Simvasterol

Package leaflet: Information for the patient

Simvasterol, 10 mg, film-coated tablets
Simvasterol, 20 mg, film-coated tablets
Simvasterol, 40 mg, film-coated tablets
Simvastatinum
Please read the entire leaflet carefully before using this 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. This medicine may harm others, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What Simvasterol is and what it is used for

Simvasterol belongs to a group of medicines called statins.
Simvasterol is a medicine used to lower blood levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and fatty substances called triglycerides.
Additionally, Simvasterol increases the level of "good" cholesterol (HDL cholesterol).
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 buildup 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 being treated with Simvasterol, a low-cholesterol diet should be followed.
Simvasterol, in combination with diet, is used when:

• there is elevated blood cholesterol (primary hypercholesterolemia) or elevated blood lipids (mixed hyperlipidemia);
• homozygous familial hypercholesterolemia (a hereditary condition causing high blood cholesterol levels). Other treatment methods may also be used in such cases.
• ischemic heart disease (coronary artery disease) or high risk of developing ischemic heart disease (due to diabetes, previous stroke, or other blood vessel disease). Simvasterol may prolong life by reducing the risk of heart disease, regardless of blood cholesterol levels.

In most people, elevated cholesterol levels do not cause direct symptoms. Your doctor can assess cholesterol levels by ordering a simple blood test. Regular follow-up visits are recommended to monitor blood cholesterol levels and discuss treatment goals with your doctor.

2. Important information before using Simvasterol

When not to use Simvasterol

• if the patient is allergic to simvastatin or any of the other ingredients of this medicine (listed in section 6);
• if there are currently liver function abnormalities;
• if the patient is pregnant or breastfeeding;
• if the following medicinal product(s) containing one or more of the active substances listed below are being used simultaneously:
  • itraconazole, ketoconazole, posaconazole, or voriconazole (medicines used to treat fungal infections);
  • erythromycin, clarithromycin, or telithromycin (antibiotics used to treat bacterial infections);
  • HIV protease inhibitors such as indinavir, nelfinavir, ritonavir, and saquinavir (HIV protease inhibitors are used in the treatment of HIV infection);
  • boceprevir, telaprevir (medicines used in the treatment of hepatitis C virus infection);
  • nefazodone (a medicine used to treat depression);
  • cobicistat (used to boost the effect of antiretroviral medicines);
  • gemfibrozil (a medicine used to reduce cholesterol levels);
  • cyclosporine (a medicine 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, orally or by injection, a medicine containing fusidic acid (a medicine used in bacterial infections). Taking fusidic acid together with Simvasterol may lead to severe muscle damage (rhabdomyolysis).

Do not use Simvasterol at doses higher than 40 mg if the patient is taking lomitapid
(used in the treatment of a severe and rare genetic disorder affecting cholesterol levels).
If in doubt whether any of the above-mentioned medicines are being used, consult a doctor.
Warnings and precautions
Before starting Simvasterol, discuss this with your doctor or pharmacist.
Inform your doctor:

• 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), as statins may sometimes worsen symptoms or lead to the development of myasthenia (see section 4).

• about all current health conditions, past illnesses, and allergies.

• about consumption of large amounts of alcohol.

• about a history of liver disease. In such cases, Simvasterol may be contraindicated.

• about any planned surgical procedures. In such cases, temporary discontinuation of Simvasterol may be necessary.

• if the patient is of Asian origin, as a different dose may be appropriate for this patient.

Before starting treatment, the doctor should order a blood test to check liver function.
After starting treatment with Simvasterol, the doctor may also consider it necessary to perform blood tests to monitor liver function.
Patients with diabetes or those at risk of developing diabetes will be under close medical supervision during treatment with this medicine. Patients with high blood sugar and fat levels, overweight, and high blood pressure may be at risk of developing diabetes.
Inform the doctor if the patient has a severe lung disease.
Seek immediate medical attention if unexplained muscle pain,
tenderness, or muscle weakness occurs, as in rare cases this may lead to serious muscle problems,
including breakdown of muscle tissue (rhabdomyolysis), which may cause kidney damage; very rare cases of patient deaths have been reported.
The risk of muscle tissue breakdown is higher in patients taking Simvasterol at higher doses, particularly 80 mg. The risk of muscle tissue breakdown is also higher in certain patients. Inform the doctor if:

• the patient consumes large amounts of alcohol;
• the patient has kidney problems;
• the patient has thyroid problems;
• the patient is 65 years of age or older;
• the patient is female;
• the patient has ever experienced muscle problems during treatment with cholesterol-lowering medicines belonging to the statin or fibrate group;
• the patient or their close relatives have been diagnosed with an inherited muscle disorder.

