Tofacitinib (Xeljanz) has been approved by the Food and Drug Administration (FDA) to treat adults with moderate-to-severe rheumatoid arthritis who've had an inadequate response to, or who cannot tolerate, methotrexate. The drug can be used alone or in combination with methotrexate. It shouldn't be used in combination with biological disease-modifying antirheumatic drugs, such as adalimumab (Humira) or etanercept (Enbrel), or potent immunosuppressants, such as azathioprine or cyclo-sporine.
Rheumatoid arthritis is an autoimmune disease. Tofacitinib works by blocking molecules called Janus kinases, which are intracellular enzymes that transmit signals that alter cellular activity, including hematopoiesis and immune cell function. These functions play a role in the joint inflammation that occurs in rheumatoid arthritis. Tofacitinib use decreases serum C-reactive protein levels. It is administered orally twice a day.
Tofacitinib carries a boxed warning to highlight the possibility of serious, potentially fatal, infections and malignancy, such as lymphoma, during its use. The most common serious infections reported include pneumonia, cellulitis, herpes zoster, and urinary tract infection. Tuberculosis and other opportunistic infections are also possible. The drug's label also carries a warning that tofacitinib can cause gastrointestinal perforation in at-risk patients (such as those with a history of diverticulitis). The drug may produce low lymphocyte counts, neutropenia, low hemoglobin levels, elevated liver enzyme levels, and elevated lipid levels. The most common infections, however—upper respiratory tract infections and nasopharyngitis—aren't serious. Headache and diarrhea are also fairly common.
Tofacitinib is metabolized predominantly through the cytochrome P-450 (CYP) enzyme system, and drug interactions through the isoenzymes CYP3A4 or CYP2C19 are possible. Dose reductions are necessary if tofacitinib is coadministered with a potent inhibitor of CYP3A4 or a drug that's both a moderate inhibitor of CYP3A4 and a potent inhibitor of CYP2C19. Potent CYP inducers should also be avoided because their use may result in a loss of or reduction in clinical response to tofacitinib. Nurses administering tofacitinib should use an online drug database system to determine whether other drugs will interact with it.
Tofacitinib shouldn't be administered if any infection is present. Nurses administering it should carefully assess patients for signs of active infection, including localized infection. If a serious infection develops, treatment with tofacitinib should be discontinued until the infection is gone. Live vaccines shouldn't be administered to patients taking tofacitinib. Patients should be assessed for latent or active tuberculosis prior to the start of therapy; antitubercular drug therapy may be warranted. Teach patients how to assess for infection, and instruct them to report any infection that occurs.
Prior to the start of tofacitinib therapy, assess the patient for altered blood cell counts. Don't start treatment with tofacitinib if the lymphocyte count is less than 500 cells/mm3, the absolute neutrophil count (ANC) is less than 1,000 cells/mm3, or the hemoglobin level is less than 9 g/dL. If the ANC is persistently between 500 and 1,000 cells/mm3 during tofacitinib therapy, the drug should be stopped until the ANC rises higher than 1,000 cells/mm3. Discontinue tofacitinib therapy if the lymphocyte count drops below 500 cells/mm3, the ANC drops below 500 cells/mm3, or the hemoglobin falls to less than 8 g/dL (once the hemoglobin stabilizes, tofacitinib may be restarted).
Assess liver enzyme levels during treatment because they can rise as a result of tofacitinib use. If drug-induced liver injury is suspected, tofacitinib therapy should be interrupted until that diagnosis is excluded. Lipid levels should be assessed about four to eight weeks after tofacitinib therapy is begun; treatment for elevated lipid levels may be necessary.
Tofacitinib prescriptions come with a medication guide that outlines the most current information on major risks and patient safety. Instruct patients to read the guide thoroughly each time the prescription is filled.
To read the FDA news release regarding tofacitinib, go to http://1.usa.gov/YEq96X. Complete FDA prescribing information can be found at http://1.usa.gov/VrSefo.