Digifab

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Digifab

Classes

Antidotes, Systemic

Administration

If possible, determine the serum digoxin or digitoxin concentration before administration of digoxin immune Fab. This measurement establishes the level of serum digoxin or digitoxin at the time of diagnosis of digitalis intoxication. At least 6 to 8 hours are required for digoxin equilibration between tissue and serum. Consider the time for equilibration in the interpretation of serum digoxin concentrations.
Following administration of digoxin immune Fab, standard serum digoxin concentration measurements may be clinically misleading until the Fab fragments are eliminated from the body. Measure free (unbound) serum digitalis concentration to determine an accurate concentration.

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intravenous Administration

Digoxin immune Fab is administered by intravenous infusion or bolus injection.
Closely monitor the patient's temperature, blood pressure, electrocardiogram, and serum potassium concentration before and after digoxin immune Fab administration.
 
Reconstitution/Dilution
Reconstitute by adding 4 mL of Sterile Water for Injection to the vial and gently mixing. The resulting solution should be clear, colorless, approximately isosmotic, and contain 10 mg/mL of digoxin immune Fab. The reconstituted product may be diluted with 0.9% Sodium Chloride Injection to a convenient volume.
For patients receiving relatively small doses, the appropriate dose of the reconstituted solution may be withdrawn using a tuberculin syringe and then injected IV or diluted in 0.9% Sodium Chloride Injection and infused or injected IV.
For patients receiving doses less than 3 mg, dilute the reconstituted solution with 36 mL of 0.9% Sodium Chloride Injection to give a solution containing 1 mg/mL of digoxin immune Fab.
Storage: If reconstituted digoxin immune Fab is not used immediately, it may be stored under refrigeration at 2 to 8 degrees C (36 to 46 degrees F) for up to 4 hours. Digoxin immune Fab has no preservatives.
 
Infusion
Infuse IV slowly over at least 30 minutes. If infusion rate-related reactions occur, stop the infusion and restart at a slower rate. If cardiac arrest is imminent, bolus administration is acceptable. An increased incidence of infusion-related reactions may be expected with bolus injection.

Adverse Reactions
Severe

heart failure / Delayed / 13.0-13.0
atrial fibrillation / Early / 7.0-7.0
angioedema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known

Moderate

hypokalemia / Delayed / 13.0-13.0
orthostatic hypotension / Delayed / 1.0-10.0
phlebitis / Rapid / 1.0-10.0
wheezing / Rapid / Incidence not known
hypotension / Rapid / Incidence not known
infusion-related reactions / Rapid / Incidence not known
antibody formation / Delayed / Incidence not known

Mild

injection site reaction / Rapid / 1.0-10.0
rash / Early / Incidence not known
pruritus / Rapid / Incidence not known
urticaria / Rapid / Incidence not known

Common Brand Names

Digifab

Dea Class

Rx

Description

Fab portion of ovine immuneglobulin used as an antidote for digitalis toxicity
Fab fragments are smaller, less antigenic, and are eliminated faster than IgG
Binds both digoxin and digitoxin (affinity for digoxin > digitoxin)

Dosage And Indications
For the treatment of life-threatening or potentially life-threatening digoxin toxicity, digitoxin toxicity, digoxin overdose, or digitoxin overdose including known suicidal or accidental consumption of fatal doses of digoxin (i.e., 10 mg or more digoxin in adults, 4 mg or more or 0.1 mg/kg or more in children, or ingestion resulting in serum concentrations greater than 10 ng/mL; chronic ingestions resulting in steady-state digoxin concentrations greater than 6 ng/mL in adults or greater than 4 ng/mL in children; and manifestations of digoxin toxicity due to overdose (e.g., life-threatening cardiac glycoside-induced arrhythmias, progressive bradycardia, second or third degree heart block unresponsive to atropine, serum potassium greater than 5.5 mEq/L in adults or greater than 6 mEq/L in children). For acute ingestion of an unknown amount of digoxin or digitoxin (e.g., either the serum concentration or the amount ingested is not known). Intravenous dosage Adults, Adolescents, and Children

800 mg (20 vials) IV; this dose should be adequate to treat most life-threatening overdoses. May administer as a single dose or alternatively, may give 400 mg (10 vials) with careful monitoring of the patient's response, followed by an additional 400 mg (10 vials) if necessary. In patients less than 20 kg, monitor closely for volume overload. In general, a large dose has a faster onset, but may also enhance the possibility of a febrile reaction. Failure to respond to digoxin immune Fab should alert the clinician to the possibility that the problem may not be caused by digitalis toxicity.

