InfoCons Consumer Protection informs you – Yuvanci – Package Leaflet

Before anything else

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.  Keep this leaflet. You may need to read it again.  If you have any further questions, ask your docto r orpharmacist.  This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of i llness are the same as yours.  If you get any side effects, talk to your doctor orpharmacist. This includes any possible side effects not listed in this leaflet . See section 4.

ℹ️ 1. What Yuvanci is and what it is used for

Yuvanci contains two activ e substances , macitentan and tadalafil. Macitentan belongs to a class of medicines called endothelin receptor antagonists (ERAs) .Tadalafil belongs to a class of medicines called phosphodiesterase type 5 inhibitors (PDE5i) .

Yuvanci is used in adults for the long -term treatment of World Health Organization (WHO) Class II or Class III pulmonary arterial hypertension (PAH ). It is used as an alternative to taking both macitentan and tadalafil as single tablets.

PAH is high blood pressure in the blood vessels that carry blood from the heart to the lungs (the pulmonary arteries). In people with PAH, these arteries get narrower, so the heart has to work harder to pump blood through them. This causes people to feel tired, dizzy, and short of breath. The class reflects the se riousness of the disease: patients with Class II PAH have slight limitation of physical activity and those with Class III disease have marked limitation of physical activity.

Yuvanci widens the pulmonary arteries, making it easier for the heart to pump bl ood through them.

This lowers the blood pressure, relieves the symptoms and results in an improved ability to do physical activity and improves the course of the disease.

⚠️ 2. What you need to know before you take Yuvanci

Do not take Yuvanci if you

 are allergic to macitentan, tadalafil, or any of the other ingredients of this medicine (listed in section 6).  have had a heart attack within the last 90 days.  are pregnant or if you could become pregnant because you are not using reliable birth control (contraception). See section 2‘Pregnancy and breastfeeding’.  are breastfeeding. See section 2 ‘Pregnancy and breastfeeding’.

34 have severe liver disease or if you have very hig h levels of liver enzymes in your blood. Talk to your doctor, who will decide whether this medicine is suitable for you.  have very low blood pressure (90/50 mmHg).  are taking nitrates or riociguat. See section 2 ‘ Other medicines and Yuvanci’  have ever had non-arteritic anterior isch aemic optic neuropathy (NAION ,a condition also described as “ stroke of the eye”), a loss of vision due to reduced blood flow to the eye.

If any of these apply to you, please tell your doctor .

Warnings and precautions

You will need laboratory tests before using Yuvanci and during treatment , as indicated by your doctor :

If you are a woman who could become pregnant, your doctor will ask you to take a pregnancy test before you start taking Yuvanci and regularly (once a mo nth) during treatment. See section 2 ‘Pregnancy and breastfeeding’.

Your doctor will take blood to test:  whether your liver is working properly  whether you have anaemia (a reduced number of red blood cells) Yuvanci may cause increases in liver enzymes (proteins), which may be a sign that your liver is not working properly. Other signsthat your liver may not be working properly include the following symptoms :  feeling sick (nausea)  vomiting  fever  pain in your stomach (abdomen)  yellowing of your skin or t he whites of your eyes (jaundice)  dark-coloured urine  itching of your skin  unusual tiredness or exhaustion (lethargy or fatigue)  flu-like syndrome (joint and muscle pain with fever) If you notice any of these signs during treatment with Yuvanci , tell your doctor immediately .

