selexipag

Absorption: 49% absorbed following oral administration; food delays and ↓ extent of absorption. IV administration results in complete bioavailability

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).

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1–3 hr (selexipag); 3–4 hr (active metabolite)	unknown
IV	rapid	end of infusion	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
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.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: flushing, rash

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

Hemat: anemia

MS: arthralgia, myalgia

Neuro: headache

Resp: PULMONARY EDEMA

Interactions ⬆ ⬇

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.

Route/Dosage ⬆ ⬇

IV route should be used for patients who are temporarily unable to tolerate oral therapy.
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.
IV (Adults ): IV dose should be based on patient's current dose of oral selexipag: Previously taking selexipag 200 mcg PO twice daily: 225 mcg IV twice daily; Previously taking selexipag 400 mcg PO twice daily: 450 mcg IV twice daily; Previously taking selexipag 600 mcg PO twice daily: 675 mcg IV twice daily; Previously taking selexipag 800 mcg PO twice daily: 900 mcg IV twice daily; Previously taking selexipag 1000 mcg PO twice daily: 1125 mcg IV twice daily; Previously taking selexipag 1200 mcg PO twice daily: 1350 mcg IV twice daily; Previously taking selexipag 1400 mcg PO twice daily: 1575 mcg IV twice daily; Previously taking selexipag 1600 mcg PO twice daily: 1800 mcg IV twice daily.

Hepatic Impairment

PO (Adults ): Moderate hepatic impairment: 200 mcg once daily; ↑ dose by 200 mcg once daily on weekly basis as tolerated.

Availability ⬆ ⬇

(Generic available)

Tablets: 200 mcg; 400 mcg; 600 mcg; 800 mcg; 1000 mcg; 1200 mcg; 1400 mcg; 1600 mcg
Lyophilized powder for injection: 1800 mcg/vial

Assessment ⬆ ⬇

Monitor hemodynamic parameters and exercise tolerance prior to and periodically during therapy.
Assess for pulmonary edema during therapy. If associated pulmonary veno-occlusive disease confirmed,discontinue selexipag.

Lab Test Considerations:

May cause hyperthyroidism.
- May cause ↓ hemoglobin.

Implementation ⬆ ⬇

PO: Administer twice daily; food may improve tolerability. DNC: 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.

IV Administration:

Patient/Family Teaching ⬆ ⬇

Instruct patient to take selexipag as directed. Take missed doses as soon as possible unless next dose is within 6 hr. If ≥3 days are missed, restart at lower dose and titrate. Do not stop selexipag without consulting health care professional.
Advise patient to read Patient Information prior to starting therapy and with each Rx refill in case of changes.
Advise patient to notify health care professional of difficulty breathing, cough, chest pain, or fatigue.
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.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