For toxicity during chronic therapy for patients in acute distress or for whom serum digoxin concentrations are not available. Intravenous dosage Adults, Adolescents, and Children weighing 20 kg or more

240 mg (6 vials) IV should be sufficient to reverse most cases of toxicity. Failure to respond to digoxin immune Fab should alert the clinician to the possibility that the problem may not be caused by digitalis toxicity.

Infants and Children weighing less than 20 kg

40 mg (1 vial) IV should be sufficient to reverse most cases of toxicity. Failure to respond to digoxin immune Fab should alert the clinician to the possibility that the problem may not be caused by digitalis toxicity.

Dosage calculation based on steady-state serum DIGOXIN concentrations.
NOTE: If toxicity has not adequately reversed after several hours or appears to recur, another dose of digoxin immune Fab may be necessary. Measurement of serum drug concentrations may also be necessary. Failure to respond to digoxin immune Fab should alert the clinician to the possibility that the problem may not be caused by digitalis toxicity.
Intravenous dosage Adults with a serum digoxin concentration of 1 ng/mL

Intravenous dose in vials = (serum digoxin concentration in ng/mL x body weight in kg)/100. Alternatively, the estimated number of vials needed based on a steady-state serum digoxin concentration of 1 ng/mL and patient weight (kg) is as follows: 40 to 69 kg give 0.5 vial; 70 to 100 kg or more give 1 vial.

Adults with a serum digoxin concentration of 2 ng/mL

Intravenous dose in vials = (serum digoxin concentration in ng/mL x body weight in kg)/100. Alternatively, the estimated number of vials needed based on a steady-state serum digoxin concentration of 2 ng/mL and patient weight (kg) is as follows: 40 to 69 kg give 1 vial; 70 to 100 kg or more give 2 vials.

Adults with a serum digoxin concentration of 4 ng/mL

Intravenous dose in vials = (serum digoxin concentration in ng/mL x body weight in kg)/100. Alternatively, the estimated number of vials needed based on a steady-state serum digoxin concentration of 4 ng/mL and patient weight (kg) is as follows: 40 to 59 kg give 2 vials; 60 to 99 kg give 3 vials; and 100 kg or more give 4 vials.

Adults with a serum digoxin concentration of 8 ng/mL

Intravenous dose in vials = (serum digoxin concentration in ng/mL x body weight in kg)/100. Alternatively, the estimated number of vials needed based on a steady-state serum digoxin concentration of 8 ng/mL and patient weight (kg) is as follows: 40 to 59 kg give 3 vials; 60 to 69 kg give 5 vials; 70 to 79 kg give 6 vials; 80 to 99 kg give 7 vials; and 100 kg or more give 8 vials.

Adults with a serum digoxin concentration of 12 ng/mL

Intravenous dose in vials = (serum digoxin concentration in ng/mL x body weight in kg)/100. Alternatively, the estimated number of vials needed based on a steady-state serum digoxin concentration of 12 ng/mL and patient weight (kg) is as follows: 40 to 59 kg give 5 vials; 60 to 69 kg give 7 vials; 70 to 79 kg give 9 vials; 80 to 99 kg give 10 vials; and 100 kg or more give 12 vials.

Adults with a serum digoxin concentration of 16 ng/mL

Intravenous dose in vials = (serum digoxin concentration in ng/mL x body weight in kg)/100. Alternatively, the estimated number of vials needed based on a steady-state serum digoxin concentration of 16 ng/mL and patient weight (kg) is as follows: 40 to 59 kg give 7 vials; 60 to 69 kg give 10 vials; 70 to 79 kg give 11 vials; 80 to 99 kg give 13 vials; and 100 kg or more give 16 vials.

Adults with a serum digoxin concentration of 20 ng/mL

Intravenous dose in vials = (serum digoxin concentration in ng/mL x body weight in kg)/100. Alternatively, the estimated number of vials needed based on a steady-state serum digoxin concentration of 20 ng/mL and patient weight (kg) is as follows: 40 to 59 kg give 8 vials; 60 to 69 kg give 12 vials; 70 to 79 kg give 14 vials; 80 to 99 kg give 16 vials; and 100 kg or more give 20 vials.

