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Potential Interaction Between Telithromycin and Warfarin

Resident, Department of Pulmonary Medicine, Hellenic Air Force and Veterans General Hospital, Athens, Greece

George K Anagnostopoulos, MD

Resident, Department of Internal Medicine, Hellenic Air Force and Veterans General Hospital

Ioannis Lampaditis, MD

Resident, Department of Pulmonary Medicine, Hellenic Air Force and Veterans General Hospital

Iordanis Eleftheriadis, MD

Head, Department of Pulmonary Medicine, Hellenic Air Force and Veterans General Hospital

Reprints: Likurgos Kolilekas MD, 5 Kountouriotou St., 15351 Pallini, Athens, Greece, lykol{at}yahoo.gr

OBJECTIVE: To report a case of warfarin–telithromycin interaction resulting in an elevated international normalized ratio (INR) and hemoptysis.

CASE SUMMARY: A 73-year-old white man developed an elevated INR and mild hemoptysis as a result of an interaction between warfarin and telithromycin 800 mg/day. The INR increased from 3.1 before telithromycin was started to 11 after 5 days of telithromycin therapy. The INR returned to the therapeutic range 4 days after telithromycin was discontinued.

DISCUSSION: Telithromycin is the first member of the macrolide subclass of ketolides and offers potential advantages over traditional macrolides/azalides for community-acquired respiratory tract infections caused by macrolide-resistant pathogens. As of July 16, 2004, bleeding complications and an increased INR as a result of an interaction between warfarin and telithromycin have not been described. Although the mechanism for this interaction remains unknown, it is suspected that it is a result of the inhibition of the metabolism of the R-isomer of warfarin, which is metabolized predominantly by CYP1A2 and less by CYP3A4. Further research is required to elucidate this issue. An objective causality assessment revealed that this adverse drug event as a result of the warfarin and telithromycin interaction was probable.

CONCLUSIONS: We recommend close monitoring of INR levels in patients on warfarin who receive telithromycin therapy in an effort to control and prevent bleeding complications.

Key Words: international normalized ratio, telithromycin, warfarin

Published Online, July 27, 2004. www.theannals.com, DOI 10.1345/aph.1D567

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