Pharmacologic Management of Crotalid Envenomation

Around 9,000 Americans are treated for snake bites and 5 die each year. Most are bitten by members of the Crotalinae subfamily (a.k.a.

crotalids) of the pit viper family which includes copperheads, water moccasins, and rattlesnakes.

Crotalid envenomation’s can cause broad range of adverse effects, including local tissue, hematologic, and/or systemic effects

including shock and life-threatening bleeding.

Use symptom progression such as swelling beyond 1 major joint or hematologic effects (decreased fibrinogen, thrombocytopenia, or

increased PT) as an indicator for initial or additional doses of antivenom. Identification of the snake can be helpful but should not

determine decision to initiate or continue therapy in place of symptom progression.

Patients can develop delayed or recurrent hematologic symptoms up to a week after treatment cessation, especially following a severe

envenomation.

Crotalidae Polyvalent Immune Fab (Ovine)

(Crofab®)

Crotalidae Immune F(ab’)2 (Equine)

(Anavip®)

Mechanism of

Action

Fab fragment of IgG antibody isolated from sheep

serum; antibody binds to venom and removes it from

tissue

F(ab’)2 fragment of IgG antibody isolated from horse serum;

antibody binds to venom and removes it from tissue

Dose

Initial Dose

o

Progressing tissue/hematologic effects: 4 – 6

vials

o

Systemic effects including shock: 8 – 12 vials



May repeat every hour as

needed until initial control of

local, hematological, and

systemic symptoms is achieved

Maintenance: 2 vials q6h x 3 after control is

achieve

Initial dose: 10 vials

o

May repeat every hour as needed until initial

control of local, hematological, and systemic

symptoms is achieved

Maintenance: 4 vials as needed; may administer for any

re-emerging symptoms

Administration

Inject >=18 mL NS (or SWFI) into each vial; more

volume will speed up dissolution

Gently swirl or roll vials in hand or combine all vials

Author, year Design/ sample size

Intervention & Comparison

Outcome

Dart RC,

1997

Prospective, multicenter trial

(n = 11)

Patients received 4 vials of Crofab® for

initial control of symptoms following

minimal or moderate crotalid

envenomation

Ten of 11 patients were deemed to

have a clinical response and

reduction in snakebite severity score;

one patient required 4 addition vials

Dart RC,

2001

Multicenter, randomized,

prospective, open-label trial

(n = 31)

Initial 6 vials of Crofab® patients were

randomized to receive either 2 vials

PRN vs 2 vials Q6h x 18 hours

No statistical difference between

groups in snakebite severity score;

Overall severity was reduced from

Boyer LV,

2013

Phase 2, RCT for rattlesnake

bites in Tuscon, AZ

(n = 12)

Crofab® vs Anavip® for reduction in

serum venom levels at various pre-

defined times following crotalid

envenomation

Venom levels were insignificantly

lower following initial control in the

Crofab® group, but significantly lower

following maintenance and during

follow-up in the Anavip® group (p =

Crofab® and Anavip® seem to be comparable for initial symptom control, although due to the longer half-life,

Anavip® may have a larger role in prevention of late-onset or recurrent coagulopathy.

Each health-system will likely need to make a formulary decision on which agent to use. This decision should

be based on which snake species are endemic to that region, preparation time, agent costs, and the

prevalence of recurring coagulopathy in their patient population.

Overview of Evidence

Author, year Design/ sample size

Intervention & Comparison

Outcome

Dart RC,

1997

Prospective, multicenter trial

(n = 11)

Patients received 4 vials of Crofab® for

initial control of symptoms following

minimal or moderate crotalid

envenomation

Ten of 11 patients were deemed to

Lavonas et al. BMC Emerg Med. 2011;11:2.

Cocchio C, et alAm J Health Syst Pharm. 2020;77(3):175-187.

Crotalidae Polyvalent Immune FAB (Ovine). Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available

at: http://online.lexi.com. Accessed April 28, 2020.

Crofab® [package insert]. West Conshohocken, PA: BTG International Inc; 2000.

Crotalidae Immune F(ab’)2 (Equine). Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at:

http://online.lexi.com. Accessed April 28, 2020.

Anavip® [package insert]. Franklin, TN: Instituto Bioclon, S.A. de C.V.; 2015.

Dart RC, et al. Ann Emerg Med. 1997;30(1):33-9.

Dart RC, et al. Arch Intern Med. 2001;161(16):2030-6.

Boyer LV, et al. Toxicon. 2013;74:101-8.

Control of Venom-Induced Tissue Injury in Copperhead Snakebite Patients. Annals of Emergency Medicine 76(4) Supp:S29Dec;26(4):472-