Selexipag

Indications

Selexipag is used for: Pulmonary Arterial Hypertension

Adult Dose

Pulmonary Arterial Hypertension Indicated for pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH Starting dose: 200 mcg PO BID Increase dose by increments of 200 mcg BID, usually at weekly intervals, to the highest tolerated dose; not to exceed 1600 mcg BID Hepatic impairment Mild (Child-Pugh A): No dosage adjustment required Moderate (Child-Pugh B): Starting dose is 200 mcg qDay; increase by increments of 200 mcg/day at weekly intervals, as tolerated Severe (Child-Pugh C): Avoid use

Child Dose

Renal Dose

Renal impairment: No dosage adjustment required

Administration

Swallow tablet whole; do not split, crush, or chew Tolerability may be improved when taken with food Dose interruptions and discontinuations If a dose is missed, patients should take a missed dose as soon as possible unless the next dose is within the next 6 hr If treatment is missed for ?3 days, restart selexipag at a lower dose and then titrate to desired effect and tolerance

Contra Indications

Concomitant use of strong CYP2C8 inhibitors (eg, gemfibrozil)

Precautions

If signs of pulmonary edema occur, consider the possibility of associated pulmonary veno-occlusive disease (PVOD); if PVOD is confirmed, discontinue selexipag Lactation Unknown if distributed in human breast milk Selexipag or its metabolites were present in the milk of rats

Pregnancy-Lactation

Pregnancy No adequate and well-controlled studies with selexipag exist in pregnant women Animal studies Reproduction studies performed with selexipag showed no clinically relevant effects on embryofetal development and survival A slight reduction in maternal as well as in fetal body weight was observed when pregnant rats were administered selexipag during organogenesis at a dose producing an exposure ~47 times that in humans at the maximum recommended human dose Lactation Unknown if distributed in human breast milk Selexipag or its metabolites were present in the milk of rats Because many drugs are present in the human milk and because of the potential for serious adverse reactions in nursing infants, discontinue nursing or discontinue selexipag

Interactions

Coadministration with strong CYP2C8 inhibitors may result in a significant increase in exposure to selexipag and its active metabolite Avoid concomitant administration with strong inhibitors of CYP2C8 Concomitant administration with an inducer of CYP2C8 and UGT 1A3 and 2B7 enzymes (rifampin) halved exposure to active metabolite; increase dose up to twice of the normal dose when co-administered with rifampin; reduce therapy dose when rifampin is stopped

Side Effects

Side effects of Selexipag : >10% Headache (65%) Diarrhea (42%) Jaw pain (26%) Nausea (33%) Vomiting (18%) Pain in extremity (17%) Myalgia (16%) Flushing (12%) Arthralgia (11%) Rash (11%) 1-10% Hemoglobin decreased below 10 g/dL (8.6%) Anemia (8%) Decreased appetite (6%) Frequency Not Defined TSH reduced (up to −0.3 MU/L from a baseline of 2.5 MU/L) Symptomatic hypotension

Mode of Action

Selectively activates the prostacyclin receptor (ie, IP-receptor), one of 5 types of prostanoid receptors Unlike prostacyclin analogs, selexipag is selective for the IP receptor over other prostanoid receptors (ie, EP1-4, DP, FP, TP) Activating the IP receptor induces vasodilation and inhibits proliferation of vascular smooth muscle cells