Ezehron duo

Patient Information Leaflet

Ezehron Duo, 5 mg + 10 mg, tablets
Ezehron Duo, 10 mg + 10 mg, tablets
Ezehron Duo, 20 mg + 10 mg, tablets
Rosuvastatin + Ezetimibe
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm someone else, even if their symptoms are similar to yours.
• If you experience any side effects, including any not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Leaflet Contents:

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

1. What Ezehron Duo is and what it is used for

Ezehron Duo contains two different active substances in one tablet. One of the active substances is rosuvastatin, which belongs to a group of medicines called statins, and the other active substance is ezetimibe.
Ezehron Duo is a medicine used to lower blood levels of total cholesterol, so-called "bad" cholesterol (LDL cholesterol), and fatty substances called "triglycerides", while also increasing levels of so-called "good" cholesterol (HDL cholesterol). The medicine reduces cholesterol levels by acting in two ways: it reduces the amount of cholesterol absorbed from the gastrointestinal tract and the amount of cholesterol produced in the body.
In most people, high cholesterol does not affect well-being, as it causes no symptoms. However, if left untreated, fatty deposits may accumulate in the walls of blood vessels, causing them to narrow. This narrowing may lead to complete blockage of the blood vessel, cutting off blood supply to the heart or brain, resulting in a heart attack or stroke. By lowering cholesterol levels, the risk of heart attack, stroke, or other related health problems can be reduced.
Ezehron Duo is used in patients in whom diet alone is not sufficient to maintain normal cholesterol levels. While taking this medicine, you must continue to follow a cholesterol-lowering diet.
Your doctor may prescribe Ezehron Duo if you are already taking rosuvastatin and ezetimibe at the same doses as those contained in the combination medicine.
Ezehron Duo is used in patients:

• with elevated blood cholesterol levels (primary hypercholesterolemia)
• with heart disease – Ezehron Duo reduces the risk of heart attack, stroke, need for a surgical procedure to improve blood flow to the heart, or hospitalization due to chest pain.

Ezehron Duo does not help reduce body weight.

2. Important information before using Ezehron Duo

When not to use Ezehron Duo

• if the patient is allergic to rosuvastatin, ezetimibe, or any of the other ingredients of this medicine (listed in section 6)
• if the patient has liver disease
• if the patient has severe kidney function impairment
• if the patient experiences recurrent, unexplained muscle pain (myopathy)
• if the patient is taking the combination sofosbuvir/velpatasvir/voxilaprevir (used to treat viral hepatitis C)
• if the patient is taking a medicine containing cyclosporine (e.g. used after organ transplantation)
• if the patient is pregnant or breastfeeding. If pregnancy occurs during treatment with Ezehron Duo, the patient must stop taking the medicine immediately and inform her doctor. Effective contraception must be used during treatment with Ezehron Duo to avoid pregnancy (see section "Pregnancy and breastfeeding")
• if the patient has previously experienced severe skin rash, skin peeling, blisters, and/or oral ulcers after taking Ezehron Duo or other similar medicines.

