Simratio 20

Leaflet accompanying the packaging: patient information

Simratio 10, 10 mg, film-coated tablets

Simratio 20, 20 mg, film-coated tablets

Simratio 40, 40 mg, film-coated tablets

Simvastatin
This medicine is absolutely contraindicated in pregnancy

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

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

Table of contents of the leaflet:

• 1. What is Simratio and what is it 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 is Simratio and what is it used for

• homozygous familial hypercholesterolemia, a genetic disorder that causes high levels of cholesterol in the blood. Other treatments may also be used;
• ischemic heart disease (coronary heart disease) or a high risk of developing ischemic heart disease (due to diabetes, a history of stroke or other vascular diseases). Simratio may prolong life by reducing the risk of heart disease, regardless of cholesterol levels in the blood.

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

2. Important information before taking Simratio

When not to take Simratio

• if you are allergic to simvastatin or any of the other ingredients of this medicine (listed in section 6: Contents of the pack and other information),
• if you currently have liver problems,
• if you are pregnant or breastfeeding,
• if you are taking any of the following medicines:
• 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 to treat 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 with transplanted organs),
• danazol (a synthetic hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside the uterus).
• if you are currently taking or have taken in the last 7 days a medicine called fusidic acid (an antibiotic used to treat bacterial infections) orally or by injection. Taking fusidic acid with Simratio can cause serious muscle problems (rhabdomyolysis). Do not take Simratio at a dose greater than 40 mg if you are taking lomitapide (used to treat a rare genetic cholesterol disorder).

In case of doubt, whether any of the above-mentioned medicines are being taken, consult your doctor.

Warnings and precautions

Before starting treatment with Simratio, tell your doctor:

• about all your illnesses, including allergies,
• about consuming large amounts of alcohol,
• about having had liver disease in the past. Taking Simratio may not be suitable,
• about planned surgery. It may be necessary to stop taking Simratio for a short time,

Consult your doctor or pharmacist before starting treatment with Simratio:

• if you are of Asian origin, as a different dose may be suitable for you.
• if you have or have had muscle weakness (a disease that causes general muscle weakness, including in some cases muscles involved in breathing) or eye muscle weakness (a disease that causes muscle weakness in the eyes), as statins can sometimes exacerbate symptoms or cause myasthenia (see section 4).

Your doctor should perform a blood test before starting treatment with Simratio and during treatment if you have any liver problems. The test will assess liver function.
Your doctor may also perform blood tests to assess liver function after starting treatment with Simratio.
During therapy, your doctor will closely monitor your health if you have diabetes or are at risk of developing diabetes. The risk of developing diabetes is higher in people with high levels of sugar and fat in the blood, overweight, and high blood pressure.
Tell your doctor about any serious lung diseases.

You should contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness. In rare cases, muscle problems can 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 Simratio, especially the 80 mg dose. The risk of muscle breakdown is also higher in some patients. Tell your doctor if:

• you drink 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 had muscle problems while taking cholesterol-lowering medicines called "statins" or fibrates,
• you or a close relative have had hereditary muscle disorders.

Tell your doctor or pharmacist if muscle weakness persists. To diagnose and treat this condition, additional tests and medications may be necessary.

Children and adolescents

The safety and efficacy of Simratio have been studied in boys aged 10-17 years and girls who have started menstruating (at least one year before). Simratio has not been studied in children under the age of 10. For more information, consult your doctor.

Simratio and other medicines

Tell your doctor about all the medicines you are taking, including those you have bought without a prescription, and any you plan to take. Some medicines can increase the risk of muscle problems when taken with Simratio (some of these are listed above in the "When not to take Simratio" section).

• If it is necessary to take fusidic acid orally for the treatment of a bacterial infection, it will be necessary to temporarily stop taking Simratio.

Your doctor will inform you when it will be safe to restart taking Simratio. Taking Simratio with fusidic acid can, in rare cases, cause muscle weakness, tenderness, or pain (rhabdomyolysis). Additional information on rhabdomyolysis can be found in section 4.

• cyclosporine (often used in patients with transplanted organs),
• danazol (a synthetic hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside the uterus),
• medicines containing the active substances itraconazole, ketoconazole, fluconazole, posaconazole, or voriconazole (used to treat fungal infections),
• fibrates containing the active substances gemfibrozil or 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 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 irregular heartbeats),
• verapamil, diltiazem, or amlodipine (used to treat high blood pressure, chest pain related to heart disease, or other heart diseases),
• lomitapide (used to treat a rare genetic cholesterol disorder),
• daptomycin (an antibiotic used to treat complicated skin and soft tissue infections and bacteremia). It is possible that side effects affecting the muscles may be greater when this medicine is taken with simvastatin (e.g., Simratio). Your doctor may decide to stop taking Simratio for a while.
• colchicine (used to treat gout),
• tikagrelor (an antiplatelet medicine).

Similarly, to the medicines listed above, tell your doctor or pharmacist about any medicines you have taken recently, including those you have bought without a prescription. In particular, tell your doctor about medicines containing any of the following active substances:

• medicines that prevent blood clots, such as warfarin, phenprocoumon, or acenocoumarol (anticoagulant medicines),
• fenofibrate (also used to lower cholesterol levels),
• niacin (also used to lower cholesterol levels),
• rifampicin (used to treat tuberculosis).

Also, inform any doctor who prescribes you a new medicine that you are taking Simratio.
Patient 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 some medicines in the body, including Simratio. You should avoid drinking grapefruit juice.

