| Lab monitoring recommendations for patients taking XELJANZ1 | |||
|---|---|---|---|
| At initiation | After 4 to 8 weeks | Every 3 months thereafter | |
| Lymphocytes |  |
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| Neutrophils | |
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| Hemoglobin | |
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| Lipids | After 8 weeks following initiation of therapy | ||
| Liver enzymes | Routine monitoring of liver test and prompt investigation of the cause of liver enzyme elevation are also recommended | ||
| Avoid initiating treatment in patients with: | Lymphocyte count <0.75 cells x109/L |
Absolute neutrophil count <1.0 cells
x109/L
|
Hemoglobin levels <9 g/dL |
- Prior to initiating XELJANZ, it is recommended that all patients be brought up to date with all immunisations in agreement with current immunisation guidelines
- It is recommended that live vaccines not be given concurrently with XELJANZ. The decision to use live vaccines prior to XELJANZ treatment should take into account the pre-existing immunosuppression in a given patient
- Prophylactic zoster vaccination should be considered in accordance with vaccination guidelines. Particular consideration should be given to patients with longstanding rheumatoid arthritis who have received two or more prior biological DMARDs. If the history of chickenpox is considered doubtful or unreliable it is recommended to test for antibodies against VZV
- XELJANZ has not been studied and its use should be avoided in patients in combination with biologics such as TNF antagonists, IL-1R antagonists, IL-6R antagonists, anti-CD20 monoclonal antibodies, IL‑17 antagonists, IL‑12/IL‑23 antagonists, anti-integrins, and selective co-stimulation modulators and potent immunosuppressants such as azathioprine, 6-mercaptopurine, cyclosporine, and tacrolimus because of the possibility of increased immunosuppression and increased risk of infection
- There is a higher incidence of adverse events for the combination of XELJANZ plus MTX vs XELJANZ as monotherapy in RA clinical trials
- Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving tofacitinib. The risk of opportunistic infections is higher in Asian geographic regions (see section 4.4 of the XELJANZ Product Information). 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
- who are over 65 years of age
- Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with XELJANZ. Treatment must be interrupted if a patient develops a serious infection, an opportunistic infection, or sepsis. A patient who develops a new infection during treatment with XELJANZ 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
- As there is a higher incidence of infections in the elderly and in the diabetic populations in general, caution should be used when treating the elderly and patients with diabetes. In patients over 65 years of age tofacitinib should only be considered if no suitable alternative treatment is available
- 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. Discontinuation and monitoring criteria for lymphopenia are discussed in section 4.2 of the XELJANZ Product Information
- Patients should be evaluated and tested for latent or active infection prior to administration of XELJANZ and continue to be evaluated while on treatment.
- Patients with latent tuberculosis should be treated with standard antimycobacterial therapy before administering XELJANZ.
- Antituberculosis therapy should be considered prior to administration of XELJANZ in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but who have risk factors for tuberculosis infection. Consultation with a health care professional with expertise in the treatment of tuberculosis is recommended to aid in the decision about whether initiating antituberculosis therapy is appropriate for an individual patient.
- Patients should be closely monitored for the development of signs and symptoms of
tuberculosis, including patients who tested negative for latent tuberculosis infection prior to initiating therapy. The need for repeat testing should be considered during therapy if symptoms develop or if re-exposure occurs.
- Viral reactivation and cases of herpes virus reactivation (eg, herpes zoster) were observed in clinical studies with XELJANZ. In patients treated with XELJANZ, the risk of herpes zoster appears to be increased in:
- Japanese and Korean patients
- Patients with an absolute lymphocyte count (ALC) less than 1.0 cells x 109/L
- Patients with long standing RA who have previously received two or more biologic DMARDs
- Patients treated with 10 mg twice daily
- The risks and benefits of XELJANZ treatment should be considered prior to initiating therapy in patients with current or a history of malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing XELJANZ in patients who develop a malignancy. The possibility exists for XELJANZ to affect host defenses against malignancies
- Lymphomas have been observed in patients treated with XELJANZ. Patients with RA, particularly those with highly active disease may be at a higher risk (up to several-fold) than the general population for the development of lymphoma. The role of XELJANZ in the development of lymphoma is uncertain
- Other malignancies were observed in clinical studies and the post-marketing setting, including, but not limited to, lung cancer, breast cancer melanoma, prostate cancer and pancreatic cancer
- The effect of XELJANZ on the development and course of malignancies is not known
- Non-melanoma skin cancers (NMSCs) have been reported in patients treated with XELJANZ. The risk of NMSC may be higher in patients treated with XELJANZ 10 mg twice daily than in patients treated with 5 mg twice daily. Periodic skin examination is recommended for patients who are at increased risk for skin cancer
- Regular skin examinations are recommended, particularly for patients
with an increased risk for, or a prior history of, skin cancer
- Events of interstitial lung disease (some of which had a fatal outcome) have been reported in patients treated with XELJANZ in RA clinical trials and in the post-marketing setting although the role of Janus kinase (JAK) inhibition in these events is not known. Asian RA patients are known to be at higher risk of interstitial lung disease, thus caution should be exercised in treating these patients
- Serious VTE events including pulmonary embolism (PE), some of which were fatal, and deep vein thrombosis (DVT), have been observed in patients taking tofacitinib. A dose dependent increased risk for VTE was observed in a clinical study with tofacitinib compared to TNF inhibitors
- Tofacitnib should be used with caution in patients with known risk factors for VTE, regardless of indication and dosage
- VTE risk factors include previous VTE, patients undergoing major surgery, immobilisation, myocardial infarction (within previous 3 months), heart failure, use of combined hormonal contraceptives or hormone replacement therapy, inherited coagulation disorder, malignancy. Additional VTE risk factors such as age, obesity (BMI ≥30), diabetes, hypertension, smoking status should also be considered. Patients should be re-evaluated periodically during tofacitinib treatment to assess for changes in VTE risk
- Promptly evaluate patients with signs and symptoms of VTE and discontinue tofacitinib in patients with suspected VTE, regardless of dose or indication
- Treatment with XELJANZ was associated with an increased incidence of liver enzyme elevation in some patients
- Routine monitoring of liver tests and prompt investigation of the causes of liver enzyme elevations is recommended to identify potential cases of drug-induced liver injury. If drug-induced liver injury is suspected, XELJANZ administration should be interrupted until this diagnosis has been excluded.
- Interruption of dosing may be needed for management of dose-related laboratory abnormalities including lymphopenia, neutropenia, and anemia
- Recommendations for temporary dose interruption or permanent discontinuation of treatment are made according to the severity of laboratory abnormalities
- Treatment with XELJANZ was associated with increases in lipid parameters such as total cholesterol, LDL and HDL, maximum effects were generally observed within 6 weeks
- Patients should be managed according to clinical guidelines for the management of hyperlipidemia
ALT=alanine aminotransferase; AST=aspartate aminotransferase; BID=twice daily; BMI=body mass index; DMARD=disease-modifying antirheumatic drug; HDL=high-density lipoprotein; IL-1R=interleukin-1 receptor; IL-6R=interleukin-6 receptor; LDL=low-density lipoprotein; MTX=methotrexate; RA=rheumatoid arthritis; TNF=tumor necrosis factor.
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