Prostacyclin Receptor (IP Receptor) Agonist — Pulmonary Arterial Hypertension Pregnancy: Avoid — insufficient data; prostacyclin pathway stimulation may affect platelet aggregation in neonate

Selexipag

Brand names: Uptravi

Adult dose

Dose: 200 micrograms twice daily initially; increase by 200 micrograms BD every week to maximum tolerated dose

Route: Oral

Frequency: Twice daily (with food)

Max: 1600 micrograms twice daily

Selective IP receptor agonist — non-prostanoid; oral and stable. GRIPHON trial: largest outcomes-based PAH trial (1156 patients). Titrate weekly; back down one dose level if side effects intolerable, then re-attempt. Take with food to reduce GI side effects. Not a prodrug.

Paediatric dose

Route:

Seek specialist opinion — not licensed in paediatrics

Dose adjustments

Renal

No dose adjustment required for mild-moderate renal impairment; severe impairment — limited data

Hepatic

Child-Pugh B: 200 micrograms once daily (once-daily dosing); Child-Pugh C: avoid

Clinical pearls

GRIPHON trial (2015): selexipag reduced composite of morbidity/mortality by 40% in PAH — landmark outcomes study; benefit seen on top of ERA and/or PDE5 inhibitor background therapy
Oral prostacyclin pathway agent — avoids infusion complications of epoprostenol/treprostinil; better GI profile than oral treprostinil
Active metabolite (ACT-333679) is 37× more potent than parent — CYP2C8 interactions affect metabolite level profoundly
Gemfibrozil is absolute contraindication — check lipid medications at initiation
Individualized dosing to maximum tolerated dose is key — do not give up at low dose if patient is tolerating well

Contraindications

Severe hepatic impairment
Concurrent strong CYP2C8 inhibitors (gemfibrozil — absolute: markedly increases selexipag/metabolite levels)

Side effects

Headache (very common)
Diarrhoea
Nausea/vomiting
Jaw pain
Myalgia
Limb pain
Flushing
Nasopharyngitis

Interactions

Gemfibrozil (strong CYP2C8 inhibitor) — absolute contraindication (2× increase in active metabolite, 11× increase in parent)
Moderate CYP2C8 inhibitors (clopidogrel, trimethoprim) — reduce selexipag dose to once daily
CYP2C8 inducers (rifampicin) — reduce efficacy

Monitoring

Dose titration response (symptoms, BP, HR)
6MWD and echocardiography
LFTs
Renal function
Gemfibrozil/CYP2C8 inhibitor check at initiation and if new medications added

Reference: BNFc; BNF 90; GRIPHON Trial 2015; NICE TA397 (Selexipag for PAH); ESC/ERS PAH Guidelines 2022. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways