Management of venomous snakebite

2016 Georgia Society of
Health-System Pharmacists
Summer Meeting
Management of Venomous Snakebite
Matthew W. McAllister, Pharm.D., BCCCP
July 15, 2016
Disclosure Statement
Georgia Society of Health‐System Pharmacists  I have nothing to disclose concerning possible financial or personal relationships with commercial entities (or their competitors that may be referenced in this presentation)
Objectives
Georgia Society of Health‐System Pharmacists  Identify characteristics of venomous snakes indigenous to Georgia
 Be able to assess a patient presenting with snakebite and determine need for antivenom
 Understand strategies for the prevention and management of delayed coagulopathy
Case 1
28 yo male presents several hours after being bitten by an eastern diamondback rattlesnake (Crotalus adamanteus) on the left hand
Complains of pain to left hand/arm with moderate swelling, ecchymosis noted to left side
NKDA, vital signs stable
www.wmicentral.com
Case 2
46 yo male presents shortly after being bitten by what he claims to be an eastern coral snake (Micrurus fulvius)
Abrasion noted to right thumb, though no other complaints
www.herpetofauna.co.uk
NKDA, vital signs stable
Epidemiology
120 species of snakes native to North America
• 30 venomous species
• Crotalinae (“pit vipers”): rattlesnakes, copperheads, water moccasins
• Elapidae: coral snakes
6000‐8000 venomous snakebites per year in the US
• Majority are pit vipers
• 55% rattlesnakes
• 5% coral snakes
~5‐15 fatalities per year
www.teerhardy.com
Goldfranks Toxicologic Emergencies, 9e
Snake Bites
Most bites occur in spring and summer
• Peak July/Aug
• Most commonly 14:00‐18:00
Majority occur to extremities
• Pit viper striking range ~ ½ its length
Children, intoxicated individuals, males, snakes handlers, and collectors are frequent victims
Goldfranks Toxicologic Emergencies, 9e
www.artofmanliness.com
IDENTIFICATION
Disclaimer
Georgia Society of Health‐System Pharmacists  I am not, nor do I pretend to be, a herpetologist. The information provided in regards to identification of venomous snakes is for informational purposes only and is not to be a substitute for common sense. The best way to avoid being bitten by a venomous snake is to treat all snakes as if they were venomous and keep a safe distance.  These identifying characteristics are also only applicable to venomous snakes NATIVE TO NORTH AMERICA
– These are NOT APPLICABLE for non‐native venomous snakes (i.e. exotics)which may be kept as pets
– These are NOT APPLICABLE for snakes from other parts of the world (i.e. Africa, Asia, Australia, etc)
Identification – Pit Vipers
Pit Vipers in the US
• Triangular‐shaped head
• Vertically elliptical pupils
• Easily identifiable fangs
• Pit‐like depressions behind the nostrils
• Single row caudal scales
• Rattlesnakes MAY have a rattle
• Keeled dorsal scales
Costello MW et al. Emergency Medicine Practice 2006;8(9):1‐28 Cardwell MD. Wilderness & Environmental Medicine 2011;22:304‐8
www.herpnet.net
Identification – Pit Vipers
www.virginiaherpetologicalsociety.com
Costello MW et al. Emergency Medicine Practice 2006;8(9):1‐28 Cardwell MD. Wilderness & Environmental Medicine 2011;22:304‐8
Identification – Elapids
Absence of classic “venomous” characteristics
www.reptilefacts.tumblr.com
Costello MW et al. Emergency Medicine Practice 2006;8(9):1‐28 Cardwell MD. Wilderness & Environmental Medicine 2011;22:304‐8
• Non‐triangular shaped head
• Absence of pits
• Round pupils vs elliptical
• Fixed hollow teeth vs fangs
Identification - Elapids
Eastern Coral Snake
(M fulvius)
Scarlet Kingsnake
