Pollak P T, Slayter K L
Department of Medicine and College of Pharmacy, Dalhousie University, Halifax, Nova Scotia, Canada.
Ann Pharmacother. 1997 Jan;31(1):61-4. doi: 10.1177/106002809703100111.
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.
强调在大幅改变苯妥英钠剂量时需谨慎，并报告一种可能的环丙沙星相互作用，即癫痫控制失败导致苯妥英钠剂量过高并随后发生中毒。
一名61岁非裔美国男性，因中风继发癫痫接受苯妥英钠100 mg口服每日三次的长期治疗，因社区获得性肺炎入院。入院时其血清苯妥英钠浓度为12.6微克/毫升，处于治疗水平。入院八天后，因可能存在误吸开始口服环丙沙星750 mg每日两次。两天后他发生癫痫；血清苯妥英钠浓度为2.5微克/毫升。由于苯妥英钠浓度下降了80%，剂量逐渐上调以产生12.6微克/毫升的血清浓度。这最终需要将原来的苯妥英钠剂量加倍，他出院时服用200 mg口服每日三次。患者随后出现严重共济失调并头部受伤，为此他再次到急诊科就诊。当时血清苯妥英钠浓度为42.8微克/毫升。停用苯妥英钠后浓度以正常速率下降。
首次入院期间苯妥英钠浓度迅速下降似乎与环丙沙星的共同给药有关，可能是通过抑制吸收或诱导代谢。在认真努力将苯妥英钠浓度滴定回治疗值时，忽视了为什么需要如此大幅改变剂量的问题。因此，在试图预防进一步癫痫发作时，当患者苯妥英钠的常用剂量加倍时，他在不知不觉中第二次处于危险之中。结果，出院后停用环丙沙星时发生了苯妥英钠中毒。该病例说明了环丙沙星与苯妥英钠之间潜在的危险相互作用，并强调在任何需要大幅改变药物剂量的患者中，对药物相互作用保持高度临床怀疑的必要性。
