Uptravi

Patient Information Leaflet

Uptravi 200 microgram tablets, 400 microgram tablets, 600 microgram tablets, 800 microgram tablets, 1,000 microgram tablets, 1,200 microgram tablets, 1,400 microgram tablets, 1,600 microgram tablets (film-coated tablets)

selexipag
Please read all of this leaflet carefully before you start taking this medicine, as 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 nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, as it may be harmful to them.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse (see section 4).

Contents of this leaflet

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

1. What Uptravi is and what it is used for

in a manner similar 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 PAH medications known as endothelin receptor antagonists
and type-5 phosphodiesterase inhibitors. Uptravi may be used alone if the patient cannot take these
medications.
PAH is 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 become narrowed, making it harder for
the heart to pump blood through them. This leads to symptoms such as fatigue, dizziness, shortness of
breath, or other symptoms.
By acting in a manner similar to the natural substance prostacyclin, this medicine widens the pulmonary
arteries and reduces their stiffness, making it easier for the heart to pump blood through the pulmonary
arteries. Uptravi reduces blood pressure in the pulmonary arteries, relieves PAH symptoms, and slows
disease progression.

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 heart problems such as:
• inadequate blood supply to the heart (severe coronary artery disease or unstable angina); symptoms may include chest pain
• a heart attack within the last 6 months
• heart failure (cardiac decompensation) that is not under close medical supervision
• severely irregular heart rate
• a heart valve defect (congenital or acquired) causing inadequate heart function (not caused by pulmonary hypertension)
• if you have had a stroke within the last 3 months, or any other event that reduced oxygen supply 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 pulmonary arterial hypertension (PAH)-experienced doctor or nurse before taking Uptravi if:

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

If you notice any of these signs or a change in your condition, tell your doctor immediately.
Children and adolescents
Do not give this medicine to children under 18 years of age, as Uptravi has not been studied in children.
Elderly patients
Experience with Uptravi in patients over 75 years of age is limited. Uptravi should be used with caution in this patient 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 alter how Uptravi works.
Inform your doctor or nurse if you are taking any of the following medicines:

• Gemfibrozil (a medicine used to lower fat [lipid] levels in the blood)
• Clopidogrel (a medicine used to inhibit blood clot formation in coronary artery disease)
• Deferasirox (a medicine used to remove iron from the bloodstream)
• Teriflunomide (a medicine used to treat relapsing-remitting forms of multiple sclerosis)
• Carbamazepine (a medicine used to treat certain types of epilepsy, neuralgia, or to help control severe mood disorders when other medicines are ineffective)
• Phenytoin (a medicine used for epilepsy)
• Valproic acid (a medicine used for epilepsy)
• Probenecid (a medicine used for 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 of childbearing potential, you must use an effective method of contraception during treatment with Uptravi. If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.
Driving and using machines
Uptravi may cause side effects such as headache and low blood pressure (see section 4), which could affect your ability to drive. In addition, symptoms of your disease may also reduce your fitness to drive.

3. How to take Uptravi

Uptravi may only be prescribed by a physician experienced in the treatment of pulmonary arterial hypertension. Always take this medicine exactly as instructed by your doctor. If you have any doubts or questions, consult your doctor.
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 medicines, as they may recommend that you take Uptravi only once daily.
If you have vision problems or any type of blindness, always have another person assist you when taking Uptravi during the titration period (the process of gradually increasing the dose).

Finding the right dose for you
At the beginning of treatment, you will start with the lowest dose, consisting of one 200 microgram tablet in the morning and another 200 microgram tablet in the evening, taken approximately 12 hours apart. Starting treatment in the evening is recommended. Your doctor will instruct you on how to gradually increase the dose. This process is called titration and allows your body to adapt to the new medicine. The goal of titration is to reach the most appropriate dose—the highest dose you can tolerate—up to a maximum of 1,600 micrograms in the morning and 1,600 micrograms in the evening.
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 successive steps, usually every week, although the interval between dose increases may be longer.
At each dose increase, you will add one 200 microgram tablet to your morning dose and another 200 microgram tablet to your evening dose. It is recommended to take the first increased dose in the evening. The diagram below shows the number of tablets to take each morning and each evening for the first 4 stages.