(L triangulum)
“Red on black, venom lack. Red on yellow, kill a fellow”
Red, yellow, and black bands completely encircle the body, including across the belly
Costello MW et al. Emergency Medicine Practice 2006;8(9):1‐28 Cardwell MD. Wilderness & Environmental Medicine 2011;22:304‐8
Identification - Elapids
Eastern Coral Snake
(M fulvius)
Scarlet Kingsnake
(L triangulum)
“Red on black, venom lack. Red on yellow, kill a fellow”
Red, yellow, and black bands completely encircle the body, including across the belly
Costello MW et al. Emergency Medicine Practice 2006;8(9):1‐28 Cardwell MD. Wilderness & Environmental Medicine 2011;22:304‐8
VENOMOUS SNAKES OF
GEORGIA
Venomous Snakes of GA
Canebrake (Timber) Rattlesnake (C horridus)
www.srelherp.uga.edu
Venomous Snakes of GA
Eastern Diamondback Rattlesnake (C adamanteus)
www.srelherp.uga.edu
Venomous Snakes of GA
Pigmy Rattlesnake (S miliarius)
www.srelherp.uga.edu; www.pethobbyist.com
Venomous Snakes of GA
Copperhead
(A controtrix)
www.srelherp.uga.edu; www.thies‐times.com
Venomous Snakes of GA
Water Moccasin (Cottonmouth)
(A piscivorus)
www.srelherp.uga.edu
Venomous Snakes of GA
Eastern Coral Snake
(M fulvius)
www.srelherp.uga.edu
PATHOPHYSIOLOGY
Venom
•
•
Venom used for hunting and defense
Amount of venom released dependent on many factors: size, age, time since last meal, time of year
– Up to 20% pit viper bites “dry bites”
– Up to 50% coral snake bites “dry bites”
•
Pit viper venom acts as anticoagulant, inhibits platelets, causes local tissue damage
– Begins the digestive process
•
Costello MW et al. Emergency Medicine Practice 2006;8(9):1‐28 Coral snake venom contains neurotoxins with curare‐like effects
Clinical Manifestations:
Pit Vipers
Local reactions
• Significant soft tissue swelling
• Edema may progress to involve an entire extremity within hours
• Local myonecrosis ‐>> rhabdomyolysis
Systemic signs
• Anaphylaxis/anaphylactoid reactions to venom
• Confusion, vomiting, diarrhea, diaphoresis, tachycardia, metallic taste, blurred vision
• Myokymia
• Neurotoxicity?!?!
• Mojave Toxin ‐>> canebrake/timber
Goldfranks Toxicologic Emergencies, 9e Costello MW et al. Emergency Medicine Practice 2006;8(9):1‐28 Roykta dr et al. BMC Genomics 2013;14:1‐21
Clinical Manifestations:
Pit Vipers
Hematologic
www.emedicinehealth.com
Goldfranks Toxicologic Emergencies, 9e Costello MW et al. Emergency Medicine Practice 2006;8(9):1‐28 Ali AJ et al. Ann Emerg Med 2015;65:404‐9
• Significant rattlesnake envenomation may produce rather dramatic hematologic abnormalities
• May present with little other local or systemic effects
• Hematologic effects less common with copperheads and water moccasins
• Clinically insignificant with copperheads
Clinical Manifestations:
Coral Snakes
Georgia Society of Health‐System Pharmacists Lack of local symptoms but potentially serious systemic symptoms
Effects delayed for several hours after bite followed by precipitous deterioration
Slurred speech, paresthesia, ptosis, diplopia, dysphagia, stridor, muscle weakness, fasciculation, and respiratory paralysis
May develop total body paralysis that may take weeks to months to resolve
• Major immediate cause of death – respiratory arrest
MANAGEMENT
Field Management
Incision and suction NOT recommended
• Causes more harm than good
Snakebite kits suck
• <2% venom removed by Sawyer Extractor
• Can cause more localized issues/necrosis
Immobilization of the extremity
• DO NOT USE TOURNIQUET
• Pressure Immobilization potentially useful for coral snake bite
Timely transport to medical facility
• “The best first aid is a cellphone and a helicopter”
www.sawyer.com
Costello mw et al. Emergency Medicine Practice 2006;8(9):1‐28 Bush sp. Ann Emerg Med 2004;43:187‐8 Alberts MB et al. Ann Emerg Med 2004;43:181‐6
ED Management
•
Assess the patient
– ABCs
– Mark the leading edge of swelling and tenderness q15‐30’
•
•
Immobilize the extremity, keep at the level of the heart
Treat pain
– Opioids preferred
•
Baseline labs
– PT/INR, PTT, fibrinogen, CBC
www.summerlinhospital.com
•
•
•
Update tetanus – no ABX
Assess for signs of envenomation
Call Poison Control
– 1‐800‐222‐1222
Lavonas EJ et al. BMC Emergency Medicine 2011;11:1‐15
MANAGEMENT – PIT VIPERS
Assessing The Patient:
Pit Vipers
Wound Measurement
• Pit viper venom typically causes significant swelling
• Mark w/ time the leading edge of swelling q 15‐30 min initially
• Measure circumferences, document time and measurement
Lavonas EJ et al. BMC Emergency Medicine 2011;11:1‐15
Wound measurement in snakebites. Courtesy of Carolinas Poison Center
Assessing The Patient:
Pit Vipers
Gold BS et al. NEJM 2002;347:347‐57
Georgia Society of Health‐System Pharmacists Georgia Society of Health‐System Pharmacists Minimal – 0‐3; Moderate – 4‐7; Severe – 8‐20
Dart RC et al. Ann Emerg Med 1996;27:321‐6
Case 1
28 yo male presents several hours after being bitten by an eastern diamondback rattlesnake (C adamanteus) on the left hand
Complains of pain to left hand/arm with moderate swelling, ecchymosis noted to left side, nauseous
NKDA, vital signs stable
Labs are back: INR 6.3, PTT 82, PLT 85K, fibrinogen 93 mcg/mL
www.wmicentral.com
Case 1
28 yo male presents several hours after being bitten by an eastern diamondback rattlesnake (C adamanteus) on the left hand
Complains of pain to left hand/arm with moderate swelling, ecchymosis noted to left side, nauseous
NKDA, vital signs stable
Labs are back: INR 6.3, PTT 82, PLT 85K, fibrinogen 93 mcg/mL
www.wmicentral.com
ANTIVENOM!!
Antivenom: Pit Vipers
• 1st line therapy for moderate‐severe envenomation
• Can reverse coagulopathy and thrombocytopenia and halt progression of swelling if given in a timely manner
• Ovine immune Fab
–
–
–
–
Western diamondback
Eastern diamondback
Mojave
Water moccasin
www..savagelabs.com
Fab Technology
•
•
IgG antibodies separated from sheep serum
Cleaved with papain ‐> Fab
–
•
•
•
•
Dart RC et al. Arch Intern Med 2001:161:2030‐6 CROFAB® [package insert]
Fab complexes with venom components ‐> inactivated ‐> cleared from system
Less reactions then previous Wyeth antivenin
–
–
www..CroFab.com
Immunogenic Fc fragment discarded
Equine
IgG
Caution with papaya allergy (papain)
Caution with sheep/lanolin/wool allergy (ovine)
Dosing and Administration:
CroFab®
•
4‐6 vials initial
•
– My practice: 4 vials moderate (swelling), 6 vials severe (hematologic abnormalities)
– Total dose diluted in 250mL NS over 60 min
– If not achieved – repeat initial bolus
– “After initial control has been established, additional 2‐vial doses every 6 hours for up to 18 hours (3 doses) should be administered.”
• 25‐50ml/hr x 10 min, then increase to 250ml/hr
•
After infusion, patient needs to be monitored for at least an hour to determine need for further antivenom
– Continue to monitor swelling, repeat labs
Lavonas EJ et al. BMC Emergency Medicine 2011;11:1‐15 CROFAB® [package insert]
If symptoms improving / not worse 1 hr after end of infusion “Control” has been achieved
•
•
Dose is same for pediatrics and adults
Pregnancy category C ‐> give it if you have to
– Snake venom can cause spontaneous abortions
Reconstituting CroFab®
www.crofab.com
Gerring D et al. Toxicon 2013;69:42‐9
Georgia Society of Health‐System Pharmacists Maintenance Dosing??