Yuvanci may cause anaemia ( low levels of red blood cells). If you develop any of the following, which may be symptoms of anaemia, tell your doctor :  dizziness  tiredness  feeling generally unwell  weakness  fast heart rate,  palpitations (a forceful heartbeat that may be rapid or irregular)  pallor Before taking the tablets, tell your doctor if you have  any cardiovascular (having to do with the heart and blood vessels) conditions other than your pulmonary hypertension including: oaortic and mitral valve disease (problems with the valves in the heart that can affect blood flow) opericardial constriction (a condition where the pericardium, the sac around the heart, becomes tight, affecting the heart’s ability to function correctly) 35orestricti ve or congestive cardiomyopathy (a condition where the heart muscle becomes stiff or weak, leading to problems in pumping blood effectively) oleft ventricular dysfunction (a condition where the left side of the heart has difficulty in pumping blood efficien tly to the rest of the body) oarrhythmias (abnormal heart rhythms) ocoronary artery disease (heart disease caused by narrowing or blockage of blood vessels supplying the heart muscle) ouncontrolled hypertension (high blood pressure that is not adequately cont rolled)  problems with your blood pressure such as significant decreases in blood pressure when standing up or when blood pressure is consistently lower than normal  any inherited disease that causes damage to the retina (the light sensitive membrane at the back of the eye)  a severe liver problem  a severe kidney problem If you have kidney problems, talk to your doctor before using Yuvanci. You may have a higher risk of experiencing low blood pressure and anaemia during treatment with Yuvanci.

In patients with pulmonary veno -occlusive disease (obstruction of the lung veins), the use of medicines for treatment of PAH, including Yuvanci , may lead to pulmonary oedema (build up of fluid in the lungs). Tell your doctor immediately if you have signs o f pulmonary oedema when using Yuvanci , such as a sudden, important increase in breathlessness coughing tiredness after exertion difficulty breathing while lying flat Before taking Yuvanci , tell your doctor if you have any deformation of the penis such as: angulation, a condition where the penis becomes curved, possibly due to cavernosal fibrosis (scarring of certain tissues in the penis). Peyronie’s disease, a condition in adult men, where they have a ‘plaque’ of scar tissue that can be felt, acco mpanied by a curve to their penis. or a condition that may predispose you to priapism (a prolonged and an painful erection which may occur without sexual stimulation) such as an abnormality of red blood cells (sickle cell anaemia), cancer of the bone marro w (multiple myeloma) or cancer of the blood cells (leukaemia).

If during treatment with Yuvanci, you experience an erection lasting 4 hours or more, seek immediate medical assistance.

Visual defects and sudden loss of vision have occurred while using tadalafil and PDE5 inhibitors. If you experience sudden decrease or loss of vision or your vision is distorted or dimmed , during treatment stop taking Yuvanci and contact your doctor immedi ately.

Decreased or sudden hearing loss has been noted in some patients taking tadalafil. Although it is not known if the event is directly related to tadalafil, if you experience decreased or sudden hearing loss, contact your doctor immediately.

Children and adolescents

Do not give this medicine to children and adolescents below 18 years because Yuvanci has not been tested in children.

36Other medicines and Yuvanci Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Do not take Yuvanci if you are taking any of the following medicines

 riociguat (a medicine used to treat PAH and chronic thromboembolic pulmonary hypertension )  nitrates such as nitroglycerin , isosorbide and amyl nitrate (for chest pain) Please talk to your doctor or pharmacist if you are taking any of the following medicines including:

Medicines that may decrease the effectiveness of Yuvanci by decreasing the amount of Yuvanci in the blood, including: St John’s Wort (a herbal preparation used to treat depression) phenytoin or carbamazepine (medicines used to treat epilepsy) rifampicin (an antibiotic used to treat infections) Medicines that may increase the ri sk of side effects of Yuvanci, including:  clarithromycin, telithromycin, ciprofloxacin, erythromycin (antibiotics used to treat infections)  ritonavir, saquinavir (used to treat HIV infections)  doxazosin (used to treat high blood pressure or prostate problems )  nefazodone (used to treat depression)  ketoconazole (except when used in a shampoo), fluconazole, itraconazole, miconazole, voriconazole (medicines used against fungal infections)  amiodarone (to control the heartbeat)  cyclosporine (used to prevent organ rejection after transplant) , diltiazem, verapamil (to treat high blood pressure or specific heart problems)  prostacyclin similar medicines such as epoprostenol andiloprost (used to treat PAH, lung scarring and blocked arteries ) Yuvanci with food andalcohol If you are taking piperine as a dietary supplement, this may alter how the body responds to some medici nal products, including Yuvanci . Please talk to your doctor or pharmacist should this be the case.