If any of the above situations apply to the patient (or if the patient has any doubts),
consult a doctor.
Warnings and precautions
Before using Ezehron Duo, discuss with your doctor or pharmacist if:
the patient has impaired kidney function;
the patient has impaired liver function;
the patient has experienced recurrent or unexplained muscle pain, or previously had muscle disorders (either personally or in family members), or prior muscle-related problems associated with taking other cholesterol-lowering medicines. In case of unexplained muscle pain, especially if accompanied by malaise or fever, contact a doctor immediately. Also inform your doctor or pharmacist about persistent muscle weakness;
the patient is of Asian origin (Japan, China, Philippines, Vietnam, Korea, or India). The doctor will determine the appropriate dose of Ezehron Duo for the patient;
the patient is taking antiviral medicines, including those used to treat HIV or hepatitis C virus infection, such as ritonavir with lopinavir and/or atazanavir or simeprevir (see section "Ezehron Duo and other medicines");
the patient has severe respiratory insufficiency;
the patient is taking other lipid-lowering medicines (so-called fibrates) (see section "Ezehron Duo and other medicines");
the patient regularly consumes large amounts of alcohol;
the patient has been diagnosed with thyroid dysfunction (hypothyroidism);
the patient is over 70 years of age (as the doctor will need to select an appropriate dose of Ezehron Duo);
the patient is currently receiving or has received within the last 7 days oral or injectable fusidic acid (used to treat bacterial infections). Concomitant use of fusidic acid and Ezehron Duo may lead to serious muscle disorders (rhabdomyolysis);
the patient has or has had myasthenia (a disease causing general muscle weakness, including in some cases muscles involved in breathing) or ocular myasthenia (a disease causing weakness of eye muscles), as statins may occasionally worsen symptoms or trigger myasthenia (see section 4).
If any of the above situations apply to the patient (or if there is any uncertainty), consult again with a doctor or pharmacist before starting Ezehron Duo.

In a small number of people, statins may affect liver function. This is detected by a simple blood test measuring increased liver enzyme activity. Therefore, your doctor will recommend regular blood tests during treatment with Ezehron Duo. It is important that the patient attends scheduled medical appointments for testing.

During treatment with this medicine, the doctor will closely monitor patients with diabetes or risk factors for developing diabetes. There is an increased risk of developing diabetes if the patient has high blood sugar and lipid levels, overweight, and high blood pressure.

Serious skin reactions, including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported with Ezehron Duo. If any of the symptoms described in section 4 occur, stop taking Ezehron Duo and contact a doctor immediately.

Children and adolescents
Ezehron Duo is not recommended for use in children and adolescents under 18 years of age.

Ezehron Duo and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take.

Inform your doctor if the patient is taking any of the following medicines:

• cyclosporine (a medicine used, for example, after organ transplantation to prevent organ rejection. Cyclosporine enhances the effect of rosuvastatin when used concomitantly). Ezehron Duo must not be taken during treatment with cyclosporine.
• anticoagulants, e.g. warfarin, acenocoumarol, or fluindione (concomitant use with Ezehron Duo may enhance anticoagulant effect, increasing the risk of bleeding), ticagrelor, or clopidogrel.
• other cholesterol-lowering medicines, so-called fibrates, which also regulate blood triglyceride levels (e.g. gemfibrozil and other medicines in this class). Concomitant use increases the effect of rosuvastatin.
• cholestyramine (a medicine used to lower cholesterol levels), as it affects the way ezetimibe works.
• darolutamide, regorafenib (used in cancer treatment),
• fostamatinib (used to treat low platelet count),
• febuxostat (used to treat and prevent high blood uric acid levels),
• teriflunomide (used to treat multiple sclerosis),
• capmatinib (used in cancer treatment),
• roxadustat (used to treat anaemia in patients with chronic kidney disease),
• daptomycin (an antibiotic used to treat complicated skin and skin structure infections and bacteremia),
• tafamidis (used to treat cardiomyopathy – a disease causing, among others, enlargement and thickening of the heart muscle).
• any of the following antiviral medicines used to treat viral infections, including HIV or hepatitis C virus, used alone or in combination with other medicines (see: Warnings and precautions): ritonavir, lopinavir, atazanavir, sofosbuvir, voxilaprevir, ombitasvir, paritaprevir, dasabuvir, velpatasvir, grazoprevir, elbasvir, glecaprevir, pibrentasvir.
• medicines used to treat indigestion containing aluminium and magnesium (used to neutralize stomach acid). These medicines may reduce rosuvastatin plasma concentrations. This interaction can be minimized by taking these medicines 2 hours after rosuvastatin.
• erythromycin (an antibiotic). Concomitant use reduces the effect of rosuvastatin.
• fusidic acid. If the patient needs to take fusidic acid orally to treat a bacterial infection, Ezehron Duo must be temporarily discontinued. The doctor will advise when it is safe to resume treatment. Concomitant use of Ezehron Duo and fusidic acid may rarely cause muscle weakness, tenderness, or pain (rhabdomyolysis). More information on rhabdomyolysis is provided in section 4.
• oral contraceptives (birth control pills). Concomitant use increases the concentration of sex hormones released from the pill.
• medicines used in hormone replacement therapy (increased hormone levels in blood).

