Sinvacor

PACKAGE LEAFLET

Package leaflet: information for the patient

Sinvacor 10, 20, 40 mg film-coated tablets

Simvastatin
Please read this leaflet carefully before taking this medicine because 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 they have the same symptoms as you, because it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Sinvacor is and what it is used for

Sinvacor contains the active substance simvastatin. Sinvacor is a medicine used to reduce levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and fats known as triglycerides in the blood. In addition, Sinvacor increases levels of "good" cholesterol (HDL cholesterol). Sinvacor belongs to a group of medicines called statins.

Cholesterol is one of several types of fats found in the bloodstream. Total cholesterol is made up mainly 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 building up in the arteries and protects against heart disease.

Triglycerides are another form of fat present in the blood that may increase the risk of heart disease.

You must follow a cholesterol-lowering diet while taking this medicine. Sinvacor 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 treatments,
• 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). Sinvacor can prolong survival by reducing the risk of heart-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 cholesterol targets with your doctor.

2. What you need to know before taking Sinvacor

Do not take Sinvacor

• if you are allergic (hypersensitive) to simvastatin or to 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 a medicine containing one or more 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),
  - boceprevir or telaprevir (used to treat hepatitis C virus infection),
  - nefazodone (used to treat depression),
  - cobicistat,
  - 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).
• if you are taking or have taken, within the last 7 days, a medicine called fusidic acid (a medicine used to treat bacterial infection) taken orally or by injection. The combination of fusidic acid and Sinvacor can lead to serious muscle problems (rhabdomyolysis).
  Do not take more than 40 mg of Sinvacor if you are taking lomitapide (used to treat a rare, genetic, severe 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

Tell 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, Sinvacor may not be suitable for you,
• if you are due to undergo surgery. You may need to stop taking Sinvacor for a short period,
• if you are of Asian origin, as you may require a different dose,
• 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), since statins may sometimes worsen myasthenia or cause its onset (see section 4).

Your doctor will arrange for you to have a blood test before you start taking Sinvacor and if you develop symptoms of liver problems while taking Sinvacor. This test is performed to check whether your liver is functioning properly.

Your doctor may also prescribe blood tests to monitor liver function after you start treatment with Sinvacor.

During treatment with this medicine, your doctor will carefully monitor whether you have diabetes or are at risk of developing diabetes. You are at risk of developing diabetes if you have high levels of sugar and fats in your blood, if you are overweight, and if you have 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, cases of death have occurred.

The risk of muscle injury is higher at higher doses of Sinvacor, 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 known as "statins" or fibrates,
• you or a close family member suffer from an inherited muscle disease.

Also, inform your doctor or pharmacist if you have persistent muscle weakness. Further tests and treatment may be needed to diagnose and manage this condition.

Children and adolescents

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

Other medicines and Sinvacor

Tell your doctor if you are taking, have recently taken, or might take any other medicine containing any of the following active substances. Taking Sinvacor 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 Sinvacor").

• 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 Sinvacor treatment. Taking Sinvacor with fusidic acid may rarely lead to muscle weakness, tenderness, or pain (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 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),
• erythromycin, clarithromycin, or 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 conditions),
• lomitapide (used to treat a rare, genetic, severe cholesterol condition),
• daptomycin (used to treat complicated skin and soft tissue infections and bacteremia). The risk of muscle-related side effects may be increased when this medicine is taken during treatment with simvastatin (e.g., Sinvacor). Your doctor may decide to have you stop taking Sinvacor temporarily,
• colchicine (used to treat gout),
• ticagrelor (an antiplatelet medicine).

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

• medicines with an active substance to prevent blood clots, 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 should also inform any doctor who prescribes you a new medicine that you are taking Sinvacor.

Sinvacor with food and drink

Grapefruit juice contains one or more substances that alter how the body processes certain medicines, including Sinvacor. Consumption of grapefruit juice should be avoided.

