Assessment of Digoxin-Specific Fab Fragment Dosages in Digoxin Poisoning

Abstract

Digoxin poisoning still remains a common cause of morbidity and mortality. Fortunately, digoxin-specific Fab fragments are commercially available as an antidote. However, these Fab fragments are several thousand dollars per vial. There is a standardized formula to calculate appropriate Fab fragment dosage based on the serum digoxin concentration. This can greatly reduce the amount of Fab fragment administered. There is also an empiric dosing guideline recommending 6-10 vials be given; however, this may result in higher amounts of Fab fragments being administered than required. We performed this study to assess the amounts of digoxin-specific Fab fragments administered in the treatment of digoxin poisonings recorded in a poison control system database from January 1, 2000, to December 31, 2009, in which digoxin serum concentrations were available. This was a retrospective study of 278 patients, 107 with acute poisonings (group A) and 171 following chronic poisoning (group B). In group A, the calculated Fab dose was higher than the calculated dose based on available concentrations in 39 (36%) of group A and 15 (9%) of group B patients. The average wholesale price cost of the excessive dosages ranged from $4818 to as high as $50,589 per patient. Our data suggests that clinician education on digoxin poisoning and the use of the standardized formula to calculate the Fab dose may decrease over utilization and decrease costs associated with the administration of digoxin-specific Fab fragments in the treatment of digoxin poisonings.

Investigation of factors affecting outcome of patients with acute digoxin intoxication in two academic emergency departments during 2004-2016

“…In the present study, the prevalence of acute poisoning was higher in women (65%). In other studies, the prevalence of poisoning in women was higher than men (15,21,22). In addition, according to the comparison of patients' deaths, gender was effective in the spread of poisoning (suicide attempts were more common in women); however, it did not count risk factors in mortality rates (23,24).…”

“…One of the limitations of this study was that the ultimate cause of the patient's death was not determined. Furthermore, in other countries, Fab can be used to reduce the mortality rate (15,21,25). However, due to the limitations in Iran, Fab was not injected to the patients, and therefore the cases were not analyzed.…”

Digitalis Glycosides

“…Due to its narrow therapeutic index, chronic toxicity of digitalis has been reported in 6-23 % of treated patients, particularly in the elderly [10,11]. Several factors may alter patient's sensitivity to digitalis including acute renal impairment and drug-drug interactions (Table 2) [10][11][12][13][14][15][16][17]. Macrolides, quinidine, verapamil, diltiazem, amiodarone, and others increase digoxin concentrations, mainly by competitions on their binding sites in tissues with a risk of digitalis toxicity.…”

“…The efficacy and safety of anti-digoxin-specific Fab fragments have been consistently reported in adults [11][12][13][14][15][16][17]21] and children [35][36][37][38][39] as well as in acute and chronic poisonings (Grade I evidence). A cost-effectiveness analysis supported the use of Fab fragments in the treatment of digoxin toxicity [40].…”

“…On another hand, since equimolar neutralization with Fab fragments is expensive and sometimes not available in small hospitals, antidote administration is often delayed or withheld until serious arrhythmias occur. Under these conditions, ventricular fibrillation and asystole often result in postanoxic brain damage or refractory cardiogenic shock [11][12][13][14][15][16][17]21]. Interestingly, factors associated with the use of anti-digoxin Fab fragments were identified based on a retrospective review of patient records over 2 years in 20 city hospitals in France [17].…”