Ezehron duo

Patient Information Leaflet

Ezehron Duo, 15 mg + 10 mg, tablets
Ezehron Duo, 30 mg + 10 mg, tablets
Ezehron Duo, 40 mg + 10 mg, tablets
Rosuvastatin + Ezetimibe
Please read all of 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 further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents:

1. What Ezehron Duo is and what it is used for
2. What you need to know 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, belonging 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 fat 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 in 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 eventually block blood flow to the heart or brain, leading to 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 separately at the same doses as those contained in the fixed-dose combination.
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 infection)
• 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 should stop taking the medicine immediately and inform her doctor. Effective contraception must be used to avoid pregnancy while taking Ezehron Duo (see section "Pregnancy and breastfeeding")
• if the patient has ever 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),
the patient should consult a doctor.
Additionally, do not use Ezehron Duo, 40 mg + 10 mg (the highest dose):

• if the patient has moderately severe kidney disease (in case of doubt, consult a doctor),
• if the patient has thyroid disease,
• if the patient experiences frequent or unexplained muscle symptoms or pain, or if the patient or family members have ever had muscle disorders, or if muscle-related side effects occurred previously during treatment with cholesterol-lowering medicines,
• if the patient regularly consumes large amounts of alcohol,
• if the patient is of Asian origin (Japanese, Chinese, Filipino, Vietnamese, Korean or Indian),
• if the patient is taking fibrates (other cholesterol-lowering medicines) (see section "Ezehron Duo and other medicines").

If any of the above situations apply to the patient (or if the patient has any doubts),
the patient should consult a doctor again.
Warnings and precautions
Before using Ezehron Duo, discuss with a doctor or pharmacist if:
the patient has kidney function impairment;
the patient has liver function impairment;
the patient has experienced recurrent or unexplained muscle pain, or if the patient or relatives have had muscle disorders in the past, or if muscle-related problems occurred previously during treatment with other cholesterol-lowering medicines. In case of unexplained muscle pain, especially if associated with malaise or fever, the patient should contact a doctor immediately. The patient should also inform the 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, e.g. 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 medicines (fibrates) to lower cholesterol. The patient should read the leaflet carefully, even if they have previously taken other cholesterol-lowering medicines;
the patient regularly consumes large amounts of alcohol;
the patient has been diagnosed with abnormal thyroid function (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 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 gravis (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 sometimes worsen symptoms or trigger myasthenia gravis (see section 4);
the patient has ever experienced severe rash, skin peeling, blistering and/or oral ulcers after taking rosuvastatin or other similar medicines.
If any of the above situations apply to the patient (or if there is any doubt), do not use Ezehron Duo 40 mg + 10 mg (the highest dose), and the patient should consult a doctor or pharmacist before starting treatment with 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, the doctor will recommend regular blood tests during treatment with Ezehron Duo. It is important that the patient attends appointments for these tests.
While taking this medicine, the doctor will closely monitor patients with diabetes or risk factors for developing diabetes. There is a high probability 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 rosuvastatin use. If any of the symptoms described in section 4 occur, the patient should 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 the doctor if the patient is taking any of the following medicines:

• cyclosporine (a medicine used, for example, after organ transplantation to prevent transplant rejection. Cyclosporine enhances the effect of concomitantly administered rosuvastatin). Do not take Ezehron Duo during cyclosporine treatment;
• anticoagulants, e.g. warfarin, acenocoumarol, phenindione, ticagrelor or clopidogrel (concomitant use with Ezehron Duo may enhance anticoagulant effect, increasing the risk of bleeding);
• other cholesterol-lowering medicines, so-called fibrates, which also regulate blood triglyceride levels (e.g. gemfibrozil and other medicines in this group). Concomitant use increases the effect of rosuvastatin. Do not use Ezehron Duo 40 mg + 10 mg together with fibrates;
• colestyramine (a medicine used to lower cholesterol levels), as it affects the way ezetimibe works;
• darolutamide, regorafenib or capmatinib (used in cancer treatment);
• any of the following medicines used to treat viral infections, including HIV or hepatitis C virus infection, administered 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 concentration. This interaction can be minimized by taking these medicines 2 hours after rosuvastatin;
• erythromycin (an antibiotic). Concomitant use reduces rosuvastatin effect;
• fusidic acid. If the patient needs to take oral fusidic acid to treat a bacterial infection, temporary discontinuation of Ezehron Duo is necessary. The doctor will inform 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);
• fostamatinib (used to treat low platelet count);
• febuxostat (used to treat and prevent high blood uric acid levels);
• teriflunomide (used to treat multiple sclerosis).

