CroFab

Generic Name: Crotalidae Polyvalent Immune Fab (Ovine)
Class: Serums
ATC Class: J06AA03
VA Class: IM300

Introduction

Antivenom; ovine IgG Fab fragments capable of binding and neutralizing venom toxins of Crotalinae (pit vipers, crotalines; formerly known as Crotalidae or crotalids) native to North America.1

Uses for CroFab

North American Crotaline Snakebite Envenomation

Treatment of envenomation following snakebites involving North American Crotalinae (pit vipers, crotalines; formerly known as Crotalidae or crotalids);1 4 8 11 18 42 designated an orphan drug by FDA for this use.14

Slideshow: Fact or Fiction? The Top 15 Osteoarthritis Myths

Crotalinae subfamily of venomous snakes includes rattlesnakes, copperheads, and cottonmouth or water moccasins.1

May be effective in management of minimal, moderate, or severe envenomation involving Crotalus atrox (Western diamondback rattlesnake), C. adamanteus (Eastern diamondback rattlesnake), C. scutulatus (Mojave rattlesnake), Agkistrodon piscivorus (cottonmouth or water moccasin), and other North American crotalines.1 4 8 42 49 53

Consultation with experts experienced in treating snakebites (e.g., regional certified poison control center) recommended to guide treatment decisions regarding individual patients.1 11 53

CroFab Dosage and Administration

General

  • Initiate treatment as soon as possible after crotaline snakebite in patients with signs of progressive envenomation (e.g., worsening local injury, coagulation abnormality, other systemic signs of envenomation).1 53

  • Early use (within 6 hours of snakebite) advised to prevent clinical deterioration and systemic coagulation abnormalities.1

  • Use general supportive measures to manage manifestations such as pain, swelling, hypotension, and wound infection.1 4

Administration

IV Administration

Administer by IV infusion.1

Reconstitution and Dilution

Reconstitute and dilute number of vials required for the dose (see Dosage under Dosage and Administration).1

Reconstitute each vial of lyophilized powder with 10 mL of sterile water for injection.1 Direct sterile water toward side of vial using sterile syringe and needle;17 gently swirl until completely dissolved (usually dissolves within 15–40 minutes).1 Reconstituted solution should be colorless to opalescent pale yellow.17

Dilute contents of required number of reconstituted vials in 250 mL of 0.9% sodium chloride and gently swirl to mix.1 Because of concerns regarding fluid overload, consider lower volume of dilution fluid for children weighing <10 kg.48

Use reconstituted and diluted solutions within 4 hours.1 17 (See Stability.)

Rate of Administration

Administer by IV infusion over 60 minutes.1

Start initial infusion using reduced rate of 25–50 mL/hour for first 10 minutes; observe patient closely for sensitivity or other reactions.1 17 If reduced rate well tolerated, give remaining infusion and subsequent infusions at rate of 250 mL/hour.1 17

Dosage

Dosage expressed in terms of the number of vials.1

Base initial dose (number of vials), need for additional initial doses to achieve envenomation control, and number of subsequent doses required to sustain control on individual patient response.1

Pediatric Patients

North American Crotaline Snakebite Envenomation
Initial Dosage
IV

4–6 vials.1 Monitor patient closely for up to 1 hour after completion of infusion; determine whether initial envenomation control is achieved (i.e., complete arrest of local manifestations and normalization of coagulation abnormalities and systemic manifestations).1

If initial control not achieved, give additional 4- to 6-vial doses until envenomation is controlled.1

Patients with life-threatening symptoms (e.g., shock, serious active bleeding): Consider initial dose of 8–12 vials in consultation with experts experienced in treating crotaline snakebites.53

Maintenance Dosage
IV

After initial envenomation control is achieved, give 2-vial doses every 6 hours for up to 18 hours to maintain response.1 Use of scheduled dosage regimen after initial control may provide best control of subsequent envenomation symptoms, especially coagulopathies, that may result from continued venom release from depot sites.1

Additional 2-vial doses may be given after 18-hour scheduled dosage regimen,1 but only if considered necessary based on patient’s clinical course.1 Optimum dosage schedule not established for these additional maintenance doses after 18-hour regimen.1 4

Adults

North American Crotaline Snakebite Envenomation
Initial Dosage
IV

4–6 vials.1 Monitor patient closely for up to 1 hour after completion of infusion; determine whether initial envenomation control is achieved (i.e., complete arrest of local manifestations and normalization of coagulation abnormalities and systemic manifestations).1

If initial control not achieved, give additional 4- to 6-vial doses until envenomation is controlled.1

Patients with life-threatening symptoms (e.g., shock, serious active bleeding): Consider initial dose of 8–12 vials in consultation with experts experienced in treating crotaline snakebites.53

Maintenance Dosage
IV

After initial envenomation control is achieved, give 2-vial doses every 6 hours for up to 18 hours to maintain response.1 Use of scheduled dosage regimen after initial control may provide best control of subsequent envenomation symptoms, especially coagulopathies, that may result from continued venom release from depot sites.1

Additional 2-vial doses may be given after 18-hour scheduled dosage regimen,1 but only if considered necessary based on patient’s clinical course.1 Optimum dosage schedule not established for these additional maintenance doses after 18-hour regimen.1 4

Prescribing Limits

Pediatric Patients

North American Crotaline Snakebite Envenomation
IV

Maximum dose and maximum total dosage not known; total dosage of up to 18 vials used without toxic effects.1 17

Adults

North American Crotaline Snakebite Envenomation
IV

Maximum dose and maximum total dosage not known; total dosage of up to 18 vials used without toxic effects.1 17

Special Populations

No special population dosage recommendations.1

Cautions for CroFab

Contraindications

  • Known hypersensitivity to any component or to papaya or papain, unless benefits outweigh risks and appropriate drugs and equipment are readily available for treatment of anaphylaxis.1 (See Papain Hypersensitivity under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Contains purified immunoglobulin fragments from blood of sheep immunized with snake venom.1 (See Actions.) Heterologous animal proteins can cause severe acute hypersensitivity reactions (anaphylaxis, anaphylactoid reactions), delayed hypersensitivity reactions (late serum reaction, serum sickness), or possible febrile responses to immune complexes formed by animal antibodies and neutralized venom components.1

Skin sensitivity testing not considered necessary and not recommended.1 53

Use caution if repeat course is indicated for a subsequent envenomation episode since patients may become sensitized to the antivenom.1

Anaphylaxis and Anaphylactoid Reactions

Acute allergic reactions, including anaphylaxis and anaphylactoid reactions, may occur during or shortly after IV infusion.1 17 19 43 44

Immediate hypersensitivity reactions, including hypotension, tongue swelling, chest discomfort, angioedema, bronchospasm, wheezing, tracheal edema, dyspnea, and/or lip swelling, reported in 0.1–6% of patients.1 43 44 49 53 Rarely, immediate hypersensitivity reaction appeared to be anaphylactoid reaction related to extremely rapid IV infusion rate (i.e., 640 mL/hour).19

Monitor closely for signs and symptoms of acute hypersensitivity (e.g., urticaria, pruritus, erythema, angioedema, bronchospasm with wheezing or cough, stridor, laryngeal edema, hypotension, tachycardia).1

If anaphylaxis or any severe hypersensitivity reaction occurs, immediately discontinue IV infusion and initiate appropriate therapy (e.g., epinephrine, corticosteroids, maintenance of adequate airway, oxygen, IV fluids, IV antihistamines, albuterol, maintenance of BP) as indicated.1

Delayed Hypersensitivity or Serum Reactions

Delayed hypersensitivity or serum reactions may occur.1 20

Late serum reactions (rash, pruritus, urticaria, or serum sickness consisting of severe rash and pruritus) reported in 12% (5/42) of patients in initial clinical trials;1 delayed hypersensitivity or serum sickness reported in 5–11% of patients in other studies.1 49 53

Most common signs and symptoms are rash and fever.1 Generally mild and respond to treatment with antihistamines and corticosteroids.1 53

Monitor for signs and symptoms of delayed hypersensitivity reactions or serum sickness (e.g., rash, fever, myalgia, arthralgia) for up to 2–3 weeks; initiate appropriate treatment if necessary.1 17

Papain Hypersensitivity

Traces of papain or inactivated papain residues may be present in the antivenom;1 papain is used in manufacturing process.1

Individuals allergic to papain, chymopapain, other papaya extracts, or the pineapple enzyme bromelain may be at risk of hypersensitivity reaction.1 Patients allergic to dust mites or latex may also be allergic to papain.1 (See Contraindications under Cautions.)

Human Anti-ovine Fab Antibodies

Patients may develop ovine Fab-specific antibodies after receiving the antivenom.1 4

Thimerosal Allergy

Contains residual thimerosal, a mercury-containing preservative, from manufacturing process.1 22 (See Mercury Toxicity under Cautions.)

