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Letters to the Editor

In Reply: Low-Dose Warfarin Prophylaxis for Catheter-Associated Thrombosis in Cancer Patients. Can It Be Safely Associated with 5-Fluorouracil-Based Chemotherapy?

Hematology Oncology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

Correspondence: David J. Kuter, M.D., D. Phil., Hematology Unit, COX 640, Massachusetts General Hospital, 100 Blossom Street, Boston, Massachusetts 02114, USA. Telephone: 617-726-3908; Fax: 617-724-3166; e-mail: kuter.david{at}MGH.harvard.edu.

I agree with the comments made in the letter by Magagnoli et al. regarding the increased likelihood of an increased International Normalized Ratio (INR) and possible bleeding when low-dose warfarin is used in patients with 5-fluorouracil (5-FU)-based chemotherapy regimens. 5-FU seems to inhibit the metabolism of the more active S-enantiomer of warfarin, decrease its clearance, and thereby enhance the hypoprothrombinemic effect of warfarin [1]. Indeed, in patients on full-dose warfarin who subsequently receive 5-FU, the average warfarin dose to maintain a therapeutic INR declines by nearly half and requires careful weekly monitoring [2]. Similar effects have been noted with capecitabine (Xeloda^®; Roche Laboratories, Inc.; Nutley, NJ), the prodrug of 5-FU [3, 4].

It is for reasons such as this, as well as the lack of any demonstrable benefit of low-dose warfarin in clinical trials of catheter prophylaxis, that I personally do not use or recommend low-dose warfarin catheter prophylaxis. For patients with marginal nutrition or impaired hepatic function or who are on 5-FU or capecitabine chemotherapy regimens, I would certainly not recommend low-dose warfarin prophylaxis. However if low-dose prophylaxis is used in those settings, weekly INR monitoring is strongly recommended.

REFERENCES

1. Zhou Q, Chan E. Effect of 5-fluorouracil on the anticoagulant activity and the pharmacokinetics of warfarin enantiomers in rats. Eur J Pharm Sci 2002;17:73–80.[Medline]
2. Kolesar JM, Johnson CL, Freeberg BL et al. Warfarin-5-FU interaction—a consecutive case series. Pharmacotherapy 1999;19:1445–1449.[CrossRef][Medline]
3. Copur MS, Ledakis P, Bolton M et al. An adverse interaction between warfarin and capecitabine: a case report and review of the literature. Clin Colorectal Cancer 2001;1:182–184.[Medline]
4. Reigner B, Blesch K, Weidekamm E. Clinical pharmacokinetics of capecitabine. Clin Pharmacokinet 2001;40:85–104.[CrossRef][Medline]

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