Infants, Children, and Adolescents with a serum digoxin concentration of 1 ng/mL

Intravenous dose in vials = (serum digoxin concentration in ng/mL x body weight in kg)/100. Because infants and small children have smaller doses, the dosage may be converted to mg instead of number of vials using the following equation: Dose in mg = intravenous dose (in number of vials) x 40 mg/vial. Alternatively, the estimated dose (mg) needed based on a steady-state serum digoxin concentration of 1 ng/mL and patient weight (kg) is as follows: 1 to less than 3 kg give 0.4 mg; 3 to less than 5 kg give 1 mg; 5 to less than 10 kg give 2 mg; 10 to less than 20 kg give 4 mg; and 20 kg or more give 8 mg.

Infants, Children, and Adolescents with a serum digoxin concentration of 2 ng/mL

Intravenous dose in vials = (serum digoxin concentration in ng/mL x body weight in kg)/100. Because infants and small children have smaller doses, the dosage may be converted to mg instead of number of vials using the following equation: Dose in mg = intravenous dose (in number of vials) x 40 mg/vial. Alternatively, the estimated dose (mg) needed based on a steady-state serum digoxin concentration of 2 ng/mL and patient weight (kg) is as follows: 1 to less than 3 kg give 1 mg; 3 to less than 5 kg give 2.5 mg; 5 to less than 10 kg give 4 mg; 10 to less than 20 kg give 8 mg; and 20 kg or more give 16 mg.

Infants, Children, and Adolescents with a serum digoxin concentration of 4 ng/mL

Intravenous dose in vials = (serum digoxin concentration in ng/mL x body weight in kg)/100. Because infants and small children have smaller doses, the dosage may be converted to mg instead of number of vials using the following equation: Dose in mg = intravenous dose (in number of vials) x 40 mg/vial. Alternatively, the estimated dose (mg) needed based on a steady-state serum digoxin concentration of 4 ng/mL and patient weight (kg) is as follows: 1 to less than 3 kg give 1.5 mg; 3 to less than 5 kg give 5 mg; 5 to less than 10 kg give 8 mg; 10 to less than 20 kg give 16 mg; and 20 kg or more give 32 mg.

Infants, Children, and Adolescents with a serum digoxin concentration of 8 ng/mL

Intravenous dose in vials = (serum digoxin concentration in ng/mL x body weight in kg)/100. Because infants and small children have smaller doses, the dosage may be converted to mg instead of number of vials using the following equation: Dose in mg = intravenous dose (in number of vials) x 40 mg/vial. Alternatively, the estimated dose (mg) needed based on a steady-state serum digoxin concentration of 8 ng/mL and patient weight (kg) is as follows: 1 to less than 3 kg give 3 mg; 3 to less than 5 kg give 10 mg; 5 to less than 10 kg give 16 mg; 10 to less than 20 kg give 32 mg; and 20 kg or more give 64 mg.

Infants, Children, and Adolescents with a serum digoxin concentration of 12 ng/mL

Intravenous dose in vials = (serum digoxin concentration in ng/mL x body weight in kg)/100. Because infants and small children have smaller doses, the dosage may be converted to mg instead of number of vials using the following equation: Dose in mg = intravenous dose (in number of vials) x 40 mg/vial. Alternatively, the estimated dose (mg) needed based on a steady-state serum digoxin concentration of 12 ng/mL and patient weight (kg) is as follows: 1 to less than 3 kg give 5 mg; 3 to less than 5 kg give 14 mg; 5 to less than 10 kg give 24 mg; 10 to less than 20 kg give 48 mg; and 20 kg or more give 96 mg.

Infants, Children, and Adolescents with a serum digoxin concentration of 16 ng/mL

Intravenous dose in vials = (serum digoxin concentration in ng/mL x body weight in kg)/100. Because infants and small children have smaller doses, the dosage may be converted to mg instead of number of vials using the following equation: Dose in mg = intravenous dose (in number of vials) x 40 mg/vial. Alternatively, the estimated dose (mg) needed based on a steady-state serum digoxin concentration of 16 ng/mL and patient weight (kg) is as follows: 1 to less than 3 kg give 6.5 mg; 3 to less than 5 kg give 19 mg; 5 to less than 10 kg give 32 mg; 10 to less than 20 kg give 64 mg; and 20 kg or more give 128 mg.

