Medipo

Package leaflet: Information for the patient

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

Simvastatin
Please read all of 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 may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What MEDIPO is and what it is used for

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

Cholesterol is one of several types of fat found in the blood. 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 type of fat in the blood that may increase the risk of heart disease.

You must follow a cholesterol-lowering diet while taking this medicine.

MEDIPO is used in addition to diet to lower 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). MEDIPO can prolong survival by reducing the risk of heart-related problems, regardless of your blood cholesterol levels.

In most people, high cholesterol does not cause immediate symptoms. Your doctor can measure your cholesterol level with a simple blood test. Visit your doctor regularly, keep track of your cholesterol values, and set treatment goals together with your doctor.

2. What you need to know before taking MEDIPO

Do not take MEDIPO:

• 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(s) containing one or more of the following active substances:
  - itraconazole, ketoconazole, posaconazole, or voriconazole (medicines 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 patients who have undergone organ transplantation);
  - 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, have taken within the last 7 days, or have been administered a medicine called fusidic acid (used to treat bacterial infection). Do not take more than 40 mg of Medipo 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 among those listed above.

Warnings and precautions

Talk to your doctor or pharmacist before taking Medipo.

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, MEDIPO may not be suitable for you;
• if you are due to undergo surgery. You may need to stop taking MEDIPO temporarily;
• if you are of Asian origin, as you may require a different dose.

Your doctor will perform a blood test before you start taking Medipo and if you develop symptoms of liver problems during treatment with Medipo. This is done to monitor liver function.

Your doctor may also perform blood tests to check your liver function after you have started taking Medipo.

During treatment with this medicine, your doctor will closely monitor whether you have diabetes or are at risk of developing diabetes. Risk factors include high blood sugar and fat levels, being overweight, and having high blood pressure.

Inform your doctor if you suffer from 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 serious and include damage to muscle tissue, which may lead to kidney damage; very rarely, cases of death have occurred.

The risk of muscle injury is higher at higher doses of MEDIPO, 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 consume large amounts of alcohol;
• you have kidney problems;
• you have thyroid problems;
• you are aged 65 or older;
• you are female;
• you have previously experienced muscle problems while taking cholesterol-lowering medicines known as “statins” or “fibrates”;
• you or a close family member have a hereditary muscle disease.

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

Children and adolescents

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

Other medicines and MEDIPO

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

• cyclosporine (often used in patients who have undergone organ transplantation);
• 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 substances such as gemfibrozil and bezafibrate (used to lower cholesterol);
• erythromycin, clarithromycin, telithromycin, or fusidic acid (used to treat bacterial infections). Do not take fusidic acid while using this medicine. See also section 2 of this leaflet;
• 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);
• 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, severe genetic cholesterol condition);
• 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 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).

Also inform your doctor if you are taking niacin (nicotinic acid) or a product containing niacin, and if you are of Chinese origin. Inform any doctor prescribing a new medicine that you are taking MEDIPO.

MEDIPO with food and drinks

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

Inform your doctor if you consume large amounts of alcohol.

Pregnancy and breastfeeding

Do not take MEDIPO if you are pregnant, planning to become pregnant, or suspect you may be pregnant. If you become pregnant while taking MEDIPO, stop treatment immediately and contact your doctor.

Do not take MEDIPO while breastfeeding, as it is not known whether the medicine passes into breast milk.

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

Driving and using machines

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

MEDIPO contains lactose

MEDIPO 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 MEDIPO

Your doctor will determine the appropriate tablet dosage for you, based on your condition,
your current treatment, and your 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 MEDIPO, you must follow a diet aimed at reducing
cholesterol levels.
The recommended dose is MEDIPO 10 mg, 20 mg, or 40 mg taken orally once daily.
Adults:
The usual recommended starting dose is generally 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 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 per day
taken in the evening. The maximum recommended dose is 40 mg per day.
Method of administration:
Take MEDIPO in the evening. You may take it with or without food. Continue taking MEDIPO
unless your doctor tells you to stop treatment.
If your doctor has prescribed MEDIPO together with another cholesterol-lowering medicine
containing a bile acid sequestrant, you must take MEDIPO at least 2 hours before or
4 hours after taking the bile acid sequestrant medicine.
If you take more MEDIPO than you should
In case of accidental overdose or ingestion, contact your doctor or pharmacist immediately.
If you forget to take MEDIPO
Do not take a double dose to make up for the missed tablet; take only the usual dose of MEDIPO
the next day at the regular time.
If you stop taking MEDIPO

• 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, MEDIPO 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.

• muscle pain, tenderness, weakness, or cramps. In rare cases, these muscle problems can be severe and may include damage to muscle tissue leading to kidney damage; and very rarely, cases of death have been reported;
• hypersensitivity reactions (allergies) including:
  o swelling of the face, tongue, and throat which may cause difficulty breathing (angioedema);
  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 (dyspnea) and feeling unwell;
  o 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, 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 very rare but serious side effect has been reported:

• a severe allergic reaction causing breathing difficulties or dizziness (anaphylaxis).

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

• reduction in red blood cell count (anaemia);
• numbness or weakness in the arms and legs;
• headache, tingling sensation, dizziness;
• digestive disorders (abdominal pain, constipation, flatulence, indigestion, diarrhoea, nausea, vomiting);
• skin rash, itching, hair loss;
• weakness;
• memory loss, confusion.

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

• difficulty sleeping (very rare);
• poor memory (very rare).

Frequency not known (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 tendon rupture.

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;
• muscle pain, tenderness, or weakness that is persistent and may not resolve after stopping treatment with MEDIPO (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, please inform your doctor or pharmacist.
You can also report side effects directly via the national reporting system at: www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store MEDIPO

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 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 MEDIPO Contains
The active substance is simvastatin (10 mg, 20 mg, 40 mg).
The excipients 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 MEDIPO and Pack Contents
MEDIPO 10 mg
Packaged in blisters made of a trilayer film composed of polyvinyl chloride (PVC)/polyethylene (PE)/polyvinylidene chloride (PVDC), sealed with an aluminum foil lid, in packs of 20 tablets.

MEDIPO 20 mg
Packaged in blisters made of a trilayer film composed of polyvinyl chloride (PVC)/polyethylene (PE)/polyvinylidene chloride (PVDC), sealed with an aluminum foil lid, in packs of 10 and 28 tablets.

MEDIPO 40 mg
Packaged in blisters made of a trilayer film composed of polyvinyl chloride (PVC)/polyethylene (PE)/polyvinylidene chloride (PVDC), sealed with an aluminum foil lid, in packs of 10 and 28 tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder
NEOPHARMED GENTILI S.p.A.
Via San Giuseppe Cottolengo 15 – 20143 Milan, Italy

Manufacturer Responsible for Batch Release
Medipo 10 mg film-coated tablets:
Merck Sharp & Dohme (Italia) S.p.A. - Via Emilia 21 - 27100 Pavia
Medipo 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)
Medipo 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)