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Selexipag

Medically reviewed by Drugs.com. Last updated on Aug 17, 2020.

Pronunciation

(se LEX i pag)

Index Terms

  • ACT-293987
  • NS-304

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Uptravi: 200 mcg, 400 mcg, 600 mcg, 800 mcg, 1000 mcg, 1200 mcg, 1400 mcg, 1600 mcg

Tablet Therapy Pack, Oral:

Uptravi: 200 mcg (140s) and 800 mcg (60s) (200 ea)

Brand Names: U.S.

  • Uptravi

Pharmacologic Category

  • Prostacyclin
  • Prostacyclin IP Receptor Agonist
  • Vasodilator

Pharmacology

Selexipag is a selective prostacyclin IP receptor agonist. Prostacyclin is produced in the endothelial cells and induces vasodilation; also inhibits platelet aggregation. Patients with pulmonary arterial hypertension appear to have a dysregulation in the prostacyclin metabolic pathways (Galie 2013).

Absorption

Rapid (Kaufmann 2015)

Distribution

Vdss: 11.7L

Metabolism

Metabolism: Hepatic via CYP3A4, CYP2C8, UGT1A3 and UGT2B7; hydrolyzed by carboxylesterase1 to the active metabolite, ACT-333679, which is a major contributor to the activity (Kaufmann 2015); the active metabolite is then glucuronidated.

Excretion

Feces (~93%); urine (12%; as inactive metabolites)

Time to Peak

Selexipag: 1 to 3 hours; Active metabolite: 3 to 4 hours; Delayed with food

Half-Life Elimination

Terminal: Selexipag: 0.8 to 2.5 hours; Active metabolite: 6.2 to 13.5 hours

Protein Binding

~99%; to albumin and alpha-1 acid glycoprotein

Special Populations: Renal Function Impairment

A 40% to 70% increase in exposure to selexipag and its active metabolite was observed in severe renal impairment (estimated glomerular filtration rate ≥15 to <30 mL/minute/1.73 m2).

Special Populations: Hepatic Function Impairment

In mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment, exposure was 2- and 4-fold that seen in healthy subjects. Exposure to the active metabolite was doubled in moderate hepatic impairment.

Use: Labeled Indications

Pulmonary arterial hypertension: Treatment of pulmonary arterial hypertension (PAH) (WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH.

Contraindications

Concomitant use with strong CYP2C8 inhibitors (eg, gemfibrozil).

Canadian labeling: Additional contraindication (not in US labeling): Hypersensitivity to selexipag or any component of the formulation

Dosing: Adult

Pulmonary arterial hypertension:

Note: A clinician with expertise in pulmonary arterial hypertension should be consulted for all management decisions (ACCP [Klinger 2019]).

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.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Administration

Oral: Administer with or without food; tolerability may be improved when taken with food. Swallow tablets whole; do not split, crush, or chew.

Storage

Store at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted to 15°C and 30°C (59°F and 86°F).

Drug Interactions

CYP2C8 Inhibitors (Moderate): May increase serum concentrations of the active metabolite(s) of Selexipag. Management: Reduce the selexipag dose to once daily when combined with moderate CYP2C8 inhibitors. Revert back to twice daily selexipag dosing upon stopping the moderate CYP2C8 inhibitor. Consider therapy modification

CYP2C8 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of Selexipag. CYP2C8 Inhibitors (Strong) may increase the serum concentration of Selexipag. Avoid combination

Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C8 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase the serum concentration of CYP2C8 Substrates (High Risk with Inhibitors or Inducers). Monitor therapy

RifAMPin: May decrease serum concentrations of the active metabolite(s) of Selexipag. Management: Increase the selexipag dose (up to 2-fold) when combined with rifampin. Monitor for decreased selexipag efficacy. Consider therapy modification

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Flushing (12%)

Central nervous system: Headache (65%)

Dermatologic: Skin rash (11%)

Gastrointestinal: Diarrhea (42%), nausea (33%), vomiting (18%)

Neuromuscular & skeletal: Jaw pain (26%), limb pain (17%), myalgia (16%), arthralgia (11%)

1% to 10%:

Endocrine & metabolic: Hyperthyroidism (1%)

Gastrointestinal: Decreased appetite (6%)

Hematologic & oncologic: Decreased hemoglobin (below 10 g/dL: 9%), anemia (8%)

<1%, postmarketing, and/or case reports: Symptomatic hypotension

Warnings/Precautions

Concerns related to adverse effects:

• 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).

Monitoring Parameters

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

Pregnancy Considerations

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

Patient Education

What is this drug used for?

• It is used to treat high blood pressure in the lungs.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Diarrhea

• Jaw pain

• Nausea

• Vomiting

• Muscle pain

• Joint pain

• Painful extremities

• Flushing

• Lack of appetite

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Trouble breathing

• Wheezing

• Cough

• Severe loss of strength and energy

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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