FDA label 1cd4343a-6916-4f64-ae52-511026be23d0

WARNINGS Suicidal ingestion may involve 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. The possible risks and side-effects that attend the administration of heterologous animal proteins in humans include anaphylactic and anaphylactoid reactions, delayed allergic reactions and a possible febrile response to immune complexes formed by animal antibodies. 8 Since the Fab fragment of the antibody lacks the antigenic determinants of the Fc fragment, it should pose a reduced immunogenic threat to patients compared with intact immunoglobulin molecules. Being monovalent, the product is also unlikely to form extended immune complexes with the antigen. Although no patient in the clinical studies of DigiFab has experienced a severe anaphylactic reaction, the possibility of an anaphylactic reaction should be considered. All patients should be informed of the possibility of an anaphylactic reaction and when receiving DigiFab should be carefully monitored 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 treated immediately with appropriate emergency medical care (e.g., oxygen, diphenhydramine, corticosteroids, volume expansion and airway management). If an anaphylactic reaction occurs during the infusion, DigiFab administration should be terminated at once and appropriate treatment administered. The need for epinephrine should be balanced against its potential risk in the setting of digitalis toxicity. Patients with known allergies to sheep protein would be particularly at risk for an anaphylactic reaction, as would individuals who have previously received intact ovine antibodies or ovine Fab. Papain is used to cleave the whole antibody into Fab and Fc fragments, and trace amounts of papain or inactivated papain residues may be present in DigiFab. Patients with allergies to papain, chymopapain, other papaya extracts, or the pineapple enzyme bromelain may also be at risk for an allergic reaction to DigiFab. In addition, it has been noted in the literature that some dust mite allergens and some latex allergens share antigenic structures with papain and patients with these allergies may be allergic to papain. 9-10 DigiFab should not be administered 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. Skin testing has not proved useful in predicting allergic response to Digibind. 11 Because of this, and because it may delay urgently needed therapy, skin testing was not performed during the clinical studies of DigiFab and is not suggested prior to dosing with this product.

ADVERSE REACTIONS Based on experience with Digibind, the following adverse reactions could occur with the use of DigiFab: • Exacerbation of low cardiac output states and congestive heart failure due to the withdrawal of inotropic effect of digitalis. • Hypokalemia due to reactivation of the sodium-potassium ATPase (see Laboratory Tests ). • Rapid ventricular response in patients with atrial fibrillation due to withdrawal of the effects of digitalis on the atrioventricular node. • Rare allergic reactions (see WARNINGS ). Patients with a history of allergy, especially to antibiotics, appear to be at particular risk. 11 In the clinical trials of DigiFab, 6 of 15 patients in the digoxin overdose study had a total of 17 adverse experiences, most were mild to moderate in nature and all were deemed "remotely associated" with DigiFab. Three events were deemed "severe", all occurred in one patient and consisted of the following: pulmonary edema, bilateral pleural effusion and renal failure. After reviewing the case, it was determined that these events were likely due to the loss of digoxin inotropic support in combination with the patient's underlying medical condition. Of 8 healthy volunteers who received DigiFab, only 2 experienced an adverse reaction that was considered to be associated with DigiFab. The reactions were 1 episode of phlebitis of the infusion vein and 1 episode of moderate postural hypotension, which became mild prior to resolving.