![]() ![]() Clearance may be delayed in patients with renal failure. Ordinarily, improvement in signs or symptoms of digoxin intoxication begins within a half hour or less after initiation of Fab fragment therapy. In patients with normal renal function, digoxin-specific Fab fragments are excreted in the urine with a biological half-life of 15 to 20 hours. The kidneys provide the main route of Fab fragment elimination from the body. Assays for measurement of free digoxin levels only are necessary in such situations. ![]() Traditional digoxin assays performed by immunoassay (eg, DIG / Digoxin, Serum) measure both Fab fragment-bound (inactive) digoxin and free (active) digoxin (ie, total digoxin), and are unsuitable for managing patients when digoxin-specific Fab fragment therapy has been administered. ![]() On the other hand, the unbound (free) fraction, which is responsible for its pharmacological activity, decreases. Total digoxin concentration in blood increases approximately 10 to 30 fold after administration of Fab fragments. ![]() The Fab fragment-digoxin complex is then excreted by the kidney. These fragments bind to digoxin, block the active site of the digoxin molecule, and make it unavailable to its receptor molecule and biologically inactive. In manufacturing of Digibind, papain cleaves digoxin-specific IgG antibody into 2 antigen binding-site fragments (Fab fragments). While excess digoxin can have serious side effects (eg, cardiac dysrhythmias, heart failure, seizures, death), it is one of the few therapeutic drugs for which antidotal therapy is available.(1) In toxic situations, antibody fragment therapy, which involves the administration of antibodies to digoxin (eg, Digibind, Digoxin Immune Fab), is indicated. In the case of chronic overdose, if digoxin level (in prehospital setting for example) is missing, a dose of 3 vials is appropriate (experience-based recommendation).Digoxin, a widely prescribed cardiac drug, has a narrow therapeutic window (a very small difference exists between therapeutic and toxic tissue concentrations).This way of infusion is preferable when rhythm disturbances are not life-threatening. Slow infusion (i.e., 2 hours) improves Fab efficacy.The calculator is appropriate for vials containing (approximately) 40 mg of antibodies.Drugs including quiNIDine, verapamil, dilTIAZem, carvedilol, amiodarone, and spironolactone will result in decreased digoxin protein binding, thereby increasing free digoxin levels.Electrolyte abnormalities (specifically hypokalemia, but including hypomagnesemia, hypercalcemia, hypernatremia) may result in dysrhythmias at lower serum digoxin levels.Impaired creatinine clearance and aging (associated with decreased function of renal, hepatic, and cardiac systems) may result in clinical toxicity at lower serum digoxin levels.Correcting mild elevations in serum potassium without administering DigiFab will not improve survival (see Next Steps for details). Hyperkalemia acts as a marker of poisoning severity in acute digoxin overdose.If required, free digoxin levels will need to be measured (not readily available at all labs). Digoxin levels measured after administration of DigiFab will be falsely elevated.The serum digoxin level may be misleadingly high if obtained <6 hours after ingestion. The serum digoxin level must be considered in the context of the patient’s clinical presentation a reliable serum digoxin level must be obtained at steady-state (i.e., obtained ≥6 hours after ingestion).Cardioactive steroid toxicity can cause nearly any dysrhythmia with the exception of a rapidly conducted supraventricular tachydysrhythmia. ![]()
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