UPTRAVI Film-coated tablet Ref.[8623] Active ingredients: Selexipag

Treatment should only be initiated and monitored by a physician experienced in the treatment of PAH.

Posology

Individualised dose titration

Each patient should be up-titrated to the highest individually tolerated dose, which can range from 200 micrograms given twice daily to 1,600 micrograms given twice daily (individualised maintenance dose).

The recommended starting dose is 200 micrograms given twice daily, approximately 12 hours apart. The dose is increased in increments of 200 micrograms given twice daily, usually at weekly intervals. At the beginning of treatment and at each up-titration step it is recommended to take the first dose in the evening. During dose titration some adverse reactions, reflecting the mode of action of Uptravi (such as headache, diarrhoea, nausea and vomiting, jaw pain, myalgia, pain in extremity, arthralgia, and flushing), may occur. They are usually transient or manageable with symptomatic treatment (see section 4.8). However, if a patient reaches a dose that cannot be tolerated, the dose should be reduced to the previous dose level.

In patients in whom up-titration was limited by reasons other than adverse reactions reflecting the mode of action of Uptravi, a second attempt to continue up-titration to the highest individually tolerated dose up to a maximum dose of 1,600 micrograms twice daily may be considered.

Individualised maintenance dose

The highest tolerated dose reached during dose titration should be maintained. If the therapy over time is less tolerated at a given dose, symptomatic treatment and/or a dose reduction to the next lower dose should be considered.

Interruptions and discontinuations

If a dose is missed, it should be taken as soon as possible. The missed dose should not be taken if the next scheduled dose is within approximately 6 hours.

If treatment is missed for 3 days or more, Uptravi should be restarted at a lower dose and then up-titrated.

There is limited experience with abrupt discontinuation of Uptravi in patients with PAH. No evidence for acute rebound has been observed.

However, if the decision to withdraw Uptravi is taken, it should be done gradually while an alternative therapy is introduced.

Dosage Adjustment with Co-administration of Moderate CYP2C8 Inhibitors

When co-administered with moderate CYP2C8 inhibitors (e.g., clopidogrel, deferasirox and teriflunomide), reduce the dosing of Uptravi to once daily . If the therapy is not tolerated at a given dose, symptomatic treatment and/or a dose reduction to the next lower dose should be considered. Revert to twice daily dosing frequency of Uptravi when co-administration of moderate CYP2C8 inhibitor is stopped (see section 4.5).

Elderly (≥65 years)

No adjustment to the dose regimen is needed in elderly people (see section 5.2). There is limited clinical experience in patients over the age of 75 years, therefore Uptravi should be used with caution in this population (see section 4.4).

Hepatic impairment

Uptravi should not be administered in patients with severe liver impairment (Child-Pugh class C; see section 4.4). For patients with moderate hepatic impairment (Child-Pugh class B), the starting dose of Uptravi should be 200 micrograms once daily, and increased at weekly intervals by increments of 200 micrograms given once daily until adverse reactions, reflecting the mode of action of selexipag, that cannot be tolerated or medically managed are experienced. No adjustment to the dose regimen is needed in patients with mild hepatic impairment (Child-Pugh class A).

Renal impairment

No adjustment to the dose regimen is needed in patients with mild or moderate renal impairment. No change in starting dose is required in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m²); dose titration should be done with caution in these patients (see section 4.4).

Paediatric population (<18 years)

The safety and efficacy of Uptravi in children aged 0 to less than 18 years have not yet been established. No data are available. Administration of selexipag in the paediatric population is not recommended. Animal studies indicated an increased risk of intussusception, but the clinical relevance of these findings is unknown (see section 5.3).

Method of administration

Oral use.

The film-coated tablets are to be taken orally in the morning and in the evening. To improve tolerability, it is recommended to take Uptravi with food and, at the beginning of each up-titration phase, to take the first increased dose in the evening.

The tablets should not be split, crushed or chewed, and are to be swallowed with water.

Isolated cases of overdose up to 3,200 micrograms were reported. Mild, transient nausea was the only reported consequence. In the event of overdose, supportive measures must be taken as required. Dialysis is unlikely to be effective because selexipag and its active metabolite are highly protein bound.

3 years.

This medicinal product does not require any special storage conditions.

Polyamide/aluminium/HDPE/PE with an embedded desiccant agent/HDPE blister sealed with an aluminium foil.

Uptravi 200 microgram film-coated tablets: Cartons of 10 or 60 film-coated tablets, and 60 or 140 film-coated 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: Cartons of 60 film-coated tablets.

Not all pack sizes may be marketed.

No special requirements for disposal.