Alpheus

Patient Information Leaflet

ALPHEUS 20 mg film-coated tablets, 40 mg film-coated tablets

Simvastatin
Generic medicine
Please read this 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, 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, 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 ALPHEUS is and what it is used for
2. What you need to know before taking ALPHEUS
3. How to take ALPHEUS
4. Possible side effects
5. How to store ALPHEUS
6. Contents of the pack and other information

1. What ALPHEUS is and what it is used for

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

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 build up 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. Blocked 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.

ALPHEUS is used in addition to diet to lower cholesterol when you have:

• elevated cholesterol levels in the blood (primary hypercholesterolemia) or high 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). ALPHEUS can prolong survival by reducing the risk of heart disease-related problems, regardless of blood cholesterol levels.

In most people, high cholesterol does not cause any 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 cholesterol targets with your doctor.

2. What you need to know before taking ALPHEUS

Do not take ALPHEUS:

• 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
• 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, or 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 or gemfibrozil (used to lower cholesterol), cyclosporine (used in organ transplant patients), or 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 seven days, an oral or injectable medicine called fusidic acid (a medicine used to treat bacterial infection). The combination of fusidic acid and ALPHEUS may cause serious muscle problems (rhabdomyolysis). Do not take more than 40 mg of ALPHEUS 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
Tell your doctor or pharmacist before taking ALPHEUS:

• about all your medical conditions, including allergies
• if you consume large amounts of alcohol
• if you have ever had liver disease. In this case, ALPHEUS may not be suitable for you
• if you are scheduled for surgery. You may need to temporarily stop taking ALPHEUS
• if you are of Asian descent, as a different dose may be 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), as statins may sometimes worsen myasthenia or trigger its onset (see section 4).

Your doctor will perform a blood test before starting ALPHEUS and if you develop symptoms of liver problems during treatment with ALPHEUS. This test is to check whether your liver is functioning properly.
Your doctor may also prescribe periodic blood tests to monitor liver function after starting treatment with ALPHEUS.
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 muscle tissue damage leading to kidney damage; very rarely, fatal cases have occurred.
The risk of muscle injury is higher at higher doses of ALPHEUS, particularly at 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 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 have a hereditary muscle disease.

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 ALPHEUS 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 ALPHEUS). ALPHEUS has not been studied in children under 10 years of age. For further information, consult your doctor.

Other medicines and ALPHEUS
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
Taking ALPHEUS 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 ALPHEUS”):

• 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 ALPHEUS. Taking ALPHEUS with fusidic acid may rarely lead to muscle weakness, tenderness, or pain (rhabdomyolysis). See further information on rhabdomyolysis in section 4
• cyclosporine (commonly 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 or bezafibrate (used to lower cholesterol)
• erythromycin, clarithromycin, telithromycin (used to treat bacterial infections)
• HIV protease inhibitors such as indinavir, nelfinavir, ritonavir, or saquinavir (used to treat AIDS)
• antiviral agents for hepatitis C such as boceprevir, telaprevir, elbasvir, or grazoprevir (used to treat hepatitis C virus infections)
• 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)
• 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. ALPHEUS). Your doctor may decide to temporarily discontinue ALPHEUS
• 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 medicines, including those not requiring 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 ALPHEUS.

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

Pregnancy and breastfeeding
Do not use ALPHEUS if you are pregnant, planning to become pregnant, or suspect you are pregnant. If you become pregnant while taking ALPHEUS, stop treatment immediately and contact your doctor.
Do not use ALPHEUS 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
ALPHEUS is not expected to affect your ability to drive or operate machinery. However, you should be aware that dizziness has been reported after taking ALPHEUS.

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

3. How to take ALPHEUS

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 ALPHEUS, you must follow a diet aimed at reducing cholesterol levels.

Dosage:
The recommended dose is one ALPHEUS tablet (20 mg or 40 mg) taken orally once daily.

Adults:
The usual starting dose is typically 20 mg, or in some cases 40 mg, once daily. Your doctor may adjust the dose after at least 4 weeks, up to a maximum of 80 mg daily. 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 once daily, taken in the evening. The maximum recommended dose is 40 mg daily.

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

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

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

If you stop taking ALPHEUS
Talk to your doctor or pharmacist, as your cholesterol levels may rise again.

If you have any questions about the use of 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.
The following terms are used to describe how often 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)

The following serious rare side effects have been reported. 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 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)
  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 rash, and swelling (dermatomyositis)
  o hives, skin sensitivity to sunlight, fever, hot flushes, shortness of breath (dyspnoea), feeling unwell, or a group of symptoms resembling lupus (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 serious very rare side effects have been reported:

• a severe allergic reaction causing difficulty breathing or dizziness (anaphylaxis)
• skin rash that may appear on the skin or ulcers in the mouth (drug-induced lichenoid eruptions)
• muscle rupture
• gynaecomastia (enlargement of the breast 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 and impaired vision (may affect up to 1 in 1,000 people)
• 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 estimated from the available data (frequency not known):

• erectile dysfunction
• depression
• inflammation of the lungs 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 weakness in the arms or legs that worsens 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 dysfunction
• diabetes. This is more likely if you have high levels of sugar and fats in the 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 ALPHEUS (frequency not known).

Laboratory findings
Increases have been observed in certain blood test values related to liver function and muscle enzyme (creatine kinase).

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 http://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 ALPHEUS

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.
Store below 25°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 ALPHEUS contains
ALPHEUS 20 mg film-coated tablets
Each tablet contains:
The active substance is simvastatin 20 mg.
The other components are: monohydrate lactose, butylated hydroxyanisole, ascorbic acid, monohydrate citric acid, microcrystalline cellulose, pregelatinized starch, magnesium stearate, hypromellose, hydroxypropylcellulose, titanium dioxide, talc, yellow iron oxide, red iron oxide.
ALPHEUS 40 mg film-coated tablets
Each tablet contains:
The active substance is simvastatin 40 mg.
The other components are: monohydrate lactose, butylated hydroxyanisole, ascorbic acid, monohydrate citric acid, microcrystalline cellulose, pregelatinized starch, magnesium stearate, hypromellose, hydroxypropylcellulose, titanium dioxide, talc, red iron oxide.

Description of the appearance of ALPHEUS and contents of the pack:
ALPHEUS 20 mg film-coated tablets
Packaged in blisters of 10 and 28 tablets of 20 mg.
ALPHEUS 40 mg film-coated tablets
Packaged in blisters of 10 and 28 tablets of 40 mg.

Marketing Authorization Holder and Manufacturer:
Marketing Authorization Holder
S.F. Group S.r.l., Via Tiburtina, 1143 - 00156 Rome – Italy
Manufacturer
FAMAR ITALIA S.p.A.
Via Zambeletti, 25
20021 - Baranzate (Milan) – Italy
Special Product’s Line S.P.A.
Via Fratta Rotonda Vado Largo, 1
03012 Anagni (FR) Italy
LACHIFARMA S.r.l.
S.S. 16 Zona Industriale
73010 ZOLLINO (LE) - Italy