Uptravi 200 mcg film-coated tablets: detailed information

Patient Information Leaflet

Introduction

Package Leaflet: Information for the Patient

Uptravi 200 micrograms film-coated tablets
Uptravi 400 micrograms film-coated tablets
Uptravi 600 micrograms film-coated tablets
Uptravi 800 micrograms film-coated tablets
Uptravi 1,000 micrograms film-coated tablets
Uptravi 1,200 micrograms film-coated tablets
Uptravi 1,400 micrograms film-coated tablets
Uptravi 1,600 micrograms film-coated tablets

selexipag

This medicine is subject to additional monitoring, which will allow for faster detection of new safety information. You can help by reporting any side effects you may experience. Information on how to report side effects is provided at the end of section 4.

Read all of this leaflet carefully before taking this medicine, as 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 nurse.
This medicine has been prescribed for you only and must not be given to others, even if they have the same symptoms as you, as it may harm them.
If you experience any side effects, consult your doctor or nurse, even if they are side effects not listed in this leaflet (see section 4).

Contents of the leaflet

What Uptravi is and what it is used for
What you need to know before taking Uptravi
How to take Uptravi
Possible side effects
How to store Uptravi
Contents of the pack and other information

1. What Uptravi is and what it is used for

Uptravi is a medicine that contains the active substance selexipag. It acts on blood vessels in a similar way to the natural substance prostacyclin, causing them to relax and widen.

Uptravi is used for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients who are inadequately controlled with other types of PAH medications known as endothelin receptor antagonists and phosphodiesterase type 5 inhibitors. Uptravi may be used alone if the patient is not a candidate for these medications.

PAH is a disease characterized by 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 are narrower, so the heart must work harder to pump blood through them. This can cause fatigue, dizziness, shortness of breath, or other symptoms.

Like prostacyclin, Uptravi widens the pulmonary arteries and reduces their stiffening. This makes it easier for the heart to pump blood through the pulmonary arteries. It relieves the symptoms of PAH and improves the course of the disease.

2. What you need to know before taking Uptravi

Do not take Uptravi

if you are allergic to selexipag or to any of the other ingredients of this medicine (listed in section 6).
if you have any heart disorders, such as:
reduced blood flow to the heart muscles (severe ischemic heart disease or unstable angina); symptoms may include chest pain
myocardial infarction within the last 6 months
heart weakness (decompensated heart failure) without strict medical supervision
severe irregular heartbeat
heart valve defect (congenital or acquired) causing the heart to function with difficulty (unrelated to pulmonary hypertension)
if you have had a stroke within the last 3 months, or any other event involving reduced blood flow to the brain (e.g., transient ischemic attack)
if you are taking gemfibrozil (a medicine used to lower fat [lipid] levels in the blood)

Warnings and precautions

Talk to your doctor or nurse before starting Uptravi if you

are taking medicines for high blood pressure (hypertension)
have low blood pressure associated with symptoms such as dizziness
have recently experienced significant blood loss or fluid loss, such as from severe diarrhea or vomiting
have thyroid gland problems
have severe kidney problems or are undergoing dialysis
have or have had severe liver function problems

If you experience any of the above signs or if your condition changes, inform your doctor immediately.

Children and adolescents

Do not give this medicine to children under 18 years of age, as Uptravi has not been evaluated in children.

Elderly patients

Limited experience is available with Uptravi in patients over 75 years of age. Uptravi should be used with caution in patients in this age group.

Other medicines and Uptravi

Tell your doctor if you are taking, have recently taken, or might take any other medicines.

Taking other medicines may affect how Uptravi works.

Inform your doctor or specialist HPA nurse if you are taking any of the following medicines:

Gemfibrozil (a medicine used to reduce fat [lipid] levels in the blood)
Clopidogrel (a medicine used to prevent blood clots [thrombi] in coronary artery disease)
Deferasirox (a medicine used to remove excess iron from the body)
Teriflunomide (a medicine used to treat relapsing-remitting multiple sclerosis)
Carbamazepine (a medicine used to treat certain types of epilepsy, neuralgia, or to help control severe behavioral disorders when other medicines are ineffective)
Phenytoin (a medicine used to treat epilepsy)
Valproic acid (a medicine used to treat epilepsy)
Probenecid (a medicine used to treat gout)
Fluconazole, rifampicin, or rifapentine (antibiotics used to treat infections)

Pregnancy and breastfeeding

The use of Uptravi is not recommended during pregnancy and breastfeeding. If you are a woman who can become pregnant, you should use a reliable method of contraception while taking Uptravi. If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before taking this medicine.

Driving and use of machines

Uptravi may cause adverse effects such as headache and decreased blood pressure (see section 4), which may affect your ability to drive; your disease symptoms may also reduce your ability to drive.

3. How to take Uptravi

Treatment with Uptravi must be initiated and supervised by a physician experienced in the management of pulmonary arterial hypertension (PAH). Always follow your doctor's instructions on how to take this medicine. If you are unsure, consult your doctor again.

Inform your doctor if you experience any adverse effects, as they may recommend adjusting your Uptravi dose.

