Simratio 40

Package leaflet: Information for the patient

Simratio 10, 10 mg, film-coated tablets
Simratio 20, 20 mg, film-coated tablets
Simratio 40, 40 mg, film-coated tablets
Simvastatinum
This medicinal product is contraindicated during pregnancy
Please read the entire leaflet carefully before taking this medicine, as it contains
important information for the patient.

• Keep this leaflet for possible future reference.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm other people, 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.

Leaflet contents:

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

1. What Simratio is and what it is used for

• elevated cholesterol levels in the blood (primary hypercholesterolemia) or elevated levels of fats in the blood (mixed hyperlipidemia);
• inherited disorders (homozygous familial hypercholesterolemia) causing increased cholesterol levels in the blood. In such cases, other treatment methods may also be used;
• ischemic heart disease (coronary artery disease) or high risk of developing ischemic heart disease (due to diabetes, previous stroke, or other vascular diseases). Simratio may prolong the patient's life by helping to reduce the risk of heart disease regardless of cholesterol levels in the blood.

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

2. Important information before using Simratio

When not to use Simratio

• if the patient is allergic to simvastatin or any of the other ingredients of this medicine (listed in section 6: Contents of the pack and other information),
• if there are currently liver function disorders,
• if the patient is pregnant or breastfeeding,
• if the following medicine(s) containing any of the active substances listed below are being used:
  • 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 in the treatment of hepatitis C),
  • nefazodone (used to treat depression),
  • cobicistat,
  • gemfibrozil (used to lower 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 currently taking or has taken fusidic acid (a medicine used to treat bacterial infections) orally or by injection within the last 7 days. Taking fusidic acid together with Simratio may lead to serious muscle problems (rhabdomyolysis). Do not use Simratio at a dose higher than 40 mg if the patient is taking lomitapide (used to treat severe and rare genetic cholesterol disorder).

If in doubt whether any of the above medicines are being used, consult a doctor.
Warnings and precautions
Before starting Simratio, inform your doctor:

• about all medical conditions, including allergies,
• about heavy alcohol consumption,
• about any history of liver disease. Use of Simratio may not be appropriate,
• about any planned surgical procedure. It may be necessary to temporarily stop taking Simratio.

Consult your doctor or pharmacist before starting Simratio:

• if the patient is of Asian origin, as a different dose may be appropriate for this patient,
• if the patient has or has had myasthenia gravis (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 of the disease or lead to the development of myasthenia (see section 4).

Your doctor should perform a blood test before starting Simratio and during treatment if the patient has any liver disorders. The test will assess liver function.
Your doctor may also perform blood tests to evaluate liver function after starting Simratio.
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 sugar and fats in the blood, 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-related symptoms may be serious, including muscle breakdown leading to kidney damage, and in very rare cases, death.
The risk of muscle damage is higher when higher doses of Simratio are used, particularly the 80 mg dose. The risk of muscle breakdown is also higher in certain patients. Inform your doctor if:

• the patient consumes large amounts of alcohol,
• the patient has kidney problems,
• the patient has thyroid disorders,
• 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 called "statins" or fibrates,
• the patient or a close relative has ever been diagnosed with inherited muscle disorders.

Inform your doctor or pharmacist if muscle weakness persists. Additional tests and treatment with other medicines may be necessary to diagnose and treat this condition.
Children and adolescents
Safety and efficacy 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 use Simratio"). Simratio has not been studied in children under 10 years of age. For additional information, consult your doctor.
Simratio with other medicines
Tell your doctor about all medicines currently or recently taken, and any medicines you plan to take, especially those containing any of the following active substances. Taking Simratio together with any of the following medicines may increase the risk of muscle-related side effects (some of which are listed above in section "When not to use Simratio").

• If oral fusidic acid is necessary for the treatment of a bacterial infection, temporary discontinuation of Simratio will be required. Your doctor will advise when it is safe to restart Simratio. Taking Simratio together with fusidic acid may rarely lead to muscle weakness, tenderness or pain (rhabdomyolysis). Additional information on rhabdomyolysis is provided in section 4.
• cyclosporine (commonly used in organ transplant patients),
• danazol (a synthetic hormone used in the treatment of endometriosis),
• 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 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),
• 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. Simratio). Your doctor may decide to temporarily discontinue Simratio.
• colchicine (used to treat gout),
• ticagrelor (an antiplatelet medicine).

