The administration of dicoumarol to four elderly diabetics who were daily receiving 500 mg. tolbutamide led to an increase in the tolbutamide concentration in the blood associated with a fall in blood sugar. The accumulation of tolbutamide was due to an increase in the half-life of tolbutamide in the blood from the normal average of 4.9 hours to an average of 17.5 hours. The mechanism responsible for this increase may be inhibition of tolbutamide metabolism in the liver by dicoumarol.
This accumulation may well increase the risk of hypoglycemia, such as has been demonstrated after administration of sulfaphenazole to diabetic patients receiving tolbutamide.
Phenindione does not seem to have a similar effect and, accordingly, would appear to be preferable in anticoagulant therapy in diabetics receiving tolbutamide.