Inform your doctor if you are taking other medications, as they may recommend that you take Uptravi only once daily.

If you have poor vision or experience any type of blindness, ask someone else to help you take Uptravi during the dose-adjustment period.

Finding the right dose for you

At the beginning of treatment, you will start with the lowest dose: one 200 microgram tablet in the morning and one 200 microgram tablet at night. Treatment should be started in the evening. Your doctor will instruct you to gradually increase the dose. This is called dose titration and allows your body to adapt to the new medicine. The goal of dose titration is to reach the most appropriate dose for you—the highest dose you can tolerate, potentially reaching the maximum dose of 1,600 micrograms in the morning and 1,600 micrograms at night.

The first pack of tablets you receive will contain light yellow tablets of 200 micrograms.

Your doctor will instruct you to increase the dose in stages, usually every week, although the interval between increases may be longer.

At each stage, you will add one 200 microgram tablet to your morning dose and one 200 microgram tablet to your evening dose. The first dose at the increased level should be taken in the evening. The diagram below shows the number of tablets you should take each morning and each night during the first 4 stages.

Graphical schedule of a four-phase dosing regimen with increasing doses of 200 microgram tablets taken in the morning and at night

If your doctor instructs you to continue increasing the dose to stage 5, you can do so by taking one green 800 microgram tablet and one light yellow 200 microgram tablet in the morning, and one 800 microgram tablet and one 200 microgram tablet at night.

If your doctor tells you to keep increasing the dose, you will add one 200 microgram tablet to the morning dose and one 200 microgram tablet to the evening dose at each new stage. The first dose at the increased level should be taken in the evening. The maximum dose of Uptravi is 1,600 micrograms in the morning and 1,600 micrograms at night. However, not all patients will reach this dose, as individual dose requirements vary.

The diagram below shows the number of tablets you should take each morning and each night at each stage, starting from stage 5.

Graphical representation of a pharmacological dosing regimen divided into four phases, with instructions for 200 and 800 microgram tablets in the morning and at night

The dose-titration pack also contains a guide providing information on the dose-titration process and allowing you to record the number of tablets you take daily.

Remember to record the number of tablets you take each day in your dose-titration diary. Titration stages usually last about 1 week. If your doctor instructs you to extend each titration stage beyond 1 week, additional pages in the diary allow you to do so. Remember to communicate regularly with your PAH specialist doctor or nurse during the dose-titration phase.

Dose reduction due to adverse effects

During dose titration, you may experience adverse effects such as headache, diarrhea, feeling unwell (nausea), discomfort (vomiting), jaw pain, muscle pain, lower limb pain, joint pain, or facial flushing (see section 4). If these adverse effects are difficult to tolerate, consult your doctor on how to manage or treat them. Treatments are available to help relieve these adverse effects. For example, analgesics such as paracetamol may help relieve pain and headache.

If adverse effects cannot be managed, or do not gradually improve at your current dose, your doctor may adjust the dose by reducing the number of light yellow 200 microgram tablets, removing one tablet in the morning and one at night. The following scheme shows how to reduce the dose. This should only be done if instructed by your doctor.

Dosing chart showing phases INICIO, AUMENTAR, and DISMINUIR, illustrating the

If the adverse effects you experience become manageable after dose reduction, your doctor may decide that you should maintain this dose. For further information, see the Maintenance Dose section below.

Maintenance dose

The highest dose you can tolerate during the dose-titration phase will become your maintenance dose. Your maintenance dose is the dose you should continue taking regularly.

Your doctor will prescribe a single tablet with the strength appropriate for your maintenance dose. This allows you to take one tablet in the morning and one at night, instead of multiple tablets each time.

For a complete description of Uptravi tablets, including colors and imprints, see section 6 of this leaflet.

Over time, your doctor may adjust your maintenance dose if necessary.

If at any time, after taking the same dose for a long period, you experience adverse effects that you cannot tolerate or that interfere with daily activities, contact your doctor, as you may require a dose reduction. In such cases, your doctor may prescribe a single tablet with a lower concentration. Remember to dispose of unused tablets (see section 5).

Take Uptravi once in the morning and once at night, approximately 12 hours apart.

Take the tablets with food, as this may help improve your tolerance to the medicine. Swallow the tablets whole with a glass of water.

If you take more Uptravi than you should

If you take more tablets than prescribed, contact your doctor immediately.

If you forget to take Uptravi

If you forget to take Uptravi, take a dose as soon as you remember, and then continue taking your tablets at the usual times. However, if it is almost time for your next dose (within 6 hours of your usual dosing time), skip the missed dose and continue with your regular schedule. Do not take a double dose to make up for a missed dose.

If you stop taking Uptravi

Stopping Uptravi treatment abruptly may cause your symptoms to worsen. Do not stop taking Uptravi unless your doctor tells you to. Your doctor may advise you to gradually reduce the dose before stopping treatment completely.

If, for any reason, you stop taking Uptravi for more than 3 consecutive days (if you have missed 3 morning and 3 evening doses, or 6 consecutive doses or more), contact your doctor immediately, as you may need to have your dose adjusted to avoid adverse effects. Your doctor may decide to restart treatment at a lower dose and gradually increase it to your previous maintenance dose.

