Comparison of interactions between warfarin and cephalosporins with and without the N-methyl-thio-tetrazole side chain |
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| Affiliation: | 1. Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo Nishi 6-chome, Kita-ku, Sapporo, 060-0812, Japan;2. Department of Pharmacy, Japan Community Healthcare Organization Sapporo Hokushin Hospital, 6-2-1, Atsubetsuchuo 2-jo, Atsubetsu-Ku, Sapporo, 004-8618, Japan;3. Graduate School of Life Science, Hokkaido University, Kita 10-jo Nishi 8-chome, Kita-ku, Sapporo, 060-0810, Japan;4. Department of Hospital Pharmaceutics, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan;5. Department of Pharmacy, Hokkaido University Hospital, Kita 14-jo, Nishi 5-chome, Kita-ku, Sapporo, 060-8648, Japan;6. Global Station for Biosurfaces and Drug Discovery, Kita 8-jo Nishi 5-chome, Kita-ku, Sapporo, 060-0808, Japan;1. Division of Vascular Surgery, Department of Surgical Sciences, University of Turin, Turin, Italy;2. Department of Public Health Sciences, University of Turin, Turin, Italy;1. Graduate School of Life Science, Hokkaido University, Kita-10-jo, Nishi-8-chome, Kita-ku, Sapporo 060-0810, Japan;2. School of Pharmaceutical Sciences and Pharmacy, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan;3. Department of Pharmacy, Hokkaido University Hospital, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo 060-8648, Japan;4. Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan;5. Global Station for Biosurfaces and Drug Discovery, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan;1. Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan;2. Department of Clinical Research, National Hospital Organization, Tochigi Medical Center, 1-10-37 Nakatomatsuri, Utsunomiya-city, Tochigi, Japan;3. Department of Infectious Diseases, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan;1. Division of Pulmonary Medicine, Department of Internal Medicine, Self-Defense Forces Central Hospital, 1-2-24 Ikejiri, Setagaya, Tokyo 154-8532, Japan;2. Division of Infectious Diseases and Pulmonary Medicine, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan;3. Department of Anesthesiology, Self-Defense Forces Central Hospital, 1-2-24 Ikejiri, Setagaya, Tokyo 154-8532, Japan;4. Department of Emergency, Japan Self Defense Force Sapporo Hospital, 17 Makomanai, Minami, Sapporo 005-8543, Japan;5. Department of Internal Medicine, Japan Self Defense Forces Hospital, 1776-1 Tauraminatomachi, Yokosuka, Kanagawa 237-0071, Japan;6. Division of Infectious Disease, Department of Internal Medicine, Self-Defense Forces Central Hospital, 1-2-24 Ikejiri, Setagaya, Tokyo 154-8532, Japan |
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| Abstract: | Cephalosporins with an N-methyl-thio-tetrazole (NMTT) side chain interact with warfarin by reducing the production of blood clotting factors. However, cephalosporins without the NMTT side chain also enhance the effects of warfarin. Thus, we aimed to compare the effects of warfarin modified by cephalosporins with and without the NMTT side chain, using a Japanese health insurance claims database. The inclusion criteria were patients who (1) intravenously received second- or third-generation cephalosporins between April 2010 and March 2017 and (2) received warfarin during cephalosporin therapy. Patients were administered either cephalosporins with the NMTT side chain (NMTT group) or those without NMTT (non-NMTT group). After matching patient data by propensity score, the following outcomes were compared between the two groups: (1) proportion of patients administered vitamin K, (2) proportion of bleeding events, and (3) changes in the daily dose of warfarin. Among 203 patients, 100 patients (50 per group) were matched by the propensity score. The proportion of patients administered vitamin K was 6.0% in both groups. These patients intravenously received a single dose of menatetrenone; no bleeding was observed. The proportion of patients subjected to a reduction in the daily dose of warfarin was 6.5% and 4.3% in the NMTT and non-NMTT groups, respectively. As our study had a small sample size, we could not determine whether the risk of over anticoagulation of warfarin is affected by cephalosporins with or without NMTT side chain. However, we showed the bleeding risk was sufficiently low regardless of the presence/absence of the NMTT side chain. |
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| Keywords: | Cephalosporin Claims database Drug–drug interaction Bleeding Warfarin |
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