selexipag: clinical use

Prescribing considerations

• Initiation and monitoring should be undertaken by a clinician experienced in PAH.
• Treatment is individually titrated according to prostacyclin-like adverse effects and tolerability.
• Consider vulnerability to vasodilation in people with resting hypotension, hypovolaemia, antihypertensive treatment, severe left-ventricular outflow obstruction or autonomic dysfunction.
• Use caution in severe renal impairment and in people older than 75; avoid use during dialysis because clinical experience is absent.
• Do not use in severe hepatic impairment; moderate impairment requires an altered specialist-managed regimen.
• If withdrawal is necessary, reduce gradually while introducing an alternative PAH treatment.

Contraindications and cautions

• Hypersensitivity to selexipag or an excipient
• Severe coronary heart disease or unstable angina
• Myocardial infarction within the previous six months
• Decompensated cardiac failure unless under close medical supervision
• Severe arrhythmias
• Stroke, transient ischaemic attack or another cerebrovascular event within the previous three months
• Clinically relevant myocardial dysfunction caused by congenital or acquired valvular disease unrelated to pulmonary hypertension
• Concurrent strong CYP2C8 inhibition, including gemfibrozil

Monitoring

• Assess blood pressure and symptoms of hypotension.
• Review tolerability closely during titration, particularly headache, gastrointestinal effects, flushing and musculoskeletal pain.
• Check thyroid function when symptoms or signs suggest hyperthyroidism.
• Consider haemoglobin assessment where anaemia is suspected or clinically relevant.
• Investigate pulmonary oedema for possible pulmonary veno-occlusive disease and discontinue if that diagnosis is confirmed.
• Continue specialist assessment of PAH status and treatment response.

Clinical pharmacology

Selexipag is a non-prostanoid, selective IP-receptor agonist. Carboxylesterases convert it to a substantially more potent active metabolite; both parent and metabolite are highly protein-bound and metabolised mainly through CYP2C8, with contributions from CYP3A4 and glucuronidation pathways.

Formulation and product differences

• The selected product is a dark-yellow, round film-coated tablet marked “14” on one side.
• The coating protects the active substance from light, so tablets must not be divided or crushed.
• Other tablet strengths have different colours and markings to support individualised treatment; careful identification is important during titration.

Tablet

Route: Oral

Strengths: 200 micrograms, 400 micrograms, 600 micrograms, 800 micrograms, 1000 micrograms, 1200 micrograms, 1400 micrograms, 1600 micrograms