Liponorm

Package leaflet: Information for the patient

Liponorm 10 mg film-coated tablets, 20 mg film-coated tablets, 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 their symptoms are the same as yours, as it could 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 Liponorm is and what it is used for
2. What you need to know before taking Liponorm
3. How to take Liponorm
4. Possible side effects
5. How to store Liponorm
6. Contents of the pack and other information

1. What Liponorm is and what it is used for

Liponorm contains the active substance simvastatin (belonging to a group of medicines called statins)
and is used to reduce levels of total cholesterol, "bad" cholesterol (LDL), and fat substances called triglycerides,
in the blood.
In addition, Liponorm increases levels of "good" cholesterol (HDL).
Cholesterol is one of the fats present in the blood.
Total cholesterol is mainly composed of LDL cholesterol and HDL cholesterol.
LDL cholesterol is commonly known as "bad" cholesterol because it can accumulate in the walls
of arteries and form plaques. Over time, these plaques grow larger and
can block the arteries. This narrowing can cause a slowing or blockage of blood flow to vital organs such as the heart and brain, and consequently lead to a heart attack or stroke.
HDL cholesterol is commonly known as "good" cholesterol because it helps prevent "bad" cholesterol from accumulating in the arteries, thereby protecting against heart disease.
Triglycerides are another type of fat present in the blood. They may increase the risk of heart disease.
While being treated with this medicine, you must follow a cholesterol-lowering diet.
Liponorm is used in addition to a cholesterol-lowering diet if you have:

• high levels of cholesterol in the blood (primary hypercholesterolemia) or elevated levels of fats in the blood (mixed hyperlipidemia);
• an inherited disease (homozygous familial hypercholesterolemia) that increases cholesterol levels in the blood. You may also be receiving other treatments;
• coronary heart disease (CHD) or are at high risk of CHD (due to diabetes, previous strokes, or other blood vessel diseases). Liponorm may prolong survival by reducing the risk of heart problems, regardless of the amount of cholesterol in the blood.

In most people, high cholesterol does not cause immediate symptoms. Your doctor can
measure your cholesterol level with a simple blood test.
Have regular check-ups with your doctor, keep track of your cholesterol values, and discuss your treatment goals with your doctor.

2. What you should know before taking Liponorm

Do not take Liponorm:

• 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 medicines 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 (used to treat HIV infections),
  • boceprevir or telaprevir (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);
• if you are taking or have taken within the last 7 days an oral or injectable medicine called fusidic acid (a medicine used to treat bacterial infection). The combination of fusidic acid and Liponorm may lead to serious muscle problems (rhabdomyolysis).

Do not take more than 40 mg of Liponorm if you are taking lomitapide (used to treat a rare, inherited 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 Liponorm.
Inform your doctor:

• about your medical conditions, including allergies,
• if you drink large amounts of alcohol,
• if you have ever had liver disease. In this case, Liponorm may not be suitable for you,
• if you are due to undergo surgery. You may need to stop taking Liponorm for a short period of time,
• if you are of Asian origin, as a different dosage may be more 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), since statins may sometimes worsen myasthenia or cause its onset (see section 4).

Your doctor will perform a blood test before you start taking Liponorm and if you develop symptoms of liver problems during treatment with Liponorm, to monitor your liver function.
Your doctor may also perform blood tests to monitor your liver function after you have started taking Liponorm.
While you are being treated 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 serious lung disease.

Contact your doctor immediately if you experience unexplained muscle pain, tenderness or weakness. This is necessary because, in rare cases, muscle problems can be severe and include damage to muscle tissue that may cause kidney damage; very rarely, cases of death have occurred.
The risk of muscle injury is higher with higher doses of Liponorm, particularly with the 80 mg dose. The risk of muscle injury is also increased in certain patients. Talk to your doctor if any of the following conditions apply to you:

• you drink large amounts of alcohol,
• you have kidney problems,
• you have thyroid problems,
• you are aged 65 years or older,
• you are female,
• you have experienced muscle problems during treatment with cholesterol-lowering medicines known as “statins” or fibrates,
• you or a close family member have an inherited muscle disease.

