Yuvanci 10 mg/20 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Yuvanci 10 mg/20 mg film-coated tablets

Yuvanci 10 mg/40 mg film-coated tablets

macitentan/tadalafil

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet as 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 and must not be given to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. 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 World Health Organization (WHO) Class II or Class III pulmonary arterial hypertension (PAH). 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 (pulmonary arteries). In people with PAH, these arteries become narrowed, causing the heart to work harder to pump blood through them. As a result, affected patients feel tired and dizzy and have difficulty breathing. The WHO class reflects the severity of the disease: patients with WHO Class II PAH have slight limitation in physical activity, while those with Class III have marked limitation in physical activity.

Yuvanci widens the pulmonary arteries, making it easier for the heart to pump blood through them. This reduces blood pressure, relieves symptoms, increases the ability to perform physical activity, and improves the course of the disease.

2. What you need to 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).
• you have had a heart attack within the last 90 days.
• you are pregnant or could become pregnant because you are not using a reliable method of contraception. See section 2 "Pregnancy and breastfeeding".
• you are breastfeeding. See section 2 "Pregnancy and breastfeeding".
• 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.
• you have very low blood pressure (90/50 mm Hg).
• you are taking nitrates or riociguat. See section 2 "Other medicines and Yuvanci".
• you have ever had non-arteritic anterior ischemic optic neuropathy (NAION), a condition also described as "eye stroke", or vision loss due to reduced blood flow to the eye.

If any of the above apply to you, please inform your doctor.

Warnings and precautions

You will need blood tests before starting and during treatment with Yuvanci, as directed by your doctor:

If you are a woman of childbearing potential, your doctor will require you to take a pregnancy test before starting Yuvanci and periodically (once a month) during treatment. See section 2 "Pregnancy and breastfeeding".

Your doctor will take blood samples to check:

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

Yuvanci may cause increases in liver enzymes (proteins), which could indicate that your liver is not working properly. Other signs that your liver may not be functioning properly 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 exhaustion (lethargy or fatigue)
• flu-like symptoms (joint or muscle pain with fever)

If you experience any of these symptoms during treatment with Yuvanci, contact your doctor immediately.

Yuvanci may cause anemia (low levels of red blood cells). If you experience any of the following symptoms, which may indicate anemia, inform your doctor:

• dizziness
• fatigue
• general malaise
• weakness
• rapid heartbeat
• palpitations (a strong heartbeat that may be fast or irregular)
• paleness

Consult your doctor before starting the tablets if:

• you have any cardiovascular disease (related to the heart and blood vessels) other than pulmonary hypertension, including:

• aortic and mitral valve disease (problems with heart valves that may affect blood flow)

• constrictive pericarditis (a condition in which the sac surrounding the heart—the pericardium—becomes stiff, affecting the heart's ability to function properly)

• restrictive or congestive cardiomyopathy (a disease in which the heart muscle becomes stiff or weak, causing problems pumping blood effectively)

• left ventricular dysfunction (a condition in which the left side of the heart has difficulty effectively pumping blood to the rest of the body)

• arrhythmias (abnormal heart rhythm)

• coronary artery disease (heart disease caused by narrowing or blockage of blood vessels supplying the heart muscle)

• uncontrolled high blood pressure (hypertension that is not adequately controlled)

• you have blood pressure problems, such as significant drops in blood pressure when standing up or chronically low blood pressure

• you have any inherited disease causing damage to the retina (the light-sensitive layer at the back of the eye)

• you have severe liver disease

• you have severe kidney disease

If you have kidney problems, talk to your doctor before using Yuvanci. During treatment with Yuvanci, there may be an increased risk of low blood pressure and anemia.

