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