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

OBJECTIVE: 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. CASE SUMMARY: 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. CONCLUSIONS: 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.

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