Uptravi - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Uptravi 200 microgram film-coated tablets

Uptravi 400 microgram film-coated tablets

Uptravi 600 microgram film-coated tablets

Uptravi 800 microgram film-coated tablets

Uptravi 1,000 microgram film-coated tablets

Uptravi 1,200 microgram film-coated tablets

Uptravi 1,400 microgram film-coated tablets

Uptravi 1,600 microgram film-coated tablets selexipag

Read all of this leaflet carefully before 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 doctor or nurse.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

- If you have any side effects, talk to your doctor or nurse. This includes any possible side effects

not listed in this leaflet (see section 4).

What is in 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 package 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, making them relax and widen.

Uptravi is used for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients insufficiently controlled with other types of medicines for PAH known as endothelin receptor antagonists and phosphodiesterase type 5 inhibitors. Uptravi can be used on its own if the patient is not a candidate for these medicines.

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 narrow, so the heart has to work harder to pump blood through them. This may cause people to feel tired, dizzy, short of breath, or experience other symptoms.

By acting in a similar way to the natural substance prostacyclin, this medicine widens the pulmonary arteries and reduces their hardening. This makes it easier for the heart to pump blood through the pulmonary arteries. Uptravi lowers the pressure in the pulmonary arteries, it relieves the symptoms of PAH and slows down progression of PAH disease.

2. What you need to know before you take Uptravi

Do not take Uptravi

• – if you are allergic to selexipag or any of the other ingredients of this medicine (listed in

section 6).

– if you have a heart problem, such as:

• – poor blood flow to the heart muscles (severe coronary heart disease or unstable angina);

symptoms can include chest pain

• – heart attack within the last 6 months

• – weak heart (decompensated cardiac failure) that is not under close medical observation

• – severe irregular heartbeat

• – defect of the heart valves (inborn or acquired) that causes the heart to work poorly (not

related to pulmonary hypertension)

• – if you have had a stroke within the last 3 months, or any other occurrence that reduced the blood

supply to the brain (e.g., transient ischaemic attack)

• – if you are taking gemfibrozil (medicine used to lower the level of fats [lipids] in the blood)

Warnings and precautions

Talk to your PAH doctor or nurse before taking Uptravi if you

• – are taking medicines for high blood pressure

• – have low blood pressure associated with symptoms such as dizziness

• – have recently experienced significant blood loss or fluid loss such as severe diarrhoea or

vomiting

• – have problems with your thyroid gland

• – have severe problems with your kidneys or are undergoing dialysis

• – have or have had severe problems with your liver not working properly

If you notice any of the above signs or your condition changes, tell your doctor immediately.

Children and adolescents

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

Elderly patients

There is limited experience with Uptravi in patients older than 75 years. Uptravi should be used with caution 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.

Talk to your PAH doctor or nurse if you are taking any of the following medicines:

• – Gemfibrozil (medicine used to lower the level of fats [lipids] in the blood)

• – Clopidogrel (medicine used to inhibit blood clots in coronary artery disease)

• – Deferasirox (medicine used to remove iron from the blood stream)

• – Teriflunomide (medicine used to treat relapsing-remitting multiple sclerosis)

• – Carbamazepine (medicine used to treat some forms of epilepsy, nerve pain or to help control

serious mood disorders when some other medicines do not work)

• – Phenytoin (medicine used to treat epilepsy)

• – Valproic acid (medicine used to treat epilepsy)

• – Probenecid (medicine used to treat gout)

• – Fluconazole, rifampicin or rifapentine (antibiotics used to treat infections)

Pregnancy and breast-feeding

Uptravi is not recommended during pregnancy and breast-feeding. If you are a woman who can have children, you should use an effective contraceptive method while taking Uptravi. If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

Driving and using machines

Uptravi can cause side effects such as headaches and low blood pressure (see section 4), which may affect your ability to drive; the symptoms of your condition can also make you less fit to drive.

3.   How to take Uptravi

Uptravi should only be prescribed by a doctor experienced in the treatment of PAH. Always take this medicine exactly as your doctor has told you. Check with your doctor if you are in doubt or have any questions.