The use of medications for the treatment of pulmonary arterial hypertension (PAH), including Yuvanci, in patients with pulmonary veno-occlusive disease (obstruction of the pulmonary veins) may lead to pulmonary edema (fluid accumulation in the lungs). Contact your doctor immediately if you experience signs of pulmonary edema during treatment with Yuvanci, such as:

• sudden and significant shortness of breath
• cough
• fatigue after exertion
• difficulty breathing while lying flat

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

• angulation, a condition in which the penis curves, possibly due to cavernous fibrosis (scarring of certain penile tissues).
• Peyronie's disease, a condition affecting adult males 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 disorder (sickle cell anemia), bone marrow cancer (multiple myeloma), or blood cell cancer (leukemia).

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

Visual disturbances and sudden vision loss have occurred with the use of tadalafil and other PDE5 inhibitors. If you experience sudden reduction or loss of vision, or if your vision becomes distorted or dimmed during treatment, stop taking Yuvanci and contact your doctor immediately.

Sudden decrease or loss of hearing has been reported in some patients treated with tadalafil. Although it is not known whether this event is directly related to tadalafil, if you experience sudden decrease or loss of hearing, contact your doctor immediately.

Children and adolescents

Do not give this medicine to children and adolescents under 18 years of age, as Yuvanci has not been studied in children.

Other medicines and Yuvanci

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to 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)

Inform your doctor or pharmacist if you are taking any of the following medicines:

Medicines that may reduce the effectiveness of Yuvanci by decreasing the amount of Yuvanci in the blood, including:

• St. John's wort (a herbal medicine used to treat depression)
• phenytoin or carbamazepine (medicines used to treat epilepsy)
• rifampicin (an antibiotic used to treat infections)

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

• clarithromycin, telithromycin, ciprofloxacin, erythromycin (antibiotics used to treat infections)
• ritonavir, saquinavir (used to treat HIV infection)
• 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 transplant rejection)
• diltiazem, verapamil (used to treat high blood pressure or specific heart conditions)
• prostacyclin-like medicines such as epoprostenol and iloprost (used to treat PAH, pulmonary fibrosis, and arterial blockages)

Yuvanci with food and alcohol

If you are taking piperine as a dietary supplement, this may alter how your body responds to certain medicines such as Yuvanci. Speak with your doctor or pharmacist if this applies.

Drinking alcohol may temporarily lower blood pressure. If you have taken or plan to take Yuvanci, avoid excessive alcohol consumption (more than 5 units of alcohol), as this may increase the risk of dizziness upon standing.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using 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 a reliable method of contraception (birth control) while taking Yuvanci. Discuss contraception with your doctor.
• Do not take Yuvanci if you are pregnant or plan to become pregnant.
• If you become pregnant or think you may have become pregnant during or shortly after stopping Yuvanci (within 1 month), contact your doctor immediately.

If you are a woman of childbearing potential, your doctor will require you to take a pregnancy test before starting Yuvanci and periodically (once a month) during treatment.

It is unknown whether Yuvanci passes into breast milk. Do not breastfeed during treatment with Yuvanci. Speak with your doctor if you plan 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 plan to have children.

Driving and using machines

Yuvanci may cause side effects such as headaches and low blood pressure (listed in section 4), and symptoms of pulmonary arterial hypertension may also affect your ability to drive. Carefully assess how you react to Yuvanci before driving or operating machinery.

Yuvanci contains lactose monohydrate and sodium

• Yuvanci contains lactose monohydrate. If your doctor has informed you of an intolerance to certain sugars, consult him before taking this medicine.
• This medicine contains less than 1 mmol of sodium (23 mg) per tablet; essentially "sodium-free".

3. How to take Yuvanci

Follow exactly the instructions given by your doctor for administering this medicine. If you are unsure, 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 10 mg/20 mg once daily; this allows your body to adapt to the new medicine. If you tolerate it, 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

Inform your doctor or pharmacist immediately. You may experience any of the adverse 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, and then continue taking the tablets at your usual times. Do not take a double dose to make up for forgotten doses.

