken according to the doctor's or pharmacist's instructions. If in doubt, consult your doctor or pharmacist.
While taking Vasilip, a cholesterol-lowering diet should be followed.

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 once daily. The doctor may adjust the dose after at least 4 weeks of treatment, up to a maximum of 80 mg once daily. Do not take more than 80 mg per day.

The doctor may recommend lower doses, especially if the patient is taking any of the medicines listed above or has certain kidney problems.

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

The usual starting dose in children (aged 10–17 years) is 10 mg taken once daily in the evening. The maximum recommended dose is 40 mg per day.

Method of administration

Vasilip should be taken in the evening. The medicine can be taken with or without food. Vasilip should be taken continuously unless the doctor advises otherwise.

If your doctor has prescribed Vasilip together with another cholesterol-lowering medicine containing any bile acid sequestrant, Vasilip should be taken at least 2 hours before or 4 hours after taking the bile acid sequestrant.

Taking more Vasilip than prescribed

Contact your doctor or pharmacist immediately.

If you forget to take Vasilip

Do not take a double dose to make up for the missed dose. Take the next dose at the usual time the following day.

Stopping Vasilip

Consult your doctor or pharmacist before stopping, as cholesterol levels may increase again.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The following terms are used to describe how frequently adverse reactions have been reported:

• Rare (may affect 1 in 1,000 patients)
• Very rare (may affect 1 in 10,000 patients)
• Frequency not known (cannot be estimated from the available data)

Listed below are rare but serious adverse reactions. If any of these serious adverse reactions occur, the medicine must be discontinued and the doctor must be contacted immediately or the patient should go to the emergency department of the nearest hospital.

• Muscle pain, tenderness, weakness, muscle rupture 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 reactions (allergic reactions) such as:
  • Swelling of the face, tongue and throat causing breathing difficulties (angioedema),
  • Severe muscle pain, usually in the shoulder and hip joint areas,
  • Rash with muscle weakness in the limbs and neck,
  • Rash affecting the skin or ulceration of the oral mucosa (lupus-like skin lesions),
  • Joint pain or inflammation (polymyalgia rheumatica),
  • Inflammation of blood vessels (vasculitis),
  • Unusual bruising, skin rashes and swelling (dermatomyositis), urticaria, photosensitivity, fever, hot flushes,
  • Shallow breathing (dyspnoea) and malaise,
  • Symptoms of lupus-like disease (including rash, joint problems and blood cell abnormalities),
  • Liver inflammation with symptoms such as yellowing of the skin and eyes, itching, dark urine or pale stools, fatigue or weakness, loss of appetite, liver failure (very rare),
  • Pancreatitis, often accompanied by severe abdominal pain.

Rarely reported adverse reactions also include:

• Decreased number of red blood cells (anaemia),
• Numbness or weakness in hands and feet,
• Headache, tingling sensation, dizziness,
• Blurred vision and visual disturbances,
• Gastrointestinal disorders (abdominal pain, constipation, bloating, indigestion, diarrhoea, nausea, vomiting),
• Rash, itching, hair loss,
• Weakness,
• Sleep disorders (very rare),
• Poor memory (very rare), memory loss, confusion.

The following very rare serious adverse reactions have been reported:

• Severe allergic reaction causing breathing difficulties or dizziness (anaphylaxis),
• Gynaecomastia (enlargement of breasts in males).

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

• 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 eye muscles).

Patients should consult a doctor if they experience 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 reactions reported during the use of certain statins:

• Sleep disturbances, including nightmares,
• Sexual dysfunction,
• Diabetes. The occurrence of diabetes is more likely in individuals with high levels of blood sugar and lipids, overweight and high blood pressure. The doctor will monitor the patient's health status during treatment with Vasilip.
• Persistent muscle pain, tenderness or weakness, which may persist even after discontinuation of Vasilip (frequency not known).

Laboratory test results
Elevated levels of muscle enzymes (creatine kinase) in blood and abnormal liver function tests have been observed.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, the patient should inform their doctor or pharmacist. Adverse reactions 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 reactions can also be reported to the marketing authorisation holder. Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Vasilip

Keep this medicine out of the sight and reach of children.
10 mg and 20 mg coated tablets
Store below 25°C, in the original packaging.
40 mg coated tablets
Store below 30°C, in the original packaging.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Vasilip contains

• The active substance is simvastatin. Each coated tablet contains 10 mg, 20 mg, or 40 mg of simvastatin.
• Other ingredients are:
  Coated tablets 10 mg and 20 mg: monohydrate lactose, pregelatinized starch, butylated hydroxyanisole, citric acid, ascorbic acid, corn starch, microcrystalline cellulose, magnesium stearate; coating: hypromellose, talc, propylene glycol, titanium dioxide.
  Coated tablets 40 mg: monohydrate lactose, modified starch, butylated hydroxyanisole, citric acid, ascorbic acid, corn starch, microcrystalline cellulose, magnesium stearate; coating: hypromellose, talc, propylene glycol, titanium dioxide.
  See section 2 “Vasilip contains lactose”.

What Vasilip looks like and contents of the pack
10 mg: white, round, slightly biconvex coated tablets with bevelled edges.
20 mg: white, round, slightly biconvex coated tablets with bevelled edges.
40 mg: white, round, slightly biconvex coated tablets with bevelled edges and a central dividing line on one side.

Pack sizes:
28 coated tablets in blister packs, in a cardboard box.

Marketing Authorisation Holder
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer
Vasilip, 10 mg, 20 mg, coated tablets
KRKA-POLSKA Sp. z o.o., ul. Równoległa 5, 02-235 Warsaw, Poland
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Vasilip, 40 mg, coated tablets
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warsaw
Tel. 22 57 37 500