Pregnancy and breastfeeding

Do not use Sinvacor if you are pregnant, planning to become pregnant, or suspect you are pregnant. If you become pregnant while taking Sinvacor, stop treatment immediately and contact your doctor. Do not use Sinvacor while breastfeeding, as it is not known whether the medicine passes into breast milk.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Sinvacor is not expected to affect your ability to drive or use machines. However, you should be aware that dizziness has been reported after taking Sinvacor.

Sinvacor contains lactose

Sinvacor tablets contain a sugar called 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 Sinvacor

Your doctor will determine the appropriate tablet dosage for you based on your condition, current treatment, and risk profile.
Always take this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist.
During treatment with Sinvacor, you must follow a diet aimed at reducing cholesterol levels.

Dosage:
The recommended dose is simvastatin 5 mg, 10 mg, 20 mg, 40 mg, or 80 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 a lower dose, 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 target cholesterol level with lower doses.

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

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

If you take more Sinvacor than you should

• Contact your doctor or pharmacist immediately.

If you forget to take Sinvacor

• Do not take a double dose to make up for the missed tablet. Take only your usual dose of Sinvacor at the usual time the next day.

If you stop taking Sinvacor

• 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, Sinvacor can cause side effects, although not everybody gets them.
The following terms are used to describe how frequently side effects occur:

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

If you experience any of the serious side effects listed below, 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, or cramps. In rare cases, these muscle problems can be severe and may include muscle tissue damage leading to kidney injury; very rarely, cases of death have occurred.
• hypersensitivity reactions (allergies) including:
  o swelling of the face, tongue, and throat causing breathing difficulties (angioedema),
  o severe muscle pain, usually in the shoulders and hips,
  o skin rash with weakness in the legs and neck muscles,
  o joint pain or inflammation (polymyalgia rheumatica),
  o inflammation of blood vessels (vasculitis),
  o unusual bruising, skin rashes, and swelling (dermatomyositis),
  o hives, skin sensitivity to sunlight, fever, hot flushes,
  o shortness of breath (dyspnea) and general malaise,
  o a group of symptoms resembling lupus (including skin rash, joint problems, and effects on blood cells).
• liver inflammation with the following symptoms: yellowing of the skin and eyes (jaundice), itching, dark urine or pale stools, feeling tired or weak, loss of appetite, liver failure (very rare),
• inflammation of the pancreas, often associated with severe abdominal pain.

The following serious very rare side effects have been reported:

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

The following side effects have also been reported rarely:

• decrease in red blood cell count (anaemia),
• numbness or weakness in the arms and legs,
• headache, tingling sensation, dizziness,
• blurred vision, visual disturbances,
• digestive disorders (abdominal pain, constipation, flatulence, indigestion, diarrhoea, nausea, vomiting),
• skin rash, itching, hair loss,
• weakness,
• difficulty falling asleep (very rare),
• poor memory (very rare), memory loss, confusion.

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

• erectile dysfunction,
• depression,
• lung inflammation causing breathing problems, including persistent cough and/or shortness of breath or fever,
• tendon problems, sometimes complicated by tendon 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 the arms or legs after periods of activity, double vision or drooping eyelids, difficulty swallowing, or shortness of breath.

Additional 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 fat in your blood, are overweight, and have high blood pressure. Your doctor will monitor you during treatment with this medicine,
• persistent muscle pain, tenderness, or weakness that may not resolve after stopping treatment with Sinvacor (frequency not known).

Laboratory findings
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, talk to your doctor or pharmacist. You may also report side effects directly via the Italian Medicines Agency (Agenzia Italiana del Farmaco) website: 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 Sinvacor

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

6. Package contents and other information

What Sinvacor contains
The active substance is simvastatin (10 mg, 20 mg or 40 mg).
The other components are: butylated hydroxyanisole (E320), ascorbic acid (E300), citric acid monohydrate (E330), microcrystalline cellulose (E460), pregelatinized starch, magnesium stearate (E572) and lactose monohydrate. The tablet coating contains hypromellose (E464), hydroxypropylcellulose (E463), titanium dioxide (E171) and talc (E553b). The 10 mg and 20 mg tablets also contain yellow iron oxide (E172) and red iron oxide (E172). The 40 mg tablets also contain red iron oxide.

