Jortani SA, Voldes R Jr: Digoxin and its related endogenous factors. American Association for Clinical Chemistry Press 1984Ĥ. Moyer TP, Boeckx RL, eds: Applied Therapeutic Drug Monitoring. Jortani SA, Pinar A, Johnson NA, Valdes R Jr: Validity of unbound digoxin measurements by immunoassays in presence of antidote (Digibind).
Digoxin antidote free#
Also order total digoxin levels every other day during the time periods above, with a goal of determining whether there is correlation between changes in free and total levels.ġ. When creatinine clearance is equal to or above 30 mL/min/surface area (and the patient is not on renal-replacement therapy): order free levels daily for 72 hours, as long as the last level is not supratherapeutic (these patients are expected to have good clearance and a lower risk for reintoxication)
When creatinine clearance is less than 30 mL/min/surface area: order free digoxin levels daily for 12 days (or until dismissal) The following ordering guidelines are offered: DLIFs may be seen in certain volume-expanded patients such as neonates, patients with renal or liver disease, and in women in the third trimester of pregnancy being treated with digoxin.(2) DLIFs are strongly bound to proteins and, in this assay, are removed prior to testing. In such patients, toxicity may recur if previously bound drug is released from the Fab fragments, resulting in increased levels of free digoxin.ĭigoxin-like immunoreactive factors (DLIFs) are endogenous substances that can cross-react with testing antibodies used in some digoxin immunoassays, causing erroneous results.
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. Digoxin, a widely prescribed cardiac drug, has a narrow therapeutic window (a very small difference exists between therapeutic and toxic tissue concentrations).
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