Selexipag

Source: UK SPC (eMC) for Uptravi 1000 microgram film-coated tablets (Great Britain), §4.2. 'Treatment should only be initiated and monitored by a physician experienced in the treatment of PAH.' TITRATION: 'Each patient should be up-titrated to the highest individually tolerated dose'; 'At the beginning of treatment and at each up-titration step it is recommended to take the first dose in the evening.' During titration adverse reactions reflecting the mode of action (headache, diarrhoea, nausea and vomiting, jaw pain, myalgia, pain in extremity, arthralgia, flushing) 'are usually transient or manageable with symptomatic treatment'; '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 selexipag, 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.' MAINTENANCE: 'The highest tolerated dose reached during dose titration should be maintained.' MISSED DOSE: '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.' DISCONTINUATION: 'if the decision to withdraw Uptravi is taken, it should be done gradually while an alternative therapy is introduced.' MODERATE CYP2C8 INHIBITORS (e.g. clopidogrel, deferasirox, teriflunomide): 'the total daily dose of Uptravi should be reduced to half by administering half of each dose twice daily' — alternatively a once-daily frequency achieving half the daily dose may be used; when the inhibitor is stopped the total daily dose should be increased again, but 'The maximum dose of 1 600 micrograms twice daily should not be exceeded.' ELDERLY: 'No adjustment to the dose regimen is needed in elderly people'; there is limited clinical experience over the age of 75 years, so use with caution. VISION: 'Patients who have poor vision or are blind must be instructed to get assistance from another person when taking Uptravi during the titration period.' Some sections of the product information we used were incomplete — check the full SPC.

Presentation: Tablets: 100, 150, 200, 400, 600, 800, 1,000, 1,200, 1,400 and 1,600 microgram film-coated tablets (US strengths list). 'For pediatric patients with a body weight >=40 kg to <50 kg multiple tablet dose strengths may be needed to reach the doses up to 1,600 mcg twice daily.' NO WEIGHT-BASED (mg/kg) PAEDIATRIC DOSE EXISTS — dosePerKg deliberately left null. UK POSITION (authoritative for this page), SPC §4.2 verbatim: 'The safety and efficacy of selexipag in children aged 2 to less than 18 years have not yet been established... no recommendation on a posology can be made. Administration of selexipag in the paediatric population is not recommended. The safety and efficacy of selexipag in children aged less than 2 years have not been studied, as animal studies indicated an increased risk of intussusception.' US LABEL (openFDA/DailyMed, UPTRAVI, cross-check only — US labelling differs from the UK here): 'Safety and effectiveness of UPTRAVI have been established for the treatment of PAH in pediatric patients aged 2 years and older.' US Table 1 Pediatric Dosing Regimen, verbatim by body weight: '9 kg to less than 25 kg — 100 mcg orally twice daily starting dose, 100 mcg orally twice daily titration increments, 800 mcg orally twice daily maximum dose allowed'; '25 kg to less than 40 kg — 150 mcg orally twice daily, 150 mcg orally twice daily, 1,200 mcg orally twice daily'; '40 kg to less than 50 kg — 150 mcg orally twice daily, 150 mcg orally twice daily, 1,600 mcg orally twice daily'; '50 kg and greater — 200 mcg orally twice daily, 200 mcg orally twice daily, 1,600 mcg orally twice daily'. 'Increase the dose in increments equivalent to the starting dose... at weekly intervals... Re-evaluate further dose titration based on changes in body weight category over time.' For children who cannot swallow tablets whole, the US label permits 100 mcg or 150 mcg tablets to be dispersed in apple or orange juice ('Do not disperse the tablet(s) in water or milk. Do not crush or split the tablet(s).') or given with soft food. US §8.4 also states 'When treating pediatric patients with UPTRAVI, monitor growth' and that safety/effectiveness are not established under 2 years. DO NOT apply the US weight bands as UK practice — verify any under-18 use against a children's formulary and with the PAH specialist centre.