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Tofacitinib (Xeljanz) Modified-Release Tablets Accepted for FDA Review
The FDA has accepted for review a new drug application (NDA) for tofacitinib citrate, (Xeljanz, Pfizer) 11-mg once-daily modified-release tablets for the treatment of moderate-to-severe rheumatoid arthritis (RA) in patients who have shown an inadequate response to or are intolerant of methotrexate.
The FDA provided an anticipated Prescription Drug User Fee Act (PDUFA) action date of February 2016 for the NDA.
The NDA for tofacitinib 11-mg once-daily modified-release tablets is based on data from a clinical pharmacology program designed to demonstrate equivalence in key pharmacokinetic parameters compared with tofacitinib 5 mg twice daily.
The once-daily and twice-daily tofacitinib regimens were evaluated in 26 healthy volunteers in an open-label, randomized crossover study. Following an overnight fast, the participants were randomly assigned to receive single doses of either the modified-release (MR) formulation (11 mg once daily) or the immediate-release (IR) formulation (5 mg twice daily). The treatments were separated by a 72-hour washout period. The study’s primary endpoint was the extent of tofacitinib exposure, as measured by the area under the concentration–time curve (AUC).
All 26 volunteers completed the study and were included in the analyses. The study population had a mean age of 33.6 years, and most participants (81%) were male. For the MR and IR formulations, the geometric mean AUCinf (ng*h/mL) values were 297.5 and 286.3, respectively. The maximum plasma concentrations adjusted for formulation (Cmax, adj; ng/mL) were 40.75 and 44.10 for the MR and IR formulations, respectively, and the mean terminal half-lives were 5.71 hours and 3.41 hours. The most common adverse events (AEs) included nausea, abdominal pain, back pain, and headache. The AE rates were similar between the two treatment groups, and no serious or severe AEs were reported.
Tofacitinib is a Janus kinase (JAK) inhibitor. The recommended dosage is 5 mg twice daily. The drug is used to treat adults with moderately to severely active RA in which methotrexate did not work well. Tofacitinib may be used as a single agent or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs). The use of tofacitinib in combination with biologic DMARDs or potent immunosuppressants, such as azathioprine and cyclosporine, is not recommended. Other precautions include the following:
- It is not known whether tofacitinib is safe and effective in patients with hepatitis B or C.
- Tofacitinib is not for patients with severe liver problems.
- It is not known whether tofacitinib is safe and effective in children.