treated with XELJANZ (474 patients) included 45 (9.5%) patients aged 65 years or older and 66 (13.9%) patients with diabetes at baseline.
The safety profile observed in patients with active psoriatic arthritis treated with XELJANZ was consistent with the safety profile observed in rheumatoid arthritis patients.
7 DRUG INTERACTIONS
All information provided in this section is applicable to XELJANZ and XELJANZ XR as they contain the same active ingredient (tofacitinib).
7.1 Potent CYP3A4 Inhibitors
Tofacitinib exposure is increased when XELJANZ is coadministered with potent inhibitors of cytochrome P450 (CYP) 3A4 (e.g., ketoconazole) [see DOSAGE AND ADMINISTRATION (2.4) and FIGURE 3].
7.2 Moderate CYP3A4 and Potent CYP2C19 Inhibitors
Tofacitinib exposure is increased when XELJANZ is coadministered with medications that result in both moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (e.g., fluconazole) [see DOSAGE AND ADMINISTRATION (2.4) and FIGURE 3].
7.3 Potent CYP3A4 Inducers
Tofacitinib exposure is decreased when XELJANZ is coadministered with potent CYP3A4 inducers (e.g., rifampin) [see DOSAGE AND ADMINISTRATION (2.4) and FIGURE 3].
7.4 Immunosuppressive Drugs
There is a risk of added immunosuppression when XELJANZ/XELJANZ XR is coadministered with potent immunosuppressive drugs (e.g., azathioprine, tacrolimus, cyclosporine). Combined use of multiple-dose XELJANZ/XELJANZ XR with potent immunosuppressants has not been studied in rheumatoid arthritis and psoriatic arthritis. Use of XELJANZ/XELJANZ XR in combination with biologic DMARDs or potent immunosuppressants such as azathioprine and cyclosporine is not recommended.
8 USE IN SPECIFIC POPULATIONS
All information provided in this section is applicable to XELJANZ and XELJANZ XR as they contain the same active ingredient (tofacitinib).
8.1 Pregnancy
Pregnancy Exposure Registry
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
There are no adequate and well-controlled studies of XELJANZ/XELJANZ XR use in pregnant women.
The estimated background risks of major birth defects and miscarriage for the indicated populations are unknown. The background risks in the U.S. general population of major birth defects and miscarriages are 2–4% and 15–20% of clinically recognized pregnancies, respectively.
Based on animal studies, XELJANZ/XELJANZ XR has the potential to affect a developing fetus. Fetocidal and teratogenic effects were noted when pregnant rats and rabbits received tofacitinib during the period of organogenesis at exposures multiples of 146 times and 13 times the human dose of 5 mg twice daily, respectively [see DATA]. 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 human dose of 5 mg twice daily.
Data
Human Data
In the tofacitinib clinical development programs, birth defects and miscarriages were reported.
Animal Data
In a rat embryofetal developmental study, in which pregnant rats received tofacitinib during organogenesis, tofacitinib was teratogen |
