Details About Overdose or Poisoning Generic Salt ::  Digoxin Specific Antibodies

Digoxin-Specific Antibodies

    

Drug Pharmacology ::

I. Pharmacology. Digoxin-specificantibodies are produced in immunized sheep and have a high bindingaffinity for digoxin and, to a lesser extent, digitoxin and othercardiac glycosides. The Fab fragments used to treat poisoning arederived by cleaving the whole antibodies. The Fab fragment binds freedigoxin. Once the digoxin-Fab complex is formed, the digoxin moleculeis no longer pharmacologically active. The complex enters thecirculation, is renally eliminated and cleared by thereticuloendothelial system, and has a half-life of 14–20 hours (mayincrease 10-fold with renal impairment). Reversal of signs of digitalisintoxication usually occurs within 30–60 minutes of administration(average initial response 19 minutes), with complete reversal varyingup to 24 hours (average 88 minutes). There are two commerciallyavailable products, Digibind and DigiFab, that should be consideredtherapeutic equivalents. The decision to use either product may bebased on availability and cost.

Drug Indications ::

Indications. Digoxin-specific antibodies are used for life-threatening arrhythmias or hyperkalemia (5mEq/L) caused by acute and chronic cardiac glycoside intoxication (seeCardiac Glycosides). Treatment should be based on elevated levels aswell as the presence of significant symptoms (eg, hyperkalemia,ventricular arrhythmias, bradyarrhythmias, and hypotension).

Drug Contra-Indications ::

III. Contraindications. Nocontraindications are known. Caution is warranted in patients withknown sensitivity to ovine (sheep) products; a skin test forhypersensitivity may be performed in such patients, using dilutedreconstituted drug. There are no reports of hypersensitivity reactionsin patients who have received the drug more than once (although this isa theoretical risk). Product may contain traces of papain; therefore,caution is advised in patients with allergies to papain, chymopapain,papaya extracts, and the pineapple enzyme bromelain.

Drug Adverse Effects ::

IV. Adverse effects

   

Monitorthe patient for potential hypersensitivity reactions and serumsickness. A dose- and rate-related (anaphylactoid) reaction may occurwith rapid IV administration.

Inpatients with renal insufficiency and impaired clearance of thedigitalis-Fab complex, a delayed rebound of free serum digoxin levelsmay occur for up to 130 hours.

Removal of the inotropic effect of digitalis may exacerbate preexisting heart failure.

Withremoval of the digitalis effect, patients with preexisting atrialfibrillation may develop an accelerated ventricular response.

E. Removalof the digitalis effect may reactivate sodium-potassium ATPase andshift potassium into cells, causing a drop in the serum potassium level.

F. Use in pregnancy. FDAcategory C (indeterminate). This does not preclude its acute,short-term use for a seriously symptomatic patient (see Table III–1).

Drug Lab Interactions ::

Drug or laboratory interactions

   

Digoxin-specificFab fragments will bind other cardiac glycosides, including digitoxin,ouabain, oleander glycosides, and possibly glycosides inlily-of-the-valley, strophanthus, squill, and toad venom (Bufo spp cardenolides).

Thedigoxin-Fab complex cross-reacts with the antibody commonly utilized inquantitative immunoassay techniques. This results in falsely high serumconcentrations of digoxin owing to measurement of the inactive Fabcomplex (total serum digoxin levels may increase 10- to 21-fold).However, some assays and procedures may measure free digoxin levels,which may be useful for patients with renal impairment (to monitor arebound in free serum digoxin levels after administration of Fabfragments).

Drug Dose Management ::

Dosage and method of administration. Each vial of either digoxin-immune Fab product binds 0.5 mg of digoxin.

   

Complete neutralization/equimolar dosing; known level or amount ingested. Estimationof the dose of Fab is based on the body burden of digitalis. This maybe calculated if the approximate amount ingested is known (Table III–6)or if the steady-state (postdistributional) serum drug concentration isknown (Table III–7). (The steady-state serum drug concentration shouldbe determined at least 12–16 hours after the last dose.) Note:The calculation of digoxin body burden is based on an estimated volumeof distribution for digoxin of approximately 5–6 L/kg; however, otherestimates for the Vd range as high as 8 L/kg. If the patient fails torespond to the initial treatment, the dose may have to increase by anadditional 50%.

Empiric dosing (unknown level and severe toxicity). Ifthe amount ingested or the postdistributional level is not known andthe patient has life-threatening dysrhythmias, dosing may have to beempiric. The manufacturer recommends that 20 (10 for children) and 6vials be given empirically for acute and chronic overdoses,respectively. However, average dose requirements are 10 and 5 vials foracute and chronic digoxin intoxication, respectively.

Titration dosing. Theoretically, Fab may be used to neutralize a portionof the digoxin body burden to reverse toxicity but maintain therapeuticbenefits. The Fab dose can be estimated by subtracting the desireddigoxin level from the measured postdistributional level beforecompleting the calculation. Alternately, if the patient ishemodynamically stable, the drug can be given empirically, 1-3 vials ata time, titrating to clinical effect. A proposed strategy has been toinfuse the initial or loading dose over 1 hour and then allow 1 hourafter the end of the infusion period to assess the need for additionaldoses. However, partial dosing has been associated with recurrences ofsymptoms in some digoxin-poisoned patients.

Reconstitutethe drug according to the package instructions and administerintravenously over 30 minutes, using a 0.22-micron membrane filter.Note that longer infusion periods (1–7 hours) have been suggested tooptimize binding to Fab. It may also be given as a rapid bolus forimmediately life-threatening arrhythmias.

Drug Chemical Formulations ::

Formulations

   

Parenteral. Digibind,38 mg of lyophilized digoxin-specific Fab fragments per vial. DigiFab,40 mg of lyophilized digoxin-specific Fab fragments per vial.

The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is 20 vials of either product.

Table III–6. Approximate Digoxin-FAB Dose If Amount Ingested Is Known


Tablets Ingested (0.125-mg size) Tablets Ingested (0.25-mg size) Approximate Dose Absorbed (mg) Recommended Dose (no. vials) 52.50.51105122010245025510100501020

Table III–7. Approximate Digoxin-FAB Dose Based on Serum Concentration at Steady State (after Equilibration)



aThiscalculation provides a quick estimate of the number of vials needed butcould underestimate the actual need because of variations in the volumeof distribution (5–7 L/kg). Be prepared to increase dose by 50% ifclinical response to initial dose is not satisfactory.

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