Pharmacokinetics and efficacy of digoxin specific Fab fragments in a child following massive digoxin overdose

Abstract

The use of digoxin-specific Fab fragments (d-Fab) to treat life-threatening digitalis intoxication has been widely substantiated in adults. This reports a case of a 2-year-old girl who ingested 90-92, 0.25 mg tablets of digoxin and within four hours, developed vomiting, lethargy, tachycardia and AV block (Mobitz type I and II). These symptoms were associated with total and free serum digoxin concentrations of 17.1 and 12.4 ng/ml, respectively. Following GI decontamination, a total dFab dose of 1280 mg (32 vials) was given with resolution of electrocardiographic abnormalities within 40 minutes and a concomitant reduction in the free serum digoxin concentration to 0.11 ng/ml. Repeated blood sampling over 19 days revealed an apparent elimination half-life (t1/2) of 134.9 and 129.9 hr for total and free digoxin, respectively. The long t1/2 for digoxin corresponded to a low apparent renal clearance of total digoxin which ranged from 0.56 to 0.82 ml/minute over four separate collection intervals. The free serum digoxin concentration never exceeded 3% of the total concentration and the patient did not develop a recurrence of toxic symptoms or any adverse effects (e.g. fever) attributable to dFab. Administration of an equimolar dFab dose to children following acute, massive digoxin intoxication represents safe, effective treatment which produces a prompt, sustained reversal of toxic effects. Digoxin specific Fab fragments should be promptly administered to any infant or child with significant, life-threatening symptoms following acute digoxin intoxication.