Effect of gefitinib on warfarin antithrombotic activity.

Abstract

BACKGROUND:

Despite the literature indicating adverse interactions between warfarin and cytotoxic agents, whether such an interaction occurs when warfarin and gefitinib are used concomitantly is unknown. We analyzed the prevalence of the concomitant use of warfarin and gefitinib, and the incidence of prothrombin time-international normalized ratio (PT-INR) alterations or adverse interactions in concomitant users of warfarin and gefitinib.

METHODS:

We conducted a retrospective study of patients with non-small cell lung cancer treated at the Kitasato University Hospital who received concomitant warfarin and gefitinib between September 2002 and January 2007. Medical information, including the indication for warfarin use, warfarin dosing and dosing changes, and exposure to gefitinib were collected from computerized databases and medical records.

RESULTS:

Twelve (4.1%) of 296 patients treated with gefitinib received warfarin. PT-INR elevation occurred in 6 patients (50.0%). Two (16.7%) of the 12 patients had liver metastases. Liver dysfunction was associated with PT-INR elevation (P = 0.0100).

CONCLUSION:

As there is a possibility of PT-INR abnormalities occurring during the concomitant use of gefitinib and warfarin, clinicians should be aware of this interaction. Because of the potentially severe consequences of this interaction, close monitoring of PT-INR and warfarin dose adjustment are recommended for patients receiving warfarin and gefitinib, especially during the first 2 weeks in the beginning of warfarin therapy.

• Authors: Susumu Arai, Hisashi Mitsufuji, Yasuto Nishii, Sayaka Onoda, Shinichiro Ryuge, Mayuko Wada, Ken Katono, Maiko Iwasaki, Akira Takakura, Sakiko Otani, Michiko Yamamoto, Tomoko Yanaihara, Masanori Yokoba, Masaru Kubota, Masato Katagiri, Tomoya Fukui, Hirosuke Kobayashi, Nobuo Yanase, Ryuji Hataishi, Noriyuki Masuda
• Journal: International journal of clinical oncology (Int J Clin Oncol) Vol. 14 Issue 4 Pg. 332-6 (Aug 2009) ISSN: 1437-7772 [Electronic] Japan
• PMID: 19705244 (Publication Type: Journal Article)

Chemical References

• Anticoagulants
• Antineoplastic Agents
• Protein Kinase Inhibitors
• Quinazolines
• Warfarin
• Gefitinib

Topics

• Aged
• Anticoagulants (adverse effects, therapeutic use)
• Antineoplastic Agents (adverse effects)
• Blood Coagulation (drug effects)
• Carcinoma, Non-Small-Cell Lung (blood, drug therapy, secondary)
• Drug Interactions
• Female
• Gefitinib
• Humans
• International Normalized Ratio
• Liver Neoplasms (blood, secondary)
• Lung Neoplasms (blood, drug therapy, pathology)
• Male
• Middle Aged
• Protein Kinase Inhibitors (adverse effects, therapeutic use)
• Prothrombin Time
• Quinazolines (adverse effects, therapeutic use)
• Retrospective Studies
• Time Factors
• Warfarin (adverse effects, therapeutic use)