In the post-marketing spontaneous reporting for infliximab (Remicade), infections are the most common serious adverse event. Some of the cases have resulted in fatal outcome. Up to the middle of 2001, 202 deaths had been reported. Nearly 50% of these were associated with infections. Up to 31 October 2001 approximately 130 cases of active tuberculosis with extra-pulmonary location were reported worldwide in patients treated with infliximab (Remicade). A ‘Dear Healthcare Professional’ letter from Centocor, the Marketing Authorisation Holder for infliximab (Remicade) was posted on the US FDA’s website in October 2001 detailing labelling revisions for infliximab (Remicade) about tuberculosis (TB) and other serious infections including histoplasmosis, listeriosis and pneumocystosis reported with the use of infliximab. Centocor has added a black box warning about these opportunistic infections and revised the Warnings and Adverse Reactions sections in the product label. Centocor advises physicians to review the revised labelling for infliximab and to carefully assess the risks and benefits of initiating treatment with infliximab in patients who have lived in endemic regions.
The latest EMEA Public Statement on Infliximab issued in February 2002 also informs health professionals about the risk of infections including tuberculosis in patients undergoing treatment with inflixmab. The statement advises that:
• infliximab is contraindicated in patients with tuberculosis or other severe infections such as sepsis, abscesses or opportunistic infections;
• patients should be closely monitored for infections including tuberculosis before, during and after infliximab (remicade) therapy, in accordance with local recommendations;
• treatment with infliximab (remicade) must be discontinued if the patient develops serious infections or sepsis and that before starting treatment with infliximab all patients must be evaluated for both active and inactive (latent) tuberculosis. If active tuberculosis is diagnosed, infliximab therapy must not be initiated; if inactive (latent) tuberculosis is diagnosed, prophylactic anti-tubercular therapy must be started before initiating infliximab therapy.
The statement also informs patients that while infliximab (Remicade) continues to be an effective and safe medicine, it increases the risk of getting infections, including tuberculosis. Patients should inform their physician if they have had TB or have been in close contact with a TB patient. In addition, patients receiving infliximab should report symptoms such as shortness of breath, swelling in the feet etc. as these may be signs of heart failure. In general, patients with a severe infection and/or moderate or severe heart failure may not be treated with infliximab.
Reports in WHO-file: infection (various kinds) 46; sepsis 39
1. ‘Dear Healthcare Professional’ letter from Centocor, 5 Oct 2001.
Available from URL: http://www.fda.gov/medwatch
2. EMEA Public Statement (CPMP/32/02), 1 Feb 2002.
Available from URL: http://www.emea.eu.int