If your doctor instructs you to further increase the dose, you will continue adding one 200 microgram tablet to the morning dose and one 200 microgram tablet to the evening dose at each new stage. It is recommended to take the first increased dose in the evening.
If your doctor gives you instructions to further increase the dose and move to stage 5, this can be achieved by taking in the morning one green 800 microgram tablet and one light yellow 200 microgram tablet, and in the evening one 800 microgram tablet and one 200 microgram tablet.
The maximum dose of Uptravi is 1,600 micrograms in the morning and 1,600 micrograms in the evening. However, not all patients will reach this dose, as different patients may require different doses.
The diagram below shows the number of tablets to take each morning and each evening at each stage starting from stage 5.

You will receive a titration pack containing a titration guide and a patient leaflet. The titration guide provides information about the titration process and allows you to record the number of tablets you take each day.
Remember to record the number of tablets you take each day in the titration diary. Titration stages usually last about 1 week. If your doctor advises extending each titration stage beyond 1 week, additional pages in the diary are available to help you keep track. Remember to speak regularly with your PAH specialist doctor or nurse during titration.

Reducing to a lower dose due to adverse effects
During titration, you may experience adverse effects such as headache, diarrhea, feeling unwell (nausea), vomiting, jaw pain, muscle pain, leg pain, joint pain, or facial flushing (see section 4). If you find these adverse effects difficult to tolerate, consult your doctor on how to manage or treat them. Various treatments are available that may help relieve these effects. For example, painkillers such as paracetamol may help relieve pain and headache.
If these adverse effects cannot be managed or do not gradually improve at your current dose, your doctor may adjust the dose by removing one light yellow 200 microgram tablet from the morning dose and one light yellow 200 microgram tablet from the evening dose. The diagram below shows the stages for reducing the dose. Proceed as shown in the figure only if directed by your doctor.

If, after reducing the dose, the adverse effects become manageable, your doctor may decide not to make further dose adjustments. For more information, see the section below “Maintenance dose.”

Maintenance dose
The highest tolerated dose during titration will become your maintenance dose. The maintenance dose is the dose you will continue to take regularly.
Your doctor will prescribe the tablet strength appropriate for your maintenance dose. This allows you to take just one tablet in the morning and one in the evening, instead of taking multiple tablets at the same time.
For a complete description of Uptravi tablets, including their colors and markings, refer to section 6 of this leaflet.
Over time, your doctor may decide to adjust your maintenance dose if necessary.
If, at any time after taking the same dose for a prolonged period, you experience adverse effects that you cannot tolerate or that interfere with your daily activities, contact your doctor, as your dose may need to be reduced. Your doctor may then prescribe a single tablet with a lower strength. Remember to dispose of unused tablets properly (see section 5).

Take Uptravi once in the morning and once in the evening, approximately 12 hours apart.
Take the tablets with food, as you may tolerate the medicine better this way. The tablet coating provides protection. Swallow the tablet whole with a glass of water. Do not break, crush, or chew the tablets.

If you take more Uptravi than you should
If you have taken more tablets than you were instructed to take, consult your doctor immediately.

If you forget to take Uptravi
If you forget to take Uptravi, take a dose as soon as you remember, then continue taking the medicine at your usual times. If it is nearly time for your next dose (within 6 hours before your next scheduled dose), do not take the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for the missed one.

If you stop taking Uptravi
Suddenly stopping treatment with Uptravi may lead to worsening of symptoms. Do not stop treatment with Uptravi unless agreed with your doctor. 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 (e.g., if you miss 3 mornings and 3 evenings, or 6 consecutive doses or more), contact your doctor immediately, as your dose may need to be adjusted to avoid adverse effects. Your doctor may decide to restart treatment at a lower dose, gradually increasing it until the previous maintenance dose is reached.

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

4. Possible side effects

Like all medicines, this medicinal product can cause side effects, although not everyone experiences them. You may notice some side effects not only during the titration period, when the dose is being increased, but also after taking the same dose for long periods of time.
If you experience any of the following side effects: headache, diarrhoea, nausea, vomiting,
jaw pain, muscle pain, leg pain, joint pain or facial flushing, that you cannot tolerate or that cannot be treated,
contact your doctor, as the dose you are taking may be too high for you and may need to be reduced.