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

Other medicines and Liponorm
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 Liponorm 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 Liponorm”):

• 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 Liponorm. Taking Liponorm 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 with active ingredients gemfibrozil and bezafibrate (used to lower cholesterol),
• erythromycin, clarithromycin or telithromycin (used to treat bacterial infections),
• HIV protease inhibitors such as indinavir, nelfinavir, ritonavir and saquinavir (used to treat HIV infections),
• antiviral agents for hepatitis C such as 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),
• 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, inherited 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. Liponorm). Your doctor may decide to have you stop taking Liponorm for a period of time,
• colchicine (used to treat gout).

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

• medicines with an active ingredient 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).

Inform any doctor who prescribes you a new medicine that you are taking Liponorm.

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

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant or are planning to become pregnant, or if you are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Do not take Liponorm if you are pregnant, trying to become pregnant, or suspect you are pregnant. If you find out you are pregnant while taking Liponorm, stop taking the tablets immediately and contact your doctor.
Do not take Liponorm while breastfeeding, as it is not known whether the medicine passes into breast milk.

Driving and using machines
Liponorm is not expected to affect your ability to drive or use machines.
However, bear in mind that dizziness has been reported after taking Liponorm.

LIPONORM 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 Liponorm

Your doctor will determine the most appropriate tablet dosage for you, based on your condition, your current treatment and your risk factors.
Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.
While undergoing treatment with Liponorm, you must follow a diet aimed at reducing cholesterol levels.
Take Liponorm by mouth once daily, at the dosage prescribed by your doctor.

Dosage
Adults
The usual initial dose is 10, 20 or, in some cases, 40 mg per day. Your doctor may adjust your dose after at least 4 weeks have passed, 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 certain medicines as listed above or if you have kidney problems.
The 80 mg dose is recommended only for adult patients with very high cholesterol levels and at 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 10–17 years), the recommended usual starting dose is 10 mg per day, taken in the evening. The maximum recommended dose is 40 mg per day.

Method of administration
Take Liponorm in the evening. You may take the tablet with or without food. Continue taking Liponorm until your doctor tells you to stop.
If your doctor has prescribed Liponorm together with another medicine containing a bile acid sequestrant to lower cholesterol levels, you must take Liponorm at least 2 hours before or 4 hours after taking the bile acid sequestrant medicine.

If you take more Liponorm than you should
If you take too much Liponorm, contact your doctor or pharmacist immediately.

If you forget to take Liponorm
Do not take a double dose to make up for the missed tablet. Continue your treatment with the usual dose of Liponorm at the next scheduled time.

If you stop taking Liponorm
Consult 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, this medicine can cause side effects, although not everyone experiences them.
If you experience any of the following serious side effects, stop treatment with
Liponorm 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: swelling of the face, tongue, and throat causing breathing difficulties (angioedema), severe muscle pain usually in the shoulders and hips, skin rash with leg and neck muscle weakness, joint pain or inflammation (polymyalgia rheumatica), inflammation of blood vessels (vasculitis), unusual bruising, skin rashes and swelling (dermatomyositis), urticaria, skin sensitivity to sunlight, fever, hot flushes, shortness of breath (dyspnea), general malaise, or 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 (jaundice), itching, dark urine or pale stools, feeling tired or weak, loss of appetite;
• 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 breathing difficulties or dizziness (anaphylaxis),
• skin rash which may occur on the skin or ulcers in the mouth (drug-induced lichenoid eruptions),
• muscle rupture,
• gynecomastia (enlargement of the breast in men),
• liver failure.

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

• 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.

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

• difficulty sleeping (insomnia),
• memory impairment, memory loss, confusion.

Not known (frequency cannot be estimated from the 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). Consult your doctor if you experience worsening arm or leg weakness after periods of activity, double vision or drooping eyelids, difficulty swallowing, or laboured 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 fat in your blood, are overweight, and have high blood pressure. Your doctor will monitor you during treatment with this medicine,
• muscle pain, tenderness, or muscle weakness that is persistent and may not improve after stopping treatment with Liponorm (frequency not known).

Laboratory tests
Increases in blood test values related to liver function and 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 can 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 Liponorm

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 the word "Exp.". 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 Liponorm contains
The active substance is simvastatin. Each tablet contains 10 mg, 20 mg or 40 mg of simvastatin.
The other components are: butylhydroxyanisole (E320), ascorbic acid (E300), citric acid monohydrate (E330), microcrystalline cellulose (E460), pregelatinized starch, magnesium stearate (E572) and lactose monohydrate.
The coating of the 10 mg and 20 mg tablets contains: hypromellose (E464), hydroxypropylcellulose (E463), titanium dioxide (E171), talc (E553b), yellow iron oxide (E172) and red iron oxide (E172).
The coating of the 40 mg tablet contains: hypromellose (E464), hydroxypropylcellulose (E463), titanium dioxide (E171), talc (E553b) and red iron oxide.

