Use of digoxin-specific Fab fragments in the treatment of digitalis intoxication

The narrow margin between therapeutic and toxic effects of digitalis glycosides renders patients taking these drugs particularly susceptible to serious consequences of accidental or deliberate overdosage, including life-threatening arrhythmias. Until recently, the treatment of digitalis intoxication has been largely supportive. In the past decade, however, digoxin-specific antibodies have been developed and have proven to be effective in rapidly reversing the electrophysiologic and metabolic manifestations of digitalis intoxication, both in vitro and in vivo. Enzymatic cleavage of the intact antibody population into Fab fragments results in a more rapidly effective and less immunogenic antidote to digitalis excess. More recently, monoclonal antibodies with high affinity and specificity for digoxin have been produced by the technique of somatic cell fusion; application of this technique to the production of antidigoxin antibodies has potential implications for the production of a highly purified homogeneous product, but this approach has not yet been tested clinically.