SELEXIPAG
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SELEXIPAG (SELEXIPAG).
Selective agonist of the prostacyclin (IP) receptor, causing vasodilation and inhibition of platelet aggregation via increased cAMP levels.
| Metabolism | Primarily metabolized by CYP2C8 and CYP3A4; minor contribution from UGT1A3, UGT2B7, and CYP2C9. |
| Excretion | Primarily hepatic metabolism (approximately 97% of dose) via CYP2C8 and CYP3A4; biliary/fecal excretion of metabolites accounts for ~77% of total clearance; renal excretion <1% as unchanged drug. |
| Half-life | Terminal elimination half-life is approximately 6–8 hours following intravenous administration; with oral administration, the effective half-life is ~6–9 hours due to enterohepatic recirculation; clinical context: dosing every 6 hours is required to maintain therapeutic plasma concentrations. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution at steady state is approximately 1.7 L/kg (range 1.1–2.5 L/kg), indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 90% under fed conditions; absorption is delayed and reduced by high-fat meals, but overall systemic exposure is increased by ~30% compared to fasting. |
| Onset of Action | For oral tablets, onset of clinical effect (reduction in pulmonary vascular resistance) typically occurs within 1–2 hours; for intravenous infusion, onset is within 15–30 minutes. |
| Duration of Action | Duration of hemodynamic effect is approximately 6–8 hours after an oral dose, consistent with dosing interval; clinical effects on exercise capacity and symptoms are sustained with chronic dosing. |
Oral, starting dose 200 mcg twice daily, titrated in increments of 200 mcg twice daily at weekly intervals as tolerated to a maximum of 1600 mcg twice daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (eGFR <15 mL/min/1.73 m²) or on dialysis; use with caution. |
| Liver impairment | Contraindicated in Child-Pugh class C. For Child-Pugh class A or B, reduce starting dose to 200 mcg once daily and titrate cautiously; monitor closely. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended; initiate at 200 mcg twice daily and titrate based on tolerability, considering increased sensitivity and comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SELEXIPAG (SELEXIPAG).
| Breastfeeding | No data on selexipag in human milk. In animal studies, selexipag is excreted in rat milk. M/P ratio unknown. Breastfeeding is not recommended during treatment and for at least 7 days after last dose. |
| Teratogenic Risk | Selexipag is contraindicated in pregnancy. Animal studies show increased post-implantation loss and reduced fetal weights. No adequate human data; based on its mechanism (IP receptor agonist), risk of fetal harm cannot be excluded, particularly in the first trimester. |
| Fetal Monitoring |
■ FDA Black Box Warning
Not recommended for use in patients with severe hepatic impairment (Child-Pugh class C).
| Serious Effects |
["Severe hepatic impairment (Child-Pugh class C).","Concomitant use with strong CYP2C8 inhibitors (e.g., gemfibrozil)."]
| Precautions | ["Elderly patients may have increased exposure.","Patients with hepatic impairment: dose adjustment required for moderate impairment; avoid in severe impairment.","Concomitant use with strong CYP2C8 inhibitors (e.g., gemfibrozil) increases selexipag exposure by 11-fold; reduce dose.","Concomitant use with strong CYP3A4 inducers (e.g., rifampin) reduces exposure; monitor efficacy.","May cause headache, diarrhea, jaw pain, flushing, and nausea."] |
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| Pregnancy status should be verified before starting selexipag. Women of childbearing potential must use effective contraception. Monitor for pulmonary arterial hypertension worsening; no specific fetal monitoring recommended beyond standard obstetric care. |
| Fertility Effects | No human data on fertility. In animal studies, no effects on male or female fertility were observed at exposures up to 5 times the human exposure. However, due to limited data, effect on human fertility cannot be excluded. |