| Lab monitoring recommendations for patients taking XELJANZ1 | |||
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| 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 |
- Screening for viral hepatitis should be performed in accordance with clinical guidelines before starting therapy with XELJANZ1
- Patients should be evaluated and tested for latent or active tuberculosis prior to and per applicable guidelines during administration of XELJANZ1
-Lymphocyte count 0.75 x 109 cells/L
-Absolute neutrophil count <1.0 x 109 cells/L
-Haemoglobin levels <90 g/L
-Severe hepatic impairment
- Prior to initiating XELJANZ, it is recommended that all patients, particularly pJIA and jPsA patients, be brought up to date with all 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.
- Vaccination with live vaccines should occur in accordance with current vaccination guidelines regarding immunomodulatory medicinal products1
- XELJANZ has not been studied and its use should be avoided 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, selective co-stimulation modulators, and potent immunosuppressants such as azathioprine, 6-mercaptopurine, ciclosporine 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 XELJANZ with MTX vs XELJANZ as monotherapy in RA clinical trials1
- Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving XELJANZ. 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
- XELJANZ should not be initiated in patients with active infections, including localized infections
- The risks and benefits of treatment should be considered prior to initiating XELJANZ in patients:
- with recurrent infections
- with a history of a serious or an opportunistic infection
- who have resided or traveled in areas of endemic mycoses
- who have underlying conditions that may predispose them to infection
- with diabetes
- 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, XELJANZ should only be used if no suitable alternative treatment is available
- Risk of infection may be higher with increasing degrees of lymphopaenia and consideration should be given to lymphocyte counts when assessing individual patient risk of infection. Discontinuation and monitoring criteria for lymphopaenia 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 or XELJANZ XR and continue to be evaluated while on treatment.
- Patients with latent tuberculosis should be treated with standard antimycobacterial therapy before administering XELJANZ or XELJANZ XR.
- Antituberculosis therapy should be considered prior to administration of XELJANZ or XELJANZ XR 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 incidence of herpes zoster appears to be increased in:
- Japanese or Korean patients
- Patients with an absolute lymphocyte count (ALC) less than 1.0 x 109 cells/L
- Patients with long standing RA who have previously received two or more biologic DMARDs
- Patients treated with 10 mg twice daily*1
- Major adverse cardiovascular events (MACE) have been observed in patients taking XELJANZ
- In a randomized postauthorization safety study in patients with RA who were 50 years of age or older with at least one additional cardiovascular risk factor, an increased incidence of myocardial infarctions was observed with XELJANZ compared to TNF inhibitors (ORAL Surveillance). In patients over 65 years of age, patients who are current or past smokers, and patients with other cardiovascular risk factors, XELJANZ should only be used if no suitable treatment alternatives are available
- In patients over 65 years of age, patients who are current or past smokers, patients with other cardiovascular risk factors, or patients with other malignancy risk factors (e.g., current malignancy or history of malignancy other than a successfully treated non-melanoma skin cancer), XELJANZ should be used if no suitable treatment alternatives are available1
- XELJANZ may affect host defenses against malignancies
- In a randomised postauthorisation safety study in patients with RA who were 50 years of age or older with at least one additional cardiovascular risk factor, an increased incidence of malignancies (excluding NMSC), particularly lung cancer and lymphoma, was observed with XELJANZ compared to TNF inhibitors
- Lung cancers and lymphoma in patients treated with XELJANZ have also been observed in other clinical studies and in the postmarketing setting
- Other malignancies in patients treated with XELJANZ were observed in clinical studies and the postmarketing setting, including, but not limited to, breast cancer, melanoma, prostate cancer, and pancreatic cancer
- In patients over 65 years of age, patients who are current or past smokers, and patients with other malignancy risk factors (eg, current malignancy or history of malignancy other than a successfully treated NMSC), XELJANZ should only be used if no suitable treatment alternatives are available1
- Nonmelanoma 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 cancer1
- Caution is also recommended in patients with a history of chronic lung disease as they may be more prone to infections.
- Events of interstitial lung disease (some of which had a fatal outcome) have been reported in patients treated with XELJANZ in RA clinical studies and in the postmarketing 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 patients1
- Serious VTE events including pulmonary embolism (PE), some of which were fatal, and deep vein thrombosis (DVT), have been observed in patients taking XELJANZ. A dose dependent increased risk for VTE was observed in a clinical study with XELJANZ compared to TNF inhibitors in patients with RA who were ≥50 years of age with ≥1 additional cardiovascular risk factor (ORAL Surveillance)
- XELJANZ should be used with caution in patients with known risk factors for VTE, regardless of indication and dosage
- 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 XELJANZ-treated patients that, at 12 months treatment, had D-dimer level ≥2× ULN (upper limit of normal) 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
- 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, and malignancy. Additional VTE risk factors such as age, obesity (BMI ≥30), diabetes, hypertension, and smoking status should also be considered. Patients should be re-evaluated periodically during XELJANZ treatment to assess for changes in VTE risk
- Promptly evaluate patients with signs and symptoms of VTE and discontinue XELJANZ in patients with suspected VTE, regardless of dose or indication1
- 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 or XELJANZ XR administration should be interrupted until this diagnosis has been excluded.1
- 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 abnormalities1
- Treatment with XELJANZ was associated with increases in lipid parameters such as total cholesterol, LDL cholesterol, and HDL cholesterol. Maximum effects were generally observed within 6 weeks
- Patients should be managed according to clinical guidelines for the management of hyperlipidaemia1
Patients weighing ≥40 kg treated with 5 mL twice daily XELJANZ Oral Solution may be switched to a XELJANZ 5 mg twice daily tablet. Patients weighing <40 kg cannot be switched from XELJANZ Oral Solution.1
10 mg BD is not licensed for JIA.1
Curious about XELJANZ efficacy in JIA?