Selexipag
{{DrugProjectFormSinglePage |authorTag=Martin Nino [1] |genericName=Selexipag |aOrAn=a |drugClass=prostacyclin receptor agonist |indicationType=treatment |indication=patients with pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH |adverseReactions=headache, diarrhea, jaw pain, nausea, myalgia, vomiting, pain in extremity, and flushing (≥5%). |fdaLIADAdult=
Indications
Selexipag is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH.
Effectiveness was established in a long-term study in PAH patients with WHO Functional Class II-III symptoms.
Patients had idiopathic and heritable PAH (58%), PAH associated with connective tissue disease (29%), PAH associated with congenital heart disease with repaired shunts (10%).
Dosage
- Recommended Dosage
The recommended starting dose of Selexipag is 200 micrograms (mcg) given twice daily. Tolerability may be improved when taken with food.
Increase the dose in increments of 200 mcg twice daily, usually at weekly intervals, to the highest tolerated dose up to 1600 mcg twice daily. If a patient reaches a dose that cannot be tolerated, the dose should be reduced to the previous tolerated dose.
Do not split, crush, or chew tablets.
- Interruptions and Discontinuations
If a dose of medication is missed, patients should take a missed dose as soon as possible unless the next dose is within the next 6 hours.
If treatment is missed for 3 days or more, restart Selexipag at a lower dose and then retitrate.
- Dosage Adjustment in Patients with Hepatic Impairment
No dose adjustment of Selexipag is necessary for patients with mild hepatic impairment (Child-Pugh class A).
For patients with moderate hepatic impairment (Child-Pugh class B), the starting dose of Selexipag is 200 mcg once daily. Increase in increments of 200 mcg once daily at weekly intervals, as tolerated.
Avoid use of Selexipag in patients with severe hepatic impairment (Child-Pugh class C). |offLabelAdultGuideSupport=There is limited information regarding Off-Label Guideline-Supported Use of Selexipagin adult patients. |offLabelAdultNoGuideSupport=There is limited information regarding Off-Label Non–Guideline-Supported Use of Selexipag in adult patients. |fdaLIADPed=Safety and effectiveness in pediatric patients have not been established. |offLabelPedGuideSupport=There is limited information regarding Off-Label Guideline-Supported Use of Selexipag in pediatric patients. |offLabelPedNoGuideSupport=There is limited information regarding Off-Label Non–Guideline-Supported Use of Selexipag in pediatric patients. |contraindications=None |warnings=
Should signs of pulmonary edema occur, consider the possibility of associated PVOD. If confirmed, discontinue Selexipag. |clinicalTrials= Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of Selexipag has been evaluated in a long-term, placebo-controlled study enrolling 1156 patients with symptomatic PAH (GRIPHON study). The exposure to Selexipag in this trial was up to 4.2 years with median duration of exposure of 1.4 years.
TABLE1 presents adverse reactions more frequent on Selexipag than on placebo by ≥3%.
- Table 1 Adverse Reactions
UPTRAVI: Selexipag's Brand name
These adverse reactions are more frequent during the dose titration phase.
Hyperthyroidism was observed in 1% (n=8) of patients on Selexipag and in none of the patients on placebo.
- Laboratory Test Abnormalities
In a Phase 3 placebo-controlled study in patients with PAH, mean absolute changes in hemoglobin at regular visits compared to baseline ranged from −0.34 to −0.02 g/dL in the selexipag group compared to −0.05 to 0.25 g/dL in the placebo group. A decrease in hemoglobin concentration to below 10 g/dL was reported in 8.6% of patients treated with selexipag and 5.0% of placebo-treated patients.
- Thyroid function tests
In a Phase 3 placebo-controlled study in patients with PAH, a reduction (up to −0.3 MU/L from a baseline median of 2.5 MU/L) in median thyroid-stimulating hormone (TSH) was observed at most visits in the selexipag group. In the placebo group, little change in median values was apparent. There were no mean changes in triiodothyronine or thyroxine in either group.
|drugInteractions= Strong CYP2C8 Inhibitors: Concomitant administration with strong inhibitors of CYP2C8 may result in a significant increase in exposure to selexipag and its active metabolite. Avoid concomitant administration of Selexipag with strong inhibitors of CYP2C8 (e.g., gemfibrozil). |useInPregnancyFDA=
- Risk Summary
There are no adequate and well-controlled studies with Selexipag in pregnant women. Animal reproduction studies performed with selexipag showed no clinically relevant effects on embryofetal development and survival. A slight reduction in maternal as well as in fetal body weight was observed when pregnant rats were administered selexipag during organogenesis at a dose producing an exposure approximately 47 times that in humans at the maximum recommended human dose. No adverse developmental outcomes were observed with oral administration of selexipag to pregnant rabbits during organogenesis at exposures up to 50 times the human exposure at the maximum recommended human dose.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
- Data
- Animal Data
Pregnant rats were treated with selexipag using oral doses of 2, 6, and 20 mg/kg/day (up to 47 times the exposure at the maximum recommended human dose of 1600 mcg twice daily on an area under the curve [AUC] basis) during the period of organogenesis (gestation days 7 to 17). Selexipag did not cause adverse developmental effects to the fetus in this study. A slight reduction in fetal body weight was observed in parallel with a slight reduction in maternal body weight at the high dose.
Pregnant rabbits were treated with selexipag using oral doses of 3, 10, and 30 mg/kg (up to 50 times the exposure to the active metabolite at the maximum recommended human dose of 1600 mcg twice daily on an AUC basis) during the period of organogenesis (gestation days 6 to 18). Selexipag did not cause adverse developmental effects to the fetus in this study.
|useInNursing=
It is not known if Selexipag is present in human milk. Selexipag or its metabolites were present in the milk of rats. Because many drugs are present in the human milk and because of the potential for serious adverse reactions in nursing infants, discontinue nursing or discontinue Selexipag.
|useInPed=Safety and effectiveness in pediatric patients have not been established.
|useInGeri=Of the 1368 subjects in clinical studies of Selexipag 248 subjects were 65 years of age and older, while 19 were 75 and older. No overall differences were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity cannot be ruled out.
|useInRenalImpair=No adjustment to the dosing regimen is needed in patients with estimated glomerular filtration rate > 15 mL/min/1.73 m2.
There is no clinical experience with Selexipag in patients undergoing dialysis or in patients with glomerular filtration rates < 15 mL/min/1.73 m2. |useInHepaticImpair=No adjustment to the dosing regimen is needed in patients with mild hepatic impairment (Child-Pugh class A).
A once-daily regimen is recommended in patients with moderate hepatic impairment (Child-Pugh class B) due to the increased exposure to selexipag and its active metabolite. There is no experience with Selexipag in patients with severe hepatic impairment (Child-Pugh class C). Avoid use of Selexipag in patients with severe hepatic impairment. |administration= |overdose= Isolated cases of overdose up to 3200 mcg were reported. Mild, transient nausea was the only reported consequence. In the event of overdose, supportive measures must be taken as required. Dialysis is unlikely to be effective because selexipag and its active metabolite are highly protein-bound. |drugBox=
Selexipag
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