Ezetimibe and simvastatin Almus: detailed information

Patient Information Leaflet

EZETIMIBE AND SIMVASTATIN ALMUS 10 mg/10 mg tablets, mg/20 mg tablets, mg/40 mg tablets

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 they have the same symptoms as you, because it could be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

What EZETIMIBE AND SIMVASTATIN ALMUS is and what it is used for
What you need to know before taking EZETIMIBE AND SIMVASTATIN ALMUS
How to take EZETIMIBE AND SIMVASTATIN ALMUS
Possible side effects
How to store EZETIMIBE AND SIMVASTATIN ALMUS
Contents of the pack and other information

1. What EZETIMIBE AND SIMVASTATIN ALMUS is and what it is used for

EZETIMIBE AND SIMVASTATIN ALMUS contains the active substances ezetimibe and simvastatin.
EZETIMIBE AND SIMVASTATIN ALMUS is a medicine used to reduce the levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and fatty substances called triglycerides in the blood. In addition, EZETIMIBE AND SIMVASTATIN ALMUS increases levels of "good" cholesterol (HDL cholesterol).
EZETIMIBE AND SIMVASTATIN ALMUS works in two ways to lower cholesterol. The active substance ezetimibe reduces cholesterol absorbed from the gastrointestinal tract. The active substance simvastatin, which belongs to the class of drugs known as "statins", inhibits the body's own production of cholesterol.
Cholesterol is one of several fatty substances found in the bloodstream. Total cholesterol consists 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. Such blockage of blood flow may 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 in the blood that may increase the risk of heart disease.
EZETIMIBE AND SIMVASTATIN ALMUS is used in patients who cannot control their cholesterol levels through diet alone. While taking this medicine, you must still follow a cholesterol-lowering diet.
EZETIMIBE AND SIMVASTATIN ALMUS is used as an add-on to diet to lower cholesterol if you have:

elevated levels of cholesterol in the blood (primary hypercholesterolemia) [heterozygous familial and non-familial] or elevated levels of fats in the blood (mixed dyslipidemia):
that are not well controlled by a statin alone;
for which you have previously been treated with a statin and ezetimibe as separate tablets;
a hereditary condition (homozygous familial hypercholesterolemia) that increases your blood cholesterol levels. You may also be receiving other treatments;
heart disease; EZETIMIBE AND SIMVASTATIN ALMUS reduces the risk of heart attack, stroke, surgical procedures to improve blood flow to the heart, or hospitalization due to chest pain.

EZETIMIBE AND SIMVASTATIN ALMUS does not help with weight loss.

2. What you should know before taking EZETIMIBE AND SIMVASTATIN ALMUS

Do not take EZETIMIBE AND SIMVASTATIN ALMUS if:

you are allergic (hypersensitive) to ezetimibe, simvastatin, or any of the other ingredients of this medicine (listed in section 6)
you currently have liver problems
you are pregnant or breastfeeding
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, and saquinavir (HIV protease inhibitors are used to treat HIV infections)
- boceprevir or telaprevir (used to treat hepatitis C virus infections)
- nefazodone (used to treat depression)
- cobicistat
- gemfibrozil (used to lower cholesterol)
- ciclosporin (often used in patients who have had an organ transplant)
- danazol (a synthetic hormone used to treat endometriosis, a condition in which the lining of the uterus grows outside the uterus)
you are taking or have taken within the last 7 days a medicine called fusidic acid (used to treat bacterial infection) by mouth or by injection. The combination of fusidic acid and EZETIMIBE AND SIMVASTATIN ALMUS can cause serious muscle problems (rhabdomyolysis).
Do not take more than 10 mg/40 mg of EZETIMIBE AND SIMVASTATIN ALMUS 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 one of those listed above.

