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Pulmonary Arterial Hypertension Pregnancy: Contraindicated — animal reproductive toxicity; women of childbearing potential must use effective contraception

Selexipag

Brand names: Uptravi

Adult dose

Dose: 200 mcg twice daily starting dose; titrate by 200 mcg twice daily at weekly intervals to highest tolerated dose
Route: Oral
Frequency: Twice daily
Max: 1600 mcg twice daily
Take with food to reduce GI side effects. Titration is individualized — stop increasing if side effects not tolerated. If treatment interrupted for 3+ days, restart at lower dose and re-titrate.

Paediatric dose

Dose: Seek specialist opinion N/A/kg
Route: Oral
Frequency: N/A
Max: N/A
Not established in paediatrics; seek specialist paediatric pulmonary hypertension opinion

Dose adjustments

Renal

No dose adjustment for mild-moderate renal impairment; avoid in severe renal impairment (eGFR under 15)

Hepatic

No dose adjustment in mild impairment; 200 mcg once daily starting dose in moderate impairment; avoid in severe hepatic impairment

Paediatric weight-based calculator

Not established in paediatrics; seek specialist paediatric pulmonary hypertension opinion

Clinical pearls

  • Mechanism: selective IP (prostacyclin) receptor agonist — selexipag is a prodrug converted to active metabolite ACT-333679; stimulates IP receptors causing pulmonary vasodilation, anti-proliferative, anti-platelet, and anti-fibrotic effects; distinct from prostacyclin analogues (iloprost, treprostinil)
  • GRIPHON trial (NEJM 2015): selexipag vs placebo in PAH on ERA and/or PDE5 inhibitor background therapy — 40% relative risk reduction in composite of death or PAH complication; landmark oral prostacyclin receptor agonist study
  • Triple combination therapy: GRIPHON established selexipag as the 3rd component of oral triple therapy for PAH — ERA (macitentan/bosentan) + PDE5 inhibitor (sildenafil/tadalafil) + selexipag; goal to delay disease progression and clinical worsening
  • MHRA: licensed for PAH (Group 1 WHO) in adults to delay disease progression; NHS England NHS England Highly Specialised Services — prescribed only by PAH specialist centres
  • Jaw pain: characteristic prostacyclin class side effect (as with iloprost/treprostinil); typically bilateral, occurs during meals, related to masseter muscle vasodilation — reassure patients this is not cardiac pain
  • Gemfibrozil interaction: CYP2C8 inhibition increases selexipag AUC by ~11-fold — ABSOLUTE contraindication; check for fibrate use before prescribing

Contraindications

  • Severe coronary heart disease or unstable angina
  • Decompensated cardiac failure requiring hospitalisation
  • Severe arrhythmias
  • Recent stroke or TIA (within 3 months)
  • Congenital or acquired valvular disease with haemodynamic consequences

Side effects

  • Headache (very common — prostacyclin pathway effect)
  • Diarrhoea
  • Nausea and vomiting
  • Jaw pain (prostacyclin class effect — non-cardiac; often resolves)
  • Myalgia
  • Flushing
  • Peripheral oedema
  • Anaemia (10%)

Interactions

  • Strong CYP2C8 inhibitors (gemfibrozil — INCREASES selexipag and active metabolite exposure significantly; CONTRAINDICATED combination)
  • CYP2C8 inducers (rifampicin — reduces selexipag exposure; avoid combination)
  • Anticoagulants (additive — monitor; PAH patients often anticoagulated)

Monitoring

  • Exercise capacity (6-minute walk test at baseline and 3–6 monthly)
  • RHC (right heart catheterisation) haemodynamics annually or per specialist
  • LFTs (monthly for first 3 months, then quarterly)
  • Haemoglobin (anaemia monitoring)
  • BP and clinical signs of systemic hypotension

Reference: BNFc; BNF 90; GRIPHON trial NEJM 2015;373(26):2522-2533; ESC/ERS PAH Guidelines 2022; NICE TA569; MHRA SPC. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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