If the patient is admitted to hospital or is being treated for another illness, they should
inform healthcare professionals 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 a 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. Patients should use effective contraception methods while taking Ezehron Duo.
Breastfeeding
Ezehron Duo must not be used during breastfeeding, as it is unknown whether the medicine passes into breast milk.
Driving and operating machinery
Ezehron Duo is not expected to affect the ability to drive or operate machinery.
However, it should be noted that Ezehron Duo may cause dizziness in some patients. In such a case, the patient should consult a doctor before driving or operating machinery.
Ezehron Duo tablets contain lactose monohydrate
If the patient has been previously diagnosed with intolerance to certain sugars, they should consult a doctor before taking this medicine.
Ezehron Duo tablets contain sodium
The medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to take Ezehron Duo

This medicine should always be taken according to the doctor's or pharmacist's instructions. In case of
doubt, consult your doctor or pharmacist.
While taking Ezehron Duo, you should continue a low-cholesterol diet and maintain physical
activity.
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.
The medicine 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 medicinal products.
Only after determining the appropriate doses should you switch to Ezehron Duo of the appropriate
strength.
The maximum daily dose of rosuvastatin is 40 mg. This dose is used in patients with high
cholesterol levels and a high risk of heart attack or stroke, in whom the 30 mg dose was
insufficient to reduce cholesterol levels.
Regular monitoring of cholesterol levels
It is important to visit your doctor regularly to monitor cholesterol levels, to ensure that the target
value has been achieved and maintained.
Taking more Ezehron Duo than recommended
In case of overdose, contact your doctor or the emergency department of the nearest hospital, as
medical assistance may be required.
Missing a dose of 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 taking Ezehron Duo. After stopping Ezehron Duo,
cholesterol levels may rise again.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
It is important for the patient to be aware of the possible adverse reactions associated with the use of this medicine.
The patient should stop taking Ezehron Duo and seek immediate medical help
if any of the following occur:

• Allergic reaction: swelling of the face, lips, tongue and (or) throat, which may make breathing and swallowing difficult, severe skin itching (with hives). These are rare possible adverse reactions;
• Lupus-like syndrome (including rash, joint disorders and effects on blood cells). This is a rare possible adverse reaction;
• Muscle rupture. This is a rare possible adverse reaction;
• Red, flat, disc-shaped or circular spots on the trunk, often with blisters in the center, skin peeling, ulcers in the mouth, throat, nose, genital organs and around the eyes. These severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome). The frequency of this adverse reaction is unknown;
• Widespread rash, high body temperature and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome). The frequency of this adverse reaction is unknown.

The patient should immediately consult a doctor if any unusual, persistent muscle pain occurs.
This condition may rarely progress to life-threatening muscle damage (known as rhabdomyolysis), causing malaise, fever and kidney dysfunction.

To describe the frequency of adverse reactions, the following classification is 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 1,000 patients)
• very rare (may occur in up to 1 in 10,000 patients), including isolated cases

Common adverse reactions
headache
constipation
nausea
muscle pain
muscle tenderness
feeling of weakness
dizziness
increased protein in urine. This symptom usually resolves spontaneously and there is no need to discontinue Ezehron Duo (applies only to the 40 mg dose of rosuvastatin).
diabetes – more likely in patients with high blood sugar and fat levels, 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 (applies to rosuvastatin doses of 15 mg and 30 mg)
increased results of certain tests assessing muscle status (creatine kinase, CK activity)
cough
indigestion
heartburn
nausea
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
increased tendency to bleeding or bruising due to low 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 (gynecomastia)

Adverse reactions with unknown frequency
shortness of breath
swelling
sleep disorders, including insomnia and nightmares
sexual disorders
depression
breathing disorders, including persistent cough and (or) shortness of breath or fever
tendon injury
persistent muscle weakness
red, raised rash, sometimes with lesions in a disc-like shape (erythema multiforme)
muscle tenderness
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)

Patients should speak to their doctor if they experience weakness in hands 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 reactions occur, including any not listed in this leaflet, the patient should inform their doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of 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 collect more information on the safety of the medicine.

5. How to store Ezehron Duo

Keep the medicine in its original packaging to protect it from light.
No special temperature storage requirements.
Store the medicine in a place inaccessible and out of sight 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 in use. 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 in an amount equivalent to 15 mg, 30 mg or 40 mg of rosuvastatin. Each tablet contains 10 mg of ezetimibe.
The other ingredients are: monohydrate lactose, microcrystalline cellulose type 102, sodium croscarmellose, crospovidone type A, povidone K-30, sodium lauryl sulfate and magnesium stearate.

What Ezehron Duo looks like and contents of the pack
Ezehron Duo, 15 mg + 10 mg: white or almost white, hexagonal, biconvex, uncoated tablet, approximately 9 x 8 mm in size, with the imprint "E3" on both sides.
Ezehron Duo, tablets 30 mg + 10 mg: white or almost white, biconvex, uncoated tablet, rectangular in shape, 12 x 6 mm in size, with the imprint "X" on both sides.
Ezehron Duo, tablets 40 mg + 10 mg: white or almost white, elliptical, biconvex, uncoated tablet, approximately 13 x 6 mm in size, with the imprint "E6" on both sides.
Packs containing 28, 30, 56, 60, 90 and 100 tablets in blisters made of PA/Aluminium/PVC/Aluminium foil, placed in a cardboard carton 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.
ul. Marszałka J. Piłsudskiego 5
95-200 Pabianice