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

4. Possible adverse effects

Like all medicines, Uptravi can cause adverse effects. You may experience adverse effects not only during the dose-titration phase, when your dose is being increased, but also later on, after taking the same dose for a long period.

If you experience any of the following adverse effects: headache, diarrhoea, feeling unwell (nausea), discomfort (vomiting), jaw pain, muscle pain, lower limb pain, joint pain or facial flushing, that you cannot tolerate or that cannot be managed, you should contact your doctor, as the dose you are taking may be too high for you and may require reduction.

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

Headache
Flushing (facial redness)
Nausea and vomiting
Diarrhoea
Jaw pain, muscle pain, joint pain, lower limb pain
Nasopharyngitis (nasal congestion)

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

Anaemia (low red blood cell count)
Hyperthyroidism (overactive thyroid gland)
Decreased appetite
Weight loss
Hypotension (low blood pressure)
Stomach pain
Pain
Changes in certain laboratory test results, including those measuring blood cell levels and thyroid function
Skin rashes, including urticaria, which may cause burning or stinging sensations and skin redness

Uncommon adverse effects (may affect up to 1 in 100 people)

Increased heart rate

Reporting of adverse effects

If you experience any adverse effects, talk to your doctor, even if they are possible adverse effects not listed in this leaflet. You may 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. Storage of Uptravi

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

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

This medicine does not require any special storage conditions.

No special disposal precautions are required.

6. Contents of the pack and other information

Composition of Uptravi

The active substance is selexipag.

Uptravi 200 micrograms film-coated tablets contains 200 micrograms of selexipag

Uptravi 400 micrograms film-coated tablets contains 400 micrograms of selexipag

Uptravi 600 micrograms film-coated tablets contains 600 micrograms of selexipag

Uptravi 800 micrograms film-coated tablets contains 800 micrograms of selexipag

Uptravi 1,000 micrograms film-coated tablets contains 1,000 micrograms of selexipag

Uptravi 1,200 micrograms film-coated tablets contains 1,200 micrograms of selexipag

Uptravi 1,400 micrograms film-coated tablets contains 1,400 micrograms of selexipag

Uptravi 1,600 micrograms film-coated tablets contains 1,600 micrograms of selexipag

The other components are:

In the tablet core:

Mannitol (E421), maize starch, low-substituted hydroxypropyl cellulose, hydroxypropyl cellulose and magnesium stearate.

In the film coating:

Hypromellose, propylene glycol, titanium dioxide (E171), carnauba wax and iron oxides (see below).

Uptravi 200 micrograms film-coated tablets contains yellow iron oxide (E172).

Uptravi 400 micrograms film-coated tablets contains red iron oxide (E172).

Uptravi 600 micrograms film-coated tablets contains red iron oxide and black iron oxide (E172).

Uptravi 800 micrograms film-coated tablets contains yellow iron oxide and black iron oxide (E172).

Uptravi 1,000 micrograms film-coated tablets contains red iron oxide and yellow iron oxide (E172).

Uptravi 1,200 micrograms film-coated tablets contains black iron oxide and red iron oxide (E172).

Uptravi 1,400 micrograms film-coated tablets contains yellow iron oxide (E172).

Uptravi 1,600 micrograms film-coated tablets contains black iron oxide, red iron oxide and yellow iron oxide (E172).

Appearance of Uptravi and contents of the pack

Uptravi 200 micrograms film-coated tablets: Round, light yellow film-coated tablets marked with a "2" on one side.

Uptravi 400 micrograms film-coated tablets: Round, red film-coated tablets marked with a "4" on one side.

Uptravi 600 micrograms film-coated tablets: Round, light violet film-coated tablets marked with a "6" on one side.

Uptravi 800 micrograms film-coated tablets: Round, green film-coated tablets marked with a "8" on one side.

Uptravi 1,000 micrograms film-coated tablets: Round, orange film-coated tablets marked with a "10" on one side.

Uptravi 1,200 micrograms film-coated tablets: Round, dark violet film-coated tablets marked with a "12" on one side.

Uptravi 1,400 micrograms film-coated tablets: Round, dark yellow film-coated tablets marked with a "14" on one side.

Uptravi 1,600 micrograms film-coated tablets: Round, brown film-coated tablets marked with a "16" on one side.

Uptravi 200 micrograms film-coated tablets are supplied in blister packs containing 10 or 60 tablets and 60 or 140 tablets (dose titration packs).

Uptravi 400 micrograms, 600 micrograms, 800 micrograms, 1,000 micrograms, 1,200 micrograms, 1,400 micrograms and 1,600 micrograms film-coated tablets are supplied in blister packs containing 60 tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Manufacturer responsible

Actelion Manufacturing GmbH

Emil-Barell-Strasse 7

79639 Grenzach-Wyhlen

Germany

Actelion Pharmaceuticals Belgium NV

Bedrijvenlaan 1

2800 Mechelen

Belgium

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

Belgium/Belgium/Belgium