Tell your doctor if you experience side effects, as your doctor may recommend that you change your Uptravi dose.

Tell your doctor if you are taking other medicines as your doctor may recommend that you take Uptravi only once daily.

If you have poor vision or experience any type of blindness, get help from another person when taking Uptravi during the titration period (process of gradually increasing your dose).

Finding the right dose for you

At the start of treatment, you will take the lowest dose. This is one 200 microgram tablet in the morning and another 200 microgram tablet in the evening, about 12 hours apart. It is recommended to initiate treatment in the evening. Your doctor will instruct you to gradually increase your dose. This is called titration. It lets your body adjust to the new medicine. The goal of titration is to reach the most appropriate dose. This will be the highest dose you can tolerate, which may reach the maximum dose of 1,600 micrograms in the morning and in the evening.

The first pack of tablets you receive will contain the light-yellow 200 microgram tablets.

Your doctor will tell you to increase your dose in steps, usually every week but the interval between increases could be longer.

With each step, you will add one 200 microgram tablet to your morning dose and another

200 microgram tablet to your evening dose. The first intake of the increased dose is recommended to be in the evening. The diagram below shows the number of tablets to take every morning and every evening for the first 4 steps.

Each dosing step lasts about 1 week.

200 microgram tablet

If your doctor tells you to increase your dose further, you will add one 200 microgram tablet to your morning dose and one 200 microgram tablet to your evening dose with each new step. The first intake of the increased dose is recommended to be in the evening.

If your doctor instructs you to further increase your dose and move to step 5, this may be done 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 in the evening.

The maximum dose of Uptravi is 1,600 micrograms in the morning and 1,600 micrograms in the evening. However, not every patient will reach this dose, because different patients require different doses.

The diagram below shows the number of tablets to take every morning and every evening at each step, starting with step 5.

200 microgram tablet

You will receive the titration pack which contains a titration guide and Patient Leaflet. The titration guide is providing information on the titration process and is allowing you to record the number of tablets you take every day.

Remember to record the number of tablets you take every day in your titration diary. The titration steps usually last about 1 week. If your doctor instructs you to prolong each titration step longer than 1 week, there are additional diary pages to allow you to track this. Remember to talk to your PAH doctor or nurse regularly during titration.

Stepping down to a lower dose due to side effects

During titration, you may experience side effects such as headache, diarrhoea, feeling sick (nausea), being sick (vomiting), jaw pain, muscle pain, leg pain, joint pain, or reddening of the face (see section 4). If these side effects are difficult for you to tolerate, talk to your doctor about how to manage or treat them. There are treatments available that can help relieve the side effects. For example, painkillers such as paracetamol may help treat pain and headache.

If the side effects cannot be treated or do not gradually get better on the dose you are taking, your doctor may adjust your dose by reducing the number of 200 microgram light-yellow tablets you take by one in the morning and by one in the evening. The diagram below shows stepping down to a lower dose. Do this only if instructed to do so by your doctor.

START STEP UP

If your side effects are manageable after stepping down your dose, your doctor may decide that you should stay on that dose. Please see section Maintenance dose below for more information.

Maintenance dose

The highest dose that you can tolerate during titration will become your maintenance dose. Your maintenance dose is the dose you should continue to take on a regular basis.

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

For a full description of Uptravi tablets, including colours and marking, please see section 6 of this leaflet.

Over time, your doctor may adjust your maintenance dose as needed.

If, at any time, after taking the same dose for a long time, you experience side effects that you cannot tolerate or side effects that have an impact on your normal daily activities, contact your doctor as your dose may need to be reduced. The doctor may then prescribe you a lower single-tablet strength. Please remember to dispose of unused tablets (see section 5).

Take Uptravi once in the morning and once in the evening, about 12 hours apart.

Take the tablets with meals as you might tolerate your medicine better. The tablet coating provides protection. Swallow the tablets whole with a glass of water. Do not split, crush or chew the tablets.

If you take more Uptravi than you should

If you have taken more tablets than you have been told to take, ask your doctor for advice.

