Lipenil

Patient Information Leaflet

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

Simvastatin
Generic medicine
Read this entire leaflet carefully before 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, consult 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, as 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 LIPENIL is and what it is used for
2. What you need to know before taking LIPENIL
3. How to take LIPENIL
4. Possible side effects
5. How to store LIPENIL
6. Contents of the pack and other information

1. What LIPENIL is and what it is used for

LIPENIL contains the active substance simvastatin. LIPENIL belongs to a group of medicines known as "statins" and is used to lower levels of total cholesterol, "bad" cholesterol (LDL), and fatty substances in the blood called triglycerides. In addition, LIPENIL increases levels of "good" cholesterol (HDL).
Cholesterol is one of several types of fat 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. 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.
LIPENIL is used, in combination with a specific diet, to reduce cholesterol if you have:

• high levels of cholesterol in the blood (primary hypercholesterolemia) or high levels of fats in the blood (mixed dyslipidemia).
• an inherited condition (homozygous familial hypercholesterolemia) characterized by increased levels of cholesterol in the blood. 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). LIPENIL may 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 with your doctor the goals you should aim to achieve.

2. What you should know before taking LIPENIL

Do not take LIPENIL

• if you are allergic (hypersensitive) to simvastatin or to any of the other ingredients of this medicine (listed in section 6. Package contents and other information);
• if you currently have liver problems;
• if you are pregnant or breastfeeding;
• if you are taking a medicine(s) containing one or more of the following active substances:
  • itraconazole, ketoconazole, posaconazole or voriconazole (used to treat fungal infections);
  • HIV protease inhibitors such as indinavir, nelfinavir, ritonavir and saquinavir (used for HIV infections);
  • erythromycin, clarithromycin, telithromycin (used to treat bacterial 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 uterine lining grows outside the uterus);
• if you are taking or have taken or been administered, within the last 7 days, a medicine called fusidic acid (used to treat bacterial infection) orally or by injection. The combination of fusidic acid and LIPENIL can cause serious muscle problems (rhabdomyolysis).
• Do not take more than 40 mg of LIPENIL 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
Talk to your doctor or pharmacist before taking LIPENIL.
Inform your doctor:

• about all your medical conditions, including allergies.
• if you have ever had liver disease. In this case, LIPENIL may not be suitable for you.
• if you consume large amounts of alcohol;
• if you are due to undergo surgery, as treatment with LIPENIL should be temporarily interrupted 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), as statins may sometimes worsen myasthenia or cause its onset (see section 4).

Your doctor should perform a blood test before you start taking LIPENIL and if you develop symptoms of liver problems while taking LIPENIL. This test is performed to check whether your liver is functioning properly.
Your doctor may also prescribe blood tests to monitor liver function after starting treatment with LIPENIL.
During treatment with this medicine, your doctor will closely 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, are overweight, and have high blood pressure.
Inform your doctor if you have a severe 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 damage to muscle tissue leading to kidney damage; very rarely, cases of death have occurred.
The risk of muscle injury is higher if you take high doses of LIPENIL, particularly 80 mg doses. 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 are 65 years of age or older;
• you are female;
• you have kidney problems;
• you have thyroid problems;
• you or a family member has a hereditary muscle disease;
• you previously experienced muscle problems during treatment with cholesterol-lowering medicines called statins or fibrates;
• you consume large amounts of alcohol;

Additionally, inform your doctor or pharmacist if you have persistent muscle weakness. Further tests and medications may be needed to diagnose and treat this condition.
Children and adolescents
The safety and efficacy of LIPENIL have been evaluated in boys and girls aged between 10 and 17 years, and in girls who have had regular menstruation for at least one year (see section 3: How to take LIPENIL). The effects of LIPENIL have not been studied in patients under 10 years of age. For further information, ask your doctor.
Other medicines and LIPENIL
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription. If your doctor prescribes a new medicine, you must inform them that you are taking LIPENIL.
Avoid taking LIPENIL with any of the following medicines, as this may increase the risk of muscle problems (See section “Do not take LIPENIL”):