Infants, Children, and Adolescents with a serum digoxin concentration of 20 ng/mL

Intravenous dose in vials = (serum digoxin concentration in ng/mL x body weight in kg)/100. Because infants and small children have smaller doses, the dosage may be converted to mg instead of number of vials using the following equation: Dose in mg = intravenous dose (in number of vials) x 40 mg/vial. Alternatively, the estimated dose (mg) needed based on a steady-state serum digoxin concentration of 20 ng/mL and patient weight (kg) is as follows: 1 to less than 3 kg give 8 mg; 3 to less than 5 kg give 24 mg; 5 to less than 10 kg give 40 mg; 10 to less than 20 kg give 80 mg; and 20 kg or more give 160 mg.

Dosage calculation based on steady-state serum DIGITOXIN concentrations.
NOTE: If toxicity has not adequately reversed after several hours or appears to recur, another dose of digoxin immune Fab may be necessary. Measurement of serum drug concentrations may also be necessary. Failure to respond to digoxin immune Fab should alert the clinician to the possibility that the problem may not be caused by digitalis toxicity.
Intravenous dosage Adults, Adolescents, Children, and Infants

Intravenous dose in vials = (serum digitoxin concentration in ng/mL x body weight in kg)/1,000. Equation provides a dosage in an amount equimolar to the amount of digitoxin present. Because infants and children have smaller doses, the dosage may be converted to mg instead of vials using the following equation: intravenous dose (in mg) = dose (in number of vials) x 40 mg/vial.

Dosage calculation based on known amount of acutely-ingested digoxin tablets.
NOTE: If toxicity has not adequately reversed after several hours or appears to recur, another dose of digoxin immune Fab may be necessary. Measurement of serum drug concentrations may also be necessary. Failure to respond to digoxin immune Fab should alert the clinician to the possibility that the problem may not be caused by digitalis toxicity.
Intravenous dosage Adults

Intravenous dose in of vials = (amount of cardiac glycoside ingested (mg) x 0.8)/0.5 mg digitalis bound per vial (40 mg of digoxin immune Fab binds approximately 0.5 mg of digoxin). Alternatively, the approximate number of vials needed based on the number of tablets ingested is as follows: if 25 tablets are ingested, give 10 vials IV; if 50 tablets are ingested, give 20 vials IV; if 75 tablets are ingested, give 30 vials IV; if 100 tablets are ingested, give 40 vials IV; if 150 tablets are ingested, give 60 vials IV; if 200 tablets are ingested, give 80 vials of IV.

Infants, Children, and Adolescents

Intravenous dose in vials = (amount of cardiac glycoside administered (mg) x 0.8)/0.5 mg digitalis bound per vial (40 mg of digoxin immune Fab binds approximately 0.5 mg of digoxin). Because infants and children have smaller doses, the dosage may be converted to mg instead of number of vials using the following equation: intravenous dose (in mg) = dose (in number of vials) x 40 mg/vial.

Dosage calculation based on known amount of acutely-ingested digitoxin tablets or intravenous digoxin or digitoxin.
NOTE: If toxicity has not adequately reversed after several hours or appears to recur, another dose of digoxin immune Fab may be necessary. Measurement of serum drug concentrations may also be necessary. Failure to respond to digoxin immune Fab should alert the clinician to the possibility that the problem may not be caused by digitalis toxicity.
Intravenous dosage Adults, Adolescents, Children, and Infants

Intravenous dose in vials = amount of cardiac glycoside ingested (mg)/0.5 mg digitalis bound per vial. Because infants and children have smaller doses, the dosage may be converted to mg instead of vials using the following equation: intravenous dose (in mg) = dose (in number of vials) x 40 mg/vial.

Dosing Considerations
Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Renal Impairment

Elimination of digoxin immune Fab-digoxin complexes may be delayed in patients with renal impairment. It is not clear if deintoxification or reintoxification will occur, therefore prolonged monitoring for digoxin toxicity is recommended.

