Phil B.FontanarosaMD, Interim CoeditorIndividualAuthorMargaret A.WinkerMD, Deputy EditorIndividualAuthorStephenLurieMD PhD, Fishbein FellowIndividualAuthor
Copyright 1999 American Medical Association. All Rights Reserved.
Applicable FARS/DFARS Restrictions Apply to Government Use.1999
In Reply: The possibility raised by Drs Nissenblatt
and Karp that trastuzumab might contribute to bleeding complications would
be of concern. Bleeding and hemorrhaging are common adverse effects of warfarin
use and the instability of coagulation demonstrated in studies of debilitated
patients is well recognized. The risk of trastuzumab use should be evaluated
with this in mind.
It is difficult to imagine a mechanism by which the humanized monoclonal
antibody trastuzumab might contribute to enhanced warfarin action and bleeding.
Drug interactions with warfarin are common. Many drugs that bind to serum
proteins displace warfarin and increase its effect. Such an effect of trastuzumab
would be unexpected and the time course of bleeding (after several weeks of
therapy) would seem incompatible with this theory. Similarly, effects of trastuzumab
on hepatic function or metabolic states would be unexpected. Congestive heart
failure (a reported adverse effect of trastuzumab administration) can impair
clotting-factor production, but neither of the reported patients had this
problem. Interference of trastuzumab with the activity of 1 or more factors
in the clotting cascade is a possibility that currently is being tested at
Genentech, Inc, South San Francisco, Calif.
Stewart SJ. Bleeding Risk With Trastuzumab (Herceptin) Treatment—Reply. JAMA. 1999;282(24):2299-2301. doi:10-1001/pubs.JAMA-ISSN-0098-7484-282-24-jbk1222