Hypersensitivity reactions to thimerosal contained in vaccines reported rarely.21 31 33 These reactions usually manifest as local, delayed-type hypersensitivity reactions (e.g., erythema, swelling),21 23 25 but generalized reaction manifested as pruritus and an erythematous, maculopapular rash on all 4 extremities has been reported rarely.33 Even when patch or intradermal tests for thimerosal sensitivity are positive, most individuals receiving thimerosal-containing vaccines do not develop such hypersensitivity reactions.21 23

Coagulopathy

Coagulation abnormalities are common in many snakebite victims (especially those with severe envenomation) and occur because snake venom can activate or inhibit activity of various coagulation factors and interfere with blood coagulation cascade.1 6 40

Recurrent coagulopathy, characterized by hypofibrinogenemia, thrombocytopenia, and elevated prothrombin time 2–7 days or longer after successful initial envenomation control, can occur and may persist for 1–2 weeks or longer.1 4 18 40 41 42 50 53 55

Recurrent coagulation abnormalities reported in 7–32% of patients treated with Crotalidae polyvalent immune Fab (ovine).1 40 53 Reported in clinical studies only in patients who experienced coagulation abnormalities during initial hospitalization,1 4 but can initially appear at any time before, during, or after treatment.1

Clinical importance of recurrent coagulopathy and most appropriate strategies for prevention or management unknown.1 41 42 49 50 53 Optimum dosage schedule of the antivenom to prevent recurrent coagulopathy not determined.1 4 6 18 53 55 Because the antivenom may be cleared from circulation while crotaline venoms continue to be released from depot sites, repeated antivenom doses may be necessary to prevent and/or treat recurrence of venom effects.1 4 6 18 55 (See Dosage under Dosage and Administration.)

Monitor for signs and symptoms of recurrent coagulopathy for up to 1 week or longer; carefully assess need for retreatment with the antivenom and use of any type of anticoagulant or antiplatelet drug.1 17 Avoid use of any drug that may decrease platelet function or prolong PTT or PT.17

Consider other causes of persistent coagulation abnormalities, including cancer, collagen disease, CHF, diarrhea, elevated temperature, hepatic disorders, hyperthyroidism, poor nutritional state, steatorrhea, and vitamin K deficiency.1 17

Infusion Reactions

Monitor closely during IV infusion.1 Mild infusion reactions (fever, low back pain, wheezing, nausea) often are related to infusion rate and can be controlled by decreasing rate.1 (See Rate of Administration under Dosage and Administration.)

Mercury Toxicity

Contains mercury in the form of ethyl mercury from thimerosal, a mercury-containing preservative used in the manufacturing process.1 22 Residual mercury remains in final product;1 thimerosal not added as preservative to final product.22

Each vial contains ≤104.5 mcg of mercury; this amounts to ≤1.9 mg of mercury per dose (based on a maximum total dose of 18 vials).1

Only limited toxicology data available regarding ethyl mercury; neurologic and renal toxicities associated with high dose and acute exposures to methyl mercury.1 Developing fetuses and young children, especially neonates and infants <6 months of age, are at greatest risk of mercury toxicity.1 9 10 12

Although it has been suggested that thimerosal added as a preservative or used during manufacturing process of vaccines or plasma-derived products theoretically could have adverse effects in recipients, there is no conclusive evidence that low concentrations of thimerosal contained in vaccines cause harm in vaccine recipients.27 28 29 32 34 35 36 37 38 39 Efforts to eliminate or reduce thimerosal content in such products are recommended as a prudent measure to reduce mercury exposure in infants and children and part of an overall strategy to reduce mercury exposures from all sources, including food and drugs.9 10 12 27

Specific Populations

Pregnancy

Category C.1

Pregnancy does not preclude use when clearly needed.17 52

Contains mercury in the form of ethyl mercury from thimerosal;1 22 developing fetuses are at increased risk of mercury toxicity.1 9 10 12 (See Mercury Toxicity under Cautions.)

Lactation

Not known whether distributed into milk.1 Use with caution in nursing women.1

Pediatric Use

Specific studies not conducted in pediatric patients.1 Has been used in children as young as 14 months of age without unusual adverse effects.18 45 47 48

Age-related dosage adjustments not indicated since venom dose following snakebite is expected to be similar in children and adults.1 46 48 53 To avoid fluid overload, fluid volume used to dilute the antivenom may need to be adjusted in children weighing <10 kg.48 (See Reconstitution and Dilution under Dosage and Administration.)

