Macitentan Zentiva

Package leaflet: Information for the patient

Macitentan Zentiva 10 mg film-coated tablets

Equivalent 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 other people, even if their symptoms are the same as yours, 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

1. What Macitentan Zentiva is and what it is used for
2. What you need to know before taking Macitentan Zentiva
3. How to take Macitentan Zentiva
4. Possible side effects
5. How to store Macitentan Zentiva
6. Contents of the pack and other information

1. What Macitentan Zentiva is and what it is used for

Macitentan Zentiva contains the active substance macitentan, which belongs to a class of medicines called endothelin receptor antagonists.
Macitentan Zentiva is used for the long-term treatment of pulmonary arterial hypertension (PAH):

• in adults in WHO functional class II or III
• in children under 18 years of age and weighing at least 40 kg in WHO functional class II or III.

PAH is characterized by high blood pressure in the blood vessels (the pulmonary arteries) that carry blood from the heart to the lungs. In people with PAH, these arteries become narrowed, making it harder for the heart to pump blood through them. This leads to symptoms such as fatigue, dizziness, and difficulty breathing.
Macitentan Zentiva widens the pulmonary arteries, making it easier for the heart to pump blood through them. This reduces blood pressure in the pulmonary circulation, relieves symptoms, and improves the course of the disease.

2. What you should know before taking Macitentan Zentiva

Do not take Macitentan Zentiva

• if you are allergic (hypersensitive) to macitentan, peanuts, soy, or any of the other ingredients of this medicine (listed in section 6).
• if you are pregnant, planning to become pregnant, or if you could become pregnant because you are not using an effective method of contraception. See section “Pregnancy and breastfeeding”.
• if you are breastfeeding. See section “Pregnancy and breastfeeding”.
• if you have liver disease or very high levels of liver enzymes in your blood. Talk to your doctor, who will decide whether this medicine is suitable for you. Inform your doctor in any of these cases.

Warnings and precautions
Talk to your doctor or pharmacist before taking Macitentan Zentiva.
You will need to have blood tests as directed by your doctor:
Your doctor will prescribe blood tests before starting treatment with Macitentan Zentiva
and during treatment to monitor:

• whether you have anaemia (reduced number of red blood cells)
• whether your liver is functioning properly

If you have anaemia (reduced number of red blood cells), the following symptoms may occur:

• dizziness
• tiredness/feeling unwell/weakness
• increased heart rate, palpitations
• paleness
  If you notice any of these signs, talk to your doctor.

The following symptoms may indicate that your liver is not functioning properly:

• nausea
• vomiting
• fever
• stomach (abdominal) pain
• yellowing of the skin and whites of the eyes (jaundice)
• dark-coloured urine
• skin itching
• unusual tiredness or weakness (lethargy or fatigue)
• flu-like symptoms (joint and muscle pain with fever)

If you experience any of these symptoms, inform your doctor immediately.
If you have kidney problems, inform your doctor before using Macitentan Zentiva. Macitentan may
cause a reduction in blood pressure and lower haemoglobin levels in patients with kidney problems.
In patients with pulmonary veno-occlusive disease (obstruction of the pulmonary veins), treatment with
medicines for PAH, including Macitentan Zentiva, may lead to pulmonary oedema.
If you develop signs of pulmonary oedema while taking Macitentan Zentiva, such as a sudden and
significant worsening of breathlessness and reduced oxygen levels, contact your doctor immediately.
Your doctor may perform further tests to determine the most appropriate treatment regimen for you.

Children and adolescents
Do not give this medicine to children under 2 years of age, as efficacy and safety have not been established.

Other medicines and Macitentan Zentiva
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Macitentan Zentiva may affect other medicines.
If you take Macitentan Zentiva together with other medicines, including those listed below, the effect of Macitentan Zentiva or the other medicines may be altered. Inform your doctor or pharmacist if you are taking any of the following medicines:

• rifampicin, clarithromycin, telithromycin, ciprofloxacin, erythromycin (antibiotics used to treat infections),
• phenytoin (a medicine used for epileptic seizures),
• carbamazepine (used for depression and epilepsy),
• St. John’s wort (a herbal preparation used for depression),
• ritonavir, saquinavir (used in HIV infection),
• nefazodone (used for depression),
• ketoconazole (except shampoo), fluconazole, itraconazole, miconazole, voriconazole (medicines used to treat fungal infections),
• amiodarone (to control heart rhythm),
• cyclosporine (used to prevent organ rejection after transplantation),
• diltiazem, verapamil (for treatment of high blood pressure or certain heart conditions).

Macitentan Zentiva with food
If you take piperine as a dietary supplement, it may alter how your body responds to certain medicines, including Macitentan Zentiva. Inform your doctor or pharmacist if this applies to you.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before taking this medicine.
Macitentan Zentiva may harm the unborn child conceived before, during, or shortly after treatment.

• If you could become pregnant, use an effective method of birth control (contraception) during treatment with Macitentan Zentiva. Discuss this with your doctor.
• Do not take Macitentan Zentiva if you are pregnant or planning to become pregnant.
• If you become pregnant or suspect you are pregnant during treatment with Macitentan Zentiva or shortly after stopping the medicine (within 1 month), contact your doctor immediately.

