SUMMARY OF PRESCRIBING
INFORMATION (SPI)

Generic name of product: Tofacitinib citrate Tablets 5 mg

Brand name of product: XELJANZ^®

Presentation: White, round, immediate-release film-coated tablets for oral use, debossed with “Pfizer” on one side, and “JKI 5” on the other side.

Strength: 5 mg
 

Indication:

Rheumatoid arthritis:
Tofacitinib is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. It may be used as monotherapy or in combination with methotrexate or other non-biologic disease-modifying antirheumatic drugs (DMARDs).
 

Psoriatic Arthritis:
Tofacitinib is indicated for the treatment of adult patients with active psoriatic arthritis (PsA) who have had an inadequate response or intolerance to methotrexate or other non-biologic disease-modifying antirheumatic drugs (DMARDs).
 

Ulcerative Colitis:
Tofacitinib is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC), who have an inadequate response and who are intolerant to TNF blockers.
 

Pharmaceutical Form, Dosage and Method of Administration:

Dosage:

Tofacitinib may be used as monotherapy or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis. The recommended dose of tofacitinib is 5 mg twice daily. Tofacitinib is used in combination with nonbiologic disease modifying antirheumatic drugs (DMARDs) in psoriatic arthritis. The efficacy of Tofacitinib as a monotherapy has not been studied in psoriatic arthritis.

Ulcerative Colitis Induction: 10 mg twice daily for at least 8 weeks, evaluate patients and transition to maintenance therapy based on response. If needed continue 10 mg twice daily for a maximum of 16 weeks. Discontinue 10 mg twice daily after 16 weeks if adequate therapeutic response is not achieved.

Ulcerative Colitis Maintenance: 5 mg twice daily. For patients with loss of response during maintenance treatment, a dosage of 10 mg twice daily may be considered and limited to the shortest duration. Use the lowest effective dose needed to maintain response.
 

Method of Administration:

Tofacitinib is given orally with or without food. In patients receiving CYP3A4 inhibitors, 5 mg once daily. Discontinue dosing in patients with lymphocyte count less than 500 cells/mm³, confirmed by repeat testing. Limitations of Use: Use of Tofacitinib in combination with biologic DMARDs or potent immunosuppressants such as azathioprine, cyclosporine and Tacrolimus is not recommended.

Contraindications: None.
 

Warnings and Precautions, including special population

Serious infections:

Patients treated with Tofacitinib are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants, such as methotrexate or corticosteroids. If a serious infection develops, interrupt Tofacitinib until the infection is controlled. 
Reported infections include:

• Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before Tofacitinib use and during therapy. Treatment for latent infection should be initiated prior to Tofacitinib use.
• Invasive fungal infections, including cryptococcosis and pneumocystosis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
• Bacterial, viral, and other infections due to opportunistic pathogens. The risk and benefits of treatment with Tofacitinib should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with Tofacitinib, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.
 

In the UC population, tofacitinib treatment with 10 mg twice daily was associated with greater risk of serious infections compared to 5 mg twice daily, along with opportunistic herpes zoster infections (including meningoencephalitis, ophthalmic and disseminated cutaneous) with tofacitinib 10 mg twice daily.
 

Viral Reactivation:

Viral reactivation, including cases of herpes virus reactivation (eg, herpes zoster), was observed in clinical studies with Tofacitinib. Screening for viral hepatitis should be performed in accordance with clinical guidelines before starting therapy with Tofacitinib. Post-marketing cases of hepatitis B reactivation have been reported in patients treated with Tofacitinib. The risk of herpes zoster is increased in patients treated with Tofacitinib and appears to be higher in patients treated with Tofacitinib in Japan.
 

Mortality:

Rheumatoid arthritis patients 50 years of age and older with at least one cardiovascular (CV) risk factor treated with Tofacitinib 10 mg twice a day had a higher rate of all-cause mortality, including sudden CV death, compared to those treated with Tofacitinib 5 mg given twice daily or TNF blockers in a large, ongoing, post marketing safety study. For the treatment of UC, use tofacitinib at the lowest effective dose and for the shortest duration needed to achieve/maintain therapeutic response.
 

Lymphoma and other malignancies:

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Tofacitinib, particularly in patients with a known malignancy (other than a successfully treated NMSC), patients who develop a malignancy while on treatment, and patients who are current or past smokers. Malignancies were observed in clinical studies and the post-marketing setting, including, but not limited to, Lymphomas, lung cancer, gastric, colorectal, renal cell, breast cancer, melanoma, prostate cancer, and pancreatic cancer, malignant melanoma.
 