Georgia Society of Health‐System Pharmacists Recurrence of symptoms is common
• T1/2 of antivenom may be shorter than that of venom
• Venom may “depot” at bite site, release over time
50% of patients experienced recurrence of symptoms with “prn” dosing
• No recurrence seen with scheduled maintenance dose (2 vials, q6h, x3 doses)
CoroFab® labeling recommends use of scheduled maintenance dose
• “After initial control is established, additional 2‐vial doses every 6 hours for 18 hours (3 doses) should be administered”
Management of Recurrence
Georgia Society of Health‐System Pharmacists Delayed/Late effects (even beyond 48h) are common and difficult to manage
• Venom induced coagulopathy can recur in days to weeks after antivenom use in 1/3‐
1/2 of pts
Additional 2‐vial doses can be administered beyond 18h as deemed necessary by the treating physician
• Should be done in conjunction with PCC oversight
Case series points to possibility of continuous infusion Fab AV to control late hematologic abnormalities
• Benefit seen in very severe cases
• Could be more cost‐efficient in managing these cases (days/weeks of antivenom)
• 2 vials/24h starting dose, titrate to effect (avg 3‐4 vial/24h)
Bush SP et al. Toxicon 2013;69:29‐37 Bush SP et al. Clin Tox 2015;53:37‐45
F(ab’)2 Technology
www.rockland‐inc.com
Bush SP et al. Clin Tox 2015;53:37‐45
Georgia Society of Health‐System Pharmacists Fab vs F(ab’)2
Georgia Society of Health‐System Pharmacists 121 pts in US randomized to Fab/Fab, F(ab’)2/F(ab’)2, or F(ab’)2/placebo
• Fab/Fab: 5 vials initial, then 2 vials q6h x3
• F(ab’)2/F(ab’)2: 10 vials initial, then 4 vials q6h x3
• F(ab’)2/placebo: 10 vials initial, then placebo
Late coagulopathy:
• 29.7% Fab/Fab
• 10.3% F(ab’)2/F(ab’)2
• 5.3% F(ab’)2
F(ab’)2 10 vials IV X1 superior in preventing late coagulopathy
• NNT = 4
Mean doses of vials used same between Fab/Fab and F(ab’)2/placebo
• ~16 vials
Bush SP et al. Clin Tox 2015;53:37‐45
Crotalidae Immune F(ab’)2
(Equine) Expected 2018
•
Anavip® FDA Approved May 2015
– 10 vials IV x1 diluted in 250ml NS over 60 min
– Initial dose start at 25‐50ml/hr x10 min then increase to 250ml/hr if tolerated
– Repeat as needed q1h to achieve control
– After control achieved, no maintenance dose needed
– Can give 4 vials prn reemerging symptoms
•
Patent dispute w/ BTG (Fab‐AV)
– Settled out of court, expected US launch 2018
Anavip® [package insert] www.bloomberg.com
MANAGEMENT – CORAL
SNAKES
Assessing the Patient:
Coral Snakes
• Envenomations caused by eastern coral snakes are rare, though serious
• Prior to development of NACSAV in 1967 mortality rate 10% for coral snake bites
– Since 1967 one fatality (didn’t seek care)
• In 2003 Wyeth dc’d production of NACSAV
– Original lots “expired” in 2008
• No other FDA approved options currently available
Norris RL et al. Toxicon 2009;53:693‐7 Wood A et al. Clin Tox 2013;51:783‐8
www.poisoncentertampa.com
Don’t Throw That Away!!!
www.fda.gov
Georgia Society of Health‐System Pharmacists Assessing The Patient:
Coral Snakes
Georgia Society of Health‐System Pharmacists Because of dwindling supply of NACSAV, management has changed
• Prior to 2003: administer NACSAV to ALL patients with presumed eastern/texas coral snake bite regardless of symptoms
• Since 2003 some experts recommend withholding AV in asymptomatic patients and CLOSELY monitor for 24h
• Administer NACSAV at the earliest sign of neurotoxicity (i.e. paresthesia, ptosis)
• Not shown to worsen outcomes
• Only 5.7% of asymptomatic pts ended up receiving AV
• ~50% of coral snake bites are “dry bites”
Norris RL et al. Toxicon 2009;53:693‐7 Wood A et al. Clin Tox 2013;51:783‐8
Case 2
46 yo male presents shortly after being bitten by what he claims to be an eastern coral snake (Micrurus fulvius)
Abrasion noted to right thumb, though no other complaints
www.herpetofauna.co.uk
NKDA, vital signs stable
Case 2
46 yo male presents shortly after being bitten by what he claims to be an eastern coral snake (Micrurus fulvius)
Abrasion noted to right thumb, though no other complaints
www.herpetofauna.co.uk
NKDA, vital signs stable
Call PCC, Monitor CLOSELY!!!
Case 2
Follow Up
• 3 hr later, pt begins reporting tingling in fingers
• On exam noted ptosis in right eye
• No other complaints, VSS
www.ohiolionseyeresearch.com
Case 2
Follow Up
• 3 hr later, pt begins reporting tingling in fingers
• On exam noted ptosis in right eye
• No other complaints, VSS
www.ohiolionseyeresearch.com
ANTIVENOM!!