If you forget to take Uptravi

If you forget to take Uptravi, take a dose as soon as you remember, then continue to take your tablets at the usual times. If it is nearly time for your next dose (within 6 hours before you would normally take it), you should skip the missed dose and continue to take your medicine at the usual time. Do not take a double dose to make up for a forgotten tablet.

If you stop taking Uptravi

Suddenly stopping your treatment with Uptravi might lead to your symptoms getting worse. Do not stop taking Uptravi unless your doctor tells you to. Your doctor may tell you to reduce the dose gradually before stopping completely.

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

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. You may experience side effects not only during the titration period when your dose is being increased, but also later after taking the same dose for a long time.

If you experience any of these side effects: headache, diarrhoea, feeling sick (nausea), being sick (vomiting), jaw pain, muscle pain, leg pain, joint pain, or reddening of the face, that you cannot tolerate or that cannot be treated, you should 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

• – Flushing (reddening of the face)

• – Nausea and vomiting (feeling sick and being sick)

• – Diarrhoea

• – Jaw pain, muscle pain, joint pain, leg pain

• – Nasopharyngitis (stuffy nose)

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

• – Anaemia (low red blood cell levels)

• – Hyperthyroidism (overactive thyroid gland)

• – Reduced appetite

• – Weight loss

• – Hypotension (low blood pressure)

• – Stomach pain

• – Pain

• – Changes in some blood test results including those measuring blood cell counts or your thyroid

function

• – Rashes, including hives, may cause a burning or stinging sensation and skin redness

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

• – Increased heart rate

Reporting of side effects

If you have any side effects, talk to your doctor. 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. 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, which is stated on the carton and on the blister after “EXP.” The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

No special requirements for disposal.

6. Contents of the pack and other information

What Uptravi contains

The active substance is selexipag.

Uptravi 200 microgram film-coated tablets contain 200 micrograms of selexipag

Uptravi 400 microgram film-coated tablets contain 400 micrograms of selexipag

Uptravi 600 microgram film-coated tablets contain 600 micrograms of selexipag

Uptravi 800 microgram film-coated tablets contain 800 micrograms of selexipag

Uptravi 1,000 microgram film-coated tablets contain 1,000 micrograms of selexipag

Uptravi 1,200 microgram film-coated tablets contain 1,200 micrograms of selexipag

Uptravi 1,400 microgram film-coated tablets contain 1,400 micrograms of selexipag

Uptravi 1,600 microgram film-coated tablets contain 1,600 micrograms of selexipag

The other ingredients are:

Tablet core

Mannitol (E421)

Maize starch

Low-substituted hydroxypropyl­cellulose

Hydroxypropyl­cellulose

Magnesium stearate

Film coating

Hypromellose

Propylene glycol

Titanium dioxide (E171)

Iron oxides (E172)

Carnauba wax

Uptravi 200 microgram film-coated tablets contain iron oxide yellow (E172).

Uptravi 400 microgram film-coated tablets contain iron oxide red (E172).

Uptravi 600 microgram film-coated tablets contain iron oxide red and iron oxide black (E172).

Uptravi 800 microgram film-coated tablets contain iron oxide yellow and iron oxide black (E172).

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

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

Uptravi 1,400 microgram film-coated tablets contain iron oxide yellow (E172).

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

What Uptravi looks like and contents of the pack

Uptravi 200 microgram film-coated tablets : Round, light-yellow, film-coated tablets with “2” marked on one side.

Uptravi 400 microgram film-coated tablets : Round, red, film-coated tablets with “4” marked on one side.

Uptravi 600 microgram film-coated tablets : Round, light-violet, film-coated tablets with “6” marked on one side.

Uptravi 800 microgram film-coated tablets : Round, green, film-coated tablets with “8” marked on one side.

Uptravi 1,000 microgram film-coated tablets : Round, orange, film-coated tablets with “10” marked on one side.

Uptravi 1,200 microgram film-coated tablets : Round, dark-violet, film-coated tablets with “12” marked on one side.

