se-LEX-i-pag

Therapeutic Classification: vasodilators

Pharmacologic Classification:

• Pulmonary arterial hypertension (WHO Group I).

• Prostacyclin receptor (IP receptor) agonist that leads to dilation of the pulmonary and arterial vasculature.

• Delayed disease progression and reduced hospitalizations.

Absorption: 49% absorbed following oral administration; food delays and ↓ extent of absorption.

Distribution: Highly protein bound.

Protein Binding: 99%.

Metabolism/Excretion: Hydrolyzed by carboxylesterase–1 to form active metabolite which contributes to pharmacologic activity. Also metabolized by CYP3A4 and CYP2C8 to form inactive metabolites. Primarily excreted in feces.

Half-life: 0.8–2.5 hr (selexipag); 6.2–13.5 hr (active metabolite).

(blood levels)

Contraindicated in:

• Concurrent use of strong CYP2C8 inhibitors
• Severe hepatic impairment
• Lactation: Lactation.

Use Cautiously in:

• Moderate hepatic impairment (↓ dose recommended)
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk; women with pulmonary hypertension are usually advised to avoid pregnancy
• Pedi: Safety and effectiveness not established in children.

Derm: flushing, rash.

GI: diarrhea, jaw pain, nausea, vomiting, ↓ appetite.

Hemat: anemia.

MS: arthralgia, myalgia.

Neuro: headache.

Resp: PULMONARY EDEMA.

Drug-Drug:

• Strong CYP2C8 inhibitors, including gemfibrozil may significantly ↑ levels of selexipag and its active metabolite which may ↑ risk of toxicity and effectiveness; concurrent use contraindicated.
• Moderate CYP2C8 inhibitors, including clopidogrel, teriflunomide and deferasirox may ↑ levels of selexipag and its active metabolite; consider ↓ initial dose of selexipag to once daily.
• CYP2C8 inducers, including rifampin may ↓ exposure to active metabolite; ↑ dose (up to twice the normal dose) of selexipag.

• PO (Adults): 200 mcg twice daily; ↑ dose by 200 mcg twice daily on weekly basis to highest tolerated dose (max = 1600 mcg twice daily); Concurrent use of moderate CYP2C8 inhibitor — 200 mcg once daily; ↑ dose by 200 mcg once daily on weekly basis as tolerated.

• Tablets: 200 mcg; 400 mcg; 600 mcg; 800 mcg; 1000 mcg; 1200 mcg; 1400 mcg; 1600 mcg;

• Monitor hemodynamic parameters and exercise tolerance prior to and periodically during therapy.

• May cause hyperthyroidism.
  • May cause ↓ hemoglobin.

• PO: Administer twice daily; food may improve tolerability. Swallow tablets whole; do not break, crush, or chew. ↑ dose by 200 mcg weekly to highest dose tolerated up to 1600 mcg twice daily. If dose is not tolerated, ↓ to previous dose.

• Instruct patient to take selexipag as directed. Take missed doses as soon as possible unless next dose is within 6 hrs. If 3 days are missed, restart at lower dose and titrate. Do not stop selexipag without consulting health care professional.
• Advise patient to notify health care professional if signs and symptoms of pulmonary edema (difficulty breathing, cough, chest pain, fatigue) occur.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy.

• Slowed disease progression and reduced hospitalizations for pulmonary arterial hypertension.

Uptravi

• Activity intolerance (Indications).