Selexipag

Selexipag Uses, Dosage, Side Effects, Food Interaction and all others data.

Selexipag was approved by the United States FDA on December 22, 2015 for the treatment of pulmonary arterial hypertension (PAH) to delay disease progression and reduce risk of hospitalization. PAH is a relatively rare disease with usually a poor prognosis requiring more treatment options to prolong long-term outcomes. Marketed by Actelion Pharmaceuticals under brand name Uptravi, selexipag and its active metabolite, ACT-333679 (MRE-269), act as agonists of the prostacyclin receptor to increase vasodilation in the pulmonary circulation and decrease elevated pressure in the blood vessels supplying blood to the lungs.

At the maximum tolerated dose of 1600 mcg twice per day, selexipag was not found to prolong the QT interval to a clinically relevant extent. Both selexipag and its metabolite caused concentration-dependent inhibition of platelet aggregation in vitro with IC50 of 5.5 µM and 0.21 µM, respectively. However, at clinically relevant concentrations, there was no effect on platelet aggregation test parameters following multiple dose administration of selexipag in healthy patients.

Selexipag
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Selexipag
Availability	Prescription only
Generic	Selexipag
Selexipag Other Names	Selexipag
Related Drugs	sildenafil, tadalafil, Revatio, Adempas, Opsumit, ambrisentan
Weight	1000mcg, 1200mcg, 1400mcg, 1600mcg, 200mcg, 200mcg + 800mcg, 400mcg, 600mcg, 800mcg
Type	Oral tablet
Formula	C₂₆H₃₂N₄O₄S
Weight	Average: 496.63 Monoisotopic: 496.2144267
Protein binding	Both selexipag and its active metabolite are highly protein bound, approximately 99%.
Groups	Approved
Therapeutic Class
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Selexipag is a non prostanoid IP prostacyclin receptor agonist used to treat pulmonary arterial hypertension.

Selexipag is indicated for the treatment of pulmonary arterial hypertension (PAH) to delay disease progression and reduce risk of hospitalization.

Selexipag is also used to associated treatment for these conditions: Pulmonary Arterial Hypertension (PAH) (WHO Group 1 PH)

How Selexipag works

Selexipag is a selective prostacyclin (IP, also called PGI2) receptor agonist. The key features of pulmonary arterial hypertension include a decrease in prostacyclin and prostacyclin synthase (enzyme that helps produce prostacyclin) in the lung. Prostacyclin is a potent vasodilator with anti-proliferative, anti-inflammatory, and anti-thrombotic effects; therefore, there is strong rationale for treatment with IP receptor agonists. Selexipag is chemically distinct as it is not PGI2 or a PGI2 analogue and has high selectivity for the IP receptor. It is metabolized by carboxylesterase 1 to yield an active metabolite (ACT-333679) that is approximately 37 times more potent than selexipag. Both selexipag and its metabolite are selective for the IP receptor over other prostanoid receptors.

Toxicity

A 40-70% increase in exposure was observed in subjects with severe renal impairment.

Food Interaction

No interactions found.

[Minor] Food prolongs the gastrointestinal absorption of selexipag.

When taken with food, the time to peak concentration (Tmax) was delayed and peak plasma concentration (Cmax) was approximately 30% lower.

Selexipag systemic exposure (AUC) and that of its active metabolite did not significantly change, however.

Selexipag may be taken with or without food.

Tolerability may be improved when taken with food.

Selexipag Drug Interaction

Moderate: diltiazem, sacubitril / valsartan, dapagliflozinUnknown: fluticasone / salmeterol, fexofenadine, glimepiride, thyroid desiccated, ipratropium nasal, cranberry, diphenhydramine, multivitamin with minerals, clotrimazole, albuterol / ipratropium, cholecalciferol, roflumilast, multivitamin with minerals, glipizide, liraglutide, linagliptin, dulaglutide

Selexipag Disease Interaction

Moderate: liver impairment, renal impairment

Elimination Route

After oral administration, maximum concentrations of selexipag and its metabolite were observed to be reached at 1-3 and 3-4 hours, respectively. Absorption was impaired in the presence of food, resulting in delayed time to maximum concentration as well as ~30% lower peak plasma concentration. However, exposure was not found to be significantly affected by food.