Uptravi 1,400 microgram film-coated tablets : Round, dark-yellow, film-coated tablets with “14” marked on one side.

Uptravi 1,600 microgram film-coated tablets : Round, brown, film-coated tablets with “16” marked on one side.

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

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

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 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 Etarapna „^>KOHCtH & ^-/KOHCbH Ebarapua” EOOfl Tea.: +359 2 489 94 00 Česká republika Janssen-Cilag s.r.o. Tel: +420 227 012 227

Lietuva UAB „JOHNSON & JOHNSON“ Tel: +370 5 278 68 88 Luxembourg/Lu­xemburg Janssen-Cilag NV Tél/Tel: +32 14 64 94 11 Magyarország Janssen-Cilag Kft. Tel.: +36 1 884 2858

Danmark Janssen-Cilag A/S Tlf: +45 4594 8282

Malta AM MANGION LTD Tel: +356 2397 6000

Deutschland Janssen-Cilag GmbH Tel: +49 2137 955 955	Nederland Janssen-Cilag B.V. Tel: +31 76 711 1111
Eesti UAB „JOHNSON & JOHNSON“ Eesti filiaal Tel: +372 617 7410	Norge Janssen-Cilag AS Tlf: +47 24 12 65 00
EÀÀàôa Janssen-Cilag OappaKsuTiK^ A.E.B.E. Tql: +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 France Janssen-Cilag Tél: 0 800 25 50 75 / +33 1 55 00 40 03 Hrvatska Johnson & Johnson S.E. d.o.o. Tel: +385 1 6610 700	Polska Janssen-Cilag Polska Sp. z o.o. Tel.: +48 22 237 60 00 Portugal Janssen-Cilag Farmacéutica, Lda. Tel: +351 214 368 600 România Johnson & Johnson România SRL Tel: +40 21 207 1800
Ireland Janssen Sciences Ireland UC Tel: +353 1 800 709 122	Slovenija Johnson & Johnson d.o.o. Tel: +386 1 401 18 00
island Janssen-Cilag AB c/o Vistor hf. Sími: +354 535 7000	Slovenská republika Johnson & Johnson, s.r.o. Tel: +421 232 408 400

Italia Janssen-Cilag SpA Tel: 800.688.777 / +39 02 2510 1	Suomi/Finland Janssen-Cilag Oy Puh/Tel: +358 207 531 300
Kùnpoç Bapváßaç XaTZnnavaY^ç Ató Tip.: +357 22 207 700	Sverige Janssen-Cilag AB Tfn: +46 8 626 50 00

Latvija United Kingdom (Northern Ireland)

UAB „JOHNSON & JOHNSON“ filiäle Latvijä Janssen Sciences Ireland UC

Tel: +371 678 93561 Tel: +44 1 494 567 444

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:.

TITRATION GUIDE – TITRATION PACK

Page 1

Uptravi film-coated tablets selexipag

Titration Guide

Starting Treatment with Uptravi

Please read the accompanying patient information leaflet before starting treatment. Tell your doctor if you experience side effects, as your doctor may recommend that you change your Uptravi dose. Tell your doctor if you are taking other medications as your doctor may recommend that you take Uptravi only once daily.

Page 2	Page 3
Contents How should you take Uptravi?.....­.............­.............­....4 How should you step up your dose?........­.............­......6 What are the steps?.......­.............­.............­.............­.......8 When should you step down?........­.............­.............­.10 Stepping down.........­.............­.............­.........12	When you move to your maintenance dose.............14 If you forget to take Uptravi......­.............­.............­.....16 If you stop taking Uptravi......­.............­.............­.........17 Titration diary........­.............­.............­.............­............18
Page 4	Page 5
How should you take Uptravi? Uptravi is a medicine taken every morning and evening for the treatment of pulmonary arterial hypertension, also called PAH. The starting dose for Uptravi is 200 micrograms once in the morning and once in the evening. The first intake of Uptravi should be in the evening. You should take each dose with a glass of water, preferably during a meal.	There are 2 phases of treatment with Uptravi: Titration In the first several weeks, you will work with your doctor to find the dose of Uptravi that is right for you. Your doctor may have you step up from the starting dose to higher doses of Uptravi. Your doctor may step you down to a lower dose. This process is called titration. It lets your body gradually adjust to the medicine.
	Maintenance Once your doctor has found the dose that is right for you, this will be the dose you take on a regular basis. This is called the maintenance dose.