If you are a woman of childbearing potential, your doctor will require a pregnancy test before you start taking Macitentan Zentiva and will repeat the test regularly (once a month) during treatment.
It is not known whether macitentan passes into breast milk. Do not breastfeed while taking Macitentan Zentiva. Inform your doctor if you are breastfeeding.

Fertility
If you are a man taking Macitentan Zentiva, this medicine may reduce sperm count. Talk to your doctor if you have any questions or concerns about this.

Driving and using machines
Macitentan Zentiva may cause side effects such as headache and hypotension (listed in section 4). Additionally, symptoms of the disease itself may impair your ability to drive or operate machinery.

Macitentan Zentiva contains lactose, soya lecithin, and sodium
This medicine contains a sugar called lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
This medicine contains lecithin derived from soya. If you are allergic to peanuts or soya, do not use this medicine (see section 2 “Do not take Macitentan Zentiva”).
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially “sodium-free”.

3. How to take Macitentan Zentiva

Macitentan Zentiva can only be prescribed by a physician experienced in the treatment of pulmonary arterial hypertension.
Take this medicine exactly as your doctor has instructed you. If you are unsure, consult your doctor.

Adults and children under 18 years of age weighing at least 40 kg
The recommended dose of Macitentan Zentiva is one 10 mg tablet once daily. Swallow the tablet whole with a glass of water, without chewing or breaking the tablet. You may take Macitentan Zentiva either on an empty stomach or with food. It is preferable to take the tablet at the same time each day.

For children weighing less than 40 kg, other weight-appropriate formulations available on the market should be used.

If you take more Macitentan Zentiva than you should
If you have taken more tablets than prescribed, you may experience headache, nausea, and vomiting. Consult your doctor for advice.

If you forget to take Macitentan Zentiva
If you forget to take Macitentan Zentiva, take a dose as soon as you remember, and then continue taking your tablets at your usual time. Do not take a double dose to make up for the forgotten tablet.

If you stop taking Macitentan Zentiva
Macitentan Zentiva is a treatment that you must continue taking to control PAH. Do not stop treatment with Macitentan Zentiva unless agreed with your doctor.

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.
Serious uncommon side effects (may affect up to 1 in 100 people):

• Allergic reactions (swelling around the eyes, face, lips, tongue or throat, itching and/or skin rash). If you notice any of these signs, tell your doctor immediately.

Very common side effects (may affect more than 1 in 10 people):

• Anaemia (reduced number of red blood cells) or reduced haemoglobin concentration
• Headache
• Bronchitis (inflammation of the airways)
• Nasopharyngitis (inflammation of the throat and nasal passages)
• Oedema (swelling), especially in the ankles and feet

Common side effects (may affect up to 1 in 10 people):

• Pharyngitis (inflammation of the throat)
• Influenza
• Urinary tract infection (bladder infection)
• Hypotension (low blood pressure)
• Nasal congestion (blocked nose)
• Changes in liver function tests
• Leucopenia (low white blood cell count)
• Thrombocytopenia (low platelet count)
• Flushing (reddening of the skin)
• Increased uterine bleeding

Side effects in children and adolescents
The side effects listed above may also occur in children. Additional very common side effects observed in children include upper respiratory tract infection (infection of the sinuses or throat) and gastroenteritis (inflammation of the stomach and intestines). Rhinitis (itchy, runny or blocked nose) has been commonly observed in children.
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 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 Macitentan Zentiva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton, blister, and bottle after "Exp". The expiry date refers to the last day of that month.
This medicine requires no special storage conditions.
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 Macitentan Zentiva contains

• The active substance is macitentan. Each tablet contains 10 mg of macitentan.
• The other components are lactose monohydrate, sodium starch glycolate, povidone, sodium stearyl fumarate, polysorbate 80 (E433), polyvinyl alcohol (E1203), titanium dioxide (E171), talc (E553b), soybean lecithin (E322), xanthan gum (E415).

Description of the appearance of Macitentan Zentiva and package contents
Macitentan Zentiva 10 mg film-coated tablets are round, biconvex, white film-coated tablets with a diameter between 5.5 mm and 5.8 mm, marked "HM" on one side and "21" on the other side.
Macitentan Zentiva is available in white opaque PVC/PE/PVDC/Al blisters inside a cardboard box.
Macitentan Zentiva is also available in HDPE bottles with child-resistant polypropylene caps, induction-sealed aluminium lining, and a silica gel desiccant contained within a container, all inside a cardboard box. The container and desiccant are not for consumption.
Pack size: 30 film-coated tablets.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Zentiva Italia S.r.l.
Via P. Paleocapa, 7
20121 Milan
Italy

Manufacturer
Pharmadox Healthcare Limited,
KW20A Kordin Industrial Park
Paola, PLA 3000, Malta

This medicinal product is authorised in the European Economic Area member states under the following names:
Denmark, Finland, Norway, Sweden, Italy: Macitentan Zentiva
Austria, Germany: Macitentan Zentiva 10 mg Filmtabletten
Spain: Macitentan Zentiva 10 mg comprimidos recubiertos con película EFG
Portugal: Macitentano Zentiva
Hungary: Macitentan Zentiva 10 mg filmtabletta