signs and symptoms of infectionduring and after treatment with RENFLEXIS, including the development of tuberculosis inpatients who tested negative for latent tuberculosis infection prior to initiating therapy. Testsfor latent tuberculosis infection may also be falsely negative while on therapy withRENFLEXIS.
RENFLEXIS should be discontinued if a patient develops a serious infection or sepsis. Apatient who develops a new infection during treatment with RENFLEXIS should be closelymonitored, undergo a prompt and complete diagnostic workup appropriate for animmunocompromised patient, and appropriate antimicrobial therapy should be initiated.
Invasive Fungal Infections
For patients who reside or travel in regions where mycoses are endemic, invasive fungalinfection should be suspected if they develop a serious systemic illness. Appropriate empiricantifungal therapy should be considered while a diagnostic workup is being performed.
Antigen and antibody testing for histoplasmosis may be negative in some patients with activeinfection. When feasible, the decision to administer empiric antifungal therapy in thesepatients should be made in consultation with a physician with expertise in the diagnosis andtreatment of invasive fungal infections and should take into account both the risk for severefungal infection and the risks of antifungal therapy.
5.2 Malignancies
Malignancies, some fatal, have been reported among children, adolescents and young adultswho received treatment with TNF-blocking agents (initiation of therapy ≤ 18 years of age),including infliximab products. Approximately half of these cases were lymphomas, including Hodgkin’s and non-Hodgkin’s lymphoma. The other cases represented a variety ofmalignancies, including rare malignancies that are usually associated withimmunosuppression and malignancies that are not usually observed in children andadolescents.
The malignancies occurred after a median of 30 months (range 1 to 84 months)after the first dose of TNF blocker therapy. Most of the patients were receiving concomitantimmunosuppressants. These cases were reported post-marketing and are derived from avariety of sources, including registries and spontaneous postmarketing reports.
Lymphomas
In the controlled portions of clinical trials of all the TNF-blocking agents, more cases oflymphoma have been observed among patients receiving a TNF blocker compared withcontrol patients. In the controlled and open-label portions of infliximab clinical trials, 5patients developed lymphomas among 5707 patients treated with infliximab (median durationof follow-up 1.0 years) vs. 0 lymphomas in 1600 control patients (median duration of followup0.4 years). In rheumatoid arthritis patients, 2 lymphomas were observed for a rate of 0.08cases per 100 patient-years of follow-up, which is approximately three-fold higher thanexpected in the general population. In the combined clinical trial population for rheumatoidarthritis, Crohn’s disease, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, andplaque psoriasis, 5 lymphomas were observed for a rate of 0.10 cases per 100 patient-years offollow-up, which is approximately four-fold higher than expected in the general population.
Patients with Crohn’s disease, rheumatoid arthritis or plaque psoriasis, particularly patientswith highly active disease and/or chronic exposure to immunosuppressant therapies, m |
