Ezetimibe and simvastatin Tecnigen: detailed information

Patient Information Leaflet: Information for the User

Ezetimibe and Simvastatin Tecnigen 10 mg/10 mg tablets, mg/20 mg tablets

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, pharmacist, or nurse.
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 side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

What Ezetimibe and Simvastatin Tecnigen is and what it is used for
What you need to know before taking Ezetimibe and Simvastatin Tecnigen
How to take Ezetimibe and Simvastatin Tecnigen
Possible side effects
How to store Ezetimibe and Simvastatin Tecnigen
Contents of the pack and other information

1. What Ezetimibe and Simvastatin Tecnigen is and what it is used for

Ezetimibe and Simvastatin Tecnigen contains the active substances ezetimibe and simvastatin. Ezetimibe and Simvastatin Tecnigen is a medicine used to lower levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and fatty substances called triglycerides in the blood. In addition, Ezetimibe and Simvastatin Tecnigen increases levels of "good" cholesterol (HDL cholesterol).

Ezetimibe and Simvastatin Tecnigen works in two ways to lower cholesterol. The active substance ezetimibe reduces cholesterol absorbed from the digestive tract. The active substance simvastatin, which belongs to the class of medicines 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 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 form of fat in the blood that may increase the risk of heart disease.

Ezetimibe and Simvastatin Tecnigen is used for patients who cannot control their cholesterol levels with diet alone. While taking this medicine, you should still follow a cholesterol-lowering diet.

Ezetimibe and Simvastatin Tecnigen is used as an additional therapy to diet to lower cholesterol if you have:

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

Ezetimibe and Simvastatin Tecnigen does not help with weight loss.

2. What you need to know before taking Ezetimibe and Simvastatin Tecnigen

Do not take Ezetimibe and Simvastatin Tecnigen if:

you are allergic to ezetimibe, simvastatin, or any of the excipients of this medicine (listed in section 6: Contents of the pack and other information)
you currently have liver problems
you are pregnant or breastfeeding
you are taking a medicine containing any 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 levels)
- cyclosporine (often used in patients who have undergone organ transplantation)
- 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 an injectable or oral medicine called fusidic acid (used to treat bacterial infections). The combination of fusidic acid and Ezetimibe and Simvastatin Tecnigen can cause serious muscle problems (rhabdomyolysis).

Do not take more than 10 mg/40 mg of Ezetimibe and Simvastatin Tecnigen 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:

about all your medical conditions, including allergies
if you drink large amounts of alcohol or have ever had liver disease. Ezetimibe and Simvastatin Tecnigen may not be suitable for you.
if you are scheduled for surgery. You may need to temporarily stop taking Ezetimibe and Simvastatin Tecnigen tablets.
if you are of Asian descent, as you may require a different dose.

Your doctor will perform a blood test before you start treatment with Ezetimibe and Simvastatin Tecnigen and if you develop any symptoms of liver problems while taking this medicine, to check that your liver is functioning properly. Your doctor may also order periodic blood tests to monitor liver function after starting treatment with Ezetimibe and Simvastatin Tecnigen.

While taking this medicine, your doctor will closely monitor you if you have diabetes or are at risk of developing diabetes. You are at increased risk of developing diabetes if you have high blood sugar and fat levels, are overweight, or have high blood pressure.

Inform your doctor if you have a severe lung disease.

The combined use of Ezetimibe and Simvastatin Tecnigen with fibrates (some medicines that lower cholesterol levels) should be avoided, as the combination of ezetimibe/simvastatin with fibrates has not been studied.

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

The risk of muscle injury is higher at high doses of Ezetimibe and Simvastatin Tecnigen, particularly with the 10/80 mg dose. The risk of muscle injury is also higher in certain patients. Talk to your doctor if any of the following apply to you:

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 called "statins" (such as simvastatin, atorvastatin, and rosuvastatin) or fibrates (such as gemfibrozil and bezafibrate)
you or a close family member have a hereditary muscle disease.