North American Coral Snake
Antivenin
Georgia Society of Health‐System Pharmacists  Sensitivity testing required prior to administration (IgG)
– 0.02‐0.03 ml intradermal 1:10 dilution
– Urticarial wheal within 5‐30 min
 3‐5 vials (may require up to 10+ vials)
– Usually diluted in 250ml NS, given over at least 30 min
– Dose typically not repeated
 ADR
– Immediate hypersensitivity reactions (IgG, horse serum)
– Delayed serum sickness
 5‐24 days after administration
Wood A et al. Clin Tox 2013;51:783‐8 Wyeth® Antivenin (Micrurus fulvius) (Equine Origin) North American Coral Snake Antivenin [package insert]
Management – Coral Snake
Georgia Society of Health‐System Pharmacists Until more AV becomes available, judiciously use NACSAV • Continue symptomatic and supportive care
• May require intubation
• Use of AChE inhibitors??
• Some evidence from South America demonstrating efficacy – No literature from US
• Neostigmine 1.5‐2mg IM or edrophonium 10mg IV
• Use of foreign antivenoms??
• Not FDA approved
Goldfranks Toxicologic Emergencies, 9e Bucharetchi F et al. Rev Inst Med Trop S Paulo 2006;43141‐5
Foreign Antivenoms:
Coralmyn®
• Eastern/texas coral snakes very similar to those in Mexico/South America
• Coralmyn® is also F(ab’)2
• Coralmyn® was as effective in neutralizing eastern coral snake venom as NACSAV
– More effective for texas coral snake venom than NACSAV
• Less risk of reactions F(ab’)2
vs IgG NACSAV
Sanchez EE et al. Toxicon 2008;51:297‐303
www.bioclon.com
Coralmyn® Clinical Trial
www.clinicaltrials.gov
Georgia Society of Health‐System Pharmacists Summary
Georgia Society of Health‐System Pharmacists  Bites from venomous snakes are a fairly common occurrence in the US, especially in the Southeast
 Two major classes of venomous snakes are Crotalids/”Pit Vipers” (rattlesnakes, copperhead, water moccasin) and Elapids (coral snakes)
 Antivenom (CroFab®) is indicated for moderate to severe envenomation by Cortaid sp
– Repeat doses may be required to manage recurrent symptoms
– Expect F(ab’)2 antivenom Anavip® to be available ~2018
 Should have less recurrence
Summary
Georgia Society of Health‐System Pharmacists  Antivenom (NACSAV) is indicated for any symptoms following reported bite from eastern/texas coral snake
– Until more antivenom is available, symptomatic and supportive care may be all we can do
– Use of AChE inhibitor may offer some benefit, though data is limited
– Foreign F(ab’)2 Coral Snake Antivenom potentially useful, but not FDA approved/available outside clinical trials….yet
 Poison Control should be consulted for any venomous snake bite to assist with management
– Can be helpful in obtaining antivenom, help with unique cases
www.npic.orst.edu
Question #1
Georgia Society of Health‐System Pharmacists  Which of these is a potential contraindication to the use of CroFab®
A.
B.
C.
D.
Pregnant
Age < 18 years old
Allergy to lanolin
Received CroFab® in the past
Question #2
Georgia Society of Health‐System Pharmacists  Which of these is not an identifying characteristic for pit vipers
A. Presence of heat sensing pit between and below the nose and the eye
B. Triangular/spade shaped head
C. Vertically elliptical pupils
D. Presence of both keeled dorsal scales and undivided caudal scales
E. Presence of a rattle
Question #3
Georgia Society of Health‐System Pharmacists  Which of these is not a potential option for recurrent coagulopathy associated with pit viper envenomation
A. Continuous infusion of antivenom
B. Use of AChE inhibitors neostigmine and edrophonium
C. Administration of additional 2 vial doses as needed
D. Consult PCC (1‐800‐222‐1222)
2016 Georgia Society of
Health-System Pharmacists
Summer Meeting
Management of Venomous Snakebite
Matthew W. McAllister, Pharm.D., BCCCP
July 15, 2016
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
Georgia Society of Health‐System Pharmacists Ruha A, Riley BD, Pizon AF. Ruha A, Riley B.D., Pizon A.F. Chapter 121. Snakes and Other Reptiles. In: Nelson LS, Lewin NA, Howland M, Hoffman RS, Goldfrank LR, Flomenbaum NE. Nelson L.S., Lewin N.A., Howland M, Hoffman R.S., Goldfrank L.R., Flomenbaum N.E. eds. Goldfrank's Toxicologic Emergencies, 9e . New York: McGraw‐Hill; 2011
