Selexipag

B01A - Antithrombotic agents ATC B01AC27 Small molecule approved 2015 Oral Parenteral Prodrug Natural product

Active form: Laselipag.

JFDA label: Uptravi film-coated tablet

Mechanism of Action

Agonist of Prostacyclin receptor — Prostanoid IP receptor agonist

Target	Action	Gene / class
Prostacyclin receptor efficacy	AGONIST	PTGIR

Indications

Approved

Pulmonary arterial hypertension

Contraindications

Source: Lexicomp

Additional contraindication (not in US labeling): Hypersensitivity to selexipag or any component of the formulation Absolute
Concomitant use with strong CYP2C8 inhibitors (eg, gemfibrozil) Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (1)

Very Common Flushing

Nervous system disorders (1)

Very Common Headache

Blood and lymphatic system disorders (2)

Common anemia · Decreased hemoglobin

Metabolism and nutrition disorders (1)

Common Hyperthyroidism

Gastrointestinal disorders (4)

Very Common Diarrhea · nausea · vomiting

Common Decreased appetite

Skin and subcutaneous tissue disorders (1)

Very Common Skin rash

Musculoskeletal and connective tissue disorders (4)

Very Common arthralgia · Jaw pain · limb pain · myalgia

Dosing

Source: Lexicomp

Pulmonary arterial hypertension: Oral: Initial: 200 mcg twice daily; increase by 200 mcg twice daily, usually at weekly intervals, to the highest tolerated dose (maximum dose: 1,600 mcg twice daily). If a dose is not tolerated, reduce dose to previously tolerated dose. Missed dose: If dose is missed, take dose as soon as possible unless the next dose is within the next 6 hours. If ≥3 days of treatment are missed, restart at a lower dose and then retitrate.

Refer to adult dosing.

Glomerular filtration rate (estimated) ≥15 mL/minute/1.73 m2: No dosage adjustment necessary. Glomerular filtration rate (estimated) 2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Dialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Mild hepatic impairment (Child-Pugh class A): No dosage adjustment necessary. Moderate hepatic impairment (Child-Pugh class B): Initial: 200 mcg once daily; may increase by 200 mcg once daily at weekly intervals, as tolerated. Severe hepatic impairment (Child-Pugh class C): Avoid use.

Warnings & Precautions

Source: Lexicomp

Pulmonary edema

If signs/symptoms of pulmonary edema occur, consider the possibility of associated pulmonary veno-occlusive disease (PVOD). If PVOD is confirmed, discontinue treatment. Disease-related concerns

Hepatic impairment

Use with caution in patients with moderate hepatic impairment (dosage modification is recommended); avoid use in patients with severe hepatic impairment (has not been studied). Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information

Pregnancy & Lactation

Pregnancy

Adverse events have not been observed in animal reproduction studies. Women with pulmonary arterial hypertension (PAH) are encouraged to avoid pregnancy (McLaughlin 2009).

Lactation

It is not known if selexipag is present in breast milk. Due to the potential for serious adverse reactions in the breastfeeding infant, the manufacturer recommends a decision be made to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother.

Monitoring

Clinical pearl	Liver function tests. Monitor for signs of pulmonary edema and for improvements in pulmonary function, exercise tolerance, and quality of life.

Chemistry & Properties

Formula	C26H32N4O4S
Molecular weight	496.63 g/mol
IUPAC name	2-[4-[(5,6-diphenylpyrazin-2-yl)-propan-2-ylamino]butoxy]-N-methylsulfonylacetamide
CAS	475086-01-2
PubChem CID	9913767
InChIKey	`QXWZQTURMXZVHJ-UHFFFAOYSA-N`
logP	3.9 (XLogP 3.8)
Polar surface area	101.49 Å²
H-bond acceptors / donors	7 / 1
Drug-likeness (QED)	0.38
Lipinski violations	0

SMILES

CC(C)N(CCCCOCC(=O)NS(C)(=O)=O)c1cnc(-c2ccccc2)c(-c2ccccc2)n1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2B6	Inhibitor	—
CYP2C19	Inhibitor	—
CYP2C19	Substrate	—
CYP2C8	Inhibitor	—
CYP2C9	Inhibitor	—
CYP3A4	Substrate	—

Receptor binding (top 1)

Target	Action	Affinity
IP receptor (PTGIR)	Agonist	pKi 6.6

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)OATP1B1 (Substrate)OATP1B3 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Gemfibrozil	major
Abametapir (topical)	moderate
Abiraterone	moderate
Acebutolol	moderate
Acetazolamide	moderate
Alfuzosin	moderate
Aliskiren	moderate
Alprostadil	moderate
Amifostine	moderate
Amiloride	moderate
Amlodipine	moderate
Amyl Nitrite	moderate
Apalutamide	moderate
Apomorphine	moderate
Apraclonidine	moderate
Atenolol	moderate
Azilsartan medoxomil	moderate
Bempedoic acid	moderate
Benazepril	moderate
Bendroflumethiazide	moderate
Benzthiazide	moderate
Bepridil	moderate
Betaxolol	moderate
Bisoprolol	moderate
Brigatinib	moderate
Brimonidine (ophthalmic)	moderate
Brimonidine (topical)	moderate
Bromotheophylline	moderate
Bumetanide	moderate
Canagliflozin	moderate
Capmatinib	moderate
Captopril	moderate
Carteolol	moderate
Carvedilol	moderate
Chlorothiazide	moderate
Chlorthalidone	moderate
Clevidipine	moderate
Clonidine	moderate
Clopidogrel	moderate
Cyclandelate	moderate

Showing 40 of 100+.

Registered Products (9)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Uptravi Film-coated tablets	Film-Coated Tablet 800 mcg	60 tab	Shawi & Rushedat Drug Store	—
Uptravi Film-coated tablets	Film-Coated Tablet 1000 mcg	60 tab	Shawi & Rushedat Drug Store	—
Uptravi Film-coated tablets	Film-Coated Tablet 1200 mcg	60 tab	Shawi & Rushedat Drug Store	—
Uptravi Film-coated tablets	Film-Coated Tablet 1400 mcg	60 tab	Shawi & Rushedat Drug Store	—
Uptravi Film-coated tablets	Film-Coated Tablet 600 mcg	60 tab	Shawi & Rushedat Drug Store	—
Uptravi film-coated tablet	Film-Coated Tablet 200 mcg	140 tab pack varies	Shawi & Rushedat Drug Store	—
Uptravi film-coated tablet	Film-Coated Tablet 400 mcg	60 tab	Shawi & Rushedat Drug Store	—
Uptravi film-coated tablet	Film-Coated Tablet 200 mcg	60 tab pack varies	Shawi & Rushedat Drug Store	—
uptravi film coated tablet	Film-Coated Tablet 1600 mcg	60 tab	Shawi & Rushedat Drug Store	—