Several studies have recommended the reduction of warfarin dosage when capecitabine has been added, however, no one has suggested appropriate guidelines. Based on the
data, we tried to determine the clinically available warfarin dosage guidelines after this drug
combination.
A retrospective analysis was done for all patients with capecitabine seen by the anticoagulation service(ACS) at Samsung Medical Center from February 1, 2000 to October 30, 2009. Patients who had stable INR values on warfarin for at least 1 month and who had not received drugs known to alter INR values or interact with warfarin. A total of eight patients met the inclusion criteria.
During the first 3 cycle of capecitabine therapy, the requirement for warfarin dose was associated with duration of treatment with capecitabine. Continuous dose reduction is needed every cycles of capecitabine therapy to maintain the INR in therapeutic range. Although no major bleeding was observed in the study group, minor bleeding occurred in 3 patients. We recommend close monitoring of INR on day 0, day 10 of every cycles for a period of 21 days, with an appropriate adjustment of warfarin dose. The reductions of warfarin dose necessary for maintaining therapeutic INR is: 0-20% for 1 cycle, 20-40% for 2 cycle, 40-60% for 3 cycle. This study provide clinically available dosage guidelines after taking concomitant capecitabine and warfarin. a greater HbA1c reduction [i.e., 8.1±0.9% → 7.1±0.6%, p<0.00001] than those in ‘altered’group [7.3±0.9% → 7.1±0.8%, p=0.209], indicating that the reduction is comparable in both groups and a statistically significant reduction was noted in ‘additional’group only. In addition, FBS was found to be reduced in‘ additional’group [i.e., 146.8±46.4 mg/dL → 127.9±27.0 mg/dL, p=0.068], but not in‘ altered’group [i.e., 140.8±46.3 mg/dL → 140.3±38.1 mg/dL, p=0.963]. Adverse event profiles were not consolidated for all patients because some patients had incomplete records. The
number of patients experiencing hypoglycemia was decreased (7 pts → 3 pts, N = 15 pts) after the initiation of DPP-4 inhibitors and no incidence of new hypoglycemia was found. In addition, there was no significant decrease in body weight with the DPP-4 inhibitors (mean body weight: 61.3±8.1 kg → 61.2±8.1 kg, p=0.955). Therefore, these observations indicate that DPP-4 inhibitors offer advantages such as the ability to achieve sustainable reductions in HbA1c with a minimum risk of hypoglycemia and no appreciable gain in body weight and that DPP-4 inhibitor therapy may be more suitable for elderly patients with type 2 diabetes.

Keywords: DPP-4(Dipeptidyl Peptidase-4) 억제제, 고령환자, 제 2형 당뇨