Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium
Tofacitinib in combination with methotrexate (MTX) is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying antirheumatic drugs. Tofacitinib can be given as monotherapy in case of intolerance to MTX or when treatment with MTX is inappropriate (see sections 4.4 and 4.5).
Tofacitinib in combination with MTX is indicated for the treatment of active psoriatic arthritis (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug (DMARD) therapy (see section 5.1).
Tofacitinib is indicated for the treatment of adult patients with active ankylosing spondylitis (AS) who have responded inadequately to conventional therapy.
Tofacitinib is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent (see section 5.1).
Tofacitinib is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (rheumatoid factor positive [RF+]or negative [RF-] polyarthritis and extended oligoarthritis), and juvenile psoriatic arthritis (PsA) in patients 2 years of age and older, who have responded inadequately to previous therapy with DMARDs.
Tofacitinib can be given in combination with methotrexate (MTX) or as monotherapy in case of intolerance to MTX or where continued treatment with MTX is inappropriate.
Treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of conditions for which tofacitinib is indicated.
The recommended dose is 5 mg film-coated tablets administered twice daily, which should not be exceeded.
No dose adjustment is required when used in combination with MTX.
For information on switching between tofacitinib film-coated tablets and tofacitinib prolonged-release tablets see Table 1.
Table 1. Switching between tofacitinib film-coated tablets and tofacitinib prolonged-release tablets:
| Switching between tofacitinib 5 mg film-coated tablets and tofacitinib 11 mg prolonged-release tableta | Treatment with tofacitinib 5 mg film-coated tablets twice daily and tofacitinib 11 mg prolonged-release tablet once daily may be switched between each other on the day following the last dose of either tablet. |
a See section 5.2 for comparison of pharmacokinetics of prolonged-release and film-coated formulations.
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.
The recommended dose for maintenance treatment is tofacitinib 5 mg given orally twice daily.
Tofacitinib 10 mg twice daily for maintenance treatment is not recommended in patients with UC who have known venous thromboembolism (VTE) risk factors, unless there is no suitable alternative treatment available (see section 4.4 and 4.8).
For patients with UC who are not at increased risk for VTE (see section 4.4), 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.
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. Efficacy may be regained by 8 weeks of 10 mg twice daily therapy (see section 5.1).
Tofacitinib may be used as monotherapy or in combination with MTX.
The recommended dose in patients 2 years of age and older is based upon the following weight categories.
Table 2. Tofacitinib dose for patients with polyarticular juvenile idiopathic arthritis and juvenile PsA two years of age and older:
| Body weight (kg) | Dose regimen |
|---|---|
| 10 - <20 | 3.2 mg (3.2 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.
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. As described in Tables 3, 4 and 5 below, recommendations for temporary dose interruption or permanent discontinuation of treatment are made according to the severity of laboratory abnormalities (see section 4.4).
It is recommended not to initiate dosing in patients with an absolute lymphocyte count (ALC) less than 750 cells/mm³.
Table 3. Low absolute lymphocyte count:
| Low absolute lymphocyte count (ALC) (see section 4.4) | |
|---|---|
| Lab 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 10 mg twice daily, dosing should be reduced to tofacitinib 5 mg twice daily. 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 lab value confirmed by repeat testing within 7 days, dosing should be discontinued. |
It is recommended not to initiate dosing in adult patients with an absolute neutrophil count (ANC) less than 1,000 cells/mm³. It is recommended not to initiate dosing in paediatric patients with an absolute neutrophil count (ANC) less than 1,200 cells/mm³.
Table 4. Low absolute neutrophil count:
| Low absolute neutrophil count (ANC) (see section 4.4) | |
|---|---|
| Lab 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. For patients receiving tofacitinib 10 mg twice daily, dosing should be reduced to tofacitinib 5 mg twice daily. 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 lab value confirmed by repeat testing within 7 days, dosing should be discontinued. |
It is recommended not to initiate dosing in adult patients with haemoglobin less than 9 g/dL. It is recommended not to initiate dosing in paediatric patients with haemoglobin less than 10 g/dL.
