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Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trails of another drug and may not reflect the rates observed in clinical practice.
- The most common adverse events reported in the clinical studies were urticaria and rash. Adverse events involving the skin and appendages (primarily rash, urticaria, and pruritus) were reported in 14 of the 42 patients (Table 1).
- Of the 25 patients who experienced adverse reactions, 3
patients experienced severe or serious adverse reactions.
- The 1 patient who experienced a serious adverse event had a recurrent coagulopathy due to envenomation, which required re-hospitalization and additional antivenin administration. This patient eventually made a complete recovery.
- The other 2 had severe adverse reactions that consisted of 1 patient who developed severe hives following treatment and 1 patient who developed a severe rash and pruritus several days following treatment. Both patients recovered following treatment with antihistamines and prednisone.
- One patient discontinued CroFab® therapy due to an allergic reaction.
Table 1 : Incidence of Clinical Adverse Events in
Studies of CroFab® by Body System
Number of Events
|Body as a Whole|
|Skin and Appendages|
|* Of the 42 patients receiving CroFab® in the clinical
studies, 25 experienced an adverse event. A total of 40 adverse events was
experienced by these 25 patients.
† Allergic reaction consisted of urticaria, dyspnea and wheezing in 1 patient.
In the 42 patients treated with CroFab® for minimal or moderate crotalid envenomations, there were 7 events classified as early serum reactions and 5 events classified as late serum reactions, and none were serious (Table 2). In the clinical studies, serum reactions consisted mainly of urticaria and rash, and all patients recovered without sequelae.
Table 2 : Incidence of Early and Late Serum Reactions
(Reactions Associated with CroFab® Infusion)
Number of Events
|Early Serum Reactions|
|Late Serum Reactions|
|* 6 of 42 patients experienced an adverse event
associated with an early serum reaction and 4 experienced an adverse event
associated with a late serum reaction. Two additional patients were considered
to have a late serum reaction by the investigator, although no associated adverse
event was reported.
** Allergic reaction consisted of urticaria, dyspnea and wheezing in 1 patient.
† Serum sickness consisted of severe rash and pruritus in 1 patient.
The following adverse reactions have been identified during the post approval use of CroFab®. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to product exposure:
- Acute allergic reactions including anaphylaxis or anaphylactoid type reactions during or shortly following CroFab® infusion, manifested by one or more of the following: anxiety, bronchospasm, chills, edema, fever, hypotension, pruritis, rash, urticaria, voice alteration, and/or wheezing
- Delayed allergic reaction manifested by fever, pruritis and/or rash
- Delayed or recurrent coagulopathy or thrombocytopenia
- Failure to achieve initial control
- Recurrent swelling refractory to treatment
- Thrombocytopenia refractory to treatment
- Prolonged hospitalization
- Worsening eye sight
- Treatment failure resulting in death
A retrospective study of data collected by the Rocky Mountain Poison and Drug Center for post-marketing use of CroFab® was conducted (13.2).
- There were a total of 36 immediate adverse drug reactions
reported in 6.1% (15/247) of patients in the post-marketing retrospective
study, including one patient in the severely envenomated group (3.6%, n = 28) and
13 patients in the mild/moderate severity group (7.2%, n = 181) (not significantly
- There were 11 immediate serious adverse events related to CroFab® administration reported in four patients. The events included two episodes each of hypotension and tongue swelling, and one episode each of chest discomfort, angioedema, bronchospasm, wheezing, tracheal edema, dyspnea, and lip swelling.
- There were 22 immediate non-serious adverse events related to CroFab® administration reported in 12 patients. The events included four episodes each of rash and pruritis, three episodes of urticaria, and one episode each of tachycardia, tachypnea, erythema, swelling, hyperhidrosis, dizziness, headache, musculoskeletal chest pain, chills, feeling cold, and nervousness.
- Delayed hypersensitivity reactions were reported for two patients. In one patient the symptoms occurred 6 days post-dosing, were not serious, and described as hives, itching and epigastric pressure. In the second patient symptoms were not described in the medical records and were therefore not captured in this study.
- Recurrent coagulopathy developed in 5 severely envenomated patients and in 6 mild/moderate envenomated patients. In addition, 7 mild/moderate patients experienced delayed-onset coagulopathy. One severely envenomated patient with recurrent coagulopathy experienced medically significant bleeding.
Additional Published Clinical Studies Experience
From a literature review of nine publications on CroFab® containing patient exposure data, 15 of 313 (4.8%) patients receiving CroFab® experienced acute hypersensitivity reactions.
The most common signs and symptoms associated with these reactions were rash (10 patients) and wheezing (3 patients). Most reactions were mild, resolved after antihistamine therapy, and did not require discontinuation of antivenom therapy. No patient developed a life-threatening hypersensitivity reaction, required intubation, suffered lasting ill-effect, or died as a result of CroFab® administration.
Follow up data (minimum of six days after treatment) were available in 94 of the 313 patients and delayed hypersensitivity reactions were reported in 10 cases. The most common signs and symptoms of delayed hypersensitivity were rash (9 patients) and fever (3 patients). Most were mild and treated with antihistamines and steroids.
Read the Crofab (crotalidae polyvalent immune fab ovine) Side Effects Center for a complete guide to possible side effects
Studies of drug interactions have not been conducted with CroFab®.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 4/17/2015
Additional Crofab Information
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