Yuvanci

Package leaflet: Information for the user

Yuvanci 10 mg/20 mg film-coated tablets, 10 mg/40 mg film-coated tablets

macitentan/tadalafil
Please 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Yuvanci is and what it is used for

Yuvanci contains two active 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 pulmonary arterial hypertension (PAH) in World Health Organization (WHO) Class II or Class III. It is used as an alternative to taking macitentan and tadalafil as separate 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 become narrowed, so the heart has to work harder to pump blood through them. This causes fatigue, dizziness, and shortness of breath. The WHO class reflects the severity of the disease: patients with WHO Class II PAH have mild limitation in physical activity, while those with Class III disease have marked limitation in physical activity.
Yuvanci dilates the pulmonary arteries, making it easier for the heart to pump blood. This reduces blood pressure, relieves symptoms, improves the ability to perform physical activity, and slows disease progression.

2. What you should know before taking 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);
• if you have recently had a heart attack within the last 90 days;
• if you are pregnant or may become pregnant because you are not using an effective method of contraception. See section 2 “Pregnancy and breastfeeding”;
• if you are breastfeeding. See section 2 “Pregnancy and breastfeeding”;
• if you have severe liver disease or very high levels of liver enzymes in your blood. Consult your doctor, who will decide whether this medicine is suitable for you;
• if you have very low blood pressure (90/50 mmHg);
• if you are taking nitrates or riociguat. See section 2 “Other medicines and Yuvanci”;
• if you have experienced non-arteritic anterior ischemic optic neuropathy (NAION, a condition also described as “stroke of the eye”), or vision loss due to reduced blood flow to the eyes.

If any of these conditions apply to you, inform your doctor.
Warnings and precautions
You will need to undergo laboratory tests before starting Yuvanci and during treatment,
as directed by your doctor.
If you are a woman who could become pregnant, your doctor will request a pregnancy test before starting Yuvanci and regularly (once a month) during treatment. See section 2 “Pregnancy and breastfeeding”.
Your doctor will take a blood sample to check:

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

Yuvanci may cause an increase in liver enzymes (proteins), which could indicate that the liver is not functioning properly. Other signs suggesting possible liver dysfunction include the following symptoms:

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

Contact your doctor immediately if you experience any of these symptoms during treatment.
Yuvanci may cause anemia (low red blood cell count). If you develop any of the following symptoms, which could indicate anemia, inform your doctor:

• dizziness
• fatigue
• general feeling of being unwell
• weakness
• rapid heartbeat
• palpitations (a strong heartbeat that may be fast or irregular)
• paleness

Before taking the tablets, inform your doctor if you have

• any cardiovascular condition (affecting the heart and blood vessels) other than pulmonary arterial hypertension, including:
  o aortic and mitral valve disease (problems with heart valves that may affect blood flow)
  o constrictive pericarditis (a condition in which the pericardium, the sac around the heart, becomes narrowed, impairing the heart’s ability to function properly)
  o restrictive or congestive cardiomyopathy (a condition in which the heart muscle becomes stiff or weak, leading to problems pumping blood effectively)
  o left ventricular dysfunction (a condition in which the left side of the heart has difficulty pumping blood efficiently to the rest of the body)
  o arrhythmias (abnormal heart rhythms)
  o coronary artery disease (heart disease caused by narrowing or blockage of blood vessels supplying the heart muscle)
  o uncontrolled hypertension (high blood pressure that is not adequately controlled).

• blood pressure problems such as significant drops in blood pressure when standing up or if your blood pressure is consistently below normal.

• any inherited disease causing damage to the retina (the light-sensitive membrane at the back of the eye).

• severe liver problems.

• severe kidney problems.

If you have kidney problems, consult your doctor before using Yuvanci. There may be an increased risk of low blood pressure and anemia during treatment with Yuvanci.
In patients with pulmonary veno-occlusive disease (blockage of the pulmonary veins), the use of medications for the treatment of PAH, including Yuvanci, may lead to pulmonary edema (fluid accumulation in the lungs). Contact your doctor immediately if you experience signs of pulmonary edema while taking Yuvanci, such as:

• sudden and marked worsening of breathing difficulty
• cough
• fatigue after exertion
• difficulty breathing while lying down.