Pregnancy and breastfeeding

Do not take Simratio if you are pregnant, planning to have a baby, or think you may be pregnant. If you become pregnant while taking Simratio, stop treatment and contact your doctor immediately. Do not take Simratio while 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 use machines. However, you should take into account that some people may experience dizziness after taking Simratio.

Simratio contains lactose

Simratio tablets contain a sugar called lactose. If you have been diagnosed with intolerance to some sugars, contact your doctor before taking the medicine.

3. How to take Simratio

Your doctor will determine the dose of Simratio that is right for you, depending on your current treatment and individual risk.
Always take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.
While taking Simratio, you should follow a low-cholesterol diet.
Dosage:
The recommended dose is one Simratio 10 mg, 20 mg, 40 mg, or 80 mg tablet taken orally once a day.

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 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 problems.
A dose of 80 mg is recommended only for adult patients with very high cholesterol levels in the blood and a high risk of developing heart disease, who have not reached their target cholesterol level with a lower dose of the medicine.

Use in children and adolescents:

For children (aged 10-17 years), the recommended 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. The medicine can be taken with or without food. Simratio should be taken continuously until your doctor tells you to stop.
If your doctor has prescribed Simratio 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 a higher dose of Simratio than recommended

Contact your doctor or pharmacist.

Missing a dose of Simratio

Do not take a double dose to make up for a forgotten dose. Take the next dose of Simratio at the usual time the next day.

Stopping treatment with Simratio

Consult your doctor or pharmacist, as your cholesterol level may rise again.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Simratio can cause side effects, although not everybody gets them.
The following terms are used to describe how often side effects are experienced:

• rare (may affect up to 1 in 100 people)
• very rare (may affect up to 1 in 10,000 people)
• frequency not known (frequency cannot be estimated from the available data).

If you experience any of the following serious side effects, stop taking Simratio and contact your doctor immediately or go to the emergency department of your nearest hospital.

The following serious side effects have been reported rarely:

• muscle pain, tenderness, or weakness, muscle rupture, or muscle cramps. In rare cases, these problems can be serious and are associated with muscle breakdown leading to kidney damage; very rare cases of death have been reported.
• allergic reactions (hypersensitivity) in the form of:
• swelling of the face, tongue, and throat that can cause difficulty breathing (angioedema),
• severe muscle pain, usually in the shoulder and hip area,
• rash with muscle weakness in the arms and neck,
• rash that can occur on the skin or ulcers in the mouth (lichenoid skin changes),
• joint pain or inflammation (polymyalgia rheumatica),
• inflammation of blood vessels (vasculitis),
• unusual bruising, skin rashes, and swelling (dermatomyositis), hives, sun sensitivity, fever, and flushing.
• liver inflammation with symptoms of yellowing of the skin and eyes, itching, dark urine, or pale stools, fatigue, or weakness, liver failure (very rare),
• pancreatitis, often with severe abdominal pain.

The following very rare serious side effects have been reported:

• a severe allergic reaction that causes difficulty breathing or dizziness (anaphylaxis),
• rash that can occur on the skin or ulcers in the mouth (drug-induced lichenoid changes),
• muscle damage,
• poor memory,
• gynecomastia (breast enlargement in men),
• sleep disturbances.

The following side effects have also been reported rarely:

• decreased red blood cell count (anemia),
• numbness or weakness in the hands and feet,
• headache, tingling, dizziness,
• blurred vision, vision disturbances,
• gastrointestinal problems (abdominal pain, constipation, bloating, indigestion, diarrhea, nausea, vomiting),
• rash, itching, hair loss,
• weakness,
• memory loss, confusion.

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

• erectile dysfunction,
• depression,
• inflammation of the lungs that causes breathing problems, including persistent cough and/or shortness of breath or fever,
• tendon problems, sometimes complicated by tendon rupture,
• persistent muscle weakness,
• myasthenia (a disease that causes general muscle weakness, including in some cases muscles involved in breathing),
• ocular myasthenia (a disease that causes muscle weakness in the eyes).

Talk to your doctor if you experience weakness in your arms or legs, worsening after periods of activity, double vision, or drooping eyelids, difficulty swallowing, or shortness of breath.
Additional possible side effects reported during treatment with some statins:

• sleep disturbances, including nightmares,
• sexual problems,
• diabetes. The development of diabetes is more likely in people with high levels of sugar and fat in the blood, overweight, and high blood pressure. Your doctor will monitor your health during treatment with this medicine.
• muscle pain, tenderness, or persistent weakness, which may not resolve after stopping Simratio (frequency not known).

Laboratory test results
Elevated muscle enzyme activity (creatine kinase) in the blood and abnormal liver function test results have been observed.

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, please tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety, 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. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Simratio

Keep this medicine out of the sight and reach of children. Store in a temperature below 25°C.
Do not use this medicine after the expiry date which is stated on the blister and outer packaging after "EXP" and "Termin ważności". The expiry date (EXP) refers to the last day of the month. The batch number on the blister is after "Lot".
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Simratio contains

• The active substance is simvastatin. Simratio 10 mg film-coated tablets contain 10 mg of simvastatin. Simratio 20 mg film-coated tablets contain 20 mg of simvastatin. Simratio 40 mg film-coated tablets contain 40 mg of simvastatin.
• The other ingredients are: lactose monohydrate, microcrystalline cellulose, maize starch, citric acid monohydrate, ascorbic acid, butylhydroxyanisole, magnesium stearate. The coating contains: 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 film-coated tablets
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

ratiopharm GmbH, Graf-Arco-Str 3,
89079 Ulm
Germany
Representative of the marketing authorization 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