Pulmonary arterial hypertension
Adult: Initially, 200 mcg bid, increased in increments of 200 mcg bid at weekly intervals, according to patient's tolerability. Max: 1,600 mcg bid.
Indications and Dosage
Oral
Pulmonary arterial hypertension Adult: Initially, 200 mcg bid, increased in increments of 200 mcg bid at weekly intervals, according to patient's tolerability. Max: 1,600 mcg bid.
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Hepatic Impairment
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. |
Administration
film-coated tab: May be taken with or without food. Swallow whole, do not chew/crush/split.
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Contraindications
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.
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Special Precautions
Moderate hepatic impairment. Pregnancy and lactation.
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Adverse Reactions
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. |
Monitoring Parameters
Monitor LFT, thyroid function tests and for signs and symptoms of pulmonary oedema.
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Overdosage
Symptoms: Mild transient nausea. Management: Supportive therapy.
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Drug Interactions
Increased serum concentration w/ strong CYP2C8 inhibitor (e.g. gemfibrozil). Decreased serum concentration w/ CYP2C8 inducers (e.g. rifampicin).
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Action
Description: 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). |
Chemical Structure
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Storage
Store between 20-25°C.
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ATC Classification
B01AC27 - selexipag ; Belongs to the class of platelet aggregation inhibitors excluding heparin. Used in the treatment of thrombosis.
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References
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.
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