Similarly, inform your doctor or pharmacist about all recently taken medicines, including those available without a prescription. In particular, inform your doctor about the use of 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 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 Simratio.
Patients of Chinese origin should also inform their doctor about taking niacin (nicotinic acid) or products containing niacin.
Simratio with food and drink
Grapefruit juice contains one or more compounds that affect the action of certain medicines in the body, including Simratio. Avoid drinking beverages containing grapefruit juice.
Pregnancy and breastfeeding
Do not use Simratio if you are pregnant, planning to become pregnant, or suspect you may be pregnant. If pregnancy occurs during treatment with Simratio, stop treatment immediately and contact your doctor. Do not use Simratio during breastfeeding, as it is not known whether the medicine is excreted in breast milk.
Before taking any medicine, consult your doctor or pharmacist.
Driving and using machines
Simratio does not affect the ability to drive or operate machinery. However, consider that dizziness may occur in some people after taking Simratio.
Simratio contains lactose
Simratio 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 use Simratio
Your doctor will determine the dose of Simratio appropriate for you, depending on your current treatment and individual risk.
This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
While taking Simratio, follow a cholesterol-lowering diet.
Dosage:
The recommended dose is 1 tablet of Simratio 10 mg, 20 mg, 40 mg or 80 mg taken orally once daily.
Adults:
The initial dose is 10 mg, 20 mg or in some cases 40 mg once daily. Your doctor may adjust the dose after at least 4 weeks of treatment to a maximum of 80 mg once daily. Do not use more than 80 mg per day.
Your doctor may recommend lower doses, especially if the patient is taking certain medicines listed above or has certain kidney problems.
The 80 mg dose is recommended only for adult patients with very high cholesterol levels and high risk of heart disease, in whom target cholesterol levels have not been achieved with lower doses.
Use in children and adolescents:
For children (aged 10–17 years), the usual initial dose is 10 mg once daily in the evening. The maximum recommended dose is 40 mg per day.
Method of administration:
Simratio should be taken in the evening. It can be taken with or without food. Simratio should be taken continuously until your doctor advises stopping.
If your doctor prescribes Simratio together with another cholesterol-lowering medicine containing a bile acid sequestrant, take Simratio at least 2 hours before or 4 hours after taking the bile acid sequestrant.
Taking more Simratio than recommended
Contact your doctor or pharmacist.
Missing a dose of Simratio
Do not take a double dose to make up for a missed dose. Take the next dose of Simratio at the usual time the following day.
Stopping Simratio
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 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 people)
• Very rare (may affect 1 in 10,000 people)
• Frequency not known (frequency cannot be estimated from available data).

If any of the serious adverse reactions listed below occur, the medicine must be discontinued immediately and a doctor must be consulted without delay or the patient should go to the emergency department of the nearest hospital.
The following rare serious adverse reactions have been reported:

• Muscle pain, tenderness, weakness, muscle rupture or muscle cramps. In rare cases, these symptoms may be severe and associated with muscle tissue breakdown leading to kidney damage; very rare cases of death have been reported.
• Hypersensitivity reactions (allergic reactions) including:
  • Swelling of the face, tongue and throat, possibly causing difficulty in breathing (angioedema),
  • Severe muscle pain, usually around the shoulder and hip joints,
  • Rash with muscle weakness in limbs and neck,
  • Rash which may appear on the skin or oral mucosal ulceration (lupus-like skin lesions),
  • Joint pain or inflammation (polymyalgia rheumatica),
  • Inflammation of blood vessels (vasculitis),
  • Unusual bruising, skin lesions 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 such as yellowing of the skin and eyes, itching, dark-coloured urine or pale stools, fatigue or weakness, loss of appetite, liver failure (very rare),
• Pancreatitis, often with severe abdominal pain.

The following very rare serious adverse reactions have been reported:

• Severe allergic reaction causing difficulty in breathing or dizziness (anaphylaxis),
• Rash occurring on the skin or ulceration of the oral mucosa (drug-induced lichenoid reactions),
• Muscle damage,
• Memory impairment,
• Gynaecomastia (enlargement of breasts in males),
• Sleep disorders.

The following adverse reactions have also been rarely reported:

• Decrease in the number of red blood cells (anaemia),
• Numbness or weakness in hands and feet,
• Headaches, tingling sensation, dizziness,
• Blurred vision, visual disturbances,
• Gastrointestinal disorders (abdominal pain, constipation, bloating, indigestion, diarrhoea, nausea, vomiting),
• Rash, itching, hair loss,
• Weakness,
• Memory loss, confusion.

The following adverse reactions have also been reported, but their frequency cannot be determined from 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,
• 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 feet, worsening after periods of activity, double vision or drooping eyelids, difficulty swallowing or shortness of breath.
Additional possible adverse reactions reported during 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. The doctor will monitor the patient's health during treatment with this medicine.
• Muscle pain, tenderness or persistent muscle weakness, which may not resolve after discontinuation of Simratio (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, inform a 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 181 C, 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 provide more information on the safety of this medicine.

5. How to store Simratio

Keep this medicine out of sight and reach of children.
Store the medicine at a temperature below 25°C.
Do not use this medicine after the expiry date stated on the blister after "EXP" and on the outer packaging after "Expiry date". The expiry date (EXP) refers to the last day of the stated month. The batch number on the blister is located after the abbreviation "Lot".
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 Simratio contains

• The active substance is simvastatin. One Simratio 10 coated tablet contains 10 mg of simvastatin. One Simratio 20 coated tablet contains 20 mg of simvastatin. One Simratio 40 coated tablet contains 40 mg of simvastatin.
• Other ingredients are: lactose monohydrate, microcrystalline cellulose, pregelatinized maize starch, citric acid monohydrate, ascorbic acid, butylhydroxyanisole, magnesium stearate.
  Coating composition: hypromellose, lactose monohydrate, titanium dioxide, macrogol PEG 3350, triacetin, iron oxide red, and for 10 mg and 20 mg tablets: iron oxide yellow.

What Simratio looks like and contents of the pack
28, 30 coated tablets
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
ratiopharm GmbH, Graf-Arco-Str 3,
89079 Ulm,
Germany
Representative of the Marketing Authorisation Holder:
Teva Pharmaceuticals Polska Sp. z o.o.
Tel: + 48 22 345 93 00

Manufacturer:
Merckle GmbH, Ludwig-Merckle-Str. 3,
89143 Blaubeuren,
Germany
Teva Pharmaceutical Works Private Limited Company
Pallagi út 13
4042 Debrecen
Hungary
Teva Operations Poland Sp. z o.o.
Mogilska 80
31-546 Kraków, Poland