Selexipag

Patients concomitantly taking moderate CYP2C8 inhibitors (e.g. clopidogrel, deferasirox, teriflunomide): Reduce the dosing to once daily. When the moderate CYP2C8 inhibitor is discontinued, revert the selexipag dosing back to bid.

Patients concomitantly taking CYP2C8 inducers (e.g. rifampicin): Dose adjustment may be required (refer to local guidelines).

Moderate (Child-Pugh class B): Initially, 200 mcg once daily, then increased in increments of 200 mcg once daily at weekly intervals to the patient's highest tolerated dose. Max: 1,600 mcg once daily. Severe (Child-Pugh class C): Avoid use.

Selexipag film-coated tab: May be taken with or without food. Swallow whole, do not chew/crush/split.

Cerebrovascular event (e.g. stroke, TIA) within the last 3 months, MI within the last 6 months, decompensated cardiac failure (if not under close medical supervision); congenital or acquired valvular defects with clinically relevant myocardial function disorders (unrelated to pulmonary hypertension); severe arrhythmia, severe coronary heart disease, unstable angina. Concomitant use with strong CYP2C8 inhibitors (e.g. gemfibrozil).

Severe renal and moderate hepatic impairment. Avoid use in severe hepatic impairment. Elderly. Pregnancy and lactation. Concomitant use with CYP2C8 inducers (e.g. rifampicin) and moderate CYP2C8 inhibitors (e.g. clopidogrel, deferasirox, teriflunomide).

Significant: Pulmonary oedema (which may be associated with pulmonary veno-occlusive disease); hypotension, hyperthyroidism; moderate increase in heart rate (following each dose).
Blood and lymphatic system disorders: Anaemia.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain.
General disorders and administration site conditions: Pain.
Investigations: Decreased weight.
Metabolism and nutrition disorders: Decreased appetite.
Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, jaw pain, pain in extremity.
Nervous system disorders: Headache.
Respiratory, thoracic and mediastinal disorders: Nasopharyngitis, nasal congestion.
Skin and subcutaneous tissue disorders: Rash, urticaria, erythema, angioedema.
Vascular disorders: Flushing.

Monitor LFTs; thyroid function test as clinically indicated. Assess for improvement in pulmonary function, exercise tolerance, and quality of life; signs and symptoms of pulmonary oedema or respiratory distress.

Symptom: Mild, transient nausea. Management: Symptomatic and supportive treatment.

Concomitant use with strong CYP2C8 inhibitors (e.g. gemfibrozil) significantly increases the exposure to selexipag and its active metabolite. Increased exposure to selexipag active metabolite with moderate CYP2C8 inhibitors (e.g. clopidogrel, deferasirox, teriflunomide). May reduce the exposure to the active metabolite of selexipag with CYP2C8 inducers (e.g. rifampicin).

Prolonged absorption with food, resulting in delayed time to peak plasma concentration; however, exposure of selexipag and its active metabolite is not significantly changed.

Description:
Mechanism of Action: Selexipag is a selective non-prostanoid prostacyclin (IP) receptor agonist that stimulates the release of endogenous prostacyclin, which causes vasodilation. This activity results in vasodilatory, antiproliferative and antifibrotic effects.
Pharmacokinetics:
Absorption: Rapidly absorbed. Prolonged absorption with food, resulting in delayed time to peak concentration; however, exposure of selexipag and its active metabolite is not significantly changed. Bioavailability: Approx 49%. Time to peak plasma concentration: 1-3 hours (selexipag); 3-4 hours (ACT-333679).
Distribution: Plasma protein binding: Approx 99%, mainly to albumin and α₁-acid glycoprotein.
Metabolism: Metabolised in the liver and intestines via hydrolysis by carboxylesterases to form ACT-333679 (active metabolite); further undergoes oxidative metabolism in the liver mainly by CYP2C8 and to a lesser extent by CYP3A4 into hydroxylated and dealkylated products. ACT-333679 also undergoes glucuronidation by UGT1A3 and UGT2B7.
Excretion: Mainly via faeces (approx 93%); urine (12% as inactive metabolites). Terminal elimination half-life: 0.8-2.5 hours (selexipag); 6.2-13.5 hours (ACT-333679).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 9913767, Selexipag. https://pubchem.ncbi.nlm.nih.gov/compound/Selexipag. Accessed Aug. 27, 2025.

Store between 15-30°C.

Other Antihypertensives

B01AC27 - selexipag ; Belongs to the class of platelet aggregation inhibitors excluding heparin. Used in the treatment of thrombosis.

Brayfield A, Cadart C (eds). Selexipag. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 12/08/2025.

Janssen-Cilag (New Zealand) Ltd. Uptravi Film Coated Tablets data sheet 12 December 2024. Medsafe. http://www.medsafe.govt.nz. Accessed 12/08/2025.

Joint Formulary Committee. Selexipag. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 12/08/2025.

Selexipag. UpToDate Lexidrug, AHFS DI (Adult and Pediatric) Online. American Society of Health-System Pharmacists, Inc. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 12/08/2025.

Selexipag. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 12/08/2025.

Uptravi 400 microgram Film-coated Tablets (Janssen-Cilag Limited). MHRA. https://products.mhra.gov.uk. Accessed 12/08/2025.

Uptravi Coated Tablet, Titration Pack and Injection Powder for Solution (Actelion Pharmaceuticals US, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 12/08/2025.

Uptravi Film-coated Tablet (Johnson & Johnson Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 12/08/2025.