XELJANZ

Treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of conditions for which tofacitinib is indicated. Posology Tofacitinib may be used as monotherapy or in combination with methotrexate (MTX).

2 mL of oral solution) twice daily 20 - < 40 4 mg (4 mL of oral solution) twice daily 40 5 mg (5 mL of oral solution or 5 mg film-coated tablet) twice daily Patients 40 kg treated with tofacitinib 5 mL oral solution twice daily may be switched to tofacitinib 5 mg film-coated tablets twice daily.

Patients < 40 kg cannot be switched from tofacitinib oral solution. Dose adjustment No dose adjustment is required when used in combination with MTX. Dose interruption and discontinuation Available data suggest that clinical improvement is observed within 18 weeks of initiation of treatment with tofacitinib.

Continued therapy should be carefully reconsidered in a patient exhibiting no improvement within this timeframe. 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). It is recommended not to initiate dosing in paediatric patients with an absolute lymphocyte count (ALC) less than 750 cells/mm3.

4) Laboratory value (cells/mm3) Recommendation ALC greater than or equal to 750 Dose should be maintained. ALC 500-750 For persistent (2 sequential values in this range on routine testing) decrease in this range, dosing should be reduced or interrupted until ALC is greater than 750.

For patients receiving tofacitinib 5 mg twice daily, dosing should be interrupted. When ALC is greater than 750, treatment should be resumed as clinically appropriate. ALC less than 500 If laboratory value confirmed by repeat testing within 7 days, dosing should be discontinued.

It is recommended not to initiate dosing in paediatric patients with an absolute neutrophil count (ANC) less than 1,200 cells/mm3. 4) Laboratory Value (cells/mm3) Recommendation ANC greater than 1,000 Dose should be maintained. ANC 500-1,000 For persistent (2 sequential values in this range on routine testing) decreases in this range, dosing should be reduced or interrupted until ANC is greater than 1,000.

For patients receiving tofacitinib 5 mg twice daily, dosing should be interrupted. When ANC is greater than 1,000, treatment should be resumed as clinically appropriate. ANC less than 500 If laboratory value confirmed by repeat testing within 7 days, dosing should be discontinued.

It is recommended not to initiate dosing in paediatric patients with haemoglobin less than 10 g/dL. 0 g/dL Dose should be maintained. 0 g/dL (confirmed by repeat testing) Dosing should be interrupted until haemoglobin values have normalised.

5). Special populations Elderly The safety and efficacy of tofacitinib oral solution has not been established in the elderly.

Hepatic impairment Table 5:

Dose adjustment for hepatic impairment Hepatic impairment category Classification Dose adjustment in hepatic impairment for oral solution Mild Child Pugh A No dose adjustment required. 2). 3).

Renal impairment Table 6:

Dose adjustment for renal impairment Renal impairment category Creatinine clearance Dose adjustment in renal impairment for oral solution Mild 50-80 mL/min No dose adjustment required. Moderate 30-49 mL/min No dose adjustment required.

Severe (including patients undergoing haemodialysis) < 30 mL/min Dose should be reduced to 5 mg or weight-based equivalent once daily when the indicated dose in the presence of normal renal function is 5 mg or weight-based equivalent twice daily.

2). Paediatric population (children below 2 years of age) The safety and efficacy of tofacitinib in children below 2 years of age has not been established. No data are available. Method of administration Oral use. Tofacitinib oral solution should be administered using the included press-in bottle adapter and oral dosing syringe.

Tofacitinib is given orally with or without food.

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%). Tabulated list of adverse reactions The adverse reactions listed in the table below are from clinical studies in adult patients with RA, PsA, 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).

Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. 1). The majority of these events were serious and some resulted in death. 17)patients with events per 100patient-years, respectively.

1). In tofacitinib-treated patients where PE was observed, the majority (97%) had VTE risk factors. 9% (23 patients) in the placebo group (total 122 patients). In controlled phase 3 clinical studies with background […]

g. current malignancy or history of malignancy) 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. 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.

Patients should be re-evaluated periodically during tofacitinib treatment to assess for changes in VTE risk. For patients with RA with known risk factors for VTE, consider testing D-dimer levels after approximately 12 months of treatment.

If D-dimer test result is ≥ 2× ULN, confirm that clinical benefits outweigh risks prior to a decision on treatment continuation with tofacitinib. Promptly evaluate patients with signs and symptoms of VTE and discontinue tofacitinib in patients with suspected VTE, regardless of dose or indication.

8). The patients should be advised to promptly seek medical care in case they experience symptoms suggestive of RVT. 8). 8). Rheumatoid arthritis patients taking corticosteroids may be predisposed to infection. Tofacitinib should not be initiated in patients with active infections, including localised infections.

The risks and benefits of treatment should be considered prior to initiating tofacitinib in patients: • with recurrent infections, • with a history of a serious or an opportunistic infection, • who have resided or travelled in areas of endemic mycoses, • who have underlying conditions that may predispose them to infection.

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with tofacitinib. Treatment should be interrupted if a patient develops a serious infection, an opportunistic infection, or sepsis.

A patient who develops a new infection during treatment with tofacitinib should undergo prompt and complete diagnostic testing appropriate for an immunocompromised patient, appropriate antimicrobial therapy should be initiated, and the patient should be closely monitored.

8). 1). Risk of infection may be higher with increasing degrees of lymphopenia and consideration should be given to lymphocyte counts when assessing individual patient risk of infection. 2. Tuberculosis The risks and […]

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