SINVALIP

Package leaflet: Information for the patient

Sinvalip 10 mg film-coated tablets, 20 mg film-coated tablets, 40 mg film-coated tablets

Simvastatin
Generic medicine
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 others, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

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

1. What Sinvalip is and what it is used for

Sinvalip contains the active substance simvastatin, which belongs to a group of medicines called statins.
Sinvalip is a medicine used to reduce levels of fats in the blood: total cholesterol, "bad" cholesterol (LDL cholesterol), and fatty substances called triglycerides. In addition, Sinvalip moderately increases levels of "good" cholesterol (HDL cholesterol). 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, which may slow down or block blood flow to vital organs such as the heart and brain.
• Blockage of blood flow can cause a heart attack (myocardial infarction) or stroke.
• HDL cholesterol is often called "good" cholesterol because it removes excess "bad" cholesterol from the arteries and helps protect against heart and blood vessel diseases.
• Triglycerides are another form of fat in the blood that may increase the risk of heart and blood vessel diseases.

You must follow a cholesterol-lowering diet during treatment with this medicine.
Sinvalip is used in patients with:

• high levels of cholesterol in the blood (primary hypercholesterolemia) or high levels of fats in the blood (mixed dyslipidemia) when response to diet or other non-pharmacological treatments (e.g. exercise, weight reduction) is inadequate.

• an inherited disease (homozygous familial hypercholesterolemia) that causes increased levels of cholesterol in the blood. Sinvalip is used in addition to diet or other treatments, or when these treatments are inadequate.

• established cardiovascular atherosclerotic disease (presence of cholesterol-rich plaques in the arteries of the heart or other organs) or diabetes mellitus, with normal or elevated cholesterol levels. Sinvalip improves survival and reduces the progression of atherosclerotic disease. Sinvalip is used as an additional therapy to other treatments to protect the heart and reduce other risk factors. In most people, high cholesterol does not cause immediate symptoms. Your doctor can monitor your cholesterol levels with a simple blood test. Visit your doctor regularly, keep track of your cholesterol values, and discuss with your doctor the goals you should aim for.

2. What you need to know before taking Sinvalip

Do not take Sinvalip

• If you are allergic to simvastatin or to any of the other ingredients of this medicine (listed in section 6).
• If you currently have liver problems or if your transaminase levels (seen in blood tests) are persistently elevated and no known cause exists.
• If you are pregnant or breastfeeding (see section “Pregnancy and breastfeeding”).
• If you are taking one or more of the following medicines:
  • itraconazole, ketoconazole, posaconazole, or voriconazole (medicines used to treat fungal infections).
  • erythromycin, clarithromycin, or telithromycin (antibiotics used to treat infections).
  • HIV protease inhibitors (e.g. indinavir, nelfinavir, ritonavir, and saquinavir) (medicines used to treat HIV infections).
  • boceprevir or telaprevir (medicines used to treat hepatitis C virus infections).
  • nefazodone (a medicine used to treat depression).
  • gemfibrozil (a medicine used to lower cholesterol and triglycerides).
  • ciclosporin (a medicine used in organ transplant patients).
  • danazol (a medicine used to treat endometriosis, a condition in which the lining of the uterus, the endometrium, grows outside the uterus).
  • fusidic acid (an antibiotic) if you are currently using it or have used it within the last 7 days.

If you have any doubts, consult your doctor.
Warnings and precautions
Talk to your doctor before taking Sinvalip:
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), because statins may sometimes worsen myasthenia or cause its onset (see section 4).

Inform your doctor:

• About all medical conditions you have, including allergies.
• If you are taking any other medicines, especially those listed in the section “Other medicines and Sinvalip”.
• If you have a risk factor for developing diabetes, such as:
  • high levels of sugar and fats in your blood
  • being overweight
  • high blood pressure

In this case, during treatment with Sinvalip, your doctor will closely monitor your blood sugar levels, as Sinvalip may cause diabetes.

• If you have had liver disease. In this case, Sinvalip may not be suitable for you.
• If you are due to undergo surgery, as you may need to temporarily stop taking Sinvalip.
• If you have a lung disease.
• If you have risk factors for developing muscle problems, for example:
  • you are 65 years of age or older
  • you are female
  • you have kidney problems
  • your thyroid gland is not functioning properly and you are not taking any medicine for this condition
  • you or a family member has had muscle problems
  • you have had muscle problems during previous treatment with other cholesterol-lowering medicines such as statins or fibrates
  • you consume large amounts of alcohol

In these cases, your doctor may perform tests to assess your muscle condition before prescribing Sinvalip.