If the patient is admitted to hospital or is being treated for another illness, they should inform medical staff about taking Ezehron Duo.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.

Pregnancy
Ezehron Duo must not be used if the patient is pregnant, trying to become pregnant, or suspects she may be pregnant. If pregnancy occurs during treatment with Ezehron Duo, the patient must stop taking the medicine immediately and inform her doctor. Women of childbearing potential should use effective contraception during treatment with Ezehron Duo.

Breastfeeding
Ezehron Duo must not be used during breastfeeding, as it is unknown whether the medicine passes into breast milk.

Driving and using machines
Ezehron Duo is not expected to affect the ability to drive or operate machinery. However, bear in mind that Ezehron Duo may cause dizziness in some patients. In such cases, consult a doctor before driving or operating machinery.

Ezehron Duo tablets contain lactose monohydrate
If the patient has previously been diagnosed with intolerance to certain sugars, they should consult their doctor before taking this medicine.

Ezehron Duo tablets contain sodium
The medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning it is considered "sodium-free".

3. How to take Ezehron Duo

This medicine should always be taken exactly as directed by your doctor or pharmacist. If in
doubt, consult your doctor or pharmacist.
While taking Ezehron Duo, a low-cholesterol diet and regular physical activity should be continued.
The recommended daily dose for adults is one tablet of the specified strength.
Ezehron Duo should be taken once daily.
The medicine can be taken at any time of day, with or without food. Tablets should be swallowed
whole with water.
Ezehron Duo should be taken at the same time each day.
Ezehron Duo is not suitable for initiating treatment. If starting therapy or if a dose adjustment is
required, each active substance should be administered separately in individual medicines. Only
after the appropriate doses have been established should treatment with Ezehron Duo of the
appropriate strength be initiated.
Regular monitoring of cholesterol levels
It is important to visit your doctor regularly for monitoring of cholesterol levels to ensure that
target levels have been achieved and are being maintained.
Taking more Ezehron Duo than recommended
In case of overdose, contact your doctor or go to the nearest hospital emergency department, as
medical assistance may be necessary.
If you forget to take Ezehron Duo
If a dose is missed, take the next tablet at the usual time. Do not take a double dose to make up for
the missed dose.
Stopping Ezehron Duo
Inform your doctor if you wish to discontinue treatment with Ezehron Duo. After stopping Ezehron
Duo, cholesterol levels may increase again.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
It is important that the patient knows which adverse reactions may be associated with the use of this medicine.
Stop taking Ezehron Duo and seek immediate medical help
if the patient experiences any of the following:

• allergic reaction: swelling of the face, lips, tongue, and (or) throat, which may make breathing and swallowing difficult,
• lupus-like syndrome (including rash, joint disorders, and effects on blood cells),
• muscle rupture,
• red, flat, disc-shaped or round skin lesions on the trunk, often with blisters in the center, skin peeling, and mucosal ulcers in the mouth, throat, nose, genital organs, and around the eyes. Such severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome),
• widespread rash, high body temperature, and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).

Seek immediate medical advice if the patient experiences any unusual, persistent muscle pain.
Rarely, this condition may progress to life-threatening muscle damage (known as rhabdomyolysis), causing malaise, fever, and impaired kidney function.