Contains mercury in the form of ethyl mercury from thimerosal;1 22 young children, especially neonates and infants <6 months of age, are at increased risk of mercury toxicity.1 9 10 12 (See Mercury Toxicity under Cautions.) Current evidence suggests risks of untreated snake envenomation outweigh risks associated with thimerosal exposure.48

Geriatric Use

Specific studies not conducted.1

Common Adverse Effects

Urticaria,1 4 rash,1 4 pruritus,1 4 nausea,1 4 coagulation disorder,1 4 back pain.1 4

Interactions for CroFab

No formal drug interaction studies to date.1

CroFab Pharmacokinetics

Elimination

Half-life

Limited data indicate distribution half-life of approximately 2.5 hours55 and elimination half-life of approximately 12–30 hours.1 3 4 55

Stability

Storage

Parenteral

For Injection, for IV Infusion

2–8°C; do not freeze.1

Use reconstituted and diluted solutions within 4 hours.1 17 Should be refrigerated, but may be stored at room temperature if necessary.17

Actions

  • Preparation of venom-specific Fab fragments of ovine IgG that bind and neutralize venom toxins of Crotalinae (pit vipers, crotalines; formerly known as Crotalidae or crotalids) native to North America.1 This facilitates redistribution of venom toxins away from target tissues and elimination from the body.1

  • Mixture of 4 different monospecific antivenoms derived from serum of healthy sheep immunized with one of the following North American snake venoms: C. atrox (Western diamondback rattlesnake), C. adamanteus (Eastern diamondback rattlesnake), C. scutulatus (Mojave rattlesnake), or A. piscivorus (cottonmouth or water moccasin).1 Each monospecific antivenom is prepared by fractionating IgG from the ovine serum, digesting it with papain, and isolating venom-specific Fab fragments using ion exchange and affinity chromatography columns.1

  • Standardized by ability to neutralize lethal action of the 4 crotaline venoms following IV injection in mice (mouse LD50 neutralizing units).1 One neutralizing unit is determined as the amount of mixed monospecific Fab proteins necessary to neutralize one LD50 of each of the 4 venoms, where the LD50 is amount of venom that would be lethal in 50% of mice.1 Each vial contains at least 1270, 420, 5570, and 780 mouse LD50 neutralizing units of antivenom for C. atrox, C. adamanteus, C. scutulatus, and A. piscivorus, respectively.1

  • Murine lethality tests indicate that the antivenom has cross-neutralizing ability with venoms from some other clinically important North American crotalines, including venoms from C. horridus atricaudatus (Canebrake rattlesnake), A. contortrix contortrix (Southern copperhead), Sistrurus miliarius barbouri (Southeastern pygmy rattlesnake), and C. horridus horridus (Timber rattlesnake), but is less potent against venoms from C. viridis helleri (Southern Pacific rattlesnake) and C. molossus molossus (Mexican black-tailed rattlesnake).1

Advice to Patients

  • Importance of immediately contacting a clinician if any unusual bruising or bleeding (e.g., nosebleeds, excessive bleeding after brushing teeth, blood in stools or urine, excessive menstrual bleeding, petechiae, excessive bruising or persistent oozing from superficial injuries) occurs after hospital discharge.1 Advise patients that such bruising or bleeding may occur for 1 week or longer following initial treatment of envenomation.1

  • Importance of immediately contacting a clinician if any manifestations of delayed allergic reactions or serum sickness (e.g., rash, pruritus, urticaria) occur after hospital discharge.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Crotalidae Polyvalent Immune Fab (Ovine)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion

CroFab

Protherics

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 2, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Protherics Inc. Crofab (Crotalidae polyvalent immune fab [ovine]) prescribing information. Brentwood, TN; 2010 Sep.

2. Savage Laboratories. Take the bite out of Crotalid envenomation. Crofab product information. Melville, NY; 2001 Feb.

3. Anon. A new snake venom. Med Lett Drugs Ther. 2001; 43:55-6. [PubMed 11426191]

4. 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. [IDIS 469424] [PubMed 11525706]

5. Galli R. The antivenin is safe, but its future is uncertain. West J Med. 2001;175:91-2. Editorial.

6. Dart RC, McNally J. Efficacy, safety, and use of snake antivenoms in the United States. Ann Emerg Med. 2001;37:181-8.

7. Hill RE, Bogdan GM, Dart RC. Time to reconstitution: purified Fab antivenom vs. unpurified IgG antivenom. Toxicon. 2001;39:729-31.