Before taking Yuvanci, inform your doctor if you have any penile deformity such as:

• angulation, a condition in which the penis curves, likely due to cavernosal fibrosis (scarring of penile tissue).
• Peyronie’s disease, a condition affecting adult men in which a palpable “plaque” of scar tissue develops, accompanied by penile curvature.
• a condition that may predispose you to priapism (a prolonged and painful erection that may occur without sexual stimulation), such as a red blood cell abnormality (sickle cell anemia), bone marrow tumor (multiple myeloma), or blood cell cancer (leukemia).

If you experience an erection lasting 4 hours or longer while taking Yuvanci, seek immediate medical help.
Visual disturbances and sudden vision loss have occurred during treatment with tadalafil and other PDE5 inhibitors. If you experience sudden reduction or loss of vision, or if your vision becomes distorted or blurred during treatment, stop taking Yuvanci and contact your doctor immediately.
Sudden decrease or loss of hearing has been observed in some patients taking tadalafil. Although it is not known whether this is directly related to tadalafil, contact your doctor immediately if you experience sudden hearing decrease or loss.
Children and adolescents
Do not give this medicine to children and adolescents under 18 years of age, as Yuvanci has not been tested in this population.
Other medicines and Yuvanci
Inform 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, or amyl nitrate (used for chest pain)

Consult your doctor or pharmacist if you are taking any of the following medicines, including:
Medicines that may reduce the effectiveness of Yuvanci by decreasing its blood levels, such as:

• St. John’s wort (Hypericum perforatum) (a herbal preparation used to treat depression)
• phenytoin or carbamazepine (medicines used to treat seizures)
• rifampicin (an antibiotic used to treat infections)

Medicines that may increase the risk of Yuvanci side effects, such as:

• 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 shampoo), fluconazole, itraconazole, miconazole, voriconazole (medicines used to treat fungal infections)
• amiodarone (used to control heart rhythm)
• cyclosporine (used to prevent organ rejection after transplants), diltiazem, verapamil (used to treat high blood pressure or specific heart conditions)
• prostacyclin and similar medicines such as epoprostenol and iloprost (used to treat PAH, lung scarring, and blocked arteries)

Yuvanci with food and alcohol
If you are taking piperine as a dietary supplement, it may alter how your body responds to certain medicines, including Yuvanci. If so, inform your doctor or pharmacist.
Alcohol consumption may temporarily lower blood pressure. If you have taken or plan to take Yuvanci, avoid drinking excessive amounts (more than 5 units of alcohol), as this may increase the risk of dizziness upon standing.
Pregnancy and breastfeeding
If you are pregnant, breastfeeding, suspect you may be pregnant, or are planning a pregnancy, consult your doctor before taking this medicine.
Yuvanci must not be taken during pregnancy as it may harm the unborn baby. See section 2 “Do not take Yuvanci”.

• If you could become pregnant, use an effective method of contraception (birth control) while taking Yuvanci. Discuss contraception with your doctor.
• Do not take Yuvanci if you are pregnant or planning a pregnancy.
• If you become pregnant or suspect you are pregnant while taking Yuvanci or shortly after stopping Yuvanci (within 1 month), contact your doctor immediately.

If you are a woman of childbearing age, your doctor will request a pregnancy test before starting Yuvanci and regularly (once a month) while taking Yuvanci.
It is not known whether Yuvanci passes into breast milk. Do not breastfeed while taking Yuvanci. Talk to your doctor if you are planning to breastfeed. See section 2 “Do not take Yuvanci”.
Fertility
Yuvanci may cause a reduction in sperm count in men. Talk to your doctor if you are planning to have children.
Driving and using machines
Yuvanci may cause side effects such as headache and low blood pressure (listed in section 4), and symptoms of pulmonary arterial hypertension may also affect your ability to drive. Carefully monitor how you react to Yuvanci before driving or operating machinery.
Yuvanci contains lactose monohydrate and sodium

• Yuvanci contains lactose monohydrate. If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
• This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., it is essentially ‘sodium-free’.

