Hazards of doubling phenytoin dose in the face of an unrecognized interaction with ciprofloxacin.

Abstract

To underscore the need for caution when making dramatic changes in phenytoin dosing, and to report a possible ciprofloxacin interaction in which failure of seizure control led to inappropriately high phenytoin dosing and subsequent intoxication. A 61-year-old African-American man receiving long-term therapy with phenytoin 100 mg po tid for seizures secondary to a stroke was admitted for community-acquired pneumonia. His serum phenytoin concentration at admission was therapeutic at 12.6 micrograms/mL. Eight days after admission, ciprofloxacin 750 mg po bid was started for possible aspiration. Two days later he experienced a seizure; the serum phenytoin concentration was 2.5 micrograms/mL. In response to the 80% decline in phenytoin concentration, the dosage was gradually titrated upward to produce a serum concentration of 12.6 micrograms/mL. This eventually required a doubling of the original phenytoin dosage and he was discharged on 200 mg po tid. The patient subsequently developed severe ataxia and sustained a head injury for which he was seen again in the emergency department. Serum phenytoin concentration at that time was 42.8 micrograms/mL. Concentrations declined at a normal rate when phenytoin was withheld. It appears that a rapid decline in phenytoin concentration during the first admission was related to coadministration of ciprofloxacin, either through inhibition of absorption or induction of metabolism. In a conscientious effort to titrate phenytoin concentrations back to therapeutic values, the issue as to why this required such a dramatic change in dosage was ignored. Thus, in trying to prevent further seizures, the patient was unknowingly placed in jeopardy a second time when his usual dosage of phenytoin was doubled. As a result, phenytoin intoxication ensued after discharge when the ciprofloxacin was discontinued. This case illustrates a potentially dangerous interaction between ciprofloxacin and phenytoin, and it underscores the need to maintain a high index of clinical suspicion for drug interactions in any patient requiring a substantial change in drug dosage.