4.1 Dosing Considerations
- Use of XELJANZ/XELJANZ XR with other potent systemic immunosuppressants should be avoided. Combined use of XELJANZ/XELJANZ XR with potent immunosuppressants or biologic DMARDS (tumor necrosis factor (TNF) antagonists, interleukin 1 receptor (IL-1R) antagonists, IL-6R antagonists, anti-CD20 monoclonal antibodies, IL‑17 antagonists, IL‑12/IL‑23 antagonists and selective co-stimulation modulators) has not been studied in RA, PsA and UC patients. There is a risk of added immunosuppression when XELJANZ/XELJANZ XR is coadministered with potent immunosuppressive drugs (e.g. azathioprine, tacrolimus, cyclosporine).
- XELJANZ/XELJANZ XR should not be initiated in patients with an absolute neutrophil count (ANC) less than 1 x 109 cells/L, hemoglobin (Hgb) levels <90 g/L, or with a lymphocyte count less than 0.5 x 109 cells/L (see 7 WARNINGS AND PRECAUTIONS).
- XELJANZ/XELJANZ XR is contraindicated in patients with severe hepatic impairment; XELJANZ XR should not be used in patients with moderate hepatic impairment.
4.2 Recommended Dose and Dosage Adjustment
Rheumatoid Arthritis
XELJANZ/XELJANZ XR is to be used in combination with methotrexate.
XELJANZ/XELJANZ XR, monotherapy may be considered in cases of intolerance to methotrexate and to one or more DMARDs.
The recommended dose of XELJANZ is 5 mg administered twice daily (BID). The recommended dose of XELJANZ XR is 11 mg once daily.
A dosage of XELJANZ 10 mg BID is not recommended for the treatment of rheumatoid arthritis (see 7 WARNINGS AND PRECAUTIONS).
Switching between XELJANZ Tablets and XELJANZ XR Tablets: Where appropriate, patients treated with XELJANZ 5 mg BID may be switched to XELJANZ XR 11 mg once daily the day following the last dose of XELJANZ 5 mg.
Where appropriate, patients treated with XELJANZ XR 11 mg once daily may be switched to XELJANZ 5 mg BID 24 hours following the last dose of XELJANZ XR 11 mg.
Patients treated with XELJANZ XR 11 mg once daily who require a dose reduction due to renal or hepatic impairment or drug interactions may be switched to XELJANZ 5 mg once daily, 24 hours following the last dose of XELJANZ XR 11 mg once daily (see 7 WARNINGS AND PRECAUTIONS and 9 DRUG INTERACTIONS).
Psoriatic Arthritis
The recommended dose of XELJANZ is 5 mg administered BID in combination with MTX or another csDMARD.
A dosage of XELJANZ 10 mg BID is not recommended for the treatment of psoriatic arthritis (see 7 WARNINGS and PRECAUTIONS, Thrombosis).
Ulcerative Colitis
The recommended dose is 10 mg given orally BID for induction for at least 8 weeks and 5 mg given BID for maintenance.
Depending on therapeutic response; 10 mg BID may also be used for maintenance in some patients. However, the lowest effective dose possible should be used for maintenance therapy to minimize adverse effects (see 7 WARNINGS AND PRECAUTIONS).
XELJANZ induction therapy should be discontinued in patients who show no evidence of adequate therapeutic benefit by Week 16.
In patients who have responded to treatment with XELJANZ, corticosteroids may be cautiously reduced and/or discontinued in accordance with standard of care.
Dose Interruption or Discontinuation due to Serious Infections and Cytopenias
- Avoid use of XELJANZ/XELJANZ XR if a patient develops a serious infection until the infection is controlled.
- Dose interruption is recommended for management of anemia, lymphopenia, and neutropenia as described in Table 1 (see 7 WARNINGS AND PRECAUTIONS and 8 ADVERSE REACTIONS).
