warnings and cautions
5 WARNINGS AND PRECAUTIONS Rapid drop in serum potassium concentration after treatment with DigiFab ® . Monitor frequently, especially after the first several hours of DigiFab administration. ( 5.1 ) Anaphylaxis and hypersensitivity reactions are possible. Patients with allergies to papain, chymopapain, other papaya extracts, or the pineapple enzyme bromelain may be at risk for an allergic reaction to DigiFab ® . ( 5.2 ) Clinically misleading reading of standard serum digoxin concentration may occur after administration of DigiFab ® due to interference with digitalis immunoassay measurements. ( 5.4 ) 5.1 General 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 5.4 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 re-digitalization, 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. 5.2 Hypersensitivity Reactions 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 one occurs. 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 available.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. 5.3 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 5.4 Laboratory Tests 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 intoxication. 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.