HAZARDS OF DOUBLING PHENYTOIN DOSE IN THE FACE OF AN UNRECOGNIZED INTERACTION WITH CIPROFLOXACIN

OBJECTIVE: To underscore the need for caution when making dramatic cha nges in phenytoin dosing, and to report a possible ciprofloxacin inter action 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 1 00 mg po tid for seizures secondary to a stroke was admitted for commu nity-acquired pneumonia. His serum phenytoin concentration at admissio n was therapeutic at 12.6 mu g/mL. Eight days after admission, ciprofl oxacin 750 mg po bid was started for possible aspiration. Two days lat er he experienced a seizure; the serum phenytoin concentration was 2.5 mu g/mL. In response to the 80% decline in phenytoin concentration, t he dosage was gradually titrated upward to produce a serum concentrati on of 12.6 mu g/mL. This eventually required a doubling of the origina l phenytoin dosage and he was discharged on 200 mg po rid. The patient subsequently developed severe ataxia and sustained a head injury for which he was seen again in the emergency department. Serum phenytoin c oncentration at that time was 42.8 mu g/mL. Concentrations declined at a normal rate when phenytoin was withheld, CONCLUSIONS: It appears th at a rapid decline in phenytoin concentration during the first admissi on was related to coadministration of ciprofloxacin, either through in hibition 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 wa s ignored. Thus, in trying to prevent further seizures, the patient wa s unknowingly placed in jeopardy a second time when his usual dosage o f phenytoin was doubled. As a result, phenytoin intoxication ensued af ter discharge when the ciprofloxacin was discontinued. This case illus trates a potentially dangerous interaction between ciprofloxacin and p henytoin, and it underscores the need to maintain a high index of clin ical suspicion for drug interactions in any patient requiring a substa ntial change in drug dosage.