Simbatrix

Package leaflet: Information for the patient

SIMBATRIX 10 mg FILM-COATED TABLETS, 20 mg FILM-COATED TABLETS, 40 mg FILM-COATED TABLETS

Simvastatin
Generic Medicine
Please read this leaflet carefully before you start taking this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What SIMBATRIX is and what it is used for

SIMBATRIX contains the active substance simvastatin. SIMBATRIX is a medicine used to
reduce levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and fat substances called triglycerides in the blood. In addition, SIMBATRIX increases levels of "good" cholesterol (HDL cholesterol). SIMBATRIX belongs to a group of medicines called statins. Cholesterol is one of several fatty substances found in the bloodstream.
Total cholesterol is mainly composed of LDL cholesterol and HDL cholesterol.
LDL cholesterol is often called "bad" cholesterol because it can accumulate in the walls of arteries, forming plaques. Over time, this plaque buildup can lead to narrowing of the arteries. This narrowing can slow down or block blood flow to vital organs such as the heart and brain. This blockage of blood flow can cause a heart attack or stroke.
HDL cholesterol is often called "good" cholesterol because it helps prevent bad cholesterol from accumulating in the arteries and protects against heart disease.
Triglycerides are another form of fat in the blood that can increase the risk of heart disease.
You must follow a cholesterol-lowering diet while taking this medicine.
SIMBATRIX is used in addition to diet to reduce cholesterol if you have:

• elevated cholesterol levels in the blood (primary hypercholesterolemia) or elevated levels of fats in the blood (mixed hyperlipidemia);
• an inherited condition (homozygous familial hypercholesterolemia) that increases your blood cholesterol levels. You may also be receiving other medicines.
• coronary heart disease (CHD) or are at high risk of CHD (because you have diabetes, have had a stroke, or have another blood vessel disease). SIMBATRIX may prolong survival by reducing the risk of heart disease-related problems, regardless of blood cholesterol levels.

In most people, high cholesterol does not cause immediate symptoms. Your doctor can check your cholesterol levels with a simple blood test. Visit your doctor regularly, keep track of your cholesterol values, and discuss target goals with your doctor.

2. What you need to know before taking SIMBATRIX

Do not take SIMBATRIX:

• if you are allergic (hypersensitive) to simvastatin or to any of the other ingredients of this medicine (listed in section 6);
• if you currently have liver problems;
• if you are pregnant or breastfeeding;
• if you are taking a 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 are used for HIV infections),
  • antiviral agents for hepatitis C, for example boceprevir, telaprevir, elbasvir or grazoprevir (used to treat hepatitis C virus infection),
  • nefazodone (used to treat depression),
  • cobicistat (used in the treatment of HIV infections),
  • gemfibrozil (used to lower cholesterol),
  • cyclosporine (used in organ transplant patients),
  • danazol (an artificial hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside the uterus).
    Do not take SIMBATRIX if you are taking, have taken within the last 7 days, or have been administered a medicine called fusidic acid (used to treat bacterial infection, taken orally or by injection). The combination of fusidic acid and SIMBATRIX can cause serious muscle problems (rhabdomyolysis).

Do not take more than 40 mg of SIMBATRIX if you are taking lomitapide (used to treat a rare, severe genetic cholesterol condition).
Ask your doctor for advice if you are unsure whether the medicine you are taking is one of those listed above.

Warnings and precautions
Talk to your doctor or pharmacist before taking SIMBATRIX:
Inform your doctor:

• about all your medical conditions, including allergies;
• if you consume large amounts of alcohol;
• if you have ever had liver disease. In this case, SIMBATRIX may not be suitable for you;
• if you are scheduled for surgery. You may need to temporarily stop taking SIMBATRIX;
• if you are of Asian origin, as a different dose may be appropriate for you;
• if you have or have had myasthenia (a disease characterized by generalized muscle weakness, including in some cases the muscles used for breathing) or ocular myasthenia (a disease causing weakness of the eye muscles), as statins may sometimes worsen myasthenia or cause its onset (see section 4).

Your doctor will perform a blood test before starting SIMBATRIX and if you develop symptoms of liver problems during treatment. This test checks whether your liver is functioning properly.
Your doctor may also prescribe blood tests to monitor liver function after starting SIMBATRIX.
During treatment with this medicine, your doctor will closely monitor whether you have diabetes or are at risk of developing diabetes. Risk factors for developing diabetes include high levels of sugar and fats in the blood, being overweight, and having high blood pressure.
Inform your doctor if you have a serious lung disease.
Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness.
This is because, rarely, muscle problems can be serious and may include muscle tissue damage leading to kidney damage; very rarely, death has occurred.
The risk of muscle injury is higher at higher doses of SIMBATRIX, particularly with the 80 mg dose. The risk of muscle injury is also higher in certain patients. Talk to your doctor if any of the following conditions apply to you:

• 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 previously experienced muscle problems during treatment with cholesterol-lowering medicines called "statins" or fibrates;
• you or a close family member have a hereditary muscle disease.

