Version May 2024
Pulmonary arterial hypertension (adjunctive agent):
Note: Consult a pulmonary arterial hypertension specialist for all management decisions; choice of therapy is dependent on etiology, risk stratification, cardiopulmonary comorbidities, and response to other agents (Ref).
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.
IV: Note: For use only in patients temporarily unable to take oral medication. Dosage is based on patient's current oral dose:
|
Selexipag current oral dose |
Selexipag corresponding IV dose |
|---|---|
|
200 mcg twice daily |
225 mcg twice daily |
|
400 mcg twice daily |
450 mcg twice daily |
|
600 mcg twice daily |
675 mcg twice daily |
|
800 mcg twice daily |
900 mcg twice daily |
|
1,000 mcg twice daily |
1,125 mcg twice daily |
|
1,200 mcg twice daily |
1,350 mcg twice daily |
|
1,400 mcg twice daily |
1,575 mcg twice daily |
|
1,600 mcg twice daily |
1,800 mcg twice daily |
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.
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).
Oral: Note: For patients temporarily unable to take oral therapy, the IV formulation may be used; refer to adult dosing for the suggested IV equivalent dose.
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 up to a maximum of 1,600 mcg once daily.
Severe hepatic impairment (Child-Pugh class C): Avoid use.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. As reported for the oral formulation unless otherwise indicated.
>10%:
Cardiovascular: Flushing (12%)
Dermatologic: Skin rash (11%)
Gastrointestinal: Diarrhea (42%), nausea (33%), vomiting (18%)
Nervous system: Headache (65%)
Neuromuscular & skeletal: Arthralgia (11%), jaw pain (26%), limb pain (17%), myalgia (16%)
1% to 10%:
Endocrine & metabolic: Hyperthyroidism (1%)
Gastrointestinal: Decreased appetite (6%)
Hematologic & oncologic: Anemia (8%)
Frequency not defined: Local: Infusion site reaction (IV: Including erythema at injection site, infusion-site pain, swelling at injection site)
Postmarketing: Cardiovascular: Symptomatic hypotension
Hypersensitivity to selexipag or any component of the formulation; concomitant use with strong CYP2C8 inhibitors (eg, gemfibrozil).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Uptravi: 1800 mcg (1 ea)
Tablet, Oral:
Uptravi: 200 mcg, 400 mcg, 600 mcg, 800 mcg, 1000 mcg, 1200 mcg, 1400 mcg, 1600 mcg [contains corn starch]
Tablet Therapy Pack, Oral:
Uptravi Titration: 200 mcg (140s) and 800 mcg (60s) (200 ea) [contains corn starch]
No
Solution (reconstituted) (Uptravi Intravenous)
1800 mcg (per each): $442.82
Tablet Therapy Pack (Uptravi Titration Oral)
200 & 800 mcg (per each): $199.70
Tablets (Uptravi Oral)
200 mcg (per each): $285.29
400 mcg (per each): $443.68
600 mcg (per each): $443.68
800 mcg (per each): $443.68
1000 mcg (per each): $443.68
1200 mcg (per each): $443.68
1400 mcg (per each): $443.68
1600 mcg (per each): $443.68
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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 [contains corn starch]
IV: Administer as an IV infusion over 80 minutes via an infusion set made of DEHP-free PVC, natural latex rubber-free microbore tubing that is protected from light. Do not filter. Once solution in glass container is infused, continue infusion at the same rate with NS to empty remaining solution in IV line and ensure all contents are administered.
Oral: Administer with or without food; tolerability may be improved when taken with food. Swallow tablets whole; do not split, crush, or chew.
Pulmonary arterial hypertension: Treatment of pulmonary arterial hypertension (PAH) (WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH.
Substrate of BCRP/ABCG2, CYP2C8 (major), CYP3A4 (minor), OATP1B1/1B3 (SLCO1B1/1B3); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
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. Risk D: 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. Risk X: 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). Risk C: 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. Risk D: Consider therapy modification
Adverse events have not been observed in animal reproduction studies. Women with pulmonary arterial hypertension (PAH) are encouraged to avoid pregnancy (McLaughlin 2009).
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.
Liver function tests. Monitor for signs of pulmonary edema and for improvements in pulmonary function, exercise tolerance, and quality of life.
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: 11.7 L.
Protein binding: ~99%; to albumin and alpha-1 acid glycoprotein.
Metabolism: Hepatic via CYP3A4, CYP2C8, UGT1A3 and UGT2B7; hydrolyzed by carboxylesterase 1 to the active metabolite, ACT-333679, which is a major contributor to the activity (Kaufmann 2015); the active metabolite is then glucuronidated.
Bioavailability: ~49%.
Half-life elimination: Terminal: Selexipag: 0.8 to 2.5 hours; Active metabolite: 6.2 to 13.5 hours.
Time to peak: Oral: Selexipag: 1 to 3 hours; Active metabolite: 3 to 4 hours; Delayed with food.
Excretion: Feces (~93%); urine (12%; as inactive metabolites).
Altered kidney function: 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).
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.
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