Uptravi 200 microgram Film-coated Tablets (Great Britain)

• 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).

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

• 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)

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.

Do not give this medicine to children under 18 years of age.

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

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)

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.

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.

If your doctor prescribes 200-microgram tablets

At the start of treatment, most patients will take a 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.

A visual dosing guide shows how the medicine dose increases step by step. Each step lasts about 1 week.

Step 1 (starting dose):

• Morning: 1 tablet of 200 micrograms
• Evening: 1 tablet of 200 micrograms
• Total daily dose: 400 micrograms

Step 2:

• Morning: 2 tablets of 200 micrograms
• Evening: 2 tablets of 200 micrograms
• Total daily dose: 800 micrograms

Step 3:

• Morning: 3 tablets of 200 micrograms
• Evening: 3 tablets of 200 micrograms
• Total daily dose: 1,200 micrograms

Step 4:

• Morning: 4 tablets of 200 micrograms
• Evening: 4 tablets of 200 micrograms
• Total daily dose: 1,600 micrograms

A note indicates that the yellow tablet represents a 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.

The guide showing increasing doses using two strengths of tablet:

• Yellow tablet: 200 micrograms
• Green tablet: 800 micrograms (used from Steps 5–8 to reduce the number of tablets)

Step 5:

• Morning: One 800 microgram tablet and one 200 microgram tablet
• Evening: One 800 microgram tablet and one 200 microgram tablet
• Total daily dose: 2,000 micrograms

Step 6:

• Morning: one 800 microgram tablet and two 200 microgram tablets
• Evening: One 800 microgram tablet and two 200 microgram tablets
• Total daily dose: 2,400 micrograms

Step 7:

• Morning: One 800 microgram tablet and three 200 microgram tablets
• Evening: One 800 microgram tablet and three 200 microgram tablets
• Total daily dose: 2,800 micrograms

Step 8 (highest dose shown):

• Morning: One 800 microgram tablet and four 200 microgram tablets
• Evening: One 800 microgram tablet and four 200 microgram tablets
• Total daily dose: 3,200 micrograms

If your doctor prescribes 100-microgram tablets

If your liver is not working properly or you are taking certain medicines, your doctor may prescribe 100-microgram tablets as your starting dose.

At the start of treatment, you will take one 100-microgram tablet in the morning and another 100-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 800 micrograms in the morning and in the evening.

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 100-microgram tablet to your morning dose and another 100-microgram tablet to your evening dose. The first intake of the increased dose is recommended to be in the evening. Please refer to the Patient titration guide included in the titration pack, for instructions on how to step up your dose.

Tell your doctor if you stop taking or might stop taking any medicines, as your dose of selexipag may need to be adjusted.

If your doctor tells you to increase your dose further, you will add one 100-microgram tablet to your morning dose and one 100-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 above 400 micrograms, this may be done by taking one red 400-microgram tablet and one light-yellow 100-microgram tablet in the morning and one 400-micrograms tablet and one 100-microgram tablet in the evening. Please refer to the patient titration guide included in the titration pack, for instructions on how to step up your dose.

When uptitrating with the 100-micrograms tablets, the maximum dose of Uptravi is 800 micrograms in the morning and 800 micrograms in the evening. However, not every patient will reach this dose, because different patients require different doses.

Using the titration guide during titration

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 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.

Titration with 200-microgram tablets

A simplified diagram explains how to increase or decrease the dose:

• Start - Step 1:
  • Morning: One 200 microgram tablet
  • Evening: One 200 microgram tablet
  • Total daily dose: 400 micrograms
• Step up - Steps 2–5:
  • Increase your dose about every week by adding a 200 microgram tablet to your morning and evening dose
• Step 6:
  • The goal is to reach the highest dose with side effects that you can tolerate
• Step down:
  • Step down if side effects cannot be tolerated - go back to step 5

If you are titrating with 100-microgram tablets, please refer to the patient titration guide included in the titration pack for instructions for stepping down.

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.

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 suitable tablet strength(s) for your maintenance dose. This may allow 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 dose. 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 or crush the tablets.

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

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.

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 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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects, you can help provide more information on the safety of this medicine.

The active substance is selexipag.

Uptravi 100 microgram film-coated tablets contain 100 micrograms of 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 (E464)

Propylene glycol (E1520)

Titanium dioxide (E171)

Iron oxides (E172)

Carnauba wax

Uptravi 100 microgram film-coated tablets contain iron oxide yellow, iron oxide black (E172) and talc.

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).

Uptravi 100 microgram film-coated tablets: Round, 3.0 mm diameter, light-yellow, film-coated tablets with “1” marked on one side.

Uptravi 200 microgram film-coated tablets: Round, 7.3 mm diameter, light-yellow, film-coated tablets with “2” marked on one side.

Uptravi 400 microgram film-coated tablets: Round, 7.3 mm diameter, red, film-coated tablets with “4” marked on one side.

Uptravi 600 microgram film-coated tablets: Round, 7.3 mm diameter, light-violet, film-coated tablets with “6” marked on one side.

Uptravi 800 microgram film-coated tablets: Round, 7.3 mm diameter, green, film-coated tablets with “8” marked on one side.

Uptravi 1 000 microgram film-coated tablets: Round, 7.3 mm diameter, orange, film-coated tablets with “10” marked on one side.

Uptravi 1 200 microgram film-coated tablets: Round, 7.3 mm diameter, dark-violet, film-coated tablets with “12” marked on one side.

Uptravi 1 400 microgram film-coated tablets: Round, 7.3 mm diameter, dark-yellow, film-coated tablets with “14” marked on one side.

Uptravi 1 600 microgram film-coated tablets: Round, 7.3 mm diameter, brown, film-coated tablets with “16” marked on one side.

Uptravi 100 microgram film-coated tablets are supplied in bottles of 60 tablets and 140 tablets (titration pack).

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.