3. How to take Yuvanci

Take this medicine exactly as your doctor has told you. If you have any doubts, consult your doctor or pharmacist.
The recommended dose of Yuvanci is one 10 mg/40 mg tablet once daily. In some situations, your doctor may decide to start with a lower dose of one 10 mg/20 mg tablet once daily. This allows your body to adjust to the new medicine. If tolerated, your doctor will then increase the dose to one 10 mg/40 mg tablet once daily.
Swallow the tablet whole with a glass of water. Do not chew or break the tablet. You may 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 listed 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 taking the tablets at your usual time. Do not take a double dose to make up for the missed tablet.
If you stop taking Yuvanci
Yuvanci is a treatment that you need to continue taking to control PAH. Do not stop taking Yuvanci unless your doctor has advised you to do so.
If you have any questions about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
The side effects listed below have been observed with Yuvanci or have previously been reported with the active substances (macitentan or tadalafil) in Yuvanci and may therefore also occur with Yuvanci.
If you experience any of the following side effects, stop taking the medicine and seek immediate medical help:

• Severe allergic reactions (may affect up to 1 in 10 people).
  o Symptoms include swelling around the eyes, face, lips, tongue or throat, which can be life-threatening if throat swelling blocks the airways. If you experience any of these symptoms while being treated with Yuvanci, seek immediate medical help.
• Chest pain (may affect up to 1 in 10 people).
  o If you experience chest pain while being treated with Yuvanci, seek immediate medical help. Do not use nitrates to treat these symptoms.
• Priapism, a prolonged and potentially painful erection that may occur without sexual stimulation (may affect up to 1 in 100 people).
  o If you experience an erection lasting more than 4 hours while being treated with Yuvanci, seek immediate medical help.
• Sudden loss of vision, distorted central vision, blurred vision, hazy vision, or sudden reduction in vision (frequency of these side effects is not known).
  o If you experience any of these side effects while being treated with Yuvanci, seek immediate medical help.

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

• Swelling/fluid retention (edema), especially in the ankles and feet
• Headache
• Anaemia (low red blood cell count) or reduced haemoglobin (the protein in red blood cells that carries oxygen in the body)
• Nausea (feeling unwell)
• Dyspepsia (indigestion)
• Abdominal pain (stomach ache)
• Abdominal discomfort
• Nasopharyngitis (inflammation of the nose and throat)
• Bronchitis (inflammation of the airways)
• Myalgia (muscle pain)
• Back pain
• Pain in arms and legs
• Flushing (redness of the skin)

Common (may affect up to 1 in 10 people)

• Vomiting (feeling unwell)
• Gastroesophageal reflux disease (acid reflux)
• Syncope (fainting)
• Migraine
• Influenza
• Urinary tract infection (infection in parts of the body that collect and expel urine)
• Respiratory tract infection (infection of the respiratory system, chest infection, or infection of the nose, sinuses or throat, cold)
• Pharyngitis (inflammation of the throat)
• Epistaxis (nosebleed)
• Palpitations (strong heartbeat that may be rapid or irregular)
• Tachycardia (fast heartbeat)
• Increased liver enzyme levels, as shown in blood tests
• Leucopenia (low white blood cell count)
• Thrombocytopenia (low blood platelet count; platelets are components that help blood to clot)
• Hypotension (low blood pressure)
• Blurred vision
• Increased uterine bleeding
• Rash
• Hypersensitivity (allergic reactions), including itching

Uncommon (may affect up to 1 in 100 people)

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

Not known (cannot be estimated from available data)

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

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 listed in Annex 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.".
The expiry date refers to the last day of that month.
Store in the original packaging to protect the medicine from moisture.
This medicine does not require any special storage temperature.
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 Yuvanci contains
The active substances are macitentan and tadalafil.
Each 10 mg/20 mg film-coated tablet contains 10 mg of macitentan and 20 mg of tadalafil.
Each 10 mg/40 mg film-coated tablet contains 10 mg of macitentan and 40 mg of tadalafil.

