What is CroFab?
CroFab (Crotalidae Polyvalent Immune Fab, ovine) is a sheep-derived antivenom specifically designed to treat envenomations from North American pit vipers, including rattlesnakes, copperheads, and cottonmouths. 1
Composition and Mechanism
CroFab is a purified, lyophilized preparation of ovine Fab (monovalent) immunoglobulin fragments derived from sheep immunized with four specific North American snake venoms 1:
- Crotalus atrox (Western Diamondback rattlesnake)
- Crotalus adamanteus (Eastern Diamondback rattlesnake)
- Crotalus scutulatus (Mojave rattlesnake)
- Agkistrodon piscivorus (Cottonmouth/Water Moccasin)
The antivenom works by binding and neutralizing venom toxins, facilitating their redistribution away from target tissues and elimination from the body 1. Each vial contains up to 1 gram of total protein and is reconstituted with 18 mL of 0.9% sodium chloride for intravenous administration 1.
Clinical Indications
CroFab is indicated for both adult and pediatric patients with North American crotalid (pit viper) envenomation. 1 The general indication for administration is the presence of progressive venom injury, defined as worsening local injury (swelling, ecchymosis), clinically important coagulation abnormalities, or systemic effects like hypotension or altered mental status 2.
Dosing and Administration
Initial Treatment
The recommended initial dose is 12 vials for most pit viper envenomations, though 10 vials is typically sufficient for initial treatment 3. Expert consensus guidelines recommend hospitals stock 12-18 vials to adequately treat a 100-kg patient 4.
Reconstitution Technique
For fastest reconstitution, fill vials completely with 25 mL of sterile water and mix by continuous hand rolling and inverting rather than the manufacturer's recommended 10 mL 5. This technique reduces median dissolution time to 1.1 minutes compared to 26-33 minutes with other methods 5.
Pediatric Considerations
Dosing does not require adjustment for age or weight—pediatric patients receive the same initial dose as adults 1. In a post-marketing study, 89% of pediatric patients achieved initial control of envenomation, comparable to the 80% rate in adults 1.
Advantages Over Older Antivenoms
CroFab is preferred over the older Antivenin (Crotalidae) polyvalent (Wyeth product) due to its improved safety profile 4. The Fab fragment formulation produces fewer acute and delayed allergic reactions, including lower rates of serum sickness 2. Additionally, the older Wyeth antivenom has been discontinued by the manufacturer 4.
Important Clinical Considerations
Pharmacokinetics and Recurrence
The elimination half-life of CroFab ranges from 12-23 hours 1. Because Fab molecules have a shorter half-life than IgG molecules, recurrence of venom effects can occur if additional doses are not administered 2. Recurrent swelling occurred in 19% of copperhead bite cases in one study 6.
Safety Profile
In clinical trials, no patient developed life-threatening hypersensitivity reactions, required intubation, or died as a result of CroFab administration 1. Delayed hypersensitivity reactions occurred in approximately 10% of cases, most commonly presenting as mild rash (9 patients) and fever (3 patients), easily treated with antihistamines and steroids 1.
Species-Specific Efficacy Considerations
For copperhead (Agkistrodon contortrix) bites specifically, the benefit of CroFab beyond pain control remains unclear 7, 8. A retrospective study of 32 Agkistrodon bites found no tissue loss or need for surgical intervention in either treated or untreated patients 7. Another study found CroFab use associated with increased length of stay without difference in complications 8. However, when CroFab is used for copperhead bites, 88% of patients achieved rapid cessation of local tissue injury progression 6.
Hospital Preparedness
Hospitals in areas endemic for venomous snakes should perform a hazard vulnerability assessment to determine appropriate antivenom stocking levels 4, 3. This assessment should consider geographic location, endemic species, history of exotic bites, and the possibility of simultaneous bite victims 4.