NEWS - FDA issue new Remicade (infliximab) warnings

[Guest guest]

FDA issues new infliximab warnings

Rheumawire

Aug 25, 2004

Janis

The US Food and Drug Administration (FDA) and Centocor this week warned

physicians that new hematologic adverse events, some fatal, have been

identified in postmarketing surveillance of patients taking infliximab

(Remicade, Centocor) for treatment of rheumatoid arthritis (RA) or

Crohn's disease [1].

The labeling for Remicade has been revised to include these problems

[see sidebar] in addition to previously recognized risks such as

reactivation of latent tuberculosis associated with this and other TNF

inhibitors.

In an August 11 " Dear Healthcare Professional " letter, Dr Everitt

(Centocor's vice president for clinical pharmacology and global

pharmacovigilance) writes, " " Although no high-risk group(s) has been

identified, caution should be exercised in patients being treated with

Remicade who have ongoing or a history of significant hematologic

abnormalities. All patients should be advised to seek immediate medical

attention if they develop signs and symptoms suggestive of blood

dyscrasias or infection (eg, persistent fever) while on Remicade. "

The Centocor statement notes that postmarketing data on Remicade include

reports of leukopenia, neutropenia, thrombocytopenia, and pancytopenia,

" some with a fatal outcome. " Rare cases of systemic vasculitis

presenting with central nervous system (CNS) symptoms have also been

reported.

Other adverse events identified in postmarketing surveillance include

pericardial effusion and both systemic and cutaneous vasculitis.

According to the Wall Street Journal, Centocor says that 580 patients

taking the drug have died over a 6-year period, but whether deaths were

due to the underlying disease or related to the drug is unknown [2].

More than 508 000 patients have taken infliximab during that time.

Remicade is marketed by & in the US, by Tanabe Seiyaku

in Japan and parts of the Far East, and by Schering-Plough in all other

countries.

New information added to Remicade prescribing information:

Hematologic events

Cases of leukopenia, neutropenia, thrombocytopenia, and

pancytopenia, some with a fatal outcome, have been reported in patients

receiving REMICADE. The causal relationship to REMICADE therapy remains

unclear. Although no high-risk group(s) has been identified, caution

should be exercised in patients being treated with REMICADE who have

ongoing or a history of significant hematologic abnormalities. All

patients should be advised to seek immediate medical attention if they

develop signs and symptoms suggestive of blood dyscrasias or infection

(eg, persistent fever) while on REMICADE. Discontinuation of REMICADE

therapy should be considered in patients who develop significant

hematologic abnormalities.

Neurologic events

Infliximab and other agents that inhibit TNF have been

associated in rare cases with optic neuritis, seizure, and new onset or

exacerbation of clinical symptoms and/or radiographic evidence of

central nervous system demyelinating disorders, including multiple

sclerosis and CNS manifestation of systemic vasculitis. Prescribers

should exercise caution in considering the use of REMICADE in patients

with preexisting or recent onset of central nervous system demyelinating

or seizure disorders. Discontinuation of REMICADE should be considered

in patients who develop significant central nervous system adverse

reactions.

Adverse reactions

The following adverse events have been reported during

postapproval use of REMICADE: neutropenia, interstitial

pneumonitis/fibrosis, idiopathic thrombocytopenic purpura, thrombotic

thrombocytopenic purpura, pericardial effusion, systemic and cutaneous

vasculitis, Guillain-Barré syndrome, transverse myelitis, and

neuropathies (additional neurologic events have also been observed).

Because these events are reported voluntarily from a

population of uncertain size, it is not always possible to reliably

estimate their frequency or establish a causal relationship to REMICADE

exposure.

Patient information

Heart failure. If you have been told that you have a heart

problem called congestive heart failure and you are currently being

treated with REMICADE, you will need to be closely monitored by your

doctor. If you develop new or worse symptoms that are related to your

heart condition, such as shortness of breath or swelling of your ankles

or feet, you must contact your doctor immediately.

Blood problems. In some patients the body may fail to

produce enough of the blood cells that help your body fight infections

or help you stop bleeding. Some patients have died from this failure to

produce blood cells. If you develop a fever that doesn't go away, bruise

or bleed very easily, or look very pale, call your doctor right away.

Your doctor may decide to stop your treatment

Nervous system disorders. There have been rare cases where

people taking REMICADE or other TNF blockers have developed disorders

that affected their nervous system. Signs that you could be having a

problem include: changes in your vision, weakness in your arms and/or

legs, and numbness or tingling in any part of your body.

Sources

FDA. 2004 Safety Alerts for Drugs, Biologics, Medical

Devices, and Dietary Supplements. August 24, 2004; Available at:

http://www.fda.gov/medwatch/SAFETY/2004/safety04.htm#remicade

Dooren JC. FDA, J & J's Centocor issue Remicade

warning. Wall Street Journal August 24, 2004; Available at:

http://online.wsj.com/article/0,,SB109337535919299863,00.html

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org