• DOI:10.1177/106002808702101116
• Corpus ID: 7262697

Phenazopyridine-Induced Hemolytic Anemia in G-6-PD Deficiency

@inproceedings{Galun1987PhenazopyridineInducedHA,
  title={Phenazopyridine-Induced Hemolytic Anemia in G-6-PD Deficiency},
  author={Eithan Galun and R. Oren and Michael Glikson and M Friedlander and A Heyman},
  booktitle={Drug intelligence \& clinical pharmacy},
  year={1987}
}

• E. Galun, R. Oren, +2 authors A. Heyman
• Published in
  Drug intelligence & clinical…
  1 November 1987
• Medicine

TOTHEEDITOR: Amiodarone therapy is indicated for the treatment of patients with life-threatening cardiac arrhythmias that are refractory to other drugs. Amiodarone is a toxic drug, and the manufacturer recommends that it first be given in the hospital and continued in a monitored environment until control of the arrhythmia occurs. An excellent review article about amiodarone has appeared in the literature.' Since the introduction of amiodarone, it has been implicated in numerous drug interactions. Its strong affinity for serum proteins may explain why its use increases the serum level of several drugs. However, amiodarone has also been shown to inhibit hepatic metabolism, and this could be the predominant mechanism by which some interactions occur. 2 We report a case in which symptoms of phenytoin toxicity began two weeks after the initiation of amiodarone therapy and continued to increase until the phenytoin dose was reduced four weeks after concurrent therapy began. A 73-year-old man was admitted to our medical ward for cardiac arrhythmias resistant to therapy with verapamil and procainamide. The patient's kidney function was normal and his serum albumin was 31 gil (normal: 35-50 g/ L). He had a history of seizures secondary to a cerebral vascular accident for which he was receiving phenytoin 400 mg/d as extended action capsules. He was also receiving captopril, furosemide, theophylline, potassium supplements, digoxin, and warfarin on a regular basis. His prn medications consisted of chlorpromazine, sl lorazepam, triazolam, sl nifedipine, inhaled albuterol, Maalox, and sl nitroglycerin. On hospital day 2, amiodarone 200 mg po tid was starred. The dose was increased to 400 mg po tid on hospital day 5 and then to 400 mg po qid the following day. Finally, a maintenance dose of amiodarone 200 mg po qid was starred on day 22. (Veraparnil had been discontinued on hospital day 3 and procainamide on hospital day 5.) Monitoring of the serum digoxin concentration and the prothrombin time led to appropriate adjustments in the patient's digoxin and warfarin doses. A phenytoin level taken on hospital day 5 was 59 !,mol/L (normal: 40-80 !,mol/L). The first evidence of an interaction was documented after the patient had a fall on hospital day 16. At this time a nurse noted that the patient was "slightly unsteady on his feel." The following day, the physician noted that the patient was unsteady on his feet and "drowsy." On hospital day 22, the patient's gait was extremely unsteady and wide based, although there was no evidence of nystagmus. The patient was very confused and disoriented on hospital day 25, and by the following day, he showed no memory of being in the hospital. A phenytoin level drawn on hospital day 28 was 122!,mol/L. The phenytoin dose was immediately reduced to 200 mg/d and a rapid resolution of all symptoms of toxicity followed. The phenytoin level dropped to 65 !,mol/L by hospital day 33 and the patient was discharged home on hospital day 35 with prescriptions for phenytoin 200 mg/d and amiodarone 800 mg/d. A review of the literature on phenytoin-amiodarone interactions showed that the manifestations of phenytoin toxicity can develop as much as four weeks after the introduction of amiodarone,.' This is understandable given that the elimination half-life of amiodarone ranges from 30-100 days after prolonged administration.' Amiodarone's characteristic onset of action averages 9.5 days and because many patients are sent home once their arrhythmias have been brought under control,' they may only begin to experience phenytoin toxicity after they have been discharged. Although it seemed clear to us retrospectively that phenytoin toxicity was responsible for much of the patient's confusion and ataxia, amiodarone has neurological side effects. According to the manufacturer, between four and nine percent of patients on amiodarone experience fatigue, lack of coordination, dizziness and ataxia.' Thus, the symptoms we saw in our patient could have been misinterpreted as side effects of amiodarone. Had this happened, amiodarone might well have been needlessly withdrawn. We would recommend that, when patients stabilized on phenytoin are started on arniodarone, serum phenytoin levels be ordered once or twice each week for the first four to six weeks of therapy. Given the long half-life of amiodarone, it might also be prudent to continue regular monitoring of the serum phenytoin levels for three months after a new maintenance dose is established. Adjustments in the phenytoin dose should then be made as indicated by changes in the serum levels.