In addition, inform your doctor or pharmacist if you have persistent muscle weakness.
Further tests and medicines may be needed to diagnose and treat this condition.

Children and adolescents
The safety and efficacy of SIMBATRIX have been studied in boys and girls aged 10 to 17 years and in girls who have had their menstrual period (menstruation) for at least one year (see section 3 “How to take SIMBATRIX”). SIMBATRIX has not been studied in children under 10 years of age. For further information, consult your doctor.

Other medicines and SIMBATRIX
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine containing any of the following active substances.
Taking SIMBATRIX with any of the following medicines may increase the risk of muscle problems (some of these have already been listed in the section “Do not take SIMBATRIX”):

• If you need to take oral fusidic acid to treat a bacterial infection, you must temporarily stop taking this medicine. Your doctor will tell you when it is safe to restart SIMBATRIX. Taking SIMBATRIX with fusidic acid may rarely cause muscle weakness, pain, or tenderness (rhabdomyolysis). See further information on rhabdomyolysis in section 4.
• cyclosporine (often used in organ transplant patients)
• danazol (an artificial hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside the uterus)
• medicines with active substances such as itraconazole, ketoconazole, fluconazole, posaconazole or voriconazole (used to treat fungal infections)
• fibrates with active substances such as gemfibrozil and bezafibrate (used to lower cholesterol)
• erythromycin, clarithromycin, telithromycin (used to treat bacterial infections)
• HIV protease inhibitors such as indinavir, nelfinavir, ritonavir and saquinavir (used to treat AIDS)
• antiviral agents for hepatitis C 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 heartbeat)
• verapamil, diltiazem or amlodipine (used to treat high blood pressure, chest pain associated with heart disease, or other heart disorders)
• lomitapide (used to treat a rare, severe genetic cholesterol condition)
• daptomycin (used to treat complicated skin and soft tissue infections and bacteremia). Muscle-related side effects may be increased when this medicine is taken during treatment with simvastatin (e.g., Simbatrix). Your doctor may decide to temporarily stop your treatment with SIMBATRIX
• colchicine (used to treat gout)

As with the medicines listed above, inform your doctor or pharmacist if you are taking or have recently taken any other medicine, including those without a prescription. In particular, inform your doctor if you are taking a medicine(s) containing any of the following active substances:

• medicines with an active substance to prevent blood clotting, such as warfarin, phenprocoumon or acenocoumarol (anticoagulants)
• fenofibrate (also used to lower cholesterol)
• niacin (also used to lower cholesterol)
• rifampicin (used to treat tuberculosis)

You must also inform any doctor prescribing a new medicine that you are taking SIMBATRIX.

SIMBATRIX with food, drinks and alcohol
Grapefruit juice contains one or more substances that alter how the body processes certain medicines, including SIMBATRIX. Consumption of grapefruit juice must be avoided. Inform your doctor if you consume large amounts of alcohol.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
If you become pregnant while taking SIMBATRIX, stop taking it immediately and contact your doctor.
Do not use SIMBATRIX while breastfeeding, as it is not known whether the medicine passes into breast milk.
Consult your doctor or pharmacist before taking any medicine.

Driving and using machines
SIMBATRIX is not expected to affect your ability to drive or use machinery. However, dizziness has been reported after taking SIMBATRIX, and this should be taken into account.

SIMBATRIX contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him or her before taking this medicine.

3. How to take SIMBATRIX

Always take this medicine exactly as your doctor has instructed. If you are unsure, consult your doctor or pharmacist.
Your doctor will determine the appropriate tablet dose for you based on your condition, current treatment, and risk profile.
While taking SIMBATRIX, you must follow a cholesterol-lowering diet.

Dosage
The recommended dose is one SIMBATRIX tablet of 10 mg, 20 mg, or 40 mg taken orally once daily.

Adults
The usual 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 up to a maximum of 80 mg per day.
Do not take more than 80 mg per day.
Your doctor may prescribe lower doses, especially if you are taking any of the medicines listed above or have certain kidney problems.
The 80 mg dose is recommended only for adult patients with very high cholesterol levels and a high risk of heart disease who have not reached their ideal cholesterol level with lower doses.

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

Method of administration
Take SIMBATRIX in the evening. You may take it regardless of meals.
Continue taking SIMBATRIX unless your doctor tells you to stop.
If your doctor has prescribed SIMBATRIX with another cholesterol-lowering medicine containing a bile acid sequestrant, you must take SIMBATRIX at least 2 hours before or 4 hours after taking the bile acid sequestrant medicine.

If you take more SIMBATRIX than you should
Contact your doctor or pharmacist.

If you forget to take SIMBATRIX
Do not take a double dose to make up for the missed dose; take only your usual dose of SIMBATRIX the next day at the usual time.

If you stop taking SIMBATRIX
Talk to your doctor or pharmacist, as your cholesterol levels may rise again.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, SIMBATRIX can cause side effects, although not everybody gets them.
If you experience any of the following serious side effects, you must stop treatment and contact your doctor immediately or go to the nearest hospital emergency department.