Drinking alcohol may temporarily lower yo ur blood pressure. If you have taken or are planning to take Yuvanci, avoid excessive drinking (over 5 units of alcohol), since this may increase the risk of dizziness when standing up.

Pregnancy andbreast -feeding If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Yuvanci must not be taken during pregnancy as it may harm unborn bab y.See section 2 “Do not take Yuvanci if you”.  If it is possible that you could become pregnant, use a reliable form of birth control (contraception) while you are taking Yuvanci. Talk to your doctor about contraception .  Do not take Yuvanci if you are pregnant or planning to become pregnant.  Ifyou become pregnant or think t hat you may be pregnant while you are taking Yuvanci , or shortly after stopping Yuvanci (up to 1 month), see your doctor immediately.

If you are a woman who could become pregnant, your doctor will ask you to take a pregnancy test before you start taking Yuvanci and regularly (once a month) while you are taking Yuvanci .

37It is not known if Yuvanci is transferred to breast milk. Do not breastfeed while you are taking Yuvanci . Talk to your doctor if you are planning to breastfeed. See section 2 “Do not take Y uvanci if you”

Fertility

Yuvanci may cause decreased sperm count in men. T alk to your doctor if you are planning to have children.

Driving and using machines

Yuvanci can cause side effects such as headaches and low blood pressure (listed in section 4), and the symptoms of pulmonary arterial hypertension can also make you less fit to drive. Check carefully how you react to the Yuvanci before driving or using any machinery.

Yuvanci contains lactose monohydrate and sodium

 Yuvanci contains lactose monohydrate . If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.  This medicine contains less than 1 mmol sodium ( 23mg) per tablet, that is to say essentially ‘sodium -free’.

💊 3. How to take Yuvanci

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

The recommended dose of Yuvanci is one 10 mg/40mg tablet, once a day. In some situations your doctor may decide starting on a lower dose of 10mg/20 mg dose once a day . It lets your body adjust to the new medicine. If tolerated, your doctor will then increase your dose to the dose of one 10mg/40 mg ta blet, once a day .

Swallow the whole tablet, with a glass of water .Do not chew or break the tablet. You can take Yuvanci with or without food. It is best to take the tablet at the same time each day.

If you take more Yuvanci than you should

Contact your doctor or pharmacist immediately. You may experience any of the side effects described in section 4 .

If you forget to take Yuvanci

If you forget to take Yuvanci , take a dose as soon as you remember, then continue to take your tablets at the usual times. Do not take a double dose to make up for a forgotten tablet.

If you stop taking Yuvanci

Yuvanci is a treatment that you will need to keep on taking to control your PAH. Do not stop taking Yuvanci unless you have agreed this with your doctor.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

❗ 4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The side effects listed below have been observed with Yuvanci or have been previously reported with the active substances (macitentan or tadalafil) inYuvanci and may also occur with Yuvanci.

38If you experience any of the following side effects stop using the medicine and seek medical help immed iately:  serious allergic reactions (may affect up to 1 in 10 people). oSymptoms include swelling around the eyes, face, lips, tongue or throat which can be life threatening if throat swelling blocks the airway. If you experience any of these symptoms during treatment with Yuvanci seek immediate medical assistance.  chest pain (may affect up to 1 in 10 people ). oif you experience chest pain during treatment with Yuvanci seek immediate medical assistance . Do not use nitrates to treat your symptoms.  priapi sm, a prolonged and possibly painful erection which may occur without sexual stimulation (may affect up to 1 in 100 people ). oIf you experience an erection lasting more than 4 hours during treatment with Yuvanci, seek immediate medical assistance .  sudden lo ss of vision or distorted, dimmed, blurred central vision or sudden decrease of vision. (It is not known how often people may be affected by these side effects ). oIf you experience these side effects during treatment with Yuvanci seek immediate medical assistance.

