Tofacitinib

The Basics

What is Tofacitinib?

Used to treat psoriatic arthritis and moderate-to-severe forms of rheumatoid arthritis.

Brand names for Tofacitinib

Xeljanz

How Tofacitinib is classified

Antirheumatic Agents, Enzyme Inhibitors, Janus Kinase Inhibitors, Signal Transduction Inhibitors, Protein Kinase Inhibitors

Tofacitinib During Pregnancy

Tofacitinib pregnancy category

Category CNote that the FDA has deprecated the use of pregnancy categories, so for some medications, this information isn’t available. We still think it’s useful to list historical info, however, given what a common proxy this has been in the past.

What we know about taking Tofacitinib while pregnant

There are no adequate and well-controlled studies in pregnant women., XELJANZ should be used during pregnancy only if the potential benefit justifies the potential, risk to the fetus. Tofacitinib has been shown to be fetocidal and teratogenic in rats and rabbits, when given at exposures 146 times and 13 times, respectively, the maximum recommended, human dose (MRHD)., In a rat embryofetal developmental study, tofacitinib was teratogenic at exposure levels, approximately 146 times the MRHD (on an AUC basis at oral doses of 100 mg/kg/day)., Teratogenic effects consisted of external and soft tissue malformations of anasarca and, membranous ventricular septal defects, respectively, and skeletal malformations or variations, (absent cervical arch; bent femur, fibula, humerus, radius, scapula, tibia, and ulna; sternoschisis;, absent rib; misshapen femur; branched rib; fused rib; fused sternebra; and hemicentric thoracic, centrum). In addition, there was an increase in post-implantation loss, consisting of early and late, resorptions, resulting in a reduced number of viable fetuses. Mean fetal body weight was, reduced. No developmental toxicity was observed in rats at exposure levels approximately 58, times the MRHD (on an AUC basis at oral doses of 30 mg/kg/day). In the rabbit embryofetal, developmental study, tofacitinib was teratogenic at exposure levels approximately 13 times the, MRHD (on an AUC basis at oral doses of 30 mg/kg/day) in the absence of signs of maternal, toxicity. Teratogenic effects included thoracogastroschisis, omphalocele, membranous, ventricular septal defects, and cranial/skeletal malformations (microstomia, microphthalmia), mid-line and tail defects. In addition, there was an increase in post-implantation loss associated, with late resorptions. No developmental toxicity was observed in rabbits at exposure levels, approximately 3 times the MRHD (on an AUC basis at oral doses of 10 mg/kg/day). There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to XELJANZ/XELJANZ XR during pregnancy. Patients should be encouraged to enroll in the XELJANZ/XELJANZ XR pregnancy registry if they become pregnant. To enroll or obtain information from the registry, patients can call the toll free number 1-877-311-8972. Risk Summary Available data with XELJANZ/XELJANZ XR use in pregnant women are insufficient to establish a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother and the fetus associated with rheumatoid arthritis and UC in pregnancy (see Clinical Considerations). In animal reproduction studies, fetocidal and teratogenic effects were noted when pregnant rats and rabbits received tofacitinib during the period of organogenesis at exposures multiples of 73-times and 6.3-times the maximum recommended dose of 10 mg twice daily, respectively. Further, in a peri- and post-natal study in rats, tofacitinib resulted in reductions in live litter size, postnatal survival, and pup body weights at exposure multiples of approximately 73-times the recommended dose of 5 mg twice daily and approximately 36 times the maximum recommended dose of 10 mg twice daily, respectively (see Data). The estimated background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risks in the U.S. general population of major birth defects and miscarriages are 2 to 4% and 15 to 20% of clinically recognized pregnancies, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk 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. Data Animal Data In a rat embryofetal developmental study, in which pregnant rats received tofacitinib during organogenesis, tofacitinib was teratogenic at exposure levels approximately 146 times the recommended dose of 5 mg twice daily, and approximately 73 times the maximum recommended dose of 10 mg twice daily (on an AUC basis at oral doses of 100 mg/kg/day in rats). Teratogenic effects consisted of external and soft tissue malformations of anasarca and membranous ventricular septal defects, respectively; and skeletal malformations or variations (absent cervical arch; bent femur, fibula, humerus, radius, scapula, tibia, and ulna; sternoschisis; absent rib; misshapen femur; branched rib; fused rib; fused sternebra; and hemicentric thoracic centrum). In addition, there was an increase in post-implantation loss, consisting of early and late resorptions, resulting in a reduced number of viable fetuses. Mean fetal body weight was reduced. No developmental toxicity was observed in rats at exposure levels approximately 58 times the recommended dose of 5 mg twice daily, and approximately 29 times the maximum recommended dose of 10 mg twice daily (on an AUC basis at oral doses of 30 mg/kg/day in pregnant rats). In a rabbit embryofetal developmental study in which pregnant rabbits received tofacitinib during the period of organogenesis, tofacitinib was teratogenic at exposure levels approximately 13 times the recommended dose of 5 mg twice daily, and approximately 6.3 times the maximum recommended dose of 10 mg twice daily (on an AUC basis at oral doses of 30 mg/kg/day in rabbits) in the absence of signs of maternal toxicity. Teratogenic effects included thoracogastroschisis, omphalocele, membranous ventricular septal defects, and cranial/skeletal malformations (microstomia, microphthalmia), mid-line and tail defects. In addition, there was an increase in post-implantation loss associated with late resorptions. No developmental toxicity was observed in rabbits at exposure levels approximately 3 times the recommended dose of 5 mg twice daily, and approximately 1.5 times the maximum recommended dose of 10 mg twice daily (on an AUC basis at oral doses of 10 mg/kg/day in pregnant rabbits). In a peri- and postnatal development study in pregnant rats that received tofacitinib from gestation day 6 through day 20 of lactation, there were reductions in live litter size, postnatal survival, and pup body weights at exposure levels approximately 73 times the recommended dose of 5 mg twice daily, and approximately 36 times the maximum recommended dose of 10 mg twice daily (on an AUC basis at oral doses of 50 mg/kg/day in rats). There was no effect on behavioral and learning assessments, sexual maturation or the ability of the F1 generation rats to mate and produce viable F2 generation fetuses in rats at exposure levels approximately 17 times the recommended dose of 5 mg twice daily, and approximately 8.3 times the maximum recommended dose of 10 mg twice daily (on an AUC basis at oral doses of 10 mg/kg/day in rats).

Taking Tofacitinib While Breastfeeding

What are recommendations for lactation if you're taking Tofacitinib?

No information is available on the clinical use of tofacitinib during breastfeeding. Until more data become available, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. The manufacturer and an expert panel recommend that breastfeeding be discontinued during tofacitinib therapy and for 18 hours after the last dose of Xeljanz or 36 hours after the last dose of Xeljanz XR.[1]

Maternal / infant drug levels

No information is available on the clinical use of tofacitinib during breastfeeding. Until more data become available, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. The manufacturer and an expert panel recommend that breastfeeding be discontinued during tofacitinib therapy and for 18 hours after the last dose of Xeljanz or 36 hours after the last dose of Xeljanz XR.[1]

Possible effects of Tofacitinib on milk supply

Relevant published information was not found as of the revision date.

Possible alternatives to Tofacitinib

(Rheumatoid Arthritis) Auranofin, Gold Sodium Thiomalate, Hydroxychloroquine, Infliximab, Methotrexate, Penicillamine, Sulfasalazine.