|
Laboratory Measure |
Lab Value |
Recommendation |
|---|---|---|
|
Hemoglobin |
<20 g/L decrease and ≥90 g/L |
Maintain dose |
|
≥20 g/L decrease or <80 g/L (Confirmed by repeat testing) |
Interrupt the administration of XELJANZ/XELJANZ XR until hemoglobin values have normalized (above 80 g/L) |
|
|
Absolute Neutrophil Count (ANC) |
>1 x 109 cells/L |
Maintain dose |
|
0.5-1 x 109 cells/L
|
For persistent decreases in this range, interrupt or reduce administration with XELJANZ/XELJANZ XR until ANC is >1x 109 cells/L
RA patients: · When ANC is >1 x 109 cells/L, resume XELJANZ XR 11 mg once daily. UC patients: · For patients receiving XELJANZ 10 mg BID, reduce dose to XELJANZ 5 mg BID. When ANC is >1 x 109 cells/L, increase to XELJANZ 10 mg BID based on clinical response. |
|
|
<0.5 x 109 cells/L (Confirmed by repeat testing) |
Discontinue treatment with XELJANZ/XELJANZ XR |
|
|
Absolute Lymphocyte Count |
≥ 0.5 x 109cells/L |
Maintain dose |
|
< 0. 5 x 109cells/L (Confirmed by repeat testing) |
Discontinue XELJANZ/XELJANZ XR |
Dose Modification in Patients with Renal or Hepatic Impairment, or Due to Drug Interactions
- Use XELJANZ with caution in patients with moderate (CLcr ≥30 and <60 mL/min) or severe (CLcr ≥15 and <30 mL/min) renal insufficiency (including patients with ESRD but not limited to those undergoing hemodialysis). Modified dosing is indicated in Table 2.
- For patients undergoing hemodialysis, dose should be administered after the dialysis session on dialysis days. If a dose was taken before the dialysis procedure, supplemental doses are not recommended in patients after dialysis.
- Patients with severe renal insufficiency should remain on a reduced dose even after hemodialysis.
- Use XELJANZ with caution in patients with moderate hepatic impairment. Modified dosing is indicated in Table 2.
- XELJANZ XR is not recommended in patients with moderate hepatic impairment or moderate to severe renal insufficiency; XELJANZ 5 mg once daily may be considered.
- Modified dosing of XELJANZ/XELJANZ XR is recommended with concomitant CYP inhibitors as indicated in Table 3.
- Coadministration of potent inducers of CYP3A4 with XELJANZ/XELJANZ XR is not recommended. Coadministration of potent inducers of CYP3A4 (e.g. rifampin) with XELJANZ/XELJANZ XR may result in loss of efficacy or reduced clinical response to XELJANZ/XELJANZ XR (see 9.4 Drug-Drug Interactions).
|
|
XELJANZ |
XELJANZ XR |
||
|---|---|---|---|---|
|
Indicated dose (in normal renal/hepatic function) |
5 mg BID |
10 mg BID |
11 mg once daily |
|
|
Modified dosing |
Moderate Renal insufficiency (CLcr ≥30 and <60 mL/min) |
5 mg once daily |
5 mg BID |
Not recommended (Consider XELJANZ 5 mg) |
|
Severe Renal insufficiency (CLcr ≥15 and <30 mL/min) |
5 mg once daily |
5 mg BID |
Not recommended (Consider XELJANZ 5 mg) |
|
|
Moderate hepatic impairment |
5 mg once daily |
5 mg BID |
Not recommended (Consider XELJANZ 5 mg) |
|
|
Severe hepatic impairment |
Contraindicated |
Contraindicated |
Contraindicated |
|
|
XELJANZ |
XELJANZ XR |
|||
|---|---|---|---|---|
|
Indicated dose |
5 mg BID |
10 mg BID |
11 mg once daily |
|
|
Modified dosing |
Patients receiving: · Potent CYP3A4 inhibitors (e.g. ketoconazole), or · a moderate CYP3A4 inhibitor and a potent CYP2C19 inhibitor (e.g. fluconazole) |
5 mg once daily |
5 mg BID |
Not recommended (Consider XELJANZ 5 mg once daily) |
|
Patients receiving: · Potent CYP3A4 inducers (e.g. rifampin) |
Not recommended |
Not recommended |
Not recommended |
|
Special Populations
Geriatrics (>65 years): No dosage adjustment is required in patients aged 65 years and older (see 7.1.4 Geriatrics and 10 CLINICAL PHARMACOLOGY).
Pediatrics (<18 years of age): Health Canada has not authorized an indication for pediatric use. No data are available regarding the safety and efficacy of XELJANZ/XELJANZ XR in children aged from neonates to less than 18 years of age. Therefore XELJANZ/XELJANZ XR should not be used in this patient population (see 1.1 Pediatrics, 7.1.3 Pediatrics and 10 CLINICAL PHARMACOLOGY).
4.4 Administration
XELJANZ/XELJANZ XR is to be taken orally with or without food.
Swallow XELJANZ XR tablets whole and intact. Do not crush, split, or chew.
4.5 Missed Dose
For a missed dose, resume at the next scheduled dose.