8. Dart RC, Seifert SA, Carroll L et al. Affinity-purified, mixed monospecific crotalid antivenom ovine Fab for the treatment of crotalid venom poisoning. Ann Emerg Med. 1997;30:33-9.

9. Centers for Disease Control and Prevention. Recommendations regarding the use of vaccines that contain thimerosal as a preservative. MMWR Morb Mortal Wkly Rep. 1999; 48:996-8. [IDIS 435348] [PubMed 10577494]

10. American Academy of Pediatrics Committee on Infectious Diseases and Committee on Environmental Health. Thimerosal in vaccines: an interim report to clinicians (RE9935). Pediatrics. 1999; 104:570-4. [PubMed 10469789]

11. Gold BS, Dart RC, Barish RA. Bites of venomous snakes. N Engl J Med. 2002; 347:347-56. [IDIS 484398] [PubMed 12151473]

12. Centers for Disease Control and Prevention. Thimerosal in vaccines: a joint statement of the American Academy of Pediatrics and the Public Health Service. MMWR. 1999; 48:563-5. [IDIS 429225] [PubMed 10418806]

14. Food and Drug Administration. FDA Application: Search Orphan Drug Designations and Approvals. Rockville, MD. From FDA website. Accessed 2012 Mar 12.

17. Protherics Inc, Brentwood, TN: Personal communication

18. Ruha AM, Curry SC, Beuhler M et al. Initial postmarketing experience with Crotalidae polyvalent immune Fab for treatment of rattlesnake envenomation. Ann Emerg Med. 2002; 39:609-15. [IDIS 482433] [PubMed 12023703]

19. Holstege CP, Wu J, Baer AB. Immediate hypersensitivity reaction associated with the rapid infusion of Crotalidae polyvalent immune Fab (ovine). Ann Emerg Med. 2002; 39:677-9. [IDIS 482437] [PubMed 12023715]

20. Clark RF, McKinney PE, Chase PB et al. Immediate and delayed allergic reactions to Crotalidae polyvalent immune Fab (ovine) antivenom. Ann Emerg Med. 2002; 39:671-6. [IDIS 482436] [PubMed 12023714]

21. Aberer W. Vaccination despite thimerosal sensitivity. Contact Dermatitis. 1991; 24:6-10. [PubMed 2044374]

22. Food and Drug Administration (FDA). Mercury in plasma-derived products. From FDA website. Accessed 2012 Mar 12.

23. National Center for Immunization and Respiratory Diseases. General recommendations on immunization --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011; 60:1-64.

25. Food and Drug Administration. Thimerosal in vaccines. From FDA website. Accessed 2008 Oct 27.

27. Food and Drug Administration. Thimerosal in vaccines. Frequently asked questions (FAQ). From FDA website. Accessed 2008 Oct 27.

28. Institute of Medicine. Immunization safety review: thimerosal-containing vaccines and neurodevelopmental disorder. Washington DC; National Academy Press; 2001. From IOM website. Accessed 2003 Jul 24.

29. Thompson WW, Price C, Goodson B et al. Early thimerosal exposure and neuropsychological outcomes at 7 to 10 years. N Engl J Med. 2007; 357:1281-92. [PubMed 17898097]

30. Pichichero ME, Gentile A, Giglio N et al. Mercury levels in newborns and infants after receipt of thimerosal-containing vaccines. Pediatrics. 2008; 121:e208-14. [PubMed 18245396]

31. Zheng W, Dreskin SC. Thimerosal in influenza vaccine: an immediate hypersensitivity reaction. Ann Allergy Asthma Immunol. 2007; 99:574-5. [PubMed 18219843]

32. Madsen KM, Lauritsen MB, Pedersen CB et al. Thimerosal and the occurrence of autism: negative ecological evidence from Danish population-based data. Pediatrics. 2003; 112:604-6. [PubMed 12949291]

33. Lee-Wong M, Resnick D, Chong K. A generalized reaction to thimerosal from an influenza vaccine. Ann Allergy Asthma Immunol. 2005; 94:90-4. [PubMed 15702823]

34. Parker S, Todd J, Schwartz B et al. Thimerosal-containing vaccines and autistic spectrum disorder: a critical review of published original data. Pediatrics. 2005; 115:200. [PubMed 15630018]

35. Schechter R, Grether JK. Continuing increases in autism reported to California’s developmental services system: mercury in retrograde. Arch Gen Psychiatry. 2008; 65:19-24. [PubMed 18180424]