The following serious rare side effects have been reported:

• muscle pain, tenderness, weakness, cramps. In rare cases, these muscle problems can be serious and may include muscle tissue damage leading to kidney damage; very rarely, death has occurred
• hypersensitivity reactions (allergies) including:
  • swelling of the face, tongue, and throat causing difficulty breathing (angioedema)
  • severe muscle pain, usually in shoulders or hips
  • skin rash with weakness in legs and neck muscles
  • joint pain or inflammation (polymyalgia rheumatica)
  • inflammation of blood vessels (vasculitis)
  • unusual bruising, skin rash, swelling (dermatomyositis), hives, skin sensitivity to sunlight, fever, hot flushes
  • shortness of breath (dyspnea) and feeling unwell
  • lupus-like symptoms (including skin rash, joint disorders, and effects on blood cells)
• liver inflammation with the following symptoms: yellowing of the skin and eyes, itching, dark urine, pale stools, feeling tired or weak, loss of appetite
• pancreatitis, often associated with severe abdominal pain.

The following serious very rare side effects have been reported:

• a severe allergic reaction causing breathing difficulties or dizziness (anaphylaxis)
• skin rash that may appear on the skin or mouth ulcers (drug-induced lichenoid eruptions)
• muscle breakdown
• gynecomastia (enlargement of the breast in men)
• liver failure.

The following side effects have also been reported:
Rare (may affect up to 1 in 1,000 people)

• decrease in red blood cell count (anemia)
• numbness or weakness in arms and legs
• headache, tingling sensation, dizziness
• blurred vision, visual disturbances
• digestive disorders (abdominal pain, constipation, flatulence, indigestion, diarrhea, nausea, vomiting)
• skin rash, itching, hair loss
• weakness

Very rare (may affect up to 1 in 10,000 people)

• difficulty falling asleep (insomnia)
• poor memory, memory loss, confusion

Not known (frequency cannot be estimated from available data)

• erectile dysfunction
• depression
• lung inflammation causing breathing problems including persistent cough and/or shortness of breath and fever
• tendon problems, sometimes complicated by rupture
• myasthenia gravis (a disease causing generalized muscle weakness, including in some cases the muscles used for breathing)
• ocular myasthenia (a disease causing weakness of the eye muscles).

Contact your doctor if you experience worsening weakness in arms or legs after periods of activity, double vision or drooping eyelids, difficulty swallowing, or labored breathing.
Other possible side effects reported with some statins:

• sleep disorders, including nightmares
• sexual difficulties
• diabetes. This is more likely if you have high levels of sugar and fats in the blood, are overweight, and have high blood pressure. Your doctor will monitor you during treatment with this medicine
• muscle pain, tenderness, or weakness that is persistent and, in very rare cases, may not resolve after stopping SIMBATRIX (frequency not known).

Laboratory tests
Increases in certain blood test values related to liver function and a muscle enzyme (creatine kinase) have been observed.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store SIMBATRIX

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of that month.
Store below 30°C.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What SIMBATRIX contains
SIMBATRIX 10 mg film-coated tablets Each tablet contains:
Active substance: simvastatin 10 mg
Excipients: monohydrate lactose, pregelatinized starch, butylated hydroxyanisole, ascorbic acid, monohydrate citric acid, microcrystalline cellulose, magnesium stearate, hypromellose, hydroxypropylcellulose, titanium dioxide, talc, yellow iron oxide, red iron oxide.
SIMBATRIX 20 mg film-coated tablets Each tablet contains:
Active substance: simvastatin 20 mg
Excipients: monohydrate lactose, pregelatinized starch, butylated hydroxyanisole, ascorbic acid, monohydrate citric acid, microcrystalline cellulose, magnesium stearate, hypromellose, hydroxypropylcellulose, titanium dioxide, talc, yellow iron oxide.
SIMBATRIX 40 mg film-coated tablets Each tablet contains:
Active substance: simvastatin 40 mg
Excipients: monohydrate lactose, pregelatinized starch, butylated hydroxyanisole, ascorbic acid, monohydrate citric acid, microcrystalline cellulose, magnesium stearate, hypromellose, hydroxypropylcellulose, titanium dioxide, talc, red iron oxide.

Description of the appearance of SIMBATRIX and contents of the pack:
SIMBATRIX 10 mg film-coated tablets
Blister pack containing 20 tablets of 10 mg
SIMBATRIX 20 mg film-coated tablets
Blister pack containing 28 tablets of 20 mg
SIMBATRIX 40 mg film-coated tablets
Blister pack containing 28 tablets of 40 mg

Marketing Authorization Holder
S. F. GROUP srl
Via Tiburtina, n° 1143 00156 Rome
Manufacturer
Special Product’s Line S.p.A.
Via Fratta Rotonda Vado Largo, n° 1 03012, Anagni (FR)
LACHIFARMA Srl, Laboratorio Chimico Farmaceutico Salentino
S.S. 16 Zona Industriale
73010 Zollino (LE) - Italy