Selexipag

Moderate (Child-Pugh class B): Initially, 200 mcg once daily, increased by 200 mcg once daily at wkly intervals, according to patient’s tolerability. Max: 1,600 mcg once daily.
Severe (Child-Pugh class C): Avoid use.

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

Severe CHD or unstable angina, recent MI w/in 6 mth, decompensated cardiac failure, severe arrhythmias, TIA or recent stroke w/in 3 mth, congenital valvular defects. Concomitant use w/ strong CYP2C8 inhibitor. Severe hepatic impairment.

Moderate hepatic impairment. Pregnancy and lactation.

Significant: Pulmonary veno-occlusive disease, hypotension, hyperthyroidism.
Nervous: Headache.
CV: Flushing.
GI: Diarrhoea, nausea, vomiting, decreased appetite, abdominal pain.
Resp: Nasopharyngitis, nasal congestion.
Endocrine: Decreased TSH, wt decrease.
Haematologic: Decreased Hb, anaemia.
Musculoskeletal: Jaw pain, limb pain, myalgia, arthralgia.
Dermatologic: Rash, urticaria, erythema.

Monitor LFT, thyroid function tests and for signs and symptoms of pulmonary oedema.

Symptoms: Mild transient nausea. Management: Supportive therapy.

Increased serum concentration w/ strong CYP2C8 inhibitor (e.g. gemfibrozil). Decreased serum concentration w/ CYP2C8 inducers (e.g. rifampicin).

Description:
Mechanism of Action: Selexipag is a selective non prostanoid prostacyclin (IP) receptor agonist, that stimulates the release of prostacyclin, which is responsible for inducing peripheral and pulmonary vasodilation. It also inhibits platelet aggregation.
Pharmacokinetics:
Absorption: Rapidly absorbed from the GI tract. Bioavailability: Approx 49%. Time to peak plasma concentration: 1-3 hr (selexipag); 3-4 hr (ACT-333679).
Distribution: Volume of distribution: 11.7 L. Plasma protein binding: Approx 99%, to albumin and α₁-acid glycoprotein.
Metabolism: Hydrolysed in the liver by carboxylesterase 1 into active metabolite ACT-333679, which is then metabolised by UGT1A3 and UGT2B7 via glucuronidation.  Undergoes oxidative metabolism by CYP2C8 enzyme into hydroxylated and dealkylated metabolites.
Excretion: Mainly via faeces (approx 93%); urine (12%). Terminal half-life: 0.8-2.5 hr (selexipag); 6.2-13.5 (ACT-333679).

Source: National Center for Biotechnology Information. PubChem Database. Selexipag, CID=9913767, https://pubchem.ncbi.nlm.nih.gov/compound/Selexipag (accessed on Jan. 23, 2020)

Store between 20-25°C.

Other Antihypertensives

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

Anon. Selexipag. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 12/12/2017.

Buckingham R (ed). Selexipag. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 12/12/2017.

Joint Formulary Committee. Selexipag. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 12/12/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Selexipag. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 12/12/2017.

Uptravi Tablet, Coated (Actellion Pharmaceuticals US, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 12/12/2017.