SUMMARY

• It is unknown whether selexipag or its metabolites are excreted in human milk.¹ In rats, selexipag or its metabolites are excreted in the milk.² Breastfeeding is not recommended during treatment with UPTRAVI.¹
• In preclinical reproductive toxicity studies, selexipag was not teratogenic in rats or rabbits and had no effect on fertility of male and female rats. In the rat pre and postnatal development study, selexipag did not affect maternal and pup reproductive function. In addition, selexipag was not genotoxic based on the evidence from genotoxicity studies.¹
• Patients who were pregnant or planning to become pregnant were excluded from UPTRAVI clinical trials.¹
• There are limited data on the use of UPTRAVI in pregnant women. In a search of the J&J internal global safety database (cutoff date: December 20, 2024), a total of 105 confirmed pregnancies involving UPTRAVI-treated patients have been reported.³
• Please note that this document does not contain any reference to the local prescribing information. For complete prescribing recommendations and information on child-bearing potential, contraception, pregnancy, lactation, and fertility about UPTRAVI in your country, please refer to your local product information.

BACKGROUND

Information From the 2022 ESC/ERS Guidelines

Historically, pregnancy in women with PAH has been associated with high maternal mortality rates, therefore the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension recommend that women of childbearing potential with PAH be counselled about the risks and uncertainties associated with becoming pregnant.⁴  

CLINICAL DATA

Information From Preclinical Studies

Selexipag was not teratogenic in rats or rabbits and had no effect on fertility of male and female rats in the reproductive toxicity studies. In the rat pre and postnatal development study, selexipag did not affect maternal and pup reproductive function.¹

In a preclinical radiolabel experiment, radioactivity derived from a single oral dose of [14C]selexipag has been detected in milk of lactating rats, indicating transfer of selexipag or its metabolites to milk.²

Selexipag was not genotoxic based on the evidence from genotoxicity    studies.¹

Information From Clinical Studies and Post-marketing Experience

Patients who were pregnant or planning to become pregnant were excluded from UPTRAVI clinical trials.¹ In clinical trials with UPTRAVI, participating women of childbearing potential were required to have a negative pregnancy test before inclusion in the study and agree to perform monthly pregnancy tests up to 30 days after last dose of the study drug. They should also agree to use reliable contraception from screening up to 1 month following discontinuation of the study treatment.^5-14

A search of the J&J internal global safety database found that cumulatively, since UPTRAVI’s International Birth Date (21 December 2015) and up to 20 December 2024, 105 confirmed pregnancies involving UPTRAVI-treated patients have been reported. Twenty cases were from interventional clinical trials, 51 from noninterventional solicited clinical studies, and 34 from a spontaneous source (7 spontaneous cases were from literature source).³

Drug exposure was reported in the first trimester in 46 cases (including 2 cases also reporting exposure during the second trimester and 2 cases reporting exposure throughout the pregnancy), second and third trimesters in 1 case, only second trimester in 1 case, only third trimester in 1 case, and time of exposure was unknown in 54 cases. In 2 cases, exposure was reported before conception.³

Thirty-four pregnant patients gave birth, of whom 5 cases reported live birth of a term baby, 17 cases reported live births with no gestational age reported, and the remaining 12 cases reported live births of premature neonates. Twenty patients gave birth via Caesarean section: 11 babies were premature, born at week 26 (1 case), week 28 (1 case), week 31 (2 cases), week 33 (3 cases), week 34+1 day (1 case), week 35+1 day (3 cases); 4 babies were born at term, born at week 37 (2 cases), week 38 (2 cases), and 5 babies for whom gestational age was not reported.³

Four of the prematurely born babies had neonatal anomalies: A male baby (born at 31 weeks) had intense cyanosis and neonatal respiratory distress syndrome and required ventilation. The Echocardiogram showed patent ductus arteriosus and increased pulmonary arterial pressure. The baby was discharged on day 70 with his condition considered resolved with sequelae. A female baby (born at 35+1 weeks) also experienced neonatal respiratory distress syndrome and was reported as “doing well” at 10 weeks. Another female baby, born at 28 weeks, experienced fetal distress syndrome. No outcomes on the baby’s further development were available. Th fourth baby, a female, was a case of paternal exposure to UPTRAVI. She was diagnosed with hyperbilirubinemia and the case was resolved after 4 months. There were no neonatal abnormalities reported for the remaining babies.³

Twenty-four pregnancies had an outcome of abortion (10 induced/elective abortions, 9 spontaneous/missed abortions, 5 unspecified abortions), 11 cases reported an ongoing pregnancy, 1 case was lost to follow up in a patient who died, and 31 cases had an unknown outcome. Four of 105 pregnancies were unaccounted for.³

No new safety concern has been identified from the review of data referring to patients who became pregnant while being treated with UPTRAVI.³

It is unknown whether selexipag or its metabolites are excreted in human milk. Breastfeeding is not recommended during treatment with UPTRAVI.¹ As of 20 December 2024, no reports of UPTRAVI use during lactation have been received.³ Lactating/breast-feeding females were excluded from UPTRAVI clinical trials.^1,5-9,11-14 UPTRAVI use during lactation is reported as ‘missing information’ considering breastfeeding women were excluded from clinical trials across the development program.¹ ‘Missing information’ refers to information that is currently not yet available on the safety of the medicinal product and needs to be collected (eg, insufficient knowledge regarding the safety of a product for use in specific patient populations).^1,15 Lactating females are recognized as a special population in need of further characterization of the UPTRAVI safety profile.¹

Literature Search

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, DERWENT® (and/or other resources, including internal/external databases) was conducted on 31 March 2025.