Other side effects include

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

 Oedema/fluid retention (swelling), especially of the ankles and feet  Headache  Anaemia ( low number of red blood cells) or reduced haemoglobin (the protein in red blood cells that carries oxygen around the body)  Nausea (feeling sick)  Dyspepsia (indigestion)  Abdominal (belly) pain  Abdominal discomfort  Nasopharyngitis (inflammation of the throat and nose)  Bronchitis (inflammation of the airways)  Myalgia (muscle aches)  Back pain  Pain in the legs and arms  Flushing (redness of the skin)

Common (may affect up to 1 in 10 people)

 Vomiting (being sick)  Gastroesophageal reflux disease (acid reflux)  Syncope (fainting)  Migraine  Influenza (flu)  Urinary tract infection ( infection of the parts of the body that collect and pass out urine )  Respiratory tract infection ( infection of the breathing system, infected chest ornose, sinuses or throat, a cold)  Pharyngitis (inflammation of the throat)  Epistaxis (nose bleed)  Palpitations ( a forceful heartbeat that may be rapid or irregular )  Tachycardia (rapid heartbeat)  Increased levels of liver enzymes, as shown in blood tests  Leukopenia ( low levels white blood cell s)  Thrombocytopenia ( low blood levels of platelet s, components that help the blood to clot )  Hypotension (low blood pressure)  Vision blurred (blurred vision) 39 Increased uterine (relating to the womb) bleeding  Rash  Hypersensitivity (allergic reactions), including itching

Uncommon (may affect up to 1 in 100 pe ople)

 Seizure  Transient amnesia (passing memory loss)  Sudden cardiac death (when the heart unexpectedly stops beating, leading to loss of consciousness and death)  Urticaria (hives)  Hyperhidrosis (excessive sweating)  Penile haemorrhage (penile bleeding)  Haematospermia (blood in semen and/or urine)  Tinnitus (ringing in the ears)  Haematuria (blood in urine)

Not known (cannot be estimated)

 Stroke  Myocardial infarction (heart attack)  Unstable angina pectoris (chest pain)  Ventricular arrhythmia (abnormal hear t rhythm that originates in the lower chambers of the heart )  Stevens -Johnson syndrome (severe rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals)  Exfoliative dermatitis (flaking or peeling skin)  Retinal vascular oc clusion (blood clot in the blood vessels in the eye, which may cause blurred vision or blindness)  Visual field defect  Sudden hearing loss

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V . By reporting side effects, you can help provide more information on the safety of this medicine.

🌡️ 5. How to store Yuvanci

Keep this medicine out of the sight and reach of children.

Do not use Yuvanci after the expiry date which is stated on the carton and blister after “EXP”. Th e expiry date refers to the last day of that month.

Store in original package in order to protect from moisture .

This medicinal product does not require any special temperature storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

📦 6. Contents of the pack and other information

What Yuvanci contains

The active substance s are macitentan and tadalafil.

40Each 10 mg/20 mg film -coated tablet contains 10 mg macitentan and 20 mg tadalafil.

Each 10 mg/40 mg film -coated tablet contains 10 mg macitentan and 40 mg tadalafil.

The other ingredients are:

Tablet core Hydroxypropylcellulose Low-substituted hydroxypropylcellulose (E463a) Lactose monohydrate (see section 2 Yuvanci cont ains lactose) Magnesium stearate (E470b) Microcrystalline cellulose (E460i) Polysorbate 80 (E433) Povidone (E1201)

Sodium starch glycolate (see section 2 Yuvanci contains sodium)

Sodium lauryl sulfate Film -coat Hypromellose Lactose monohydrate Titanium dioxide (E171) Triacetin (E1518) Talc (E553b) Yuvanc i10mg/20 mg film-coated tablets also contain i ron oxide red (E172) and i ron oxide yellow (E172) .

What Yuvanci looks like and contents of the pack

Yuvanci 10mg/20 mg film -coated tablets are p ink, oblong, tablets debossed with “MT” on one side and “1020” on the other side. Yuvanci 10 mg/20 mg issupplied as 30×1 film-coated tablets in aluminium perforated unit dose blisters with integrated desiccant .

