Remicade (Infliximab) Warning Letter from Centocor to Health Care Frofesssionals 10/18/2001
Centocor October 18, 2001 IMPORTANT DRUG WARNING
Dear Healthcare Professional:
Centocor, Inc. would like to inform you of important new safety information for REMICADE® (infliximab). Upon review of preliminary results of its ongoing phase 2 trial in 150 patients with moderate to severe (NYHA class III-IV) congestive heart failure (CHF), higher incidences of mortality and hospitalization for worsening heart failure were seen in patients treated with REMICADE, especially those treated with the higher dose of 10 mg/kg. Seven of 101 patients treated with REMICADE died compared to no deaths among the 49 patients on
In this trial, stable but symptomatic patients with NYHA Class III-IV CHF were treated with 3 infusions of REMICADE 5 mg/kg, REMICADE 10 mg/kg, or placebo over 6 weeks. REMICADE is a biological therapeutic product indicated for the treatment of rheumatoid
arthritis and Crohn’s disease.
Centocor, in consultation with FDA, is alerting physicians to these potential adverse effects of
REMICADE in patients with CHF. At present, there are insufficient data to determine optimal patient management. However, based on these preliminary findings, and pending additional data, physicians should consider the following precautionary measures.
For patients with rheumatoid arthritis or Crohn’s disease being considered for therapy with REMICADE:
• Do not initiate therapy in patients with congestive heart failure.
Patients with CHF currently receiving chronic REMICADE treatment for rheumatoid arthritis
or Crohn’s disease should be reevaluated.
• Treatment should be discontinued in patients whose CHF is worsening.
• Treatment discontinuation should be considered in patients with stable concomitant CHF, especially in those who have not had a significant clinical response to REMICADE therapy. If a decision is made to continue treatment, cardiac status should be closely monitored.
Although experimental pre-clinical studies and prior small clinical trials had suggested that therapy
targeted at TNF might be of benefit in patients with CHF, this and other recent trials have failed to
demonstrate that agents that bind TNF can improve the clinical course in these patients.
Centocor will continue to acquire follow up data on patients in the phase 2 trial in order to better
characterize the risk posed by REMICADE® (infliximab) to patients with CHF and to provide
more definitive conclusions and recommendations to healthcare professionals, in the form of a
future update to the prescribing information.
Centocor is committed to ensuring that REMICADE is used safely and effectively and will continue to work closely with the FDA and healthcare professionals to communicate new information and updates to the prescribing information concerning the potential for risk associated with the use of REMICADE in patients with concomitant CHF.
Centocor can assure you that it will provide you with the most current product information for
REMICADE. You can assist us with monitoring the safety of REMICADE by reporting adverse events to Centocor at 1-800-457-6399. Alternatively, this information may be reported to FDA’s MedWatch reporting system by phone (1-800-FDA-1088), facsimile (1-800-FDA-0178), the MedWatch website at www.fda.gov/medwatch, or mailed to MedWatch, HF-2, 5600 Fishers Lane, Rockville, MD 20852-9787. Both healthcare professionals and consumers should use Form 3500 for reporting adverse events.
Should you have any questions or require further information regarding the use of REMICADE, please contact Centocor’s Medical Affairs Department at 1-800-457-6399.
Lawrence I. Deckelbaum, MD
Cardiac, Vascular and Pulmonary
Clinical Research and Development
Centocor, Inc. • 200 Great Valley Parkway • Malvern, Pennsylvania 19355-1307 • (610) 651-6000 • Facsimile (610) 651-6100
©2001 Centocor, Inc. 10/01 SN1001(35-1)A IN01233