Pulmonary Arterial Hypertension Pregnancy: Not recommended during pregnancy or in women of childbearing potential not using contraception (SPC section 4.6); women of childbearing potential should practise effective contraception. No data in pregnant women. Should not be used during breast-feeding - excretion in human milk unknown, present in rat milk.

Selexipag

Brand names: Uptravi

Selexipag is an orally active selective prostacyclin (IP) receptor agonist used for the long-term treatment of pulmonary arterial hypertension, often in combination with an endothelin-receptor antagonist and/or a phosphodiesterase-5 inhibitor.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Starting dose 200 micrograms twice daily; increase in increments of 200 micrograms twice daily, usually at weekly intervals, to the highest individually tolerated dose (individualised maintenance dose ranges from 200 micrograms twice daily to 1600 micrograms twice daily)

Route: Oral (film-coated tablets, swallowed whole with water; must not be split or crushed)

Frequency: Twice daily, approximately 12 hours apart (morning and evening), taken with food to improve tolerability

Max: 1600 micrograms twice daily

Indication per SPC: pulmonary arterial hypertension (PAH). Treatment should only be initiated and monitored by a physician experienced in the treatment of PAH. At the beginning of treatment and at each up-titration step, take the first (increased) dose in the evening. If a dose that cannot be tolerated is reached, reduce to the previous dose level; the highest tolerated dose reached during titration should be maintained, and if tolerability worsens over time use symptomatic treatment and/or reduce to the next lower dose. Where up-titration was limited for reasons other than prostacyclin-type adverse reactions, a second attempt to titrate up to a maximum of 1600 micrograms twice daily may be considered. Missed dose: take as soon as possible unless the next scheduled dose is within approximately 6 hours; if treatment is missed for 3 days or more, restart at a lower dose and re-titrate. Avoid abrupt discontinuation - withdraw gradually while an alternative therapy is introduced. Moderate CYP2C8 inhibitors (e.g. clopidogrel, deferasirox, teriflunomide): halve the total daily dose by giving half of each dose twice daily, or continue/apply once-daily dosing delivering half the daily dose; increase again when the inhibitor is stopped; the 1600 micrograms twice daily maximum must not be exceeded. Hepatic impairment: no adjustment in Child-Pugh A; in Child-Pugh B start 100 micrograms twice daily and increase at weekly intervals by 100 micrograms twice daily, maximum 800 micrograms twice daily; must not be administered in Child-Pugh C. Elderly (65 years and over): no dose adjustment; limited experience over 75 years - use with caution. Paediatric (SPC): safety and efficacy in children aged 2 to less than 18 years have not been established and no recommendation on a posology can be made - administration in the paediatric population is not recommended; not studied under 2 years (animal studies indicated an increased risk of intussusception). Patients with poor vision or blindness must be instructed to get assistance when taking the tablets during the titration period. NOTE for clinician: the US label (UPTRAVI) additionally carries weight-band paediatric oral dosing for children 2 years and older and a separate intravenous presentation (80-minute infusion, dose matched to the current oral dose) - neither is in the UK SPC used here; verify against a children's formulary and the relevant product literature if paediatric or IV dosing is needed.

Dose adjustments

Renal

No adjustment to the dose regimen in mild or moderate renal impairment. No change in starting dose in severe renal impairment (eGFR less than 30 mL/min/1.73 m2), but dose titration should be done with caution. No experience in patients undergoing dialysis - should not be used in these patients.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substance or to any of the excipients
Severe coronary heart disease or unstable angina
Myocardial infarction within the last 6 months
Decompensated cardiac failure if not under close medical supervision
Severe arrhythmias
Cerebrovascular events (e.g. transient ischaemic attack, stroke) within the last 3 months
Congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension
Concomitant use of strong inhibitors of CYP2C8 (e.g. gemfibrozil)

Side effects

Headache (very common; 64% during titration, 40% during maintenance)
Diarrhoea, nausea and vomiting (very common)
Jaw pain, myalgia, arthralgia and pain in extremity (very common)
Flushing (very common) and hypotension (common)
Anaemia / decreased haemoglobin, hyperthyroidism and sinus tachycardia (common)

Interactions

Strong CYP2C8 inhibitors (e.g. gemfibrozil) - contraindicated; gemfibrozil 600 mg twice daily is a strong CYP2C8 inhibitor
Moderate CYP2C8 inhibitors (e.g. clopidogrel, deferasirox, teriflunomide) - halve the total daily dose while co-administered
Selexipag and its active metabolite are metabolised mainly by CYP2C8 and to a smaller extent by CYP3A4; glucuronidation of the active metabolite via UGT1A3 and UGT2B7; both are OATP1B1/OATP1B3 substrates, selexipag is a weak P-gp substrate and the active metabolite a weak BCRP substrate
Warfarin - pharmacokinetics of selexipag and its active metabolite are not affected
Antihypertensive therapy and other causes of low blood pressure - additive effect from the vasodilatory properties of selexipag

Clinical monograph

How it works

Selexipag and its active metabolite selectively stimulate the prostacyclin IP receptor, producing pulmonary vasodilatation and inhibition of vascular smooth-muscle proliferation, thereby reducing pulmonary vascular resistance.

Prescribing in practice

Initiate and titrate under specialist supervision, increasing gradually to the highest tolerated level, as abrupt changes and the prostacyclin pharmacology drive dose-limiting effects.
Common pharmacological effects include headache, jaw pain, flushing, diarrhoea, nausea and limb pain, which are most prominent during up-titration.
Strong inhibitors of CYP2C8 markedly increase exposure and should be avoided, and the dose may need adjustment in hepatic impairment.

Monitoring

Monitor symptom control, functional status, tolerability during dose titration and concomitant interacting medicines, with specialist review of treatment response.

Counselling the patient

Side effects such as headache, jaw pain and flushing are common, especially as the dose is increased, and often ease with time.
Do not stop the medicine suddenly without specialist advice.
Tell your team about any new medicines, as some can interact.

Evidence & guidelines

The GRIPHON trial showed selexipag reduced a composite of morbidity and mortality events in pulmonary arterial hypertension, supporting its place in combination therapy.

Reference: GRIPHON trial NEJM 2015; 373(26):2522-2533; ESC/ERS PAH Guidelines 2022; NICE TA569; MHRA SPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

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