Digoxin IMMUNE FAB - Digibind ® |
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| The authors make no claims of the accuracy of the information contained herein; and these suggested doses and/or guidelines are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this document shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Usual Diluents |
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Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate] |
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| [Prescribed dose] [50 ml] [30 min]
Note: For DigiFab® (no filtering required), please see package insert (pdf - FDA). (Must use 0.22 micron filter). Improvement in signs and symptoms usually begins in 30 minutes or less. ADMINISTRATION DIGIBIND, Digoxin Immune Fab (Ovine), is administered by the intravenous route over 30 minutes. It is recommended that it be infused through a 0.22-micron membrane filter to ensure no undissolved particulate matter is administered. If cardiac arrest is imminent, it can be given as a bolus injection. |
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Stability / Miscellaneous |
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Manifestations of life-threatening toxicity include severe ventricular arrhythmias such as ventricular tachycardia or ventricular fibrillation, or progressive bradyarrhythmias such as severe sinus bradycardia or second or third degree heart block not responsive to atropine. Ingestion of more than 10 mg of digoxin in previously healthy adults or 4 mg of digoxin in previously healthy children, or ingestion causing steady-state serum concentrations greater than 10 ng/mL, often results in cardiac arrest. Digitalis-induced progressive elevation of the serum potassium concentration also suggests imminent cardiac arrest. If the potassium concentration exceeds 5 mEq/L in the setting of severe digitalis intoxication, therapy with DIGIBIND is indicated. CONTRAINDICATIONS WARNINGS One should consider the possibility of anaphylactic, hypersensitivity, or febrile reactions. If an anaphylactoid reaction occurs, the drug infusion should be discontinued and appropriate therapy initiated using aminophylline, oxygen, volume expansion, diphenhydramine, corticosteroids, and airway management as indicated. The need for epinephrine should be balanced against its potential risk in the setting of digitalis toxicity. Since the Fab fragment of the antibody lacks the antigenic determinants of the Fc fragment, it should pose less of an immunogenic threat to patients than does an intact immunoglobulin molecule. Patients with known allergies would be particularly at risk, as would individuals who have previously received antibodies or Fab fragments raised in sheep. Papain is used to cleave the whole antibody into Fab and Fc fragments, and traces of papain or inactivated papain residues may be present in DIGIBIND. Patients with allergies to papain, chymopapain, or other papaya extracts also may be particularly at risk. Skin testing for allergy was performed during the clinical investigation of DIGIBIND. Only one patient developed erythema at the site of skin testing, with no accompanying wheal reaction; this individual had no adverse reaction to systemic treatment with DIGIBIND. Since allergy testing can delay urgently needed therapy, it is not routinely required before treatment of life-threatening digitalis toxicity with DIGIBIND. Skin testing may be appropriate for high risk individuals, especially patients with known allergies or those previously treated with Digoxin Immune Fab (Ovine). The intradermal skin test can be performed by: 1.] Diluting 0.1 mL of reconstituted DIGIBIND (9.5 mg/mL) in 9.9 mL sterile isotonic saline (1:100 dilution, 95 mcg/mL). The scratch test procedure is performed by placing one drop of a 1:100 dilution of DIGIBIND on the skin and then making a ¼-inch scratch through the drop with a sterile needle. The scratch site is inspected at 20 minutes for an urticarial wheal surrounded by erythema. If skin testing causes a systemic reaction, a tourniquet should be applied above the site of testing and measures to treat anaphylaxis should be instituted. Further administration of DIGIBIND should be avoided unless its use is absolutely essential, in which case the patient should be pretreated with corticosteroids and diphenhydramine. The physician should be prepared to treat anaphylaxis PRECAUTIONS General The elimination half-life in the setting of renal failure has not been clearly defined. Patients with renal dysfunction have been successfully treated with DIGIBIND.4 There is no evidence to suggest the time-course of therapeutic effect is any different in these patients than in patients with normal renal function, but excretion of the Fab fragment-digoxin complex from the body is probably delayed. In patients who are functionally anephric, one would anticipate failure to clear the Fab fragment-digoxin complex from the blood by glomerular filtration and renal excretion. Whether failure to eliminate the Fab fragment-digoxin complex in severe renal failure can lead to reintoxication following release of newly unbound digoxin into the blood is uncertain. Such patients should be monitored for a prolonged period for possible recurrence of digitalis toxicity. Patients with intrinsically poor cardiac function may deteriorate from withdrawal of the inotropic action of digoxin. Studies in animals have shown