• 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 treatment with LIPENIL. Taking LIPENIL with fusidic acid may rarely cause muscle weakness, pain or tenderness (rhabdomyolysis). See further information on rhabdomyolysis in section 4.
• medicines containing active substances such as itraconazole, ketoconazole, fluconazole, posaconazole or voriconazole and other medicines used to treat fungal infections;
• HIV protease inhibitors such as indinavir, nelfinavir, ritonavir and saquinavir, used in the treatment of AIDS;
• hepatitis C antiviral agents, for example boceprevir, telaprevir, elbasvir or grazoprevir (used to treat hepatitis C virus infections);
• erythromycin, clarithromycin, telithromycin or fusidic acid, used to treat bacterial infections. Do not take fusidic acid while using this medicine. See also section 4 of this leaflet;
• nefazodone, used to treat depression;
• medicines containing the active substance cobicistat;
• 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. LIPENIL). Your doctor may decide to temporarily stop your treatment with LIPENIL;
• colchicine, used to treat gout;
• fibrates other than fenofibrate, containing active substances such as gemfibrozil and benzafibrate, used to lower cholesterol levels in the blood;
• cyclosporine, a medicine used after organ transplantation;
• danazol, an artificial hormone used to treat endometriosis, a condition in which tissue normally lining the uterus (endometrium) grows in other areas of the body;
• amiodarone, a medicine used to treat heart rhythm disorders;
• verapamil, diltiazem or amlodipine, medicines used to lower high blood pressure, treat chest pain associated with heart disease or other heart conditions.

Additionally, inform your doctor if you are taking:

• fenofibrate (also used to lower cholesterol);
• anticoagulant medicines such as warfarin, phenprocoumon or acenocoumarol, which are used to prevent blood clots;
• niacin, a vitamin that reduces cholesterol levels in the blood;
• rifampicin, a medicine used to treat tuberculosis;
• ticagrelor (an antiplatelet medicine).

You must also inform any doctor who prescribes you a new medicine that you are taking LIPENIL.
LIPENIL with food and drinks
Grapefruit juice contains one or more substances that alter how the body processes certain medicines, including LIPENIL.
Avoid drinking grapefruit juice and consuming large amounts of alcoholic beverages during treatment with this medicine.
Pregnancy and breastfeeding
Do not use LIPENIL if you are pregnant, suspect you may be pregnant, or are planning a pregnancy.
If you become pregnant while taking LIPENIL, stop treatment immediately and contact your doctor.
Do not use LIPENIL if you are 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
LIPENIL is not expected to affect your ability to drive or operate machinery.
However, this medicine may rarely cause dizziness. If this occurs, avoid driving or using machinery.
LIPENIL contains lactose and hydrogenated castor oil
LIPENIL contains lactose, a type of sugar. If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
LIPENIL contains hydrogenated castor oil, which may cause gastrointestinal disturbances and diarrhoea.
LIPENIL contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially 'sodium-free'.

3. How to take LIPENIL

Take this medicine exactly as your doctor has told you. If you have any doubts, consult your doctor or pharmacist.
Your doctor will decide the appropriate dose for you, based on your condition, your current treatment and your risk profile.
During treatment with LIPENIL, you must follow a diet aimed at lowering cholesterol levels.

Dosage:
The recommended dose is LIPENIL 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 once daily. Your doctor may decide to adjust the dose, either by reducing or increasing it, after at least 4 weeks, up to a maximum of 80 mg daily. Do not take more than 80 mg daily.
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 target cholesterol levels with lower doses.

Use in children and adolescents:
For children and adolescents aged 10 to 17 years, the usual recommended starting dose is 10 mg once daily, taken as a single dose in the evening. The maximum recommended dose is 40 mg daily.

Method of administration:
Take LIPENIL in the evening. You may take it with or without food. Continue taking LIPENIL unless your doctor tells you to stop.

If your doctor has prescribed LIPENIL together with another cholesterol-lowering medicine containing a bile acid sequestrant, you must take LIPENIL at least 2 hours before or 4 hours after taking the bile acid sequestrant medicine.