Drug Interactions

Cardiac glycosides: (Minor) Digoxin immune Fab can reverse desirable as well as toxic actions of cardiac glycosides.
Digoxin: (Minor) Digoxin immune Fab can reverse desirable as well as toxic actions of cardiac glycosides.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Do not give immune globulin including varicella zoster immune globulin concurrently with the varicella-zoster virus vaccine, live. Because of the potential inhibition of the immune response to vaccination by passively transferred antibodies, it is advisable not to give varicella-zoster virus vaccine, live to any patient who has received blood (except washed red blood cells), plasma transfusions, or immunoglobulins within the previous 5 months. After varicella vaccination, the CDC recommends that immune globulin products should not be given for 3 weeks, unless the benefit outweighs the risk; the manufacturer recommends waiting 2 months before administering immunoglobulins. In the case that IgG products are administered within 3 weeks of vaccination, the vaccinee should be either revaccinated at 5 months or tested for immunity and revaccinated if seronegative. Consult current CDC guidelines for recommendations.
Varicella-Zoster Virus Vaccine, Live: (Major) Do not give immune globulin including varicella zoster immune globulin concurrently with the varicella-zoster virus vaccine, live. Because of the potential inhibition of the immune response to vaccination by passively transferred antibodies, it is advisable not to give varicella-zoster virus vaccine, live to any patient who has received blood (except washed red blood cells), plasma transfusions, or immunoglobulins within the previous 5 months. After varicella vaccination, the CDC recommends that immune globulin products should not be given for 3 weeks, unless the benefit outweighs the risk; the manufacturer recommends waiting 2 months before administering immunoglobulins. In the case that IgG products are administered within 3 weeks of vaccination, the vaccinee should be either revaccinated at 5 months or tested for immunity and revaccinated if seronegative. Consult current CDC guidelines for recommendations.

How Supplied

Digifab Intravenous Inj Pwd F/Sol: 40mg

Maximum Dosage

The amount of digoxin immune Fab needed depends on patient-specific factors such as age, amount of digoxin ingested, and patient response.

Mechanism Of Action

Digoxin immune Fab is an immunoglobulin fragment with a specific and high affinity for both digoxin and digitoxin molecules. The affinity between the antidote and the cardiac glycoside is greater than the affinity between the cardiac glycoside and tissue binding sites (e.g., Na-K-ATPase). Molecules of digoxin or digitoxin are removed from tissue binding sites and are sequestered in the extracellular fluid, shifting equilibrium away from binding of the drug to its tissue receptors. Signs and symptoms of digoxin toxicity are reversed, often within minutes. In some patients, beneficial clinical actions of digitalis are also reversed. One 40 mg vial of DigiFab will bind approximately 0.5 mg of digoxin or digitoxin. Digoxin immune Fab effectively treats digitoxin toxicity, as the antidote binds both digitoxin and digoxin (10% of digitoxin is metabolized to digoxin).

Pharmacokinetics

Digoxin immune Fab is administered intravenously. Digoxin immune Fab distributes beyond the extracellular space with a volume of distribution of 0.3 L/kg. Minutes after Fab is administered, total (i.e., bound and free) digoxin serum concentrations increase by 10- to 30-fold, and free digoxin decreases from roughly 80% to 5% or less. It is unknown if the antibody fragment or the glycoside-antibody complex penetrates CSF or breast milk or crosses the placental barrier. Elimination is via the kidney. Free digoxin and the digoxin-Fab complex may be eliminated independently. In patients with normal renal function, the elimination half-life is 15 hours.
 
Administration of digoxin immune Fab led to a reduction in the serum free digoxin concentration to below the limit of assay quantitation for several hours. The cumulative urinary excretion of digoxin was comparable and exceeded 40% of the administered dose by 24 hours in patients with normal renal function.

Pregnancy And Lactation
Pregnancy

Data are limited regarding the use of digoxin immune Fab during pregnancy. It is not known if treatment can result in fetal harm or affect the reproductive capacity. Administer the drug to a pregnant woman only when clearly needed. The maternal benefits may outweigh the unknown fetal risks, as digoxin immune Fab should only be used for life-threatening or potentially life-threatening digoxin toxicity.

According to the manufacturer, it is not known whether digoxin immune Fab is excreted in human milk. Caution should be exercised when administering the drug to a woman who is breast-feeding her infant. Consider the benefits of breast-feeding, the risk of infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, health care providers are encouraged to report the adverse effect to the FDA.