Digoxin immune Fab is a protein that consists of antibody fragments, which are used as an antidote for life-threatening or potentially life-threatening digoxin toxicity or overdose. The antibody fragments are obtained by immunizing sheep with a digoxin derivative, isolating immunoglobulins from the sheep serum, digesting the immunoglobulins with papain, and obtaining the specific antibody fragments through affinity chromatography. Digoxin immune Fab is available in 40 mg vials, with each vial binding approximately 0.5 mg of digoxin. Monitor drug recipients during and after administration for infusion-related and acute allergic reactions. Additionally, closely monitor patients' temperature, blood pressure, electrocardiogram, and serum potassium concentration during and after treatment.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
-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.
Route-Specific Administration
Injectable Administration
-Administered by intravenous infusion. Alternatively, dose may be given by bolus injection if cardiac arrest is imminent.
-Closely monitor the patient's temperature, blood pressure, electrocardiogram, and serum potassium concentration during and after administration of digoxin immune Fab.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use if the solution cloudy, turbid, or if it contains particulates.
Intravenous Administration
Reconstitution/Dilution
-Reconstitute by adding 4 mL of Sterile Water for Injection to the vial and gently mixing. The resulting solution contains approximately 10 mg/mL of digoxin immune Fab. Dilute the reconstituted product with 0.9% Sodium Chloride Injection to an appropriate volume.
-For infants and children requiring very small doses, reconstitute the 40 mg vial as directed and administer the appropriate dose undiluted using a tuberculin syringe. Alternatively, the reconstituted vial can be diluted with an additional 36 mL of 0.9% Sodium Chloride Injection to achieve a concentration of 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.
Allergic reactions including anaphylaxis or anaphylactoid reactions are possible during administration of digoxin immune Fab. Carefully monitor all patients for signs and symptoms of an acute allergic reaction such as urticaria, pruritus, erythema, angioedema, bronchospasm with wheezing or cough, stridor, laryngeal edema, hypotension, rash, and sinus tachycardia. During clinical trials, 1 out of the 8 healthy volunteers who received digoxin immune Fab developed transient orthostatic hypotension. Administration of digoxin immune Fab has also been associated with the development of infusion-related reactions. These reactions are more likely to occur when the drug is administered via a bolus injection; therefore, bolus injections should be used only if cardiac arrest is imminent. If an infusion rate-related reaction or anaphylactoid reaction occurs (such as hypotension, wheezing, or urticaria), stop the infusion at once and administer appropriate treatment. Balance the need for epinephrine with the potential risk of its administration in the setting of digitalis toxicity. If appropriate, the infusion can be re-started at a slower rate.
The most common adverse reactions related to administration of digoxin immune Fab are worsening congestive heart failure (13%) and worsening atrial fibrillation (7%). Due to the high efficiency of digoxin immune Fab in removing digoxin, precipitation of heart failure may occur due to the loss of the positive inotropic effects of digoxin. Also, the loss of effects of digoxin on the atrioventricular node may lead to a rapid ventricular response in patients with atrial fibrillation.
Hypokalemia (13%) was a common adverse reaction related to administration of digoxin immune Fab. Acute digoxin overdose causes hyperkalemia and a compensatory hyperkaliuresis. Reversal of digoxin effects on sodium-potassium ATPase by digoxin immune Fab can lead to hypokalemia. Serum potassium should be monitored closely during and after therapy with digoxin immune Fab.
Antibody formation is possible, as exposure to digoxin-specific ovine immune Fab may cause sensitization to ovine serum protein. Hypothetically, the presence of human antibodies against ovine Fab could lead to diminution of the drug's efficacy. However, no clinical reports exist of human anti-ovine immunoglobulin antibodies causing a reduction in binding of ovine digoxin immune Fab or neutralization response to ovine digoxin immune Fab. Digoxin immune Fab should only be administered in specific conditions.
An injection site reaction may occur during the intravenous infusion of digoxin immune Fab. One of 8 healthy volunteer patients who received digoxin immune Fab developed phlebitis of the infusion vein.
Digoxin immune Fab is a foreign (sheep-derived) protein. Use digoxin immune Fab cautiously in patients with known ovine protein hypersensitivity. Digoxin immune Fab is prepared by isolating the immunoglobulin fraction of the ovine serum, digesting it with papain, and isolating the digoxin-specific Fab fragments by affinity chromatography. Patients with papain hypersensitivity or allergies to chymopapain, other papaya extracts, or the pineapple extract bromelain may have an allergic response to the product. Do not administer digoxin immune Fab to a patient with a known history of hypersensitivity to papaya or papain unless the benefits outweigh the risks and appropriate management for anaphylactic reactions is readily available.
Use caution when administering digoxin immune Fab to patients with renal impairment or renal failure, including geriatric patients who are more likely to have reduced renal function. In patients with severe renal impairment, monitor for possible recurrence of toxicity for a prolonged period, as the elimination half-life of digoxin immune Fab appears to be increased up to 10-fold in patients with renal impairment. Monitoring of free (unbound) digoxin concentrations after the administration of digoxin immune Fab may be appropriate in order to establish recrudescent toxicity in renal failure patients. If possible, postpone redigitalization until the Fab fragments have been eliminated from the body, which may require a week or longer in patients with impaired renal function.