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

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

If you stop taking LIPENIL
Talk to your doctor or pharmacist, 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, LIPENIL may 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 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, or cramps. In rare cases, these muscle problems can be severe and may include muscle tissue damage leading to kidney injury; and very rarely, cases of death have occurred;
• hypersensitivity reactions (allergies) including:
• swelling of the face, tongue, and throat which may cause difficulty breathing (angioedema)
• severe muscle pain, usually in the shoulders or hips
• skin rash with weakness in the legs and neck muscles
• joint pain or inflammation (polymyalgia rheumatica)
• inflammation of blood vessels (vasculitis)
• unusual bruising, skin rashes, and swelling (dermatomyositis), hives, sun sensitivity of the skin, fever, hot flushes
• shortness of breath (dyspnea) and feeling unwell
• lupus-like symptoms (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)

The following very rare serious side effect has been reported:

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

The following side effects have also been reported rarely:

• decrease in the number of red blood cells in the blood (anaemia);
• headache, tingling sensation (paraesthesia), dizziness
• numbness or weakness in arms and legs (peripheral neuropathy);
• blurred vision, visual disturbances;
• digestive disorders such as constipation, abdominal pain, flatulence (bloating), indigestion (dyspepsia), diarrhoea, nausea, vomiting;
• skin rash, itching, hair loss (alopecia);
• weakness (asthenia);
• difficulty sleeping (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):

• depression;
• erectile dysfunction;
• lung inflammation causing breathing problems, including persistent cough and/or shortness of breath or fever;
• tendon problems, sometimes complicated by tendon rupture;
• persistent muscle pain, tenderness, or weakness that may not resolve after stopping treatment with LIPENIL;
• 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 laboured breathing.
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 fats in your blood, are overweight, and have high blood pressure. Your doctor will monitor you during treatment with this medicine.

Laboratory values
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 get any side effects, 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.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store LIPENIL

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 and to the product in its original packaging,
stored correctly.
Store below 25°C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What LIPENIL contains
LIPENIL 10 mg tablets

• The active substance is simvastatin. Each tablet contains 10 mg of simvastatin.
• The other components are: monohydrate lactose, microcrystalline cellulose, sodium starch glycolate, hydrogenated castor oil, pregelatinized starch, talc, magnesium stearate, hypromellose, anhydrous colloidal silica, macrogol 6000, titanium dioxide, butyl-hydroxyanisole.

LIPENIL 20 mg tablets

• The active substance is simvastatin. Each tablet contains 20 mg of simvastatin.
• The other components are: monohydrate lactose, microcrystalline cellulose, sodium starch glycolate, hydrogenated castor oil, pregelatinized starch, talc, magnesium stearate, hypromellose, anhydrous colloidal silica, macrogol 6000, titanium dioxide, butyl-hydroxyanisole.

LIPENIL 40 mg tablets

• The active substance is simvastatin. Each tablet contains 40 mg of simvastatin.
• The other components are: monohydrate lactose, microcrystalline cellulose, sodium starch glycolate, hydrogenated castor oil, pregelatinized starch, talc, magnesium stearate, hypromellose, anhydrous colloidal silica, macrogol 6000, titanium dioxide, butyl-hydroxyanisole.

Description of the appearance of LIPENIL and contents of the pack
LIPENIL 10 mg film-coated tablets
Box containing 20 film-coated tablets.
LIPENIL 20 mg film-coated tablets
Box containing 10 or 28 film-coated tablets.
LIPENIL 40 mg film-coated tablets
Box containing 10 or 28 film-coated tablets.

Marketing Authorization Holder
S. F. Group S.r.l.
Via Tiburtina, 1143 - 00156 – Rome

Manufacturer of
LIPENIL 10 mg film-coated tablets
LIPENIL 20 mg film-coated tablets
LIPENIL 40 mg film-coated tablets
FINE FOODS & PHARMACEUTICALS N.T.M. S.p.A.
Via Grignano 43, 24041 Brembate (BG) – Italy

Manufacturer of
LIPENIL 40 mg film-coated tablets
FRANCIA FARMACEUTICI INDUSTRIA FARMACO-BIOLOGICA S.R.L.
Via dei Pestagalli, 7 – 20138 Milan

Manufacturer of
LIPENIL 20 mg film-coated tablets
LACHIFARMA Srl, Laboratorio Chimico Farmaceutico Salentino
S.S. 16 Zona Industriale - 73010 Zollino (LE) – Italy