Warnings and precautions

Tell your doctor or pharmacist before starting to take EZETIMIBE AND SIMVASTATIN ALMUS:

about all your medical conditions, including allergies
if you drink large amounts of alcohol or have ever had liver disease. EZETIMIBE AND SIMVASTATIN ALMUS may not be suitable for you
if you are due to have surgery. You may need to stop taking EZETIMIBE AND SIMVASTATIN ALMUS for a short time
if you are of Asian origin, as you may require a different dose.

Your doctor will perform a blood test before you start taking EZETIMIBE AND SIMVASTATIN ALMUS and if you develop symptoms of liver problems while taking it. This test checks whether your liver is functioning properly.

Your doctor may also want to perform periodic blood tests to monitor liver function after you start taking EZETIMIBE AND SIMVASTATIN ALMUS.

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

Inform your doctor if you have a serious lung disease.

The combined use of EZETIMIBE AND SIMVASTATIN ALMUS with fibrates (a type of cholesterol-lowering medicine) should be avoided, as the combination has not been studied.

Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness, as muscle problems can rarely be serious and lead to muscle tissue damage causing kidney damage, and very rare cases of death have occurred.

The risk of muscle damage is higher at higher doses of EZETIMIBE AND SIMVASTATIN ALMUS, particularly with the 10 mg/80 mg dose. The risk of muscle damage is also increased in certain patients. Inform your doctor if any of the following apply to you:

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” (such as simvastatin, atorvastatin, and rosuvastatin) or fibrates (such as gemfibrozil and bezafibrate)
you or your close family members have a hereditary muscle disease.

Inform your doctor or pharmacist if you experience persistent muscle weakness.
Additional tests and treatments may be needed to diagnose and manage this condition.

Children and adolescents

EZETIMIBE AND SIMVASTATIN ALMUS is not recommended for children under 10 years of age.

Other medicines and EZETIMIBE AND SIMVASTATIN ALMUS

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

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 EZETIMIBE AND SIMVASTATIN ALMUS. Taking EZETIMIBE AND SIMVASTATIN ALMUS and fusidic acid together may rarely cause muscle weakness, pain, or tenderness (rhabdomyolysis). For more information on rhabdomyolysis, see section 4.
ciclosporin (often used in patients who have received an organ transplant)
danazol (a synthetic 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 and bezafibrate (used to lower cholesterol)
erythromycin, clarithromycin, telithromycin (used to treat bacterial infections)
HIV protease inhibitors such as indinavir, nelfinavir, ritonavir, and saquinavir (used to treat AIDS)
antiviral agents for hepatitis C such as boceprevir or 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 (a medicine used to treat complicated skin and soft tissue infections and bacteremia). Adverse muscle effects may be increased when this medicine is taken during treatment with simvastatin (e.g., EZETIMIBE AND SIMVASTATIN ALMUS). Your doctor may decide to temporarily discontinue EZETIMIBE AND SIMVASTATIN ALMUS.
high doses (1 g or more per day) of niacin or nicotinic acid (also used to lower cholesterol)
colchicine (used to treat gout).

In addition to the medicines listed above, inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including those without a prescription. In particular, tell your doctor if you are taking any of the following:

medicines containing active substances used to prevent blood clots, such as warfarin, fluindione, phenprocoumon, or acenocoumarol (anticoagulants)
colestyramine (also used to lower cholesterol), as it affects how EZETIMIBE AND SIMVASTATIN ALMUS works
fenofibrate (also used to lower cholesterol)
rifampicin (used to treat tuberculosis).

You must also inform any doctor who prescribes you a new medicine that you are taking EZETIMIBE AND SIMVASTATIN ALMUS.

EZETIMIBE AND SIMVASTATIN ALMUS with food and drink

Grapefruit juice contains one or more substances that alter the metabolism of certain medicines, including EZETIMIBE AND SIMVASTATIN ALMUS. Grapefruit juice should be avoided, as it may increase the risk of muscle problems.

Pregnancy and breastfeeding

Do not take EZETIMIBE AND SIMVASTATIN ALMUS if you are pregnant, planning to become pregnant, or suspect you may be pregnant.