Costello MW, Heins A, Zirkin DA. Diagnosis and Management of North American Snake and Scorpion Envenomations. Emergency Medicine Practice 2006;8(9):1‐28
Cardwell MD. Recognizing Dangerous Snakes in the United States and Canada: A Novel 3‐step Identification Method. Wilderness & Environmental Medicine 2011;22:304‐8
Rokyta DR, Wray KP, Margres MJ. The genesis of an exceptionally lethal venom in the timber rattlesnake (Crotalus horridus) revealed through comparative venom‐gland transcriptomics. BMC Genomics 2013;394(14):1‐21
Ali AJ, Horwitz DA, Mullins ME. Lack of Coagulopathy After Copperhead Snakebites. Ann Emerg Med 2015;65:404‐9
Norris RL, Pfalzgraf RR, Laing G. Death following coral snake bite in the United States – First documented case (with ELISA confirmation of envenomation) in over 40 years. Toxicon 2009;53:693‐7
Bush SP. Snakebite Suction Devices Don’t Remove Venom: They Just Suck. Ann Emerg Med 2004;43:187‐8
Alberts MB, Shalit M, LoGalbo F. Suction for Venomous Snakebite: A Study of “Mock Venom” Extraction in a Human Model. Ann Emerg Med 2004;43:181‐6
Lavonas EJ, Ruha AM, Banner W, et al. Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence‐informed consensus workshop. BMC Emergency Medicine 2011;11(2): 1‐15
Gold BS, Dart RC, Barish RA. Bites of Venomous Snakes. NEJM 2002;347(5): 347‐56
Dart RC, Hurlbut KM, Garcia R, Boren J. Validation of a Severity Score for the Assessment of Crotalid Snakebite. Ann Emerg Med. 1996;27:321‐6
CroFab® [package insert]. West Conshohocken, PA. BTG International Inc. 2012
Dart RC, Seifert SA, Boyer LV, et al. A Randomized Multicenter Trial of Crotalinae Polyvalent Immune Fab (Ovine) Antivenom for the Treatment for Crotaline Snakebite in the United States. Arch Intern Med 2001;161:2030‐6
References
Georgia Society of Health‐System Pharmacists 14. Gerring D, King TR, Branton R. Validating a faster method for reconstitution of Crotalidae Polyvalent Immune Fab (Ovine). Toxicon 2013;69:42‐9
15. Bush SP, Seifert SA, Oakes J, et al. Continuous IV Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) for selected North American Rattlesnake bite patients. Toxicon 2013;69:29‐37
16. Bush SP, Ruha AM, Seifert SA, et al. Comparison of F(ab’)2 versus Fab antivenom for pit viper envenomation: A prospective, blinded, multicenter, randomized clinical trial. Clinical Toxicology 2015;53:37‐45
17. ANAVIP® [package insert]. Mexico D.F., Mexico. Instituto Bioclon S.A. de C.V. 2015
18. Edney A, Decker S. Price Drop for $57,000 Snakebite Drug May Arrive in 2018. BloombergBuisness website. http://www.bloomberg.com/news/articles/2014‐10‐28/price‐drop‐for‐57‐000‐snakebite‐drug‐may‐arrive‐in‐2018. October 28, 2014. Accessed July 26, 2015
19. Wood A, Schauben J, Thundiyil J et al. Review of Eastern coral snake (Micrurus fulvius fulvius) exposures managed by the Florida Poison Information Center Network: 1998‐2010. Clinical Toxicology 2013;51:783‐8
20. Expiration Date Extension for North American Coral Snake Antivenin (Micrurus fulvius) (Equine Origin) Lot 4030024 Through April 30, 2016. U.S. Food and Drug Administration. http://www.fda.gov/biologicsbloodvaccines/safetyavailability/ucm445083.htm. Updated April 7, 2015. Accessed June 26, 2016
21. Wyeth® Antivenin (Micrurus fulvius) (Equine Origin) North American Coral Snake Antivenin [package insert]. Marietta, PA. Wyeth Laboratories Inc. 2001
22. Bucharetchi F, Hyslop S, Vieira RJ, et al. Bites by Coral Snakes (Micrurus spp.) in Campinas , State of Sao Paulo, Southeastern Brazil. Rev. Inst. Med. Trop. S. Paulo 48(3):141‐5
23. Sanchez EE, Lopez‐Johnston JC, Rodriguez‐Acosta A, et al. Neutralization of two North American coral snake venoms with United States and Mexican antivenoms. Toxicon 2008;51:297‐303
24. Emergency Treatment of Coral Snake Envenomation with Antivenom. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01337245?term=coral+snake&rank=1. Updated March 7, 2016. Accessed June 25, 2016