Your doctor may request a blood test:

• To assess your muscle condition before prescribing Sinvalip and, if necessary, during treatment with Sinvalip to monitor for any muscle problems.
• To assess your liver function before prescribing Sinvalip and during treatment if you develop any symptoms of liver problems.
• To check whether you have diabetes or are at risk of developing diabetes.

Contact your doctor immediately if, during treatment with Sinvalip:

• You experience unexplained muscle pain, weakness, or cramps. This is because Sinvalip may rarely cause muscle problems, which can be serious and, very rarely, lead to death.
• You notice difficulty breathing, dry cough, fatigue, weight loss, or fever. If necessary, your doctor may instruct you to stop treatment with Sinvalip.

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

Children and adolescents
The safety and efficacy of Sinvalip have been studied in adolescents aged 10 to 17 years and in girls who have had their menstrual period for at least one year. Sinvalip has not been studied in children under 10 years of age. For further information, consult your doctor.

Other medicines and Sinvalip
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
Inform your doctor if you are taking or need to take any of the following medicines, because these must not be used together with Sinvalip:

• itraconazole, ketoconazole, posaconazole, or voriconazole (medicines used to treat fungal infections).
• erythromycin, clarithromycin, or telithromycin (antibiotics used to treat bacterial infections).
• HIV protease inhibitors (e.g. nelfinavir) (medicines used to treat HIV infections).
• antiviral agents for hepatitis C such as boceprevir, telaprevir, elbasvir, or grazoprevir (medicines used to treat hepatitis C virus infection).
• nefazodone (a medicine used to treat depression).
• gemfibrozil (a medicine used to lower cholesterol and triglycerides).
• ciclosporin (a medicine used in organ transplant patients).
• danazol (a medicine used to treat endometriosis, a condition in which the lining of the uterus, the endometrium, grows outside the uterus).
• fusidic acid (an antibiotic) if you are currently using it or have used it within the last 7 days.

Inform your doctor if you are taking or need to take any of the following medicines, because you will be closely monitored and your doctor may adjust your dose of Sinvalip:

• fluconazole (a medicine used to treat fungal infections).
• amiodarone (a medicine used to treat irregular heartbeat).
• verapamil, diltiazem, or amlodipine (medicines used to treat high blood pressure, chest pain related to heart disease, or other heart conditions).
• colchicine (a medicine used to treat gout).
• warfarin, phenprocoumon, or acenocoumarol (medicines used to prevent blood clots).
• Fibrates (medicines also used to lower triglycerides and cholesterol).
• Niacin (nicotinic acid) (a medicine used to increase “good” cholesterol (HDL cholesterol), lower “bad” cholesterol (LDL cholesterol), and reduce triglycerides).
• rifampicin (a medicine used to treat infections such as tuberculosis).

Sinvalip with food, drinks, and alcohol
Grapefruit juice may interfere with Sinvalip. Avoid consuming grapefruit juice during treatment with Sinvalip.
Inform your doctor if you consume large amounts of alcohol, as alcohol use during treatment with Sinvalip may lead to muscle problems.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Do not use Sinvalip if you are pregnant, suspect you are pregnant, or are planning a pregnancy. If you become pregnant while taking Sinvalip, stop treatment immediately and contact your doctor.

Breastfeeding
Do not use Sinvalip while breastfeeding, as it is not known whether the medicine passes into breast milk.

Driving and using machines
Sinvalip is not expected to affect your ability to drive or operate machinery. However, you should be aware that dizziness has been reported after taking Sinvalip.

Sinvalip contains lactose
Sinvalip tablets contain a sugar called lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

3. How to take Sinvalip

Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Your doctor will determine the most appropriate dose of Sinvalip for you, based on your current treatment and your individual risk profile.
During treatment with Sinvalip, you must follow a diet aimed at reducing cholesterol levels.

Use in adults
The recommended starting dose is 1 tablet of 10–20 mg daily, taken in the evening. In some cases, your doctor may prescribe a higher initial dose of 20–40 mg daily.
Your doctor may adjust your dose after at least 4 weeks and may prescribe a maximum dose of 80 mg daily. The 80 mg dose will be prescribed by your doctor for adult patients with very high cholesterol levels and a high risk of heart and blood vessel disease who have not reached their target cholesterol levels with lower doses.
Do not take more than 80 mg daily.
Your doctor may prescribe lower doses, especially if you are taking any of the medicines listed in the section “Other medicines and Sinvalip” or if you have severe kidney problems.

Use in children and adolescents aged 10 to 17 years
In children and adolescents aged 10 to 17 years, the recommended starting dose is 10 mg daily taken in the evening. The maximum recommended dose is 40 mg daily.