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

• Headache
• Facial flushing
• Nausea and vomiting
• Diarrhoea
• Jaw pain, muscle pain, joint pain, leg pain
• Nasopharyngitis (stuffy nose)

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

• Anaemia (reduced number of red blood cells in the blood)
• Hyperthyroidism (overactivity of the thyroid gland)
• Reduced appetite
• Weight loss
• Hypotension (low blood pressure)
• Stomach pain, including dyspepsia
• Pain
• Changes in certain blood test results, including red blood cell count or indicators of thyroid function
• Skin rashes, including urticaria, which may cause a burning or stinging sensation and redness of the skin

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

• Increased heart rate

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, consult your doctor. You can also report side effects directly through 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 Uptravi

Keep this medicine out of the sight and reach of children.
Do not use Uptravi after the expiry date stated on the carton after “Exp.” and on the blister after
“EXP”.
The expiry date refers to the last day of the month indicated.
This medicine requires no special storage conditions.
No special instructions for disposal.

6. Package contents and other information

What Uptravi contains
Each 200 microgram film-coated tablet of Uptravi contains 200 micrograms of
selexipag
Each 400 microgram film-coated tablet of Uptravi contains 400 micrograms of
selexipag
Each 600 microgram film-coated tablet of Uptravi contains 600 micrograms of
selexipag
Each 800 microgram film-coated tablet of Uptravi contains 800 micrograms of
selexipag
Each 1,000 microgram film-coated tablet of Uptravi contains 1,000 micrograms of
selexipag
Each 1,200 microgram film-coated tablet of Uptravi contains 1,200 micrograms of
selexipag
Each 1,400 microgram film-coated tablet of Uptravi contains 1,400 micrograms of
selexipag
Each 1,600 microgram film-coated tablet of Uptravi contains 1,600 micrograms of
selexipag

The other components are:
Tablet core
Mannitol (E421)
Maize starch
Low-substituted hydroxypropyl cellulose
Hydroxypropyl cellulose
Magnesium stearate

Coating
Hypromellose
Propylene glycol
Titanium dioxide (E171)
Iron oxides (E172)
Carnauba wax

Each 200 microgram film-coated tablet of Uptravi contains yellow iron oxide (E172).
Each 400 microgram film-coated tablet of Uptravi contains red iron oxide (E172).
Each 600 microgram film-coated tablet of Uptravi contains red iron oxide and black iron oxide (E172).
Each 800 microgram film-coated tablet of Uptravi contains yellow iron oxide and black iron oxide (E172).
Each 1,000 microgram film-coated tablet of Uptravi contains red iron oxide and yellow iron oxide (E172).
Each 1,200 microgram film-coated tablet of Uptravi contains black iron oxide and red iron oxide (E172).
Each 1,400 microgram film-coated tablet of Uptravi contains yellow iron oxide (E172).
Each 1,600 microgram film-coated tablet of Uptravi contains black iron oxide, red iron oxide, and yellow iron oxide (E172).

Description of the appearance of Uptravi and the contents of the pack
Uptravi 200 micrograms film-coated tablets: Light yellow, round, film-coated tablets with "2" engraved on one side.
Uptravi 400 micrograms film-coated tablets: Red, round, film-coated tablets with "4" engraved on one side.
Uptravi 600 micrograms film-coated tablets: Light purple, round, film-coated tablets with "6" engraved on one side.
Uptravi 800 micrograms film-coated tablets: Green, round, film-coated tablets with "8" engraved on one side.
Uptravi 1,000 micrograms film-coated tablets: Orange, round, film-coated tablets with "10" engraved on one side.
Uptravi 1,200 micrograms film-coated tablets: Dark purple, round, film-coated tablets with "12" engraved on one side.
Uptravi 1,400 micrograms film-coated tablets: Dark yellow, round, film-coated tablets with "14" engraved on one side.
Uptravi 1,600 micrograms film-coated tablets: Brown, round, film-coated tablets with "16" engraved on one side.