If you become pregnant while taking EZETIMIBE AND SIMVASTATIN ALMUS, stop taking it immediately and contact your doctor.

Do not take EZETIMIBE AND SIMVASTATIN ALMUS if you are breastfeeding, as it is not known whether the medicine passes into human milk.

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

Driving and using machines

EZETIMIBE AND SIMVASTATIN ALMUS is not expected to affect your ability to drive or operate machinery. However, you should be aware that some people have experienced dizziness after taking EZETIMIBE AND SIMVASTATIN ALMUS.

EZETIMIBE AND SIMVASTATIN ALMUS contains lactose

EZETIMIBE AND SIMVASTATIN ALMUS tablets contain a sugar called lactose.
If your doctor has informed you of an intolerance to certain sugars, contact him or her before taking this medicine.

Sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially “sodium-free.”

3. How to take EZETIMIBE E SIMVASTATINA ALMUS

Your doctor will determine the appropriate tablet dose for you, based on your current treatment and your individual risk profile.
The tablets do not have a break line and must not be divided.
Always take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

Before starting treatment with EZETIMIBE E SIMVASTATINA ALMUS, you should already be following a cholesterol-lowering diet.
During treatment with EZETIMIBE E SIMVASTATINA ALMUS, you must continue to follow this cholesterol-lowering diet.

Adults: the dose is 1 tablet taken orally once daily.
Adolescents (from 10 to 17 years of age): the dose is 1 tablet taken orally once daily (a maximum dose of 10 mg/40 mg once daily must not be exceeded).
The EZETIMIBE E SIMVASTATINA ALMUS 10 mg/80 mg dose is recommended only in adult patients with very high cholesterol levels and high risk of heart disease who have not reached their target cholesterol levels with lower doses.
Take EZETIMIBE E SIMVASTATINA ALMUS in the evening. It may be taken with or without food.
If your doctor has prescribed EZETIMIBE E SIMVASTATINA ALMUS together with another cholesterol-lowering medicine containing the active substance colestyramine or any other bile acid sequestrant, you must take EZETIMIBE E SIMVASTATINA ALMUS at least 2 hours before or 4 hours after taking the bile acid sequestrant.

If you take more EZETIMIBE E SIMVASTATINA ALMUS than you should
Contact your doctor or pharmacist.

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

If you stop taking EZETIMIBE E SIMVASTATINA ALMUS
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 everybody gets them (see section 2).
The following common side effects have been reported (may affect up to 1 in 10 people):

muscle pain
increased laboratory test values related to liver function (transaminases) and/or muscle function (CK).

The following uncommon side effects have been reported (may affect up to 1 in 100 people):

increased blood test values related to liver function; increased blood uric acid levels; prolonged blood clotting time; presence of protein in urine; decrease in body weight
dizziness; headache; tingling sensation
abdominal pain; indigestion; flatulence; nausea; vomiting; abdominal bloating
diarrhoea; dry mouth; heartburn
skin rash; itching; urticaria
joint pain; muscle pain; tenderness; weakness or spasms; neck pain; arm or leg pain; back pain
unusual tiredness or weakness; feeling of fatigue; chest pain; swelling, especially of the hands and feet
sleep disorders; difficulty falling asleep.

Additionally, the following side effects have been reported in patients taking either the combination of ezetimibe and simvastatin or medicines containing the active substances ezetimibe or simvastatin:

reduction in red blood cell count (anaemia); decrease in blood cells which may lead to bruising/bleeding (thrombocytopenia)
loss of sensation or weakness in arms and legs; poor memory; memory loss; confusion
breathing problems including persistent cough and/or shortness of breath or fever
constipation
inflammation of the pancreas, often with severe abdominal pain
liver inflammation with the following symptoms: yellowing of the skin and eyes; itching; dark-coloured urine or pale-coloured stools; feeling of tiredness or weakness; loss of appetite; liver failure; gallstones or inflammation of the gallbladder (which may cause abdominal pain, nausea and vomiting)
hair loss; red, raised skin rash, sometimes with target-like lesions (erythema multiforme)
blurred vision and impaired eyesight (may affect up to 1 in 1,000 people)
skin rash which may occur on the skin or ulcers in the mouth (drug-induced lichenoid eruptions) (may affect up to 1 in 10,000 people)
hypersensitivity reactions including some of the following: allergic reactions comprising swelling of the face, lips, tongue and/or throat which may cause difficulty breathing or swallowing and require immediate treatment (angioedema), joint pain or inflammation, inflammation of blood vessels, unusual bruising, skin rashes and swelling, urticaria, skin sensitivity to sunlight, fever, hot flushes, shortness of breath and feeling unwell, lupus-like symptoms (including skin rash, joint problems, and effects on white blood cells). A severe allergic reaction (may affect up to 1 in 10,000 people) causing difficulty breathing or dizziness, requiring immediate treatment (anaphylaxis)
muscle pain; tenderness, weakness or cramps; muscle injury, muscle breakdown (may affect up to 1 in 10,000 people); tendon problems, sometimes complicated by tendon rupture
gynaecomastia (enlargement of breast tissue in men) (may affect up to 1 in 10,000 people)
decreased appetite
hot flushes; high blood pressure
pain
erectile dysfunction
depression
changes in certain blood test values related to liver function.

Additional possible side effects reported with some statins:

sleep disturbances, 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 EZETIMIBE E SIMVASTATINA ALMUS (frequency not known).

Contact your doctor immediately if you experience unexplained muscle pain, tenderness or weakness.
This is because muscle problems can, rarely, be serious and lead to muscle tissue damage causing kidney injury; very rare cases of death have occurred.
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:
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 EZETIMIBE AND SIMVASTATIN ALMUS

Keep this medicine out of the sight and reach of children.
Do not use EZETIMIBE AND SIMVASTATIN ALMUS after the expiry date stated on the carton or blister pack after the words "EXP".
The expiry date refers to the last day of that month.
Do not store above 25°C.
Do not dispose of medicines 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 EZETIMIBE E SIMVASTATINA ALMUS contains
The active substances are ezetimibe and simvastatin. Each tablet contains 10 mg of ezetimibe
and 10 mg, 20 mg, or 40 mg of simvastatin.
The other excipients are:
Tablet core: monohydrate lactose, hypromellose, sodium croscarmellose, microcrystalline cellulose,
ascorbic acid, anhydrous citric acid, butylated hydroxyanisole, propyl gallate, magnesium stearate.
Colouring mixture: monohydrate lactose, yellow iron oxide (E172), red iron oxide (E172), and black iron oxide (E172).

Description of the appearance of EZETIMIBE E SIMVASTATINA ALMUS and package contents
EZETIMIBE E SIMVASTATINA ALMUS 10 mg/10 mg tablets: light brown, mottled, round tablet, 6 mm in diameter, biconvex, smooth on one side and marked with "511" on the other.
EZETIMIBE E SIMVASTATINA ALMUS 10 mg/20 mg tablets: light brown, mottled, round tablet, 8 mm in diameter, biconvex, smooth on one side and marked with "512" on the other.
EZETIMIBE E SIMVASTATINA ALMUS 10 mg/40 mg tablets: light brown, mottled, round tablet, 10 mm in diameter, biconvex, smooth on one side and marked with "513" on the other.
Pack size: 30 tablets
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Almus S.r.l.
Via Cesarea, 11/10
16121 - Genova (GE)
Italy

Manufacturer:
Balkanpharma-Dupnitsa AD
3 Samokovsko Shosse Str.
Dupnitza 2600
Bulgaria

This medicinal product is authorised in the European Economic Area Member States under the following names:
Denmark: NELSTATINE
Italy: EZETIMIBE E SIMVASTATINA ALMUS