(se LEX i pag)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
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.
- Prostacyclin IP Receptor Agonist
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).
Rapid (Kaufmann 2015)
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.
Feces (~93%); urine (12%; as inactive metabolites)
Time to Peak
Selexipag: 1 to 3 hours; Active metabolite: 3 to 4 hours; Delayed with food
Terminal: Selexipag: 0.8 to 2.5 hours; Active metabolite: 6.2 to 13.5 hours
~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
There are no contraindications listed in the manufacturer’s US labeling.
Canadian labeling: Hypersensitivity to selexipag or any component of the formulation
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.
Dosing: Renal Impairment
Glomerular filtration rate (estimated) ≥15 mL/minute/1.73 m2: No dosage adjustment necessary.
Glomerular filtration rate (estimated) <15 mL/minute/1.73 m2: 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).
Glomerular filtration rate (estimated) ≥30 mL/min/1.73 m2: No dosage adjustment necessary.
Glomerular filtration rate (estimated) <30 mL/minute/1.73 m2: No dosage adjustment necessary; use caution during titration.
Dialysis: Avoid use (has not been studied).
Dosing: Hepatic Impairment
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.
Oral: Administer with or without food; tolerability may be improved when taken with food. Swallow tablets whole; do not split, crush, or chew.
Store at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted to 15°C and 30°C (59°F and 86°F).
Abiraterone Acetate: May increase the serum concentration of CYP2C8 Substrates. Monitor therapy
CYP2C8 Inhibitors (Moderate): May decrease the metabolism of CYP2C8 Substrates. Monitor therapy
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
Deferasirox: May increase the serum concentration of CYP2C8 Substrates. Monitor therapy
Lumacaftor: May increase the serum concentration of CYP2C8 Substrates. Lumacaftor may decrease the serum concentration of CYP2C8 Substrates. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP2C8 Substrates. Management: Use CYP2C8 substrates at the lowest recommended dose, and monitor closely for adverse effects (including myopathy), during and in the 2 weeks following mifepristone treatment. Consider therapy modification
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%)
Frequency not defined:
Endocrine & metabolic: TSH abnormalities
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.
• 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
Liver function tests. Monitor for signs of pulmonary edema and for improvements in pulmonary function, exercise tolerance, and quality of life.
Canadian labeling (additional recommendation): Thyroid function tests as clinically indicated.
Adverse events have not been observed in animal reproduction studies. Women with pulmonary arterial hypertension (PAH) are encouraged to avoid pregnancy (McLaughlin 2009).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache, diarrhea, jaw pain, nausea, vomiting, muscle pain, joint pain, painful extremities, flushing, or lack of appetite. Have patient report immediately to prescriber difficulty breathing, wheezing, cough, or severe loss of strength and energy (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.