If you stop taking Yuvanci

Yuvanci is a treatment you should continue taking for the control of PAH. Do not stop taking Yuvanci unless agreed with your doctor.

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

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone will experience them.

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

If you experience any of the following adverse effects, stop using the medicine and seek immediate medical help:

• Severe allergic reactions (may affect up to 1 in 10 people).

• Symptoms include swelling around the eyes, face, lips, tongue, or throat, which can be potentially life-threatening if throat swelling blocks the airways. If you experience any of these symptoms during treatment with Yuvanci, seek immediate medical help.

• Chest pain (may affect up to 1 in 10 people).

• If you experience any of these symptoms during treatment with Yuvanci, seek immediate medical help. Do not use nitrates to treat your symptoms.

• Priapism, a prolonged and possibly painful erection that may occur without sexual stimulation (may affect up to 1 in 100 people).

• If during treatment with Yuvanci you experience an erection lasting 4 hours or longer, seek immediate medical help.

• Sudden loss of vision, distorted, dimmed, or blurred central vision, or sudden decrease in vision. (The frequency of these side effects is unknown.)

• If you experience these side effects during treatment with Yuvanci, seek immediate medical help.

Other adverse effects

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

• Edema/fluid retention (swelling), especially in ankles and feet
• Headache
• Anaemia (low red blood cell count) or reduced haemoglobin (the protein in red blood cells that carries oxygen throughout 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 of the parts of the body that collect and pass urine)
• Respiratory tract infection (infection of the respiratory system, chest, nose, sinuses, or throat, a cold)
• Pharyngitis (inflammation of the throat)
• Epistaxis (nosebleed)
• Palpitations (a strong heartbeat that may be fast or irregular)
• Increased liver enzyme levels, as shown in blood tests
• Leucopenia (low white blood cell count in the blood)
• Thrombocytopenia (low platelet count in the blood, components that help blood clotting)
• Hypotension (low blood pressure)
• Blurred vision (hazy vision)
• Increased uterine bleeding (related to the womb)
• Rash
• Hypersensitivity (allergic reactions), including itching

Uncommon (may affect up to 1 in 100 people)

• Epileptic seizures
• Transient amnesia (temporary memory loss)
• Sudden cardiac death (the heart stops beating unexpectedly, leading to loss of consciousness and death)
• Urticaria (hives)
• Hyperhidrosis (excessive sweating)
• Penile haemorrhage (bleeding from the penis)
• Haematospermia (blood in semen and/or urine)
• Tinnitus (ringing in the ears)
• Haematuria (blood in urine)

Frequency not known (cannot be estimated from the 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 blistering and peeling rash, especially around the mouth, nose, eyes, and genitals)
• Exfoliative dermatitis (skin peeling or shedding)
• Retinal vascular occlusion (blood clot in the blood vessels of the eye, which may cause blurred vision or blindness)
• Visual field defect
• Sudden hearing loss

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Yuvanci Storage

Keep this medicine out of sight and reach of children.

Do not use Yuvanci after the expiry date stated on the carton and blister pack after "EXP". The expiry date refers to the last day of the month indicated.

Store in the original packaging to protect from moisture.

This medicine does not require any special storage temperature conditions.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Yuvanci

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 iron oxide red (E172) and iron oxide yellow (E172).

Appearance of the product and contents of the pack

Yuvanci 10 mg/20 mg film-coated tablets are pink, oblong tablets, with the imprint "MT" on one side and "1020" on the other. Yuvanci 10 mg/20 mg is supplied as 30 × 1 film-coated tablets in single-dose aluminum blisters with integrated desiccant.

Yuvanci 10 mg/40 mg film-coated tablets are white to almost white, oblong tablets, with the imprint "MT" on one side and "1040" on the other. Yuvanci 10 mg/40 mg is supplied as 30 × 1 film-coated tablets in single-dose aluminum 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 about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet:

Detailed information on this medicine is available on the website of the European Medicines Agency: https://www.ema.euopa.eu