Major adverse cardiovascular events:

Rheumatoid arthritis patients who were 50 years of age and older with at least one cardiovascular risk factor treated with Tofacitinib 5 mg twice daily or Tofacitinib 10 mg twice daily had a higher rate of major adverse cardiovascular events (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke, compared to those treated with TNF blockers. The incidence rate of MACE per 100 patient-years was 0.91 for Tofacitinib 5 mg twice a day, 1.11 for Tofacitinib 10 mg twice a day, and 0.79 for TNF blockers. The incidence rate of fatal or non-fatal myocardial infarction per 100 patient-years was 0.36 for Tofacitinib 5 mg twice a day, 0.39 for Tofacitinib 10 mg twice a day, and 0.20 for TNF blockers (see section 5.2, Clinical Studies). Patients who are current or past smokers are at additional increased risk. Consider the benefits and risks for the  individual patient prior to initiating or continuing therapy with Tofacitinib, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue Tofacitinib in patients that have experienced a myocardial infarction or stroke. 
A Tofacitinib 10 mg twice daily dosage is not recommended for the treatment of RA or PsA.
 

Hypersensitivity

Reactions such as angioedema and urticaria that may reflect drug hypersensitivity have been observed in patients receiving Tofacitinib. Some events were serious. If a serious hypersensitivity reaction occurs, promptly discontinue tofacitinib while evaluating the potential cause or causes of the reaction.
 

Precautions:

• ​​​​​Avoid use of Tofacitinib during an active serious infection, including localized infections.
• Gastrointestinal Perforations – Use with caution in patients that may be at increased risk.
• Laboratory Monitoring – Recommended due to potential changes in lymphocytes, neutrophils,
  hemoglobin, liver enzymes and lipids.
• Immunizations – Live vaccines: Avoid use with Tofacitinib.

Special Populations:
 

Renal or Hepatic Impairment:
No dose adjustment is required in patients with mild renal and Hepatic impairment.
 

Tofacitinib dosage should be reduced to 5 mg once daily in patients:

• with moderate or severe renal insufficiency (including but not limited to those with severe insufficiency who are undergoing hemodialysis)

• with moderate hepatic impairment.

• For ulcerative colitis patients on 10 mg twice daily, reduce the dose to 5 mg twice daily. In patients on 5 mg twice daily, reduce the dose to 5 mg once daily.

Use of Tofacitinib in patients with severe hepatic impairment is not recommended. 
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.
 

Use in Diabetics:

As there is a higher incidence of infection in diabetic population in general, caution should be used when treating patients with diabetes.
 

Use in Children:

The safety and efficacy of tofacitinib in children less than 18 years of age has not yet been established.
 

Use in Pregnancy and Lactation:

There are no adequate and well-controlled studies in pregnant women. Tofacitinib should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether Tofacitinib is excreted in milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug for the mother. Drug Interactions: Strong CP3A4 Inhibitors (e.g., ketoconazole): Increased exposure to tofacitinib. Dosage adjustment of Tofacitinib is recommended. Moderate CYP3A4 Inhibitors Co-administered with Strong CYP2C19 Inhibitors (e.g., fluconazole): Increased exposure to tofacitinib. Dosage adjustment of Tofacitinib is recommended. Strong CYP3A4 Inducers (e.g., rifampin): Decreased exposure to tofacitinib and may result in loss of or reduced clinical response. Co-administration with Tofacitinib is not recommended. Immunosuppressive Drugs (e.g., azathioprine, tacrolimus, cyclosporine): Risk of added immunosuppression; coadministration with biologic DMARDs or potent immunosuppressants has not been studied in patients with rheumatoid arthritis, psoriatic arthritis. Coadministration with Tofacitinib is not recommended.

Overdose:

There is no specific antidote for overdose with tofacitinib. Treatment should be symptomatic and supportive. In case of an overdose, it is recommended that the patient be monitored for signs and symptoms of adverse reactions.
 

Adverse Reactions (Very common and common)

Adverse events:

The most commonly reported adverse reactions during the first 3 months in controlled clinical trials (occurring in greater than or equal to 2% of patients treated with Tofacitinib monotherapy or in combination with DMARDs) were upper respiratory tract infections, headache, diarrhea and nasopharyngitis and hypertension. Clinically significant adverse reactions as described in detail are Serious Infections, Malignancy and Lymphoproliferative Disorders, Major Adverse Cardiovascular Events, Gastrointestinal Perforations, Thrombosis, Hypersensitivity, Mortality, Laboratory Abnormalities (Lymphopenia, Neutropenia, Liver enzyme elevations, Lipid elevations and serum creatinine elevations).
 

Pharmaceutical precautions:

Storage Condition: Recommended storage condition: Store below 30°C. No specific handling requirements.
 

Pharmacokinetics/Pharmacodynamics:

Following oral administration of tofacitinib, peak plasma concentrations are reached within 0.5-1 hour, elimination half-life is about 3 hours and a dose-proportional increases in systemic exposure was observed in the therapeutic dose range. Steady-state concentrations are achieved in 24-48 hours with negligible accumulation after twice daily administration.

AUC₂₄ (ng.h/mL): 263.4 (15)
C_max (ng/mL): 42.7 (26)
T_max (hours): 1.0 (0.5 to 14.0)
 

CLD Version and date: SPI_ LPDTOFA012022 : Based on Xeljanz LPDTOFA012022 
Last Updated on date: This package insert was last revised in January 2022.

Refer full prescribing information for additional information.