For the purpose of classifying frequency of adverse reactions, the following categories are used:

• very common (may occur in more than 1 in 10 patients)
• common (may occur in up to 1 in 10 patients)
• uncommon (may occur in up to 1 in 100 patients)
• rare (may occur in up to 1 in 1000 patients)
• very rare (may occur in up to 1 in 10,000 patients), including isolated cases

Common adverse reactions
headache
constipation
nausea
muscle pain
feeling of weakness
dizziness
diabetes – more likely in patients with high levels of sugar and fats in the blood, overweight, and high blood pressure. The doctor will monitor the patient's condition during treatment with this medicine.
stomach pain
diarrhea
flatulence (excess gas in the intestines)
feeling of fatigue
increased results of certain blood tests assessing liver function (aminotransferase activity)

Uncommon adverse reactions
rash, itching, urticaria
increased protein in urine, which usually resolves spontaneously without the need to discontinue Ezehron Duo tablets
increased results of certain tests assessing muscle status (creatine kinase, CK activity)
cough
indigestion
heartburn
joint pain
muscle cramps
neck pain
decreased appetite
pain
chest pain
hot flushes
high blood pressure
tingling
dry mouth
gastritis (inflammation of the stomach lining)
back pain
muscle weakness
pain in arms and legs
swelling, especially of hands and feet

Rare adverse reactions
pancreatitis causing severe abdominal pain, which may radiate to the back
reduced platelet count

Very rare adverse reactions
jaundice (yellowing of the skin and eyes)
hepatitis (liver inflammation)
trace amounts of blood in urine
nerve damage in arms and legs (e.g. numbness)
memory loss
breast enlargement in men (gynaecomastia)

Adverse reactions with unknown frequency
shortness of breath
swelling
sleep disorders, including insomnia and nightmares
sexual dysfunction
depression
breathing disorders, including persistent cough and (or) shortness of breath or fever
tendon damage
persistent muscle weakness
gallstones or cholecystitis (which may cause abdominal pain, nausea, vomiting)
myasthenia (a disease causing general muscle weakness, including in some cases muscles involved in breathing)
ocular myasthenia (a disease causing weakness of eye muscles)

Talk to your doctor if the patient experiences weakness in the arms or legs, worsening after periods of activity, double vision or drooping eyelids, difficulty swallowing, or shortness of breath.

Reporting of adverse reactions
If any adverse symptoms occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw
tel.: + 48 22 49 21 301, fax: + 48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of this medicine.

5. How to store Ezehron Duo

Keep the medicine in its original packaging to protect it from light.
There are no special requirements regarding storage temperature.
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister pack following EXP.
The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Ezehron Duo contains
The active substances are: rosuvastatin (as rosuvastatin calcium) and ezetimibe.
The tablets contain rosuvastatin calcium equivalent to 5 mg, 10 mg or 20 mg of rosuvastatin. Each tablet contains 10 mg of ezetimibe.
Other ingredients are: monohydrate lactose, microcrystalline cellulose, sodium croscarmellose,
crospovidone type A, povidone K-30, sodium lauryl sulphate and magnesium stearate.

What Ezehron Duo looks like and contents of the pack
Ezehron Duo 5 mg/10 mg tablets: white or almost white, round, flat, uncoated tablet, embossed with "E2" on one side and "2" on the other side. The tablet diameter is 10 mm.
Ezehron Duo 10 mg/10 mg tablets: white or almost white, oval, biconvex, uncoated tablet, embossed with "E1" on one side and "1" on the other side. The tablet dimensions are 15 mm x 7 mm.
Ezehron Duo 20 mg/10 mg tablets: white or almost white, round, biconvex, uncoated tablet. The tablet diameter is 11 mm.
Packs containing 28, 56 and 84 tablets in blisters made of PA/Aluminium/PVC/Aluminium foil, placed in a cardboard box with a patient information leaflet.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
tel.: +48 22 732 77 00

Manufacturer:
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
Special Product's Line S.p.A.
Via Fratta Rotonda Vado Largo,1
03012 Anagni (FR)
Italy