Vol.73 No.6 November 2025
Investigation of prolongation of the prothrombin time-international normalized ratio (PT-INR) following administration of cefmetazole (CMZ) and the risk factors
1)Department of Pharmacy, Kawasaki Medical School General Medical Center, 2-6-1 Nakasange, Kita-ku, Okayama City, Okayama, Japan
2)Department of Laboratory Medicine, Kawasaki Medical School General Medical Center
3)Department of Surgery, Kawasaki Medical School General Medical Center
4)Department of Urology, Kawasaki Medical School General Medical Center
Abstract
The cephamycin antibiotic cefmetazole (CMZ) contains an N-methylthiotetrazole group (NMTT group) in its structure, which is known to inhibit vitamin K epoxide reductase and disrupt vitamin K metabolism, thereby affecting the blood coagulation system. As a result, patients receiving CMZ often show prolongation of the prothrombin time-international normalized ratio (PT-INR), raising concerns about an increased risk of bleeding in these patients. Although there are scattered case reports of PT-INR prolongation caused by antibiotics containing the NMTT group, reports summarizing the timing of PT prolongation and the risk factors for PT prolongation from a large number of cases are scarce. In this study, we retrospectively investigated prolongation of the PT-INR and the timing of prolongation in 149 patients who received CMZ. Patients receiving CMZ showed significant prolongation of the PT-INR after the start of CMZ administration as compared with the value recorded before the start of CMZ administration (1.05 vs. 1.09, p<0.01). Significant prolongation of the PT-INR following CMZ administration was also more likely to be observed in elderly patients (aged 70 years and older) (n=104), patients with renal dysfunction (eGFR less than 60 mL/min/1.73 m2) (n=55), and patients who received CMZ in the perioperative period (n=94) (1.05 vs. 1.16, p<0.01; 1.05 vs. 1.14, p=0.03; 1.02 vs. 1.09, p<0.01, respectively). The median PT-INR prolongation in the patients was 0.21 (IQR, 0.15-0.28). Of all the patients, 85.7% showed PT-INR prolongation within two days after the start of CMZ administration, suggesting that early PT-INR monitoring would be useful. On the other hand, the median time required for normalization of the prolonged PT-INR was three days after discontinuation of CMZ, indicating that early discontinuation of CMZ in cases showing abnormal PT-INR prolongation may help prevent serious bleeding. Since CMZ is widely used as a prophylactic antibiotic for postoperative infections, it is considered appropriate to continue monitoring the PT-INR for about three days postoperatively, particularly in elderly patients taking anticoagulants and those receiving CMZ in the perioperative period.
Key word
cefmetazole, cephamycin, coagulopathy, prothrombin time, risk factor
Received
February 7, 2025
Accepted
July 7, 2025
Jpn. J. Chemother. 73 (6): 588-596, 2025