The other components are:
Tablet core
Hydroxypropyl cellulose
Low-substituted hydroxypropyl cellulose (E463a)
Lactose monohydrate (see section 2, Yuvanci contains 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 coating
Hypromellose
Lactose monohydrate
Titanium dioxide (E171)
Triacetin (E1518)
Talc (E553b)

Yuvanci 10 mg/20 mg film-coated tablets also contain red iron oxide (E172) and yellow iron oxide (E172).

Description of the appearance of Yuvanci and contents of the pack
Yuvanci 10 mg/20 mg film-coated tablets are pink, oblong tablets, marked with “MT” on one side and “1020” on the other. Yuvanci 10 mg/20 mg is available in unit dose blisters of 30 film-coated tablets, perforated aluminium blisters with integrated desiccant.

Yuvanci 10 mg/40 mg film-coated tablets are white to almost white, oblong tablets, marked with “MT” on one side and “1040” on the other. Yuvanci 10 mg/40 mg is available in unit dose blisters of 30 film-coated tablets, perforated aluminium blisters with integrated desiccant.

Marketing Authorization Holder
Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

Manufacturer
Janssen Pharmaceutica NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien
Janssen-Cilag NV
Tel/Tél: +32 14 64 94 11
[email protected]

Lietuva
UAB “JOHNSON & JOHNSON”
Tel: +370 5 278 68 88
[email protected]

България
„Джонсън & Джонсън България” ЕООД
Тел.: +359 2 489 94 00
[email protected]

Luxembourg/Luxemburg
Janssen-Cilag NV
Tél/Tel: +32 14 64 94 11
[email protected]

Česká republika
Janssen-Cilag s.r.o.
Tel: +420 227 012 227
[email protected]

Magyarország
Janssen-Cilag Kft.
Tel.: +36 1 884 2858
[email protected]

Danmark
Janssen-Cilag A/S
Tlf.: +45 4594 8282
[email protected]

Malta
AM MANGION LTD
Tel: +356 2397 6000

Deutschland
Janssen-Cilag GmbH
Tel: 0800 086 9247 / +49 2137 955 6955
[email protected]

Nederland
Janssen-Cilag B.V.
Tel: +31 76 711 1111
[email protected]

Eesti
UAB “JOHNSON & JOHNSON” Eesti filiaal
Tel: +372 617 7410
[email protected]

Norge
Janssen-Cilag AS
Tlf: +47 24 12 65 00
[email protected]

Ελλάδα
Janssen-Cilag Φαρμακευτική Μονοπρόσωπη Α.Ε.Β.Ε.
Tηλ: +30 210 80 90 000

Österreich
Janssen-Cilag Pharma GmbH
Tel: +43 1 610 300

España
Janssen-Cilag, S.A.
Tel: +34 91 722 81 00
[email protected]

Polska
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]

Portugal
Janssen-Cilag Farmacêutica, Lda.
Tel: +351 214 368 600

Hrvatska
Johnson & Johnson S.E. d.o.o.
Tel: +385 1 6610 700
[email protected]

România
Johnson & Johnson România SRL
Tel: +40 21 207 1800

Ireland
Janssen Sciences Ireland UC
Tel: 1 800 709 122
[email protected]

Slovenija
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]

Slovenská republika
Johnson & Johnson, s.r.o.
Tel: +421 232 408 400

Italia
Janssen-Cilag SpA
Tel: 800.688.777 / +39 02 2510 1
[email protected]

Suomi/Finland
Janssen-Cilag Oy
Puh/Tel: +358 207 531 300
[email protected]

Κύπρος
Βαρνάβας Χατζηπαναγής Λτδ
Τηλ: +357 22 207 700

Sverige
Janssen-Cilag AB
Tel: +46 8 626 50 00
[email protected]

Latvija
UAB “JOHNSON & JOHNSON” filiāle Latvijā
Tel: +371 678 93561
[email protected]

United Kingdom (Northern Ireland)
Janssen Sciences Ireland UC
Tel: +44 1 494 567 444
[email protected]

More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu.