Animal studies have revealed evidence of fetolethality and teratogenicity. After administration to pregnant rats during organogenesis, this drug was teratogenic at exposure levels about 73 times the MRHD of 10 mg twice daily (on an AUC basis at 100 mg/kg/day orally in rats); teratogenic effects consisted of external and soft tissue malformations and skeletal malformations/variations. An increase in postimplantation loss (consisting of early and late resorptions) was observed, resulting in a reduced number of viable fetuses, and mean fetal body weight was reduced; no developmental toxicity was seen in rats at exposure levels about 29 times the MRHD of 10 mg twice daily (on an AUC basis at 30 mg/kg/day orally in pregnant rats). After administration to pregnant rabbits during organogenesis, this drug was teratogenic at exposure levels about 6.3 times the MRHD of 10 mg twice daily (on an AUC basis at 30 mg/kg/day orally in rabbits) without signs of maternal toxicity; teratogenic effects included thoracogastroschisis, omphalocele, membranous ventricular septal defects, cranial/skeletal malformations, midline defects, and tail defects. An increase in postimplantation loss (associated with late resorptions) was observed; no developmental toxicity was seen in rabbits at exposure levels about 1.5 times the MRHD of 10 mg twice daily (on an AUC basis at 10 mg/kg/day orally in pregnant rabbits). There are no controlled data in human pregnancy.

Based on animal studies, this drug may result in reduced fertility in females of childbearing potential; it is not known if this effect is reversible.

Published data suggest that increased disease activity is associated with the risk of developing adverse pregnancy outcomes in women with rheumatoid arthritis or ulcerative colitis; adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth.

To monitor the outcomes of pregnant women exposed to this drug, a pregnancy registry has been established. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-877-311-8972 or visiting https://mothertobaby.org/ongoing-study/xeljanz/.

AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D and X are being phased out.

Use is not recommended.
-According to some authorities: As a precaution, use is contraindicated.

AU TGA pregnancy category: D
US FDA pregnancy category: Not assigned.

Risk summary: Insufficient data are available on use of this drug in pregnant women to inform a drug-related risk; in animal studies, adverse embryofetal findings were observed with this drug at exposures 6.3 times the maximum recommended human dose (MRHD).

Comments:
-A pregnancy exposure registry is available.
-According to some authorities: This drug should not be used during pregnancy or by women attempting to become pregnant.
-According to some authorities: Women of childbearing potential should be advised to use effective contraception during therapy and for at least 4 weeks after the last dose; local protocol should be consulted regarding contraception timing.
-According to some authorities: Pregnancy planning and prevention should be considered for females of childbearing potential.

See references

Until more data become available, an alternate drug may be preferred, particularly while breastfeeding newborn or preterm infants.
-According to some authorities: Breastfeeding is not recommended during use of this drug.
-According to some authorities: As a precaution, use is contraindicated.

Excreted into human milk: Unknown
Excreted into animal milk: Yes

Comments:
-No information is available on the clinical use of this drug during breastfeeding.
-Due to the serious adverse reactions observed with this drug, patients should be advised to discontinue breastfeeding during therapy and for at least 18 hours after the last dose of the immediate-release formulation or 36 hours after the last dose of the extended-release formulation (about 6 elimination half-lives).
-The effects in the nursing infant are unknown.

See references