Page 6 Page 7

Page 10 _____________­________________________­___ Page 11

^ When should you step down? As with all medicines, you may experience side effects with Uptravi as you step up to higher doses. Talk to your doctor or nurse if you have side effects. There are treatments available that can help relieve them. The most common side effects (may affect more than 1 in 10 people) you may experience while taking Uptravi are: Headache Diarrhoea Nausea Vomiting Jaw pain Muscle pain Leg pain Joint pain Facial redness For a full list of side effects see package leaflet for further information.

If you cannot tolerate the side effects even after your doctor or nurse has tried to treat them, he or she may recommend you step down to a lower dose. If your doctor or nurse tells you to step down to a lower dose, you should take one less 200 microgram tablet in the morning and one less in the evening. You should only step down after speaking with your PAH doctor or nurse. This stepping-down process will help you find the dose that is right for you, also called your maintenance dose.

Page 14 _____________­________________________­___ Page 15

When you move to your maintenance dose The highest dose that you can tolerate during titration will become your maintenance dose. Your maintenance dose is the dose you should continue to take on a regular basis. Your doctor or nurse can prescribe an equivalent single-tablet strength for your maintenance dose. This lets you take just one tablet in the morning and one in the evening, instead of multiple tablets for each dose.

For example, if your highest tolerated dose during titration was 1,200 micrograms once in the morning and once in the evening: i-» Highest Maintenante ’ tolerated dose dose Morning Highest Maintenance . tolerated dose dose Evening Over time, your doctor or nurse may adjust your maintenance dose as needed.

Page 16	Page 17
If you forget to take Uptravi	If you stop taking Uptravi
If you miss a dose, take the dose as soon as you remember, then continue to take your tablets at the usual times. If it is within 6 hours of when you would normally take your next dose, you should skip the missed dose and continue to take your medicine at the usual time. Do not take a double dose to make up for a forgotten tablet.	Do not stop taking Uptravi unless your doctor or nurse tells you to. If, for any reason, you stop taking Uptravi for more than 3 consecutive days (if you missed 6 doses in a row), contact your PAH doctor or nurse immediately as your dose may need to be adjusted to avoid side effects. Your doctor or nurse may have you resume treatment at a lower dose, gradually increasing to your previous maintenance dose.

Page 18

Page 19

Titration diary Please read the instructions in the package leaflet carefully.	Remember to talk to your PAH doctor or nurse regularly. Write down your doctor or nurse’s instruc­tions:
The following diary pages help you keep track of the number of tablets you need to take in the morning and evening during titration.
Use them to write down the number of tablets you take in the morning and the evening.	Doctor’s office telephone and e-mail:
Each step usually lasts about 1 week, unless your doctor or nurse instructs you otherwise. If your titration steps last longer than 1 week there are	Pharmacist’s te­lephone:
additional diary pages to track this. Use pages 20 to 27 to track the first weeks of treatment, when you are using 200 microgram tablets only (steps 1–4). If you have been prescribed both 200 and 800 microgram tablets, use pages 30 to 37 (steps 5–8).	Notes:

Page 28 _____________­_____________________ Page 29

Use the following diary pages if your doctor or nurse prescribes 800 microgram tablets in addition to your 200 microgram tablets. On the diary pages, check off that you have taken one 800 microgram tablet every day in the morning and in the evening with your prescribed number of 200 microgram tablets. 200 microgram tablet 800 microgram tablet (Use with steps 5 through 8 to reduce the number of tablets needed per dose.)

Remember to talk to your PAH doctor or nurse regularly. Write down your doctor or nurse’s instruc­tions: Doctor’s office telephone and e-mail: Pharmacist’s te­lephone: Notes:

32

33

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Page 36

Page 37

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Notes

Page 40

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