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

Children and adolescents

Ezetimibe and Simvastatin Tecnigen is not recommended for children under 10 years of age.

Other medicines and Ezetimibe and Simvastatin Tecnigen

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 Tecnigen with any of the following medicines may increase the risk of muscle problems (some of which have already been listed in the section above "Do not take Ezetimibe and Simvastatin Tecnigen"):

if you need oral fusidic acid to treat a bacterial infection, you must temporarily stop taking this medicine. Your doctor will advise you when it is safe to restart Ezetimibe and Simvastatin Tecnigen. Taking Ezetimibe and Simvastatin Tecnigen with fusidic acid may rarely lead to muscle weakness or pain (rhabdomyolysis). For more information on rhabdomyolysis, see section 4.
cyclosporine (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 with 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, or telithromycin (used to treat bacterial infections)
HIV protease inhibitors such as indinavir, nelfinavir, ritonavir, and saquinavir (used to treat AIDS)
antiviral agents 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)
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, have recently taken, or might take any other medicine, including those without a prescription. In particular, tell your doctor if you are taking any of the following medicines:

medicines with active substances used to prevent blood clots, such as warfarin, fluindione, phenprocoumon, or acenocoumarol (anticoagulants)
colestyramine (also used to lower cholesterol), as it may affect how Ezetimibe and Simvastatin Tecnigen works
fenofibrate (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 Ezetimibe and Simvastatin Tecnigen.

Ezetimibe and Simvastatin Tecnigen with food, drinks, and alcohol

Grapefruit juice contains one or more substances that alter the metabolism of certain medicines, including Ezetimibe and Simvastatin Tecnigen. Grapefruit juice should be avoided, as it may increase the risk of muscle problems.

Pregnancy and breastfeeding

Do not take Ezetimibe and Simvastatin Tecnigen if you are pregnant, suspect you may be pregnant, or are planning a pregnancy. If you become pregnant while taking Ezetimibe and Simvastatin Tecnigen, stop taking the medicine immediately and contact your doctor.

Do not take Ezetimibe and Simvastatin Tecnigen 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

Ezetimibe and Simvastatin Tecnigen is not expected to affect your ability to drive or use machines. However, you should be aware that some people have experienced dizziness after taking Ezetimibe and Simvastatin Tecnigen.

Ezetimibe and Simvastatin Tecnigen contains lactose

Ezetimibe and Simvastatin Tecnigen tablets contain a sugar called lactose. If you have been diagnosed by your doctor with an intolerance to certain sugars, contact your doctor before taking this medicine.

Ezetimibe and Simvastatin Tecnigen contains sodium

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

3. How to take Ezetimibe and Simvastatin Tecnigen

Your doctor will determine the appropriate tablet strength for you, based on your current treatment and individual risk profile.
The score line is not intended for dividing the tablets.
Always take this medicine exactly as instructed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
Before starting Ezetimibe and Simvastatin Tecnigen, you must begin a cholesterol-lowering diet.
During treatment with Ezetimibe and Simvastatin Tecnigen, you must continue to follow this cholesterol-lowering diet.
Adults: The dose is 1 tablet orally once daily.
Use in adolescents (aged 10 to 17 years): The dose is 1 tablet orally once daily (the maximum dose of 10 mg/40 mg once daily must not be exceeded).
The 10 mg/80 mg dose of Ezetimibe and Simvastatin Tecnigen is recommended only for adult patients with very high cholesterol levels and high risk of heart disease who have not reached their target cholesterol level with lower doses.
Take Ezetimibe and Simvastatin Tecnigen in the evening. It may be taken with or without food.
If your doctor has prescribed Ezetimibe and Simvastatin Tecnigen together with another cholesterol-lowering medicine containing the active substance cholestyramine or any other bile acid sequestrant, you must take Ezetimibe and Simvastatin Tecnigen at least 2 hours before or 4 hours after taking the bile acid sequestrant.