Description of the appearance of Liponorm and contents of the pack
Liponorm 10 mg
Packaged in trilayer film blisters composed of polyvinyl chloride (PVC)/polyethylene (PE)/polyvinylidene chloride (PVDC), with an aluminium foil lid.
Pack sizes: 1, 4, 10, 14, 15, 20, 28, 30, 50, 60, 98 or 100 tablets.
Packaged in blisters composed of polyvinyl chloride (PVC), with an aluminium foil lid.
Pack sizes: 4, 10, 28 or 30 tablets.
Amber glass bottle with metal closure.
Pack sizes: 30 or 50 tablets.
Polypropylene bottle.
Pack size: 50 tablets.
High-density polyethylene (HDPE) bottle.
Pack sizes: 30, 50 or 100 tablets.
Unit-dose blisters containing trilayer film composed of polyvinyl chloride (PVC)/polyethylene (PE)/polyvinylidene chloride (PVDC), with an aluminium foil lid.
Pack sizes: 49 or 500 tablets.

Liponorm 20 mg
Packaged in trilayer film blisters composed of polyvinyl chloride (PVC)/polyethylene (PE)/polyvinylidene chloride (PVDC), with an aluminium foil lid.
Pack sizes: 1, 4, 10, 14, 15, 20, 28, 30, 50, 56, 60, 84, 90, 98, 100 or 168 tablets.
Packaged in blisters composed of polyvinyl chloride (PVC), with an aluminium foil lid.
Pack sizes: 14, 28, 30, 50 or 90 tablets.
Amber glass bottle with metal closure.
Pack sizes: 30 or 50 tablets.
Polypropylene bottle.
Pack size: 50 tablets.
High-density polyethylene (HDPE) bottle.
Pack sizes: 30, 50 or 100 tablets.
Unit-dose blisters containing trilayer film composed of polyvinyl chloride (PVC)/polyethylene (PE)/polyvinylidene chloride (PVDC), with an aluminium foil lid.
Pack sizes: 28, 49, 84, 98 or 500 tablets.

Liponorm 40 mg
Packaged in trilayer film blisters composed of polyvinyl chloride (PVC)/polyethylene (PE)/polyvinylidene chloride (PVDC), with an aluminium foil lid.
Pack sizes: 1, 4, 7, 10, 14, 15, 20, 28, 30, 49, 50, 56, 60, 84, 90, 98, 100 or 168 tablets.
Packaged in blisters composed of polyvinyl chloride (PVC), with an aluminium foil lid.
Pack sizes: 7, 14, 28, 30, 49, 50 or 90 tablets.
Amber glass bottle with metal closure.
Pack sizes: 30 or 50 tablets.
Polypropylene bottle.
Pack size: 50 tablets.
High-density polyethylene (HDPE) bottle.
Pack sizes: 30, 50 or 100 tablets.
Unit-dose blisters containing trilayer film composed of polyvinyl chloride (PVC)/polyethylene (PE)/polyvinylidene chloride (PVDC), with an aluminium foil lid.
Pack sizes: 28, 49, 98 or 100 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Neopharmed Gentili S.p.A.
Via San Giuseppe Cottolengo, 15
20143 Milan, Italy

Manufacturer
Liponorm 10 mg film-coated tablets:
Vamfarma S.r.l.
Via Kennedy, 5 – 26833 Comazzo (Lodi)

Liponorm 20 mg film-coated tablets:
Doppel farmaceutici S.r.l.
Via Volturno, 48, Quinto dè Stampi - 20089 Rozzano (Milan)
Vamfarma S.r.l.
Via Kennedy, 5 – 26833 Comazzo (Lodi)

Liponorm 40 mg film-coated tablets:
Doppel farmaceutici S.r.l.
Via Volturno, 48, Quinto dè Stampi - 20089 Rozzano (Milan)
Vamfarma S.r.l.
Via Kennedy, 5 – 26833 Comazzo (Lodi)