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 pregnant patients 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 lactating patient. 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 administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Closely monitor serum potassium concentrations and electrocardiogram during and after treatment with digoxin immune Fab. During severe digoxin intoxication, life-threatening elevation of serum potassium can occur due to digoxin causing a shift of potassium from inside to outside the cell. This may lead to increased urinary excretion of potassium so that a patient may have hyperkalemia but a whole body potassium deficiency. When digoxin immune Fab is administered, potassium shifts back into the cell with a resulting decline in serum potassium concentration. This digoxin immune Fab induced hypokalemia can develop rapidly, and may require cautious treatment with potassium supplementation. Additionally, patients with cardiac disease may deteriorate secondary to the withdrawal of the inotropic action of digoxin by digoxin immune Fab. If needed, provide additional support by using other intravenous inotropes, such as dopamine, dobutamine, or vasodilators. Take care not to aggravate the digitalis induced rhythm disturbances.
Patients with suicidal ideation may ingest more than 1 drug, and the toxic effects of other drugs or poisons must not be overlooked. If a patient fails to respond to treatment with digoxin immune Fab, consider the possibility that the clinical problem is not caused by digitalis intoxication.
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 10 ng/mL or greater; 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 life-threatening digoxin toxicity due to overdose such as 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 with rapidly progressive signs and symptoms of toxicity):
-for acute ingestion of unknown amounts of digoxin and toxicity in the absence of a serum digitalis concentration or estimated ingestion amount:
Intravenous dosage:
Adults: 800 mg (20 vials) IV. Give 400 mg (10 vials) IV with careful monitoring of the patient's response, followed by an additional 400 mg (10 vials) if necessary. Administering the entire 800 mg (20 vials) as a single dose may 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.
Children and Adolescents: 800 mg (20 vials) IV. Give 400 mg (10 vials) IV with careful monitoring of the patient's response, followed by an additional 400 mg (10 vials) if necessary. Administering the entire 800 mg (20 vials) as a single dose may enhance the possibility of a febrile reaction. In patients less than 20 kg, closely monitor for volume overload. 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 in the absence of a serum digitalis concentration:
Intravenous dosage:
Adults: 240 mg (6 vials) IV. Failure to respond to digoxin immune Fab should alert the clinician to the possibility that the problem may not be caused by digitalis toxicity.
Children and Adolescents weighing 20 kg or more: 240 mg (6 vials) IV. 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. 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 known amount of acutely-ingested digoxin tablets:
NOTE: Each vial of digoxin immune Fab binds approximately 0.5 mg digoxin.
NOTE: If toxicity has not adequately reversed after several hours or appears to recur, another dose guided by clinical judgement may be necessary. Consider measuring free (unbound) serum digitalis concentrations in patients who require another dose, since digoxin immune Fab may still be present in the body.
NOTE: Failure to respond to digoxin immune Fab should alert the clinician to the possibility that the problem may not be caused by digitalis toxicity.
NOTE: If the dose calculated based on ingested amount differs substantially from the dose calculated based on the serum digoxin or digitoxin concentration, it may be preferable to use the higher dose estimate.
Intravenous dosage:
Adults: Intravenous dose in vials = (amount of cardiac glycoside ingested (mg) x 0.8)/0.5 mg digitalis bound per vial. 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 ingested (mg) x 0.8)/0.5 mg digitalis bound per vial. 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.
-dosage calculation based on known amount of acutely-ingested digoxin capsules or digitoxin:
NOTE: Each vial of digoxin immune Fab binds approximately 0.5 mg digoxin.
NOTE: If toxicity has not adequately reversed after several hours or appears to recur, another dose guided by clinical judgement may be necessary. Consider measuring free (unbound) serum digitalis concentrations in patients who require another dose, since digoxin immune Fab may still be present in the body.
NOTE: Failure to respond to digoxin immune Fab should alert the clinician to the possibility that the problem may not be caused by digitalis toxicity.
NOTE: If the dose calculated based on ingested amount differs substantially from the dose calculated based on the serum digoxin or digitoxin concentration, it may be preferable to use the higher dose estimate.
Intravenous dosage:
Adults: Intravenous dose in vials = amount of cardiac glycoside ingested (mg)/0.5 mg digitalis bound per vial. Alternatively, for digoxin capsules, the approximate number of vials needed based on the number of capsules ingested is as follows: if 25 caps are ingested, give 10 vials IV; if 50 caps are ingested, give 20 vials IV; if 75 caps are ingested, give 30 vials IV; if 100 caps are ingested, give 40 vials IV; if 150 caps are ingested, give 60 vials IV; if 200 caps are ingested, give 80 vials of IV.
Infants, Children, and Adolescents: Intravenous dose in vials = amount of cardiac glycoside ingested (mg)/0.5 mg digitalis bound per vial. Alternatively, for digoxin capsules, the approximate number of vials needed based on the number of capsules ingested is as follows: if 25 caps are ingested, give 10 vials IV; if 50 caps are ingested, give 20 vials IV; if 75 caps are ingested, give 30 vials IV; if 100 caps are ingested, give 40 vials IV; if 150 caps are ingested, give 60 vials IV; if 200 caps are ingested, give 80 vials of IV.
