Drug reference

Selexipag

Vasodilator · Pulmonary arterial hypertension

Also known as Uptravi

VasodilatorPulmonary arterial hypertension

CDSCO approvedSchedule H

EXCRETION

—

not curated

INTERACTIONS

2 major

incl. contraindicated

PREGNANCY

Manufacturer advises avoid—no information available.

FDA category + note

Top interactionssee all 3 →

Strong Cyp2c8 InhibitorsContraindicatedTextbookG&G 14e · p702
GemfibrozilSevereDatabaseDDInter

Mechanism

Selexipag is a selective prostacyclin (IP) receptor agonist. It is an oral nonprostanoid prodrug that is rapidly hydrolyzed to the selective prostaglandin I receptor agonist ACT-333679. It has a mechanism of action similar to prostacyclin.

Indications

Pulmonary arterial hypertension either as combination therapy (if insufficiently controlled with an endothelin receptor antagonist and/or a phosphodiesterase type-5 inhibitor), or as monotherapy (initiated under specialist supervision)Long-term treatment of pulmonary arterial hypertension in adults with WHO functional class III, as combination therapy in patients insufficiently controlled with an endothelin receptor antagonist and a phosphodiesterase type-5 inhibitorTriple combination therapy for the treatment of pulmonary arterial hypertension (PAH) in adults with WHO functional class (FC) III who are insufficiently controlled on dual therapy with an endothelin receptor antagonist and a phosphodiesterase type-5 inhibitorreduced risk of morbidity and mortality in patients with PAHalternative for epoprostenol in combination therapy for severe PAH (functional class IV)

Dosing

Adult: Initially 200 micrograms twice daily, increased in steps of 200 micrograms twice daily at weekly intervals up to the highest tolerated dose, usual maintenance 200–1600 micrograms twice daily. Initial dose and first dose after each dose increase should be taken in the evening. Dose frequency should be reduced to once daily with concurrent use of clopidogrel or moderate CYP2C8 inhibitors.
Renal adjustment: Caution with dose titration in severe impairment.
Hepatic adjustment: Caution in moderate impairment (risk of increased exposure); avoid in severe impairment (no information available). Initial dose reduction to 200 micrograms once daily in moderate impairment, increased in steps of 200 micrograms once daily at weekly intervals up to the highest tolerated dose.
Max dose: 3200 micrograms per day

Pharmacokinetics

Half-life

1–2 h (selexipag), 10–14 h (active metabolite ACT-333679)

Metabolism

Rapidly hydrolyzed in the liver to an active metabolite (ACT-333679). Substrate of CYP2C8, CYP3A4, and P-glycoprotein.

Contraindications

Cerebrovascular event (within the last 3 months)
Congenital or acquired valvular defects with myocardial function disorders (not related to pulmonary hypertension)
Decompensated cardiac failure (unless under close medical supervision)
Myocardial infarction (within last 6 months)
Severe arrhythmias
Severe coronary heart disease
Unstable angina

Side effects

Common

Abdominal painAnaemiaAppetite decreasedArthralgiaDiarrhoeaFlushingHeadacheHyperthyroidismHypotensionMyalgiaNasal congestionNasopharyngitisNauseaPainSkin reactionsVomitingWeight decreasedjaw paindizzinessdiarrhea

Serious