General Standard therapy for digitalis intoxication includes withdrawal of the drug and correction of factors that may contribute to toxicity, such as electrolyte disturbances, hypoxia, acid-base disturbances, and agents such as catecholamines. Also, treatment of arrhythmias may include judicious potassium supplements, lidocaine, phenytoin, procainamide, and/or propranolol; treatment of sinus bradycardia or atrioventricular block may involve atropine or pacemaker insertion. Massive digitalis intoxication can cause hyperkalemia; administration of potassium supplements in the setting of massive intoxication may be hazardous (see Laboratory Tests). After treatment with DIGIBIND (digoxin immune fab) , the serum potassium concentration may drop rapidly2 and must be monitored frequently, especially over the first several hours after DIGIBIND (digoxin immune fab) is given (see Laboratory Tests). The elimination half-life in the setting of renal failure has not been clearly defined. Patients with renal dysfunction have been successfully treated with DIGIBIND (digoxin immune fab) .4 There is no evidence to suggest the time-course of therapeutic effect is any different in these patients than in patients with normal renal function, but excretion of the Fab fragment-digoxin complex from the body is probably delayed. In patients who are functionally anephric, one would anticipate failure to clear the Fab fragment-digoxin complex from the blood by glomerular filtration and renal excretion. Whether failure to eliminate the Fab fragment-digoxin complex in severe renal failure can lead to reintoxication following release of newly unbound digoxin into the blood is uncertain. Such patients should be monitored for a prolonged period for possible recurrence of digitalis toxicity. Patients with intrinsically poor cardiac function may deteriorate from withdrawal of the inotropic action of digoxin. Studies in animals have shown that the reversal of inotropic effect is relatively gradual, occurring over hours. When needed, additional support can be provided by use of intravenous inotropes, such as dopamine or dobutamine, or vasodilators. One must be careful in using catecholamines not to aggravate digitalis toxic rhythm disturbances. Clearly, other types of digitalis glycosides should not be used in this setting. Redigitalization should be postponed, if possible, until the Fab fragments have been eliminated from the body, which may require several days. Patients with impaired renal function may require a week or longer. Laboratory Tests DIGIBIND (digoxin immune fab) will interfere with digitalis immunoassay measurements.6 Thus, the standard serum digoxin concentration measurement can be clinically misleading until the Fab fragment is eliminated from the body. Serum digoxin or digitoxin concentration should be obtained before administration of DIGIBIND (digoxin immune fab) if at all possible. These measurements may be difficult to interpret if drawn soon after the last digitalis dose, since at least 6 to 8 hours are required for equilibration of digoxin between serum and tissue. Patients should be closely monitored, including temperature, blood pressure, electrocardiogram, and potassium concentration, during and after administration of DIGIBIND (digoxin immune fab) . The total serum digoxin concentration may rise precipitously following administration of DIGIBIND (digoxin immune fab) , but this will be almost entirely bound to the Fab fragment and therefore not able to react with receptors in the body. Potassium concentrations should be followed carefully. Severe digitalis intoxication can cause life-threatening elevation in serum potassium concentration by shifting potassium from inside to outside the cell. The elevation in serum potassium concentration can lead to increased renal excretion of potassium. Thus, these patients may have hyperkalemia with a total body deficit of potassium. When the effect of digitalis is reversed by DIGIBIND (digoxin immune fab) , potassium shifts back inside the cell, with a resulting decline in serum potassium concentration.4 Hypokalemia may thus develop rapidly. For these reasons, serum potassium concentration should be monitored repeatedly, especially over the first several hours after DIGIBIND (digoxin immune fab) is given, and cautiously treated when necessary. Carcinogenesis, Mutagenesis, Impairment of Fertility There have been no long-term studies performed in animals to evaluate carcinogenic potential. Pregnancy Pregnancy Category C. Animal reproduction studies have not been conducted with DIGIBIND (digoxin immune fab) . It is also not known whether DIGIBIND (digoxin immune fab) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. DIGIBIND (digoxin immune fab) should be given to a pregnant woman only if clearly needed. Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when DIGIBIND (digoxin immune fab) is administered to a nursing woman. Pediatric Use DIGIBIND (digoxin immune fab) has been successfully used in infants with no apparent adverse sequelae. As in all other circumstances, use of this drug in infants should be based on careful consideration of the benefits of the drug balanced against the potential risk involved. Geriatric Use Of the 150 subjects in an open-label study of DIGIBIND (digoxin immune fab) , 42% were 65 and over, while 21% were 75 and over. In a post-marketing surveillance study that enrolled 717 adults, 84% were 60 and over, and 60% were 70 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. The kidney excretes the Fab fragment-digoxin complex, and the risk of digoxin release with recurrence of toxicity is potentially increased when excretion of the complex is slowed by renal failure. However, recurrence of toxicity was reported for only 2.8% of patients in the surveillance study and the only factor associated with recurrence of toxicity was inadequacy of initial dose—not renal function. Calculation of dose is the same for patients of all ages and for patients with normal and impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function and to observe for possible recurrence of toxicity. REFERENCES 2. Smith TW, Haber E, Yeatman L, Butler VP Jr. Reversal of advanced digoxin intoxication with Fab fragments of digoxin-specific antibodies. N Engl J Med. 1976; 294:797-800. 4. Wenger TL, Butler VP Jr, Haber E, Smith TW. Treatment of 63 severely digitalis-toxic patients with digoxin-specific antibody fragments. J Am Coll Cardiol. 1985; 5:118A-123A. 6. Gibb I, Adams PC, Parnham AJ, Jennings K. Plasma digoxin: Assay anomalies in Fab-treated patients. Br J Clin Pharmacol. 1983; 16:445-447. Last reviewed on RxList: 10/14/2008
This monograph has been modified to include the generic and brand name in many instances.