Yuvanci 10mg/40 mg film -coated tablets are w hite to almost white, oblong, tablets debossed with “MT” on one side and “1040” on the other side. Yuvanci 10 mg /40 mg issupplied as 30×1 film-coated tablets in aluminium perforated unit dose blisters with integrated desiccant.

Marketing Authorisation Holder

Janssen -Cilag International NV Turnhoutseweg 30 B-2340 Beerse Belgium

Manufacturer

Janssen Pharmaceutica NV Turnhoutseweg 30 B-2340 Beerse Belgium For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Janssen -Cilag NV Tel/Tél: +32 14 64 94 11 [email protected] UAB “JOHNSON & JOHNSON” Tel: +370 5 278 68 88 [email protected] 41България „Джонсън & Джонсън България” ЕООД Тел.: +359 2 489 94 00 [email protected]/Luxemburg Janssen -Cilag NV Tél/Tel: +32 14 64 94 11 [email protected] Česká republika Janssen -Cilag s.r.o.

Tel: +420 227 012 227Magyarország Janssen -Cilag Kft.

Tel.: +36 1 884 2858 [email protected] Danmark Janssen -Cilag A/S Tlf.: +45 4594 8282 [email protected] AM MANGION LTD Tel: +356 2397 6000 Deutschland Janssen -Cilag GmbH Tel: 0800 086 9247 / +49 2137 955 6955 [email protected] Janssen -Cilag B.V.

Tel: +31 76 711 1111 [email protected] Eesti UAB “JOHNSON & JOHNSON” Eesti filiaal Tel: +372 617 7410 [email protected] Janssen -Cilag AS Tlf: +47 24 12 65 00 [email protected] Ελλάδα Janssen -Cilag Φαρμακευτική Μονοπρόσωπη Α.Ε.Β.Ε.

Tηλ: +30 210 80 90 000Österreich Janssen -Cilag Pharma GmbH Tel: +43 1 610 300 España Janssen -Cilag, S.A.

Tel: +34 91 722 81 00 [email protected] Janssen -Cilag Polska Sp. z o.o.

Tel.: +48 22 237 60 00 France Janssen -Cilag Tél: 0 800 25 50 75 / +33 1 55 00 40 03 [email protected] Janssen -Cilag Farmacêutica, Lda.

Tel: +351 214 368 600 Hrvatska Johnson & Johnson S.E. d.o.o.

Tel: +385 1 6610 700 [email protected]ânia Johnson & Johnson Rom ânia SRL Tel: +40 21 207 1800 Ireland Janssen Sciences Ireland UC Tel: 1 800 709 122 [email protected] Johnson & Johnson d.o.o.

Tel: +386 1 401 18 00 [email protected] Ísland Janssen -Cilag AB c/o Vistor hf.

Sími: +354 535 7000 [email protected]á republika Johnson & Johnson, s.r.o.

Tel: +421 232 408 400 42Italia Janssen -Cilag SpA Tel: 800.688.777 / +39 02 2510 1 [email protected]/Finland Janssen -Cilag Oy Puh/Tel: +358 207 531 300 [email protected] Κύπρος Βαρνάβας Χατζηπαναγής Λτδ Τηλ: +357 22 207 700Sverige Janssen -Cilag AB Tfn: +46 8 626 50 00 [email protected] Latvija UAB “JOHNSON & JOHNSON” filiāle Latvijā Tel: +371 678 93561 [email protected] Kingdom (Northern Ireland) Janssen Sciences Ireland UC Tel: +44 1 494 567 444 [email protected]

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site: https://www.ema.europa.eu

📄 Package Leaflet – official source

This article reproduces the information in the official package leaflet, as authorised in the European Union. You can consult the original document here: Product information Yuvanci (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/24/1859).

⚠️ Important: This article is for information purposes only and does not replace medical advice or the package leaflet inside the medicine box. Read the leaflet carefully before use. For any questions about your treatment, talk to your doctor or pharmacist. If you experience side effects, tell your doctor or pharmacist and report them through your national reporting system.