XELJANZ

Treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of conditions for which tofacitinib is indicated. Posology Rheumatoid arthritis and psoriatic arthritis The recommended dose is 5 mg film-coated tablets administered twice daily or 11 mg prolonged-release tablets once daily, which should not be exceeded.

See XELJANZ 5 mg film-coated tablets and XELJANZ 11 mg film-coated tablets SmPC for information. Ankylosing spondylitis The recommended dose of tofacitinib is 5 mg administered twice daily. Ulcerative colitis Induction treatment The recommended dose is 10 mg given orally twice daily for induction for 8 weeks.

For patients who do not achieve adequate therapeutic benefit by week 8, the induction dose of 10 mg twice daily can be extended for an additional 8 weeks (16 weeks total), followed by 5 mg twice daily for maintenance. Tofacitinib induction therapy should be discontinued in any patient who shows no evidence of therapeutic benefit by week 16.

Maintenance treatment The recommended dose for maintenance treatment is tofacitinib 5 mg given orally twice daily. 8). 4), tofacitinib 10 mg orally twice daily may be considered if the patient experiences a decrease in response on tofacitinib 5 mg twice daily and failed to respond to alternative treatment options for ulcerative colitis such as tumour necrosis factor inhibitor (TNF inhibitor) treatment.

Tofacitinib 10
mg twice daily for maintenance treatment should be used for the shortest duration possible. The lowest effective dose needed to maintain response should be used. In patients who have responded to treatment with tofacitinib, corticosteroids may be reduced and/or discontinued in accordance with standard of care.

Retreatment in UC If therapy is interrupted, restarting treatment with tofacitinib can be considered. If there has been a loss of response, reinduction with tofacitinib 10 mg twice daily may be considered. The treatment interruption period in clinical studies extended up to 1 year.

1). Dose interruption and discontinuation in adult patients Tofacitinib treatment should be interrupted if a patient develops a serious infection until the infection is controlled. Interruption of dosing may be needed for management of dose-related laboratory abnormalities including lymphopenia, neutropenia, and anaemia.

4). 2%). Among opportunistic infections, TB and other mycobacterial infections, cryptococcus, histoplasmosis, oesophageal candidiasis, multidermatomal herpes zoster, cytomegalovirus infection, BK virus infections and listeriosis were reported with tofacitinib.

Some patients have presented with disseminated rather than localised disease. , coccidioidomycosis). 2%). 8% for patients taking tofacitinib. 15%). Psoriatic arthritis Overall, the safety profile observed in patients with active PsA treated with tofacitinib was consistent with the safety profile observed in patients with RA treated with tofacitinib.

Ankylosing spondylitis Overall, the safety profile observed in patients with active AS treated with tofacitinib was consistent with the safety profile observed in patients with RA treated with tofacitinib. Ulcerative colitis The most commonly reported adverse reactions in patients receiving tofacitinib 10 mg twice daily in the induction studies were headache, nasopharyngitis, nausea, and arthralgia.

In the induction and maintenance studies, across tofacitinib and placebo treatment groups, the most common categories of serious adverse reactions were gastrointestinal disorders and infections, and the most common serious adverse reaction was worsening of UC.

Overall, the safety profile observed in patients with UC treated with tofacitinib was consistent with the safety profile of tofacitinib in the RA indication. Tabulated list of adverse reactions The adverse reactions listed in the table below are from clinical studies in patients with RA, PsA, AS, and UC and are presented by System Organ Class (SOC) and frequency categories, defined using the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), or not known (cannot be estimated from the available data).

g. 1). Combination with other therapies Tofacitinib has not been studied and its use should be avoided in combination with biologics such as TNF antagonists, interleukin (IL)-1R antagonists, IL-6R antagonists, anti-CD20 monoclonal antibodies, IL-17 antagonists, IL-12/IL-23 antagonists, anti- integrins, selective co-stimulation modulators and potent immunosuppressants such as azathioprine, 6-mercaptopurine, ciclosporin and tacrolimus because of the possibility of increased immunosuppression and increased risk of infection.

There was a higher incidence of adverse events for the combination of tofacitinib with MTX versus tofacitinib as monotherapy in RA clinical studies. The use of tofacitinib in combination with phosphodiesterase 4 inhibitors has not been studied in tofacitinib clinical studies.

8). 1). In a post hoc exploratory analysis within this study, in patients with known VTE risk factors, occurrences of subsequent VTEs were observed more frequently in tofacitinib- treated patients that, at 12 months treatment, had D-dimer level ≥2× ULN versus those with D-dimer level <2× ULN; this was not evident in TNF inhibitor-treated patients.

Interpretation is limited by the low number of VTE events and restricted D-dimer test availability (only assessed at Baseline, Month 12, and at the end of the study). In patients who did not have a VTE during the study, mean D-dimer levels were significantly reduced at Month 12 relative to Baseline across all treatment arms.

However, D-dimer levels ≥2× ULN at Month 12 were observed in approximately 30% of patients without subsequent VTE events, indicating limited specificity of D-Dimer testing in this study. 2). 4 “Major adverse cardiovascular events (including myocardial infarction)” and “Malignancies and lymphoproliferative disorders”) tofacitinib should only be used if no suitable treatment alternatives are available.

In patients with VTE risk factors other than MACE or malignancy risk factors, tofacitinib should be used with caution. VTE risk factors other than MACE or malignancy risk factors include previous VTE, patients undergoing major surgery, immobilisation, use of combined hormonal contraceptives or hormone replacement therapy, inherited coagulation disorder.

1. 4). 2). 6).