Uptravi 200 microgram film-coated tablets are available in blisters of 10, 60 or 140 tablets (titration pack).
Uptravi 400 microgram, 600 microgram, 800 microgram, 1,000 microgram, 1,200 microgram, 1,400 microgram, and 1,600 microgram film-coated tablets are available in 60-tablet blisters.
Not all pack sizes may be marketed.

Marketing Authorisation 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 medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Janssen-Cilag NV UAB "JOHNSON & JOHNSON"
Tel/Tél: +32 14 64 94 11 Tel: +370 5 278 68 88
[email protected] [email protected]

България Luxembourg/Luxemburg
„Джонсън & Джонсън България” ЕООД Janssen-Cilag NV
Тел.: +359 2 489 94 00 Tél/Tel: +32 14 64 94 11
[email protected] [email protected]

Česká republika Magyarország
Janssen-Cilag s.r.o. Janssen-Cilag Kft.
Tel: +420 227 012 227 Tel.: +36 1 884 2858
[email protected]

Danmark Malta
Janssen-Cilag A/S AM MANGION LTD
Tlf: +45 4594 8282 Tel: +356 2397 6000
[email protected]

Deutschland Nederland
Janssen-Cilag GmbH Janssen-Cilag B.V.
Tel: +49 2137 955 955 Tel: +31 76 711 1111
[email protected] [email protected]

Eesti Norge
UAB "JOHNSON & JOHNSON" Eesti filiaal Janssen-Cilag AS
Tel: +372 617 7410 Tlf: +47 24 12 65 00
[email protected] [email protected]

Ελλάδα Österreich
Janssen-Cilag Φαρμακευτική Α.Ε.Β.Ε. Janssen-Cilag Pharma GmbH
Tηλ: +30 210 80 90 000 Tel: +43 1 610 300

España Polska
Janssen-Cilag, S.A. Janssen-Cilag Polska Sp. z o.o.
Tel: +34 91 722 81 00 Tel.: +48 22 237 60 00
[email protected]

France Portugal
Janssen-Cilag Janssen-Cilag Farmacêutica, Lda.
Tél: 0 800 25 50 75 / +33 1 55 00 40 03 Tel: +351 214 368 600
[email protected]

Hrvatska România
Johnson & Johnson S.E. d.o.o. Johnson & Johnson România SRL
Tel: +385 1 6610 700 Tel: +40 21 207 1800
[email protected]

Ireland Slovenija

Johnson & Johnson d.o.o.
Tel: +386 1 401 18 00
[email protected]
Iceland Slovak Republic

Italy Finland
Janssen-Cilag SpA Janssen-Cilag Oy
Tel: 800.688.777 / +39 02 2510 1 Puh/Tel: +358 207 531 300
[email protected] [email protected]
Cyprus Sweden
Barnabas Hadjipanagis Ltd Janssen-Cilag AB
Tel: +357 22 207 700 Tfn: +46 8 626 50 00
[email protected]
Latvia United Kingdom (Northern Ireland)
UAB "JOHNSON & JOHNSON" filiāle Latvijā Janssen Sciences Ireland UC
Tel: +371 678 93561 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: http://www.ema.europa.eu.
TITRATION GUIDE - TITRATION PACK
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Uptravi film-coated tablets
selexipag
Titration guide (dose escalation)
Starting Uptravi Treatment
Read the package leaflet before starting treatment.
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 medicines, as they may recommend taking
Uptravi once daily.
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Transition to the maintenance dose The highest tolerated dose during titration will become the maintenance dose. The maintenance dose is the dose you must continue to take regularly. Your doctor or nurse may prescribe you a single tablet corresponding to the required maintenance dose. This allows you to take just one tablet in the morning and one in the evening, instead of taking multiple tablets for each dose.

For example, if the highest tolerated dose during titration was 1,200 micrograms in the morning and in the evening: Over time, your doctor or nurse may decide to adjust the maintenance dose as necessary.

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Use the following diary pages if your doctor or nurse prescribes 800 microgram tablets together with 200 microgram tablets. Using the diary, check that you have taken one 800 microgram tablet every morning and evening, and write down the number of 200 microgram tablets prescribed.

Remember to speak regularly with your IAP specialist doctor or nurse. Write here the instructions given by your doctor or nurse:Doctor's office phone number or email:Pharmacist's phone number:Notes:

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