Table 5. Low haemoglobin value:
| Low haemoglobin value (Section 4.4) | |
|---|---|
| Lab value (g/dL) | Recommendation |
| Less than or equal to 2 g/dL decrease and greater than or equal to 9.0 g/dL | Dose should be maintained. |
| Greater than 2 g/dL decrease or less than 8.0 g/dL (confirmed by repeat testing) | Dosing should be interrupted until haemoglobin values have normalised. |
Tofacitinib total daily dose should be reduced by half in patients receiving potent inhibitors of cytochrome P450 (CYP) 3A4 (e.g. ketoconazole) and in patients receiving 1 or more concomitant medicinal products that result in both moderate inhibition of CYP3A4 as well as potent inhibition of CYP2C19 (e.g. fluconazole) (see section 4.5) as follows:
Only in paediatric patients: 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 clinical improvement within this timeframe.
Available data suggest that clinical improvement in AS is observed within 16 weeks of initiation of treatment with tofacitinib. Continued therapy should be carefully reconsidered in a patient exhibiting no clinical improvement within this timeframe.
No dose adjustment is required in patients aged 65 years and older. There are limited data in patients aged 75 years and older.
Table 6. Dose adjustment for hepatic impairment:
| Hepatic impairment category | Classification | Dose adjustment in hepatic impairment for different strength tablets |
|---|---|---|
| Mild | Child Pugh A | No dose adjustment required. |
| Moderate | Child Pugh B | Dose should be reduced to 5 mg once daily when the indicated dose in the presence of normal hepatic function is 5 mg twice daily. Dose should be reduced to 5 mg twice daily when the indicated dose in the presence of normal hepatic function is 10 mg twice daily (see section 5.2). |
| Severe | Child Pugh C | Tofacitinib should not be used in patients with severe hepatic impairment (see section 4.3). |
Table 7. Dose adjustment for renal impairment:
| Renal impairment category | Creatinine clearance | Dose adjustment in renal impairment for different strength tablets |
|---|---|---|
| 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 once daily when the indicated dose in the presence of normal renal function is 5 mg twice daily. Dose should be reduced to 5 mg twice daily when the indicated dose in the presence of normal renal function is 10 mg twice daily. Patients with severe renal impairment should remain on a reduced dose even after haemodialysis (see section 5.2). |
The safety and efficacy of tofacitinib in children less than 2 years of age with polyarticular JIA and juvenile PsA has not been established. No data are available.
The safety and efficacy of tofacitinib in children less than 18 years of age with other indications (e.g., ulcerative colitis) has not been established. No data are available.
Oral use.
Tofacitinib is given orally with or without food.
For patients who have difficulties swallowing, tofacitinib tablets may be crushed and taken with water.
In case of an overdose, it is recommended that the patient be monitored for signs and symptoms of adverse reactions. There is no specific antidote for overdose with tofacitinib. Treatment should be symptomatic and supportive.
Pharmacokinetic data up to and including a single dose of 100 mg in healthy volunteers indicate that more than 95% of the administered dose is expected to be eliminated within 24 hours.
4 years.
This medicinal product does not require any special temperature storage conditions.
Store in the original package in order to protect from moisture.
XELJANZ 5 mg film-coated tablets:
HDPE bottles with silica gel desiccant and child-resistant polypropylene closure containing 60 or 180 film-coated tablets.
Aluminium foil/PVC backed aluminium foil blisters containing 14 film-coated tablets. Each pack contains 56, 112, or 182 film-coated tablets.
XELJANZ 10 mg film-coated tablets:
HDPE bottles with silica gel desiccant and child-resistant polypropylene closure containing 60 or 180 film-coated tablets.
Aluminium foil/PVC backed aluminium foil blisters containing 14 film-coated tablets. Each pack contains 56, 112, or 182 film-coated tablets.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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