Safety Profile

A Safety Profile You Can Count On1

 

Incidence of clinical adverse reactions in studies of CroFab®

Adverse Reactions Number of Adverse Reactions (N=42)

*Of the 42 patients receiving CroFab® in the clinical studies, 19 experienced an adverse reaction. A total of 26 adverse reactions were experienced by these 19 patients.

Allergic reactions consisted of urticaria, dyspnea, and wheezing in 1 patient.

Serum sickness consisted of severe rash and pruritus in 1 patient.

§Six of 42 patients experienced an adverse reaction associated with an early serum reaction, and 4 experienced an adverse reaction associated with a late serum reaction. Two additional patients were considered to have a late serum reaction by the investigator, although no associated adverse reaction was reported.

Body as a Whole 4 - Back pain (2), allergic reactions (1), serum sickness (1)
Skin and Appendages 13 - Urticaria (7), rash (3), pruritus (2), subcutaneous nodule (1)
Respiratory System 1 - Cough (1)
Digestive System 4 - Nausea (3), anorexia (1)
Hematologic System 2 - Coagulation disorder (1), ecchymosis (1)
Musculoskeletal 1 - Myalgia
Nervous System - Nervousness (1)
Early Serum Reactions§ 7 - Urticaria (5), cough (1), allergic reactions† (1)
Late Serum Reactions§ 5 - Rash (2), pruritus (1), urticaria (1), serum sickness‡ (1)

Real-World Evidenceǁ

Since 2001, safety data have been collected on CroFab® in the treatment of North American pit viper envenomation.

In a meta-analysis of 11 studies involving 504 patients treated with CroFab®, which included 2 pre-marketing studies, the incidence of immediate hypersensitivity reactions and serum sickness was 8% (95% CI = 5% to 11%) and 13% (95% CI = 7% to 21%), respectively.

  • Sensitivity analysis excluding 2 premarketing trials, one with potential Fc contamination, reduced the estimated serum sickness to 8% (95% CI = 4% to 16%)

In the American College of Medical Toxicology’s North American Snake Bite Registry, a prospective case registry of snake envenomed patients, 373 patients were treated with CroFab over a 3 year period (2013–2015).3

  • Acute adverse events were observed in 10 of the 373 patients (2.7%)
  • Rash, including urticaria, was the most common event, occurring in 6 patients (1.6%)
  • Hypotension, bronchospasm, and angioedema occurred in 4 patients (1.1%)
  • Limitations of this publication include that it is based on a post-marketing registry, which is limited by the voluntary nature of the reporting
 

ǁThese data were not reviewed by the FDA.
Meta-analysis of CroFab® studies from January 1997 (prior to FDA approval in 2000) to September 2010.


A retrospective study of postmarketing use of CroFab® reported 36 immediate adverse drug reactions in 6.1% (15/247) of patients, including4:

 
  • 11 immediate serious adverse reactions related to CroFab® in 4 patients: 2 episodes each of hypotension and tongue swelling, and 1 episode each of chest discomfort, angioedema, bronchospasm, wheezing, tracheal edema, dyspnea, and lip swelling
  • 22 immediate nonserious adverse reactions related to CroFab® in 12 patients: 4 episodes each of rash and pruritus, 3 of urticaria, and 1 each of tachycardia, tachypnea, erythema, swelling, hyperhidrosis, dizziness, headache, musculoskeletal chest pain, chills, feeling cold, and nervousness
  • 2 patients reported delayed hypersensitivity reactions

Dosing and administration guidance for every stage of envenomation.

References:

1. CroFab® [prescribing Information]. BTG International Inc; May 2017. 2. Schaeffer TH, Khatri V, Reifler LM, Lavonas EJ. Incidence of immediate hypersensitivity reaction and serum sickness following administration of crotalidae polyvalent immune fab antivenom: A meta-analysis. Acad Emerg Med. 2012;19:121-131. 3. Ruha AM, Kleinschmidt KC, Greene S, et al. The epidemiology, clinical course, and management of snakebites in the North American Snakebite Registry. J Med Toxicol. 2017;13(4):309-320. 4. Lavonas EJ, Kokko J, Schaeffer TH, Mlynarchek SL, Bogdan GM, Dart RC. Short-term outcomes after Fab antivenom therapy for severe crotaline snakebite. Ann Emerg Med. 2011;57(2):128-137.e3.