-dosage calculation based on steady-state serum DIGOXIN concentrations:
NOTE: Inaccurate estimates of the amount of digitalis ingested or absorbed may occur due to non-steady state concentrations or due to digitalis assay limitations. Most assay kits are designed to measure concentrations less than 5 ng/mL; therefore, sample dilution is required to accurately measure serum concentrations greater than 5 ng/mL.
NOTE: Dosage calculations are based on a steady state volume of distribution of approximately 5 L/kg for digoxin, which is used to convert serum digoxin concentrations to total body burden of digoxin in milligrams. This volume of distribution is a population average and may vary among individuals. Many patients may require higher doses for complete neutralization and doses should usually be rounded up to the nearest whole vial.
NOTE: If toxicity has not adequately reversed after several hours or appears to recur, another dose guided by clinical judgement may be necessary. Consider measuring free (unbound) serum digitalis concentrations in patients who require another dose, since digoxin immune Fab may still be present in the body.
NOTE: 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: The formula for digitoxin toxicity differs from the digoxin toxicity formula in the denominator due to a 10-fold decrease in volume of distribution of digitoxin as compared to digoxin.
NOTE: Inaccurate estimates of the amount of digitalis ingested or absorbed may occur due to non-steady state concentrations or due to digitalis assay limitations.
NOTE: If toxicity has not adequately reversed after several hours or appears to recur, another dose guided by clinical judgement may be necessary. Consider measuring free (unbound) serum digitalis concentrations in patients who require another dose, since digoxin immune Fab may still be present in the body.
NOTE: 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 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.
Infants, Children, and Adolescents: 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.
Therapeutic Drug Monitoring:
-Measure serum digoxin concentrations prior to administration of digoxin Immune Fab, if possible.
-The total serum digoxin concentration may rise precipitously following administration of digoxin immune Fab; however, this will be almost entirely bound to the Fab fragment. Digoxin bound to Fab fragments is not able to react with receptors in the body and therefore cannot result in toxicity. Standard serum digoxin concentration measurements may be clinically misleading until the Fab fragments are eliminated from the body. This may take several days or a week or more in patients with markedly impaired renal function.
-The serum concentration of digoxin obtained prior to administration of digoxin Immune Fab will establish the level of serum digoxin at the time of diagnosis of digitalis intoxication. Absorption of the last dose may continue from the intestine, because at least 6 to 8 hours are required for equilibration of digoxin between serum and tissue. Therefore, serum measurements may be difficult to interpret if samples are drawn soon after the last digitalis dose.
-Closely monitor temperature, blood pressure, electrocardiogram, and potassium concentration, during and after administration of digoxin immune Fab.
-If toxicity has not adequately reversed after several hours, or appears to recur, readministration of digoxin immune Fab, at a dose guided by clinical judgment, may be necessary. If a patient is in need of readministration of digoxin immune Fab due to recurrent toxicity, or to a new toxic episode that occurs soon after the first episode, measurement of free (unbound) serum digitalis concentrations should be considered since Fab may still be present in the body.
Maximum Dosage Limits:
The amount of digoxin immune Fab needed depends on patient-specific factors such as age, amount of digoxin ingested, and patient response.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Elimination of digoxin immune Fab-digoxin complexes may be delayed in patients with renal impairment. For patients with severe renal impairment, monitor for recurrence of digoxin toxicity for a prolonged period.
*non-FDA-approved indication
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.
Digoxin immune Fab treats digoxin toxicity or overdose. The drug is an immunoglobulin fragment that has a high affinity for digoxin molecules, with each vial binding approximately 0.5 mg of digoxin. The affinity between the antidote and the cardiac glycoside is greater than the affinity between the cardiac glycoside and tissue binding sites. By binding molecules of digoxin, digoxin immune Fab reduces the free digoxin concentration and shifts the equilibrium away from the receptors; thereby reversing the cardiotoxic effects of digoxin. Minutes after administration of digoxin immune Fab, free digoxin concentrations decrease from roughly 80% to 5% or less and total (i.e., bound and free) digoxin serum concentrations increase by 10- to 30-fold. Subsequently, the digoxin immune Fab-digoxin complexes are cleared from the body by the kidneys and reticuloendothelial system.
Digoxin immune Fab is administered intravenously. The drug 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. The digoxin immune Fab-digoxin complex is eliminated via the kidney and reticuloendothelial system. In patients with normal renal function, the elimination half-life is 15 to 20 hours.
Affected cytochrome P450 isoenzymes and drug transporters: None
-Special Populations
Hepatic Impairment
No pharmacokinetic data are available in patients with hepatic impairment.
Renal Impairment
In patients with renal impairment, the elimination half-life appears to be increased up to 10-fold, but the volume of distribution is unaffected. The elimination half-life for the digoxin-Fab complex averages 118 hours in patients with various degrees of renal dysfunction.