Effect of cimetidine on phenytoin serum levels

Cimetidine, 300 mg p.o. four times a day, was administered for 5 days to nine epileptics who were stabilized while receiving phenytoin. Five patients had statistically significant increases in phenytoin serum levels, including two who became clinically toxic. One patient had a statistically significant decrease in phenytoin serum concentration. A relationship was not found between cimetidine levels and change in phenytoin serum levels. Cimetidine can cause significant changes in phenytoin serum levels which may be manifested clinically.