"By Megan Brooks
Medscape Medical News
The US Food and Drug Administration (FDA) will require makers of prescription testosterone products to clarify the approved uses of these medications on the product label and add information"...
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 (digoxin immune fab) . 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 (digoxin immune fab) . 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 (digoxin immune fab) . Since allergy testing can delay urgently needed therapy, it is not routinely required before treatment of life-threatening digitalis toxicity with DIGIBIND (digoxin immune fab) .
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:
- Diluting 0.1 mL of reconstituted DIGIBIND (digoxin immune fab) (9.5 mg/mL) in 9.9 mL sterile isotonic saline (1:100 dilution, 95 mcg/mL).
- Injecting 0.1 mL of the 1:100 dilution (9.5 mcg) intradermally and observing for an urticarial wheal surrounded by a zone of erythema. The test should be read at 20 minutes.
The scratch test procedure is performed by placing one drop of a 1:100 dilution of DIGIBIND (digoxin immune fab) 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 (digoxin immune fab) 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.
Standard therapy for digitalis intoxication includes withdrawal of the drug and correction of factors that may contribute to toxicity, such as electrolyte disturbances, hypoxia, acid-base disturbances, and agents such as catecholamines. Also, treatment of arrhythmias may include judicious potassium supplements, lidocaine, phenytoin, procainamide, and/or propranolol; treatment of sinus bradycardia or atrioventricular block may involve atropine or pacemaker insertion. Massive digitalis intoxication can cause hyperkalemia; administration of potassium supplements in the setting of massive intoxication may be hazardous (see Laboratory Tests). After treatment with DIGIBIND (digoxin immune fab) , the serum potassium concentration may drop rapidly2 and must be monitored frequently, especially over the first several hours after DIGIBIND (digoxin immune fab) is given (see Laboratory Tests).
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 (digoxin immune fab) .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.
DIGIBIND (digoxin immune fab) will interfere with digitalis immunoassay measurements.6 Thus, the standard serum digoxin concentration measurement can be clinically misleading until the Fab fragment is eliminated from the body.
Serum digoxin or digitoxin concentration should be obtained before administration of DIGIBIND (digoxin immune fab) 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 (digoxin immune fab) . The total serum digoxin concentration may rise precipitously following administration of DIGIBIND (digoxin immune fab) , 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 (digoxin immune fab) , 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 (digoxin immune fab) is given, and cautiously treated when necessary.
Carcinogenesis, Mutagenesis, Impairment of Fertility
There have been no long-term studies performed in animals to evaluate carcinogenic potential.
Pregnancy Category C. Animal reproduction studies have not been conducted with DIGIBIND (digoxin immune fab) . It is also not known whether DIGIBIND (digoxin immune fab) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. DIGIBIND (digoxin immune fab) should be given to a pregnant woman only if clearly needed.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when DIGIBIND (digoxin immune fab) is administered to a nursing woman.
DIGIBIND (digoxin immune fab) has been successfully used in infants with no apparent adverse sequelae. As in all other circumstances, use of this drug in infants should be based on careful consideration of the benefits of the drug balanced against the potential risk involved.
Of the 150 subjects in an open-label study of DIGIBIND (digoxin immune fab) , 42% were 65 and over, while 21% were 75 and over. In a post-marketing surveillance study that enrolled 717 adults, 84% were 60 and over, and 60% were 70 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
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.
2. Smith TW, Haber E, Yeatman L, Butler VP Jr. Reversal of advanced digoxin intoxication with Fab fragments of digoxin-specific antibodies. N Engl J Med. 1976; 294:797-800.
4. Wenger TL, Butler VP Jr, Haber E, Smith TW. Treatment of 63 severely digitalis-toxic patients with digoxin-specific antibody fragments. J Am Coll Cardiol. 1985; 5:118A-123A.
6. Gibb I, Adams PC, Parnham AJ, Jennings K. Plasma digoxin: Assay anomalies in Fab-treated patients. Br J Clin Pharmacol. 1983; 16:445-447.
Last reviewed on RxList: 10/14/2008
This monograph has been modified to include the generic and brand name in many instances.
Additional Digibind Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Get the latest treatment options.