Included as part of the PRECAUTIONS section.
Suicidal ingestion may result from more than one drug.
Toxic effects of other drugs or poisons should not be overlooked, especially in
cases where signs and symptoms of digitalis toxicity are not relieved by
administration of DigiFab®.
Rapid drop in serum potassium concentration may occur
after treatment with DigiFab®. Monitor frequently, especially after the first
several hours of DigiFab® administration (see Laboratory Tests).
Patients with poor cardiac function may deteriorate
secondary to the withdrawal of the inotropic action of digoxin by DigiFab®. If
needed, provide additional support by using other intravenous inotropes such as
dopamine, dobutamine or vasodilators. However, take additional care not to aggravate
the digitalis induced rhythm disturbances. Postpone redigitalization, if
possible, until the Fab fragments have been eliminated from the body, which may
require several days, and patients with impaired renal function may require a
week or longer.
Anaphylaxis and hypersensitivity reactions are possible.
Carefully monitor all patients treated with DigiFab® for signs and symptoms of
an acute allergic reaction (e.g., urticaria, pruritus, erythema, angioedema, bronchospasm
with wheezing or cough, stridor, laryngeal edema, hypotension, tachycardia) and
treat immediately with appropriate emergency medical care (e.g., oxygen,
diphenhydramine, corticosteroids, volume expansion and airway management), if
If an anaphylactic reaction occurs during the infusion,
terminate DigiFab® administration at once and administer appropriate treatment.
Balance the need for epinephrine against its potential risk in the setting of
digitalis toxicity. Patients with known allergies to sheep protein are
particularly at risk for an anaphylactic reaction, as are individuals who have
previously received intact ovine antibodies or ovine Fab.
Do not administer DigiFab® to patients with a known
history of hypersensitivity to papaya or papain unless the benefits outweigh
the risks and appropriate management for anaphylactic reactions is readily
Prior treatment with digoxin-specific ovine immune Fab
carries a theoretical risk of sensitization to ovine serum protein and possible
diminution of the efficacy of the drug due to the presence of human antibodies
against ovine Fab. To date, there have been no clinical reports of human
anti-ovine immunoglobulin antibodies causing a reduction in binding of ovine
digoxin immune Fab or neutralization response to ovine digoxin immune Fab.
Use Of DigiFab® In Renal Failure
The elimination half-life of DigiFab® in renal failure
has not been clearly defined. Monitor patients with severe renal failure who
receive DigiFab® for digitalis toxicity for a prolonged period for possible
recurrence of toxicity.
Monitoring of free (unbound) digoxin concentrations after
the administration may be appropriate in order to establish recrudescent
toxicity in renal failure patients.5
DigiFab® may interfere with digitalis immunoassay
measurements. Thus, 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. Therefore, serum samples for digoxin concentration should be obtained
before DigiFab® administration, if at all possible. Such measurements would
establish the level of serum digoxin at the time of diagnosis of digitalis
At least 6 to 8 hours are required for equilibration of digoxin
between serum and tissue, so absorption of the last dose may continue from the
intestine. Therefore, serum measurements may be difficult to interpret if
samples are drawn soon after the last digitalis dose.
The total serum digoxin concentration may rise
precipitously following administration of DigiFab®, but this will be almost
entirely bound to the Fab fragment and therefore not able to react with
receptors in the body.
Patients should be closely monitored, including
temperature, blood pressure, electrocardiogram, and potassium concentration,
during and after administration of DigiFab®. Digoxin causes a shift of
potassium from inside to outside the cell, such that severe intoxication can
cause a life-threatening elevation of serum potassium. This may lead to
increased urinary excretion of potassium so that a patient may have
hyperkalemia but a whole body deficit of potassium. When the toxic effects of
digoxin are reversed by DigiFab®, potassium shifts back into the cell with a
resulting decline in serum potassium concentration. This hypokalemia may
develop rapidly. For these reasons, serum potassium concentration should be
followed closely, especially during the first several hours after DigiFab® administration.
Cautious potassium supplementation should then be given when necessary.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Animal carcinogenicity and reproduction studies have not
been conducted with DigiFab.
Use In Specific Populations
Pregnancy Category C
Animal reproduction studies have not been conducted with
DigiFab®. It is also not known whether DigiFab® can cause fetal harm when
administered to a pregnant woman or can affect reproduction capacity. DigiFab® should
be given to a pregnant woman only if clinically needed.
It is not known whether DigiFab® is excreted in human
breast milk. Because many drugs are excreted in human milk, caution should be exercised
when DigiFab® is administered to a nursing woman. DigiFab® should be given to
nursing mothers only if clinically needed.
Safety data in pediatric population is limited. The
pediatric dosing estimation is based on calculations for adult dosing.
Specific studies in elderly patients have not been
conducted. Of the 15 patients given DigiFab® for digoxin toxicity in one
clinical trial, the average age of all patients was 64 years and over half of
the patients (8 of the 15) were 65 years of age or older. The oldest patient
studied was 86 years old. There is no evidence that the efficacy of DigiFab® would
be altered due to advanced age alone; however, elderly patients have a higher
chance of having impaired renal function and therefore should be monitored more
closely for recurrent toxicity (See Use of DigiFab® in renal failure).
5. Valdes R, Jortani SA. Monitoring of unbound digoxin in
patients with antidigoxin antigen-binding fragments: a model for the future ?
Clin Chem 1998; 44(9):1883-1885.