36. Andrews N, Miller E, Grant A et al. Thimerosal exposure in infants and developmental disorders: a retrospective cohort study in the United kingdom does not support a causal association. Pediatrics. 2004; 114:584-91. [PubMed 15342825]

37. Verstraeten T, Davis RL, DeStefano F et al. Safety of thimerosal-containing vaccines: a two-phased study of computerized health maintenance organization databases. Pediatrics. 2003; 112:1039-48. [PubMed 14595043]

38. Hviid A, Stellfeld M, Wohlfahrt J et al. Association between thimerosal-containing vaccine and autism. JAMA. 2003; 290:1763-6. [PubMed 14519711]

39. Institute of Medicine. Immunization safety review: vaccines and autism. Washington DC; National Academy Press; 2004. From IOM website. Accessed 2008 Oct 28.

40. Ruha AM, Curry SC, Albrecht C et al. Late hematologic toxicity following treatment of rattlesnake envenomation with crotalidae polyvalent immune Fab antivenom. Toxicon. 2011; 57:53-9. [PubMed 20920516]

41. Miller AD, Young MC, DeMott MC et al. Recurrent coagulopathy and thrombocytopenia in children treated with crotalidae polyvalent immune fab: a case series. Pediatr Emerg Care. 2010; 26:576-82. [PubMed 20693856]

42. Lavonas EJ, Schaeffer TH, Kokko J et al. Crotaline Fab antivenom appears to be effective in cases of severe North American pit viper envenomation: an integrative review. BMC Emerg Med. 2009; 9:13. [PubMed 19545426]

43. Cannon R, Ruha AM, Kashani J. Acute hypersensitivity reactions associated with administration of crotalidae polyvalent immune Fab antivenom. Ann Emerg Med. 2008; 51:407-11. [PubMed 18191286]

44. Schaeffer TH, Khatri V, Reifler LM et al. Incidence of Immediate Hypersensitivity Reaction and Serum Sickness Following Administration of Crotalidae Polyvalent Immune Fab Antivenom: A Meta-analysis. Acad Emerg Med. 2012; 19:121-31. [PubMed 22320362]

45. Pizon AF, Riley BD, LoVecchio F et al. Safety and efficacy of Crotalidae Polyvalent Immune Fab in pediatric crotaline envenomations. Acad Emerg Med. 2007; 14:373-6. [PubMed 17296804]

46. Behm MO, Kearns GL. Crotaline Fab antivenom for treatment of children with rattlesnake envenomation. Pediatrics. 2003; 112:1458-9; author reply 1458-9. [PubMed 14654633]

47. Richardson WH, Barry JD, Tong TC et al. Rattlesnake envenomation to the face of an infant. Pediatr Emerg Care. 2005; 21:173-6. [PubMed 15744196]

48. Offerman SR, Bush SP, Moynihan JA et al. Crotaline Fab antivenom for the treatment of children with rattlesnake envenomation. Pediatrics. 2002; 110:968-71. [PubMed 12415038]

49. Lavonas EJ, Kokko J, Schaeffer TH et al. Short-term outcomes after Fab antivenom therapy for severe crotaline snakebite. Ann Emerg Med. 2011; 57:128-137.e3. [PubMed 20952098]

50. Camilleri C, Offerman S, Gosselin R et al. Conservative management of delayed, multicomponent coagulopathy following rattlesnake envenomation. Clin Toxicol (Phila). 2005; 43:201-6. [PubMed 15902796]

51. Johnson PN, McGoodwin L, Banner W. Utilisation of Crotalidae polyvalent immune fab (ovine) for Viperidae envenomations in children. Emerg Med J. 2008; 25:793-8. [PubMed 19033492]

52. LaMonica GE, Seifert SA, Rayburn WF. Rattlesnake bites in pregnant women. J Reprod Med. 2010 Nov-Dec; 55:520-2.

53. 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 Emerg Med. 2011; 11:2. [PubMed 21291549]

54. Seifert SA, Boyer LV. Recurrence phenomena after immunoglobulin therapy for snake envenomations: Part 1. Pharmacokinetics and pharmacodynamics of immunoglobulin antivenoms and related antibodies. Ann Emerg Med. 2001; 37:189-95. [PubMed 11174238]

55. Boyer LV, Seifert SA, Cain JS. Recurrence phenomena after immunoglobulin therapy for snake envenomations: Part 2. Guidelines for clinical management with crotaline Fab antivenom. Ann Emerg Med. 2001; 37:196-201. [PubMed 11174239]

Hide
(web3)