Selexipag

• Pulmonary Arterial Hypertension (PAH) (WHO Group 1):
  Indicated for the treatment of PAH to delay disease progression and reduce the risk of hospitalization. It is used in patients with WHO functional class II–III symptoms.
• Clinical Use:
  Can be used as monotherapy or in combination with other PAH therapies such as endothelin receptor antagonists or phosphodiesterase-5 inhibitors.

• Route: Oral administration
• Initial Dose: 200 mcg twice daily
• Titration: Increase dose by 200 mcg twice daily increments at weekly intervals as tolerated
• Maintenance Dose: Individualized based on patient tolerability and clinical response, with a maximum recommended dose of 1600 mcg twice daily
• Duration: Continuous treatment as prescribed by a healthcare provider
• Special Populations:
• Hepatic Impairment: Not recommended in severe impairment (Child-Pugh class C). Use with caution in mild to moderate hepatic impairment.
• Renal Impairment: No dose adjustment required for mild to moderate impairment. Data limited for severe impairment.
• Elderly: No specific dose adjustment; monitor for tolerability.

Selexipag is a selective agonist of the prostacyclin (IP) receptor, leading to activation of adenylate cyclase and increased cyclic adenosine monophosphate (cAMP) production in vascular smooth muscle cells. This results in vasodilation of pulmonary arteries, reducing pulmonary vascular resistance and improving cardiac output. The active metabolite, ACT-333679, contributes substantially to its therapeutic effects due to a longer half-life.

• Absorption: Rapidly absorbed with peak plasma concentrations achieved approximately 1 hour post-dose.
• Bioavailability: Approximately 49%.
• Distribution: Volume of distribution is approximately 119 liters.
• Metabolism: Extensively metabolized in the liver by hydrolysis to active metabolite ACT-333679; further metabolized by CYP2C8 and CYP3A4 enzymes.
• Half-life: Selexipag: 0.8 to 2.5 hours; Active metabolite: 6.2 to 13.5 hours.
• Elimination: Primarily excreted via urine (77%) and feces (14%) as metabolites.

• Pregnancy: No FDA pregnancy category assigned. Animal studies do not indicate teratogenicity; however, there are no adequate human studies. Use only if potential benefits justify potential risks.
• Lactation: Unknown if excreted in human milk. Breastfeeding is not recommended during treatment due to potential risks to the infant.

• Primary Therapeutic Class: Pulmonary vasodilator
• Subclass: Prostacyclin receptor (IP receptor) agonist

• Known hypersensitivity to Selexipag or any of its excipients
• Severe hepatic impairment (Child-Pugh class C)
• Concomitant use with strong CYP2C8 inhibitors without appropriate dose adjustment

• Monitor for systemic hypotension; risk of low blood pressure especially when combined with other vasodilators
• Increased risk of bleeding; caution when used with anticoagulants or in patients with bleeding disorders
• Avoid use in patients with pulmonary veno-occlusive disease due to risk of pulmonary edema
• Monitor liver function in patients with hepatic impairment
• Watch for signs of hypersensitivity reactions

Common:

• Headache
• Diarrhea
• Nausea
• Jaw pain
• Vomiting
• Myalgia and arthralgia
• Flushing
• Pain in extremities

Serious (Rare):

• Hypotension
• Bleeding complications
• Pulmonary edema
• Anemia

• Strong CYP2C8 inhibitors (e.g., gemfibrozil) can increase Selexipag plasma levels; concomitant use may require dose adjustment or avoidance
• CYP3A4 modulators may affect metabolism but to a lesser extent; monitor therapy accordingly
• Concomitant use with anticoagulants or antiplatelets may increase bleeding risk
• Additive hypotensive effects with other vasodilators

• Recent pulmonary hypertension guidelines recommend Selexipag as part of combination therapy in PAH management to improve clinical outcomes
• Post-marketing surveillance has emphasized vigilance for hypotension and bleeding risks
• No significant changes to dosing or new major safety warnings recently reported

• Store at controlled room temperature, 20°C to 25°C (68°F to 77°F)
• Protect from moisture and light
• Keep in original container tightly closed
• Do not freeze
• Keep out of reach of children