XELJANZ Rx

Indication(s):

Treatment of adults with moderately-to-severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate (MTX); may be used as monotherapy or in combination with MTX or other nonbiologic disease-modifying anti-rheumatic drugs (DMARDs). Do not use in combination with biologic DMARDs or potent immunosuppressants (eg, azathioprine, cyclosporine).

Pharmacology:

Tofacitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of Signal Transducers and Activators of Transcription (STATs).

Clinical Trials:

The efficacy and safety of Xeljanz were based on two dose-ranging trials and five confirmatory trials.

In all confirmatory trials, patients treated with either 5mg or 10mg twice daily doses had higher ACR20, ACR50, and ACR70 response rates versus placebo, with or without background DMARDs, at Months 3 and 6. Higher ACR20 response rates were observed within 2 weeks compared to placebo. In the 12-month trials, ACR response rates in Xeljanz-treated patients were consistent at 6 and 12 months.

Improvement in physical functioning was measured by the HAQ-DI. Patients receiving Xeljanz 5mg and 10mg twice daily demonstrated greater improvement from baseline in physical functioning compared to placebo at Month 3.

The FDA has approved the 5mg twice-daily dose in the second-line setting and has indicated that further data are required to assess the benefit: risk profile of the 10mg twice-daily dose.

Legal Classification:

Rx

Adults:

5mg twice daily. Moderate-to-severe renal impairment or moderate hepatic impairment; concomitant potent CYP3A4 inhibitors, or drugs that result in both moderate CYP3A4 and potent CYP2C19 inhibition: 5mg once daily. Dose adjustments: see full labeling.

Children:

Not established.

Warnings/Precautions:

Increased risk of serious or fatal infections (eg, TB, bacterial, viral, invasive fungal, or other opportunistic pathogens). Active infections: do not initiate therapy. Chronic or history of recurring infections. Travel to, or residence in, areas with endemic TB or mycoses. Conditions that predispose to infection. Test/treat latent TB infection prior to initiating therapy. Monitor closely if new infection, or active TB (even if initial latent test is negative) occurs; interrupt treatment if serious or opportunistic infection, or sepsis develops. Known malignancy. History of GI perforations. Monitor lymphocytes, neutrophils, hemoglobin at baseline and during treatment; do not initiate therapy if lymphocytes <500cells/mm³, ANC <1000cells/mm³, or hemoglobin <9g/dL. Severe hepatic impairment: not recommended. Routinely monitor liver enzymes; interrupt therapy if drug-induced liver injury suspected. Monitor lipids 4–8 weeks following initiation. Elderly. Pregnancy (Cat. C). Nursing mothers: not recommended.

Interaction(s)

Concomitant live vaccines: not recommended. Potentiated by potent CYP3A4 inhibitors (eg, ketoconazole), or drugs that result in both moderate CYP3A4 and potent CYP2C19 (eg, fluconazole) inhibition. Antagonized by potent CYP3A4 inducers (eg, rifampin). Concomitant immunosuppressants (eg, azathioprine, tacrolimus, cyclosporine) or corticosteroids may increase risk of infections.

Adverse Reaction(s)

Upper respiratory tract infections, headache, diarrhea, nasopharyngitis; serious or opportunistic infections, TB, malignancies (eg, lymphoma).

How Supplied:

Tabs—28, 60, 180

LAST UPDATED:

12/21/2012