Inform the doctor or pharmacist if muscle weakness persists. Additional tests and medications may be necessary 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 (menarche) at least one year prior (see section 3, "How to use Simvasterol"). Simvastatin has not been studied in children under 10 years of age. For additional information, consult a doctor.
Simvasterol and other medicines
Inform your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines the patient plans to take. The medicines listed below may be marketed under several different brand names. They will not be listed here by brand name; only active substances or their groups are mentioned. Therefore, carefully check the package and leaflet of any medicine being taken for the name of its active ingredient.

• If treatment with oral or injectable fusidic acid is required for a bacterial infection, temporarily discontinue Simvasterol. The doctor will inform the patient when it is safe to resume Simvasterol. Taking Simvasterol with fusidic acid may rarely lead to muscle weakness, tenderness, or pain (rhabdomyolysis). More information on rhabdomyolysis can be found in section 4.

Concomitant use of simvastatin with the following medicines increases the risk of muscle-related side effects (some of which are listed above under "When not to use Simvasterol"):

• cyclosporine (a medicine 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 such as itraconazole, ketoconazole, fluconazole, posaconazole, or voriconazole (medicines used in fungal infections);
• fibrates such as gemfibrozil and bezafibrate (cholesterol-lowering medicines);
• erythromycin, clarithromycin, telithromycin, or fusidic acid (antibiotics used in bacterial infections). Do not take fusidic acid while using Simvasterol. More information on rhabdomyolysis can be found in section 4.
• HIV protease inhibitors such as indinavir, nelfinavir, ritonavir, and saquinavir (medicines used in the treatment of AIDS);
• boceprevir, telaprevir, elbasvir, or grazoprevir (medicines used in the treatment of hepatitis C virus infection);
• nefazodone (a medicine used to treat depression);
• medicines containing the active substance cobicistat (used to enhance the effect of antiretroviral medicines);
• amiodarone (a medicine used in heart rhythm disorders);
• verapamil, diltiazem, or amlodipine (medicines used in high blood pressure, chest pain related to heart disease, or other heart conditions);
• lomitapid (used in the treatment of a severe and rare genetic disorder affecting cholesterol levels);
• colchicine (a medicine used in the treatment of gout).

Inform the doctor about all recently taken medicines, including those available without a prescription, especially:

• medicines preventing blood clots such as warfarin, phenprocoumon, acenocoumarol, or ticagrelor (anticoagulant medicines);
• fenofibrate (another cholesterol-lowering medicine);
• niacin (nicotinic acid) (another cholesterol-lowering medicine), particularly if the patient is of Asian origin;
• rifampicin (a medicine used in the treatment of tuberculosis).

Inform any doctor prescribing a new medicine that the patient is taking Simvasterol.
Simvasterol with food and drink
Grapefruit juice contains one or more compounds that affect the action of certain medicines in the body, including Simvasterol. Therefore, avoid drinking grapefruit juice, as it may increase the risk of muscle damage.
Pregnancy and breastfeeding
This medicine is absolutely contraindicated during pregnancy.
The safety of simvastatin use in pregnant women has not been established.
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult a doctor or pharmacist before using this medicine. If pregnancy occurs during treatment with simvastatin, discontinue simvastatin and contact a doctor immediately.
There is no data on the excretion of simvastatin into human breast milk. Since many medicines are excreted in breast milk and may cause serious adverse effects, breastfeeding is not permitted during treatment with simvastatin.
Driving and operating machinery
Simvasterol does not affect the ability to drive or operate machinery.
However, rare cases of dizziness have been reported in patients taking simvastatin tablets (see section 4). If such symptoms occur, do not drive or operate machinery requiring concentration.
Simvasterol contains monohydrate lactose
Simvasterol 10 mg: each coated tablet contains 65.73 mg of monohydrate lactose.
Simvasterol 20 mg: each coated tablet contains 131.46 mg of monohydrate lactose.
Simvasterol 40 mg: each coated tablet contains 262.92 mg of monohydrate lactose.
If the patient has previously been diagnosed with intolerance to certain sugars, consult a doctor before taking this medicine.

3. How to take Simvasterol

This medicine should always be taken as directed by your doctor. If in doubt, consult your doctor or pharmacist.
While taking Simvasterol, a low-cholesterol diet should be followed.

Dosage:
The recommended dose is 5 mg, 10 mg, 20 mg, 40 mg, or 80 mg of Simvasterol, taken orally once daily.

Adults
The initial 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, up to a maximum of 80 mg per day.
Do not take more than 80 mg per day.
Your doctor may recommend a lower dose, especially if you are taking certain medicines listed above or have 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.

Children and adolescents
In children (aged 10 to 17 years) with heterozygous familial hypercholesterolemia, the recommended initial dose is 10 mg once daily in the evening. The maximum recommended dose is 40 mg per day.