Take Sinvalip in the evening. You may take it with or without food.
Continue taking Sinvalip unless your doctor tells you to stop.
If your doctor has prescribed Sinvalip together with another cholesterol-lowering medicine containing a bile acid sequestrant, you must take Sinvalip at least 2 hours before or 4 hours after taking the bile acid sequestrant medicine.

If you take more Sinvalip than you should
In case of accidental overdose, contact your doctor immediately or go to the nearest hospital.

If you forget to take Sinvalip
Do not take a double dose to make up for the missed dose. Take only your usual dose the next day at the regular time.

If you stop taking Sinvalip
Do not stop treatment with Sinvalip without first consulting your doctor, as your cholesterol levels may rise again.
If you have any questions about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following serious side effects have been reported in rare cases (may affect up to 1 in 1,000 people).
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.

• Muscle pain, tenderness, weakness, or cramps. In rare instances, these muscle problems may be severe and may include muscle tissue damage leading to kidney injury; and very rarely, cases of death have occurred.
• Hypersensitivity reactions (allergies) including:
  o swelling of the face, tongue, and throat which may cause difficulty breathing (angioedema). The following very rare serious side effect has been reported:
  o a severe allergic reaction causing difficulty breathing or dizziness (anaphylaxis)
  o Severe muscle pain, usually in the shoulders or 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), hives, skin sensitivity to sunlight, fever, hot flushes.
  o Shortness of breath (dyspnoea) and feeling unwell.
  o A group of lupus-like symptoms (including skin rash, joint problems, and effects on blood cells).
• Inflammation of the liver 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 side effects have also been reported:
Rare side effects (may affect up to 1 in 1,000 people)

• decrease in the number of red blood cells (anaemia)
• dizziness, headache
• peripheral nervous system disorder, tingling sensations
• abdominal pain, constipation, flatulence, diarrhoea, indigestion, nausea, vomiting
• skin rash, itching, localized or widespread hair loss
• increase in certain blood parameters (alanine aminotransferase, aspartate aminotransferase (transaminases), γ-glutamyl transferase (γGT), alkaline phosphatase, creatine kinase (CPK))
• increases in glycated haemoglobin (HbA1c) and fasting blood glucose levels
• weakness

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

• insomnia
• memory problems

Side effects with unknown frequency (frequency cannot be estimated from the available data)

• erectile dysfunction
• depression
• inflammation of the lungs causing breathing problems, including persistent cough and/or shortness of breath and fever
• tendon problems, sometimes resulting in tendon rupture
• persistent muscle weakness
• Myasthenia gravis (a condition causing generalized muscle weakness, including in some cases the muscles used for breathing)
• Ocular myasthenia (a condition causing weakness of the eye muscles). Consult your doctor if you experience worsening weakness in the arms or legs after periods of activity, double vision, drooping eyelids, difficulty swallowing, or shortness of breath.

Additional possible side effects reported with some statins:

• sleep disorders, including nightmares
• Sexual difficulties
• Diabetes. The risk is higher if you have high levels of sugar and fats in your blood, are overweight, and have high blood pressure. Your doctor will monitor you during treatment with this medicine.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to 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 Sinvalip

Keep this medicine out of the 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 that month.
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 Sinvalip contains
The active substance is simvastatin. Each film-coated tablet contains 10 mg, 20 mg or 40 mg of simvastatin.
The other components are: Butylated hydroxyanisole (E320), ascorbic acid (E300), monohydrate citric acid (E330), microcrystalline cellulose (E460), pregelatinized starch, magnesium stearate (E572) and lactose monohydrate.
The tablet coating contains hypromellose (E464), hydroxypropylcellulose (E463), titanium dioxide (E171), talc (E553b), iron oxide red (E172).

Description of the appearance of Sinvalip and package contents
Sinvalip 10 mg is available in packs of 20, 60 or 90 tablets in trilayer film blisters made of PVC/PE/PVDC, with an aluminum foil lid.
Sinvalip 20 mg is available in packs of 28, 60 or 90 tablets in trilayer film blisters made of PVC/PE/PVDC, with an aluminum foil lid.
Sinvalip 40 mg is available in packs of 28, 60 or 90 tablets in trilayer film blisters made of PVC/PE/PVDC, with an aluminum foil lid.
It is possible that not all pack sizes are marketed.

Marketing Authorization Holder
Genetic S.p.A., Via Della Monica n. 26, 84083 Castel San Giorgio (SA)

Manufacturer
Genetic S.p.A., Contrada Canfora, 84084 Fisciano (SA)