that the reversal of inotropic effect is relatively gradual, occurring over hours. When needed, additional support can be provided by use of intravenous inotropes, such as dopamine or dobutamine, or vasodilators. One must be careful in using catecholamines not to aggravate digitalis toxic rhythm disturbances. Clearly, other types of digitalis glycosides should not be used in this setting. Redigitalization should be postponed, if possible, until the Fab fragments have been eliminated from the body, which may require several days. Patients with impaired renal function may require a week or longer. Laboratory Tests Serum digoxin or digitoxin concentration should be obtained before administration of DIGIBIND if at all possible. These measurements may be difficult to interpret if drawn soon after the last digitalis dose, since at least 6 to 8 hours are required for equilibration of digoxin between serum and tissue. Patients should be closely monitored, including temperature, blood pressure, electrocardiogram, and potassium concentration, during and after administration of DIGIBIND. The total serum digoxin concentration may rise precipitously following administration of DIGIBIND, but this will be almost entirely bound to the Fab fragment and therefore not able to react with receptors in the body. Potassium concentrations should be followed carefully. Severe digitalis intoxication can cause life-threatening elevation in serum potassium concentration by shifting potassium from inside to outside the cell. The elevation in serum potassium concentration can lead to increased renal excretion of potassium. Thus, these patients may have hyperkalemia with a total body deficit of potassium. When the effect of digitalis is reversed by DIGIBIND, potassium shifts back inside the cell, with a resulting decline in serum potassium concentration.4 Hypokalemia may thus develop rapidly. For these reasons, serum potassium concentration should be monitored repeatedly, especially over the first several hours after DIGIBIND is given, and cautiously treated when necessary. Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Nursing Mothers Pediatric Use Geriatric Use The kidney excretes the Fab fragment-digoxin complex, and the risk of digoxin release with recurrence of toxicity is potentially increased when excretion of the complex is slowed by renal failure. However, recurrence of toxicity was reported for only 2.8% of patients in the surveillance study and the only factor associated with recurrence of toxicity was inadequacy of initial dose—not renal function. Calculation of dose is the same for patients of all ages and for patients with normal and impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function and to observe for possible recurrence of toxicity. ADVERSE REACTIONS DOSAGE AND ADMINISTRATION General Guidelines Dosage for Acute Ingestion of Unknown Amount Dosage for Toxicity During Chronic Therapy Methods for calculating the dose of DIGIBIND required to neutralize the known or estimated amount of digoxin or digitoxin in the body are given below (see DOSAGE CALCULATION section). When determining the dose for DIGIBIND, the following guidelines should be considered:
DOSAGE CALCULATION Acute Ingestion of Known Amount For toxicity from an acute ingestion, total body load in milligrams will be approximately equal to the amount ingested in milligrams for digoxin capsules and digitoxin, or the amount ingested in milligrams multiplied by 0.80 (to account for incomplete absorption) for digoxin tablets. Table 1 gives dosage estimates in number of vials for adults and children who have ingested a single large dose of digoxin and for whom the approximate number of tablets or capsules is known. The dose of DIGIBIND (in number of vials) represented in Table 1 can be approximated using the following formula:
* 0.25 mg tablets with 80% bioavailability or 0.2 mg LANOXICAPS® Capsules with 100% bioavailability. Calculations Based on Steady-State Serum Digoxin Concentrations
V = vials Table 3 gives dosage estimates in milligrams for infants and small children based on the steady-state serum digoxin concentration. The dose of DIGIBIND represented in Table 3 can be estimated by multiplying the dose (in number of vials) calculated from Formula 2 by the amount of DIGIBIND contained in a vial (38 mg/vial) (see Formula 3). Since infants and small children can have much smaller dosage requirements, it is recommended that the 38-mg vial be reconstituted as directed and administered with a tuberculin syringe. For very small doses, a reconstituted vial can be diluted with 34 mL of sterile isotonic saline to achieve a concentration of 1 mg/mL. Formula 3: Dose (in mg) = (Dose [in # of vials]) (38 mg/vial)
*Dilution of reconstituted vial to 1 mg/mL may be desirable. Calculation Based on Steady-State Digitoxin Concentration
If the dose based on ingested amount differs substantially from that calculated from the serum digoxin or digitoxin concentration, it may be preferable to use the higher dose. ADMINISTRATION DIGIBIND, Digoxin Immune Fab (Ovine), is administered by the intravenous route over 30 minutes. It is recommended that it be infused through a 0.22-micron membrane filter to ensure no undissolved particulate matter is administered. If cardiac arrest is imminent, it can be given as a bolus injection. HOW SUPPLIED STORAGE REFERENCES
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Digoxin Immune Fab