Method of administration
Simvasterol should be taken in the evening. Simvasterol tablets should be swallowed with water.
The medicine may be taken during or independently of meals.
If your doctor has prescribed Simvasterol together with bile acid sequestrants, it should be taken at least 2 hours before or at least 4 hours after taking the bile acid sequestrants.

Duration of treatment
Treatment with simvastatin is long-term. The duration of treatment is determined by your doctor.

Overdose of Simvasterol
If you accidentally take more than the prescribed dose, contact your doctor or pharmacist immediately.
Several cases of overdose have been reported. No specific symptoms occurred in any of the patients, and all recovered without consequences. In case of overdose, standard supportive measures should be applied.

Missed dose of Simvasterol
If you realize you have missed a dose within a short time, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and take the next dose at the scheduled time.
Do not take a double dose to make up for a missed tablet.

Stopping Simvasterol
Consult your doctor 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 effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The frequency of the possible adverse effects listed below is defined using the following convention:

• Rare (affects fewer than 1 in 1,000 patients)
• Very rare (affects fewer than 1 in 10,000 patients)
• Unknown (frequency cannot be estimated from available data).

The following severe adverse effects occur rarely.
If any of these severe adverse effects occur, the medicine must be discontinued immediately
and the prescribing physician should be contacted without delay or the patient should go to the
nearest hospital emergency department:

• muscle pain, tenderness, weakness, or cramps; in rare cases, these symptoms may be severe and associated with breakdown of muscle tissue leading to kidney damage; very rare cases of death have been reported.
• hypersensitivity (allergic) reactions such as:
• swelling of the face, tongue, and throat which may cause difficulty in breathing (angioedema);
• severe muscle pain, usually in the shoulder and hip joint areas;
• rash with muscle weakness in the limbs and neck;
• joint pain or inflammation (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 a lupus-like disease (including rash, joint problems, and blood cell changes);
• increased number of eosinophils – a type of white blood cells;
• elevated ESR (erythrocyte sedimentation rate);
• hepatitis with symptoms such as yellowing of the skin and whites of the eyes (jaundice), itching, dark-coloured urine or pale-coloured stools, fatigue or weakness, loss of appetite;
• pancreatitis, often accompanied by severe abdominal pain.

The following very rare severe adverse effect has been reported:

• severe allergic reaction causing difficulty in breathing or dizziness (anaphylaxis).

Other adverse effects:
Rare:

• decreased number of red blood cells (anaemia);
• numbness or weakness in arms or legs;
• headache, tingling sensation, dizziness;
• rash, itching, hair loss;
• weakness;
• memory loss, confusion;
• increased activity of muscle enzymes (creatine kinase) in blood and abnormal liver function tests, increased alkaline phosphatase levels;
• gastrointestinal disturbances (abdominal pain, constipation, bloating, indigestion, diarrhoea, nausea, vomiting);
• blurred vision and visual disturbances.

Very rare:

• insomnia;
• memory disorders;
• liver failure;
• skin rash or oral mucosal ulceration (lichenoid mucocutaneous lesions);
• muscle damage;
• gynaecomastia (enlargement of breasts in males).

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;
• persistent muscle weakness;
• 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 hands or legs worsening with activity, double vision or drooping eyelids, difficulty swallowing, or dyspnoea.

Additionally, adverse effects which have occurred with some statins may also occur:

• sleep disorders, including nightmares;
• sexual dysfunction;
• diabetes. The risk of developing diabetes is higher in people who have high blood sugar and fat levels, overweight, and high blood pressure. Your doctor will monitor your condition during treatment with this medicine.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the 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 to provide more information on the safety of the medicine.

5. How to store the medicine Simvasterol

Keep in the original packaging. Do not store above 25°C.
Keep the medicine out of 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 the stated month.
The marking on the packaging after the abbreviation EXP indicates the expiry date, and after the abbreviation Lot/LOT indicates the batch number.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Simvasterol contains

• The active substance is simvastatin in doses of: 10 mg, 20 mg and 40 mg respectively.
• The other ingredients are: tablet core: monohydrate lactose, microcrystalline cellulose, pregelatinized starch, butylated hydroxyanisole (E320), ascorbic acid, citric acid, colloidal anhydrous silica, talc, magnesium stearate. tablet coating: hypromellose, hypromellose, iron oxide red (E172), iron oxide yellow (E172), triethyl citrate, titanium dioxide (E171), talc, povidone K-30.

What Simvasterol looks like and contents of the pack
Simvasterol 10 mg is a pink-beige, oval, biconvex film-coated tablet with a score line on one side. The tablet can be divided into two equal parts.
Simvasterol 20 mg is an orange, oval, biconvex film-coated tablet.
Simvasterol 40 mg is a pink, oval, biconvex film-coated tablet.
The tablets are packed in blisters and then placed in cardboard boxes containing:
28 tablets (10 mg and 20 mg tablets)
14 or 28 tablets (40 mg tablets).
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. + 48 22 364 61 01