If you take more Ezetimibe and Simvastatin Tecnigen than you should
Contact your doctor or pharmacist.

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

If you stop taking Ezetimibe and Simvastatin Tecnigen
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, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them (see section 2, What you should know before taking Ezetimibe and Simvastatina Tecnigen).

The following common side effects have been reported (may affect more than 1 in 10 people):

Muscle pain
Increases in blood laboratory test values related to liver function (transaminases) and/or muscle (CK)

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

Increases in blood test values related to liver function; increases in 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 swelling; diarrhoea; dry mouth; heartburn
Skin rash; itching; urticaria
Joint pain; muscle pain; tenderness; weakness or spasms; neck pain; pain in arms and legs; back pain
Unusual tiredness or weakness; feeling of fatigue; chest pain; swelling, especially of the hands and feet
Sleep disorder; difficulty falling asleep

In addition, the following side effects have been reported in people taking the combination of ezetimibe/simvastatin or medicines containing the active substances ezetimibe or simvastatin:

Decrease in the number of red blood cells (anaemia); decrease in blood cells which may cause 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
Inflammation of the liver 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)
Hypersensitivity reaction including some of the following manifestations: allergic reactions including swelling of the face, lips, tongue and/or throat which may cause difficulty in breathing or swallowing and requires immediate treatment (angioedema), joint pain or inflammation, inflammation of blood vessels, abnormal 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 very rare severe allergic reaction (may affect up to 1 in 10,000 people) may occur, causing breathing problems and dizziness, and requires immediate treatment (anaphylaxis).
Muscle pain; tenderness; weakness or muscle cramps; muscle damage; tendon problems, sometimes complicated by tendon rupture
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 problems
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.
Persistent muscle pain, tenderness or weakness that may not resolve after stopping treatment with Ezetimibe and Simvastatina Tecnigen (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 damage; very rare cases of death have occurred.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please inform your doctor, pharmacist, or nurse. 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 Ezetimibe and Simvastatin Tecnigen

Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage temperature conditions.
Store in the original packaging to protect the medicine from light.
Do not use this medicine after the expiry date stated on the label after "Exp.". The expiry date refers to the last day of that month.
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 and Simvastatina Tecnigen contains
The active substances are ezetimibe and simvastatin.
Each tablet contains 10 mg of ezetimibe and 10 mg of simvastatin.
Each tablet contains 10 mg of ezetimibe and 20 mg of simvastatin.
The other ingredients are monohydrate lactose, anhydrous lactose, hypromellose, butylhydroxytoluene,
sodium croscarmellose, sodium stearyl fumarate.

Description of the appearance of Ezetimibe and Simvastatina Tecnigen and contents of the pack
Ezetimibe and Simvastatina Tecnigen 10 mg/10 mg tablets are white, oblong, with a length of 8.0 mm ± 0.2 mm and a width of 4.4 mm ± 0.2 mm.
Ezetimibe and Simvastatina Tecnigen 10 mg/20 mg tablets are white, oblong, with a score line on one side, with a length of 10.0 mm ± 0.2 mm and a width of 5.5 mm ± 0.2 mm.
Ezetimibe and Simvastatina Tecnigen 10 mg/10 mg is available in packs of 30 tablets.
Ezetimibe and Simvastatina Tecnigen 10 mg/20 mg is available in packs of 28 and 30 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
TECNIGEN S.r.l.
Via Galileo Galilei, 40
20092 Cinisello Balsamo (MI)
Italy

Manufacturer
Atlantic Pharma – Produções Farmacêuticas, S.A.
Rua da Tapada Grande, n.º 2; Abrunheira
2710-089 Sintra
Portugal

This medicinal product is authorised in the European Economic Area Member States under the
following names:
Portugal: Sinvastatina + Ezetimiba Tecnigen
Italy: Ezetimibe e Simvastatina Tecnigen
Spain: Ezetimiba/Simvastatina TecniGen 10 mg/20 mg comprimidos EFG