Description of the appearance of Sinvacor and contents of the pack
Simvastatin 10 mg tablet: film-coated oval tablet, peach-colored, with "MSD 735" engraved on one side and smooth on the other side.
Simvastatin 20 mg tablet: film-coated oval tablet, light brown in color, with "MSD 740" engraved on one side and smooth on the other side.
Simvastatin 40 mg tablet: film-coated oval tablet, brick red in color, with "MSD 749" engraved on one side and smooth on the other side.

Pack sizes:
Sinvacor 10 mg
Blister packs made of a trilayer film composed of polyvinyl chloride (PVC)/polyethylene (PE)/polyvinylidene chloride (PVDC), sealed with an aluminum foil lid, in pack sizes of 1, 4, 10, 14, 15, 20, 28, 30, 50, 60, 98 or 100 tablets.
Blister packs composed of polyvinyl chloride (PVC), sealed with an aluminum foil lid, in pack sizes of 4, 10, 28 or 30 tablets.
Amber glass bottles with metal closure, in pack sizes of 30 or 50 tablets.
Polypropylene bottles, in pack sizes of 50 tablets.
High-density polyethylene (HDPE) bottles, in pack sizes of 30, 50 or 100 tablets.
Unit-dose blisters containing the trilayer film composed of polyvinyl chloride (PVC)/polyethylene (PE)/polyvinylidene chloride (PVDC), sealed with an aluminum foil lid, in pack sizes of 49 or 500 tablets.

Sinvacor 20 mg
Blister packs made of a trilayer film composed of polyvinyl chloride (PVC)/polyethylene (PE)/polyvinylidene chloride (PVDC), sealed with an aluminum foil lid, in pack sizes of 1, 4, 10, 14, 15, 20, 28, 30, 50, 56, 60, 84, 90, 98, 100 or 168 tablets.
Blister packs composed of polyvinyl chloride (PVC), sealed with an aluminum foil lid, in pack sizes of 14, 28, 30, 50 or 90 tablets.
Amber glass bottles with metal closure, in pack sizes of 30 or 50 tablets.
Polypropylene bottles, in pack sizes of 50 tablets.
High-density polyethylene (HDPE) bottles, in pack sizes of 30, 50 or 100 tablets.
Unit-dose blisters containing the trilayer film composed of polyvinyl chloride (PVC)/polyethylene (PE)/polyvinylidene chloride (PVDC), sealed with an aluminum foil lid, in pack sizes of 28, 49, 84, 98 or 500 tablets.

Sinvacor 40 mg
Blister packs made of a trilayer film composed of polyvinyl chloride (PVC)/polyethylene (PE)/polyvinylidene chloride (PVDC), sealed with an aluminum foil lid, in pack sizes of 1, 4, 7, 10, 14, 15, 20, 28, 30, 49, 50, 56, 60, 84, 90, 98, 100 or 168 tablets.
Blister packs composed of polyvinyl chloride (PVC), sealed with an aluminum foil lid, in pack sizes of 7, 14, 28, 30, 49, 50 or 90 tablets.
Amber glass bottles with metal closure, in pack sizes of 30 or 50 tablets.
Polypropylene bottles, in pack sizes of 50 tablets.
High-density polyethylene (HDPE) bottles, in pack sizes of 30, 50 or 100 tablets.
Unit-dose blisters containing the trilayer film composed of polyvinyl chloride (PVC)/polyethylene (PE)/polyvinylidene chloride (PVDC), sealed with an aluminum foil lid, in pack sizes of 28, 49, 98 or 100 tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Organon Italia S.r.l.
Piazza Carlo Magno, 21
00162 Rome
Italy

Manufacturer
Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

Organon Heist bv
Industriepark 30
2220 Heist-op-den-Berg
Belgium

N.V. Organon
Kloosterstraat 6
5349 AB Oss
The Netherlands

This medicinal product is authorized in the European Economic Area countries under the following names:
Belgium, Finland, France, Germany, Greece, Ireland, Luxembourg, Norway, The Netherlands, Portugal, Spain: ZOCOR.
Austria, Sweden: ZOCORD.
Italy: Sinvacor.