AHFS Class:

• Antitoxins and Immune Globulins 80:04

Generic Name(s):

• Antivenin (Micrurus fulvius) (Equine)

Antivenin (Micrurus fulvius) (equine) is a preparation of equine immunoglobulins capable of neutralizing the venom of the Eastern coral snake ( Micrurus fulvius fulvius ) and Texas coral snake ( M. fulvius tenere ).1,2

Antivenin (Micrurus fulvius) (equine) is used in the treatment of envenomation caused by bites of the Eastern coral snake ( Micrurus fulvius fulvius ) and the Texas coral snake ( M. f. tenere ).1 The antivenom is not effective against the venoms of the Arizona or Sonoran coral snake ( Micruroides euryxanthus ) or the venoms of Crotalinae (pit vipers, crotalines; formerly known as Crotalidae or crotalids) and should not be used in the management of envenomations related to these snakes.1,30,31 Antivenin (Micrurus fulvius) (equine) should never be administered prophylactically in asymptomatic patients.1 Sensitivity testing (e.g., intradermal skin test) should be conducted in all individuals prior to administration of antivenin (Micrurus fulvius) (equine) .1 (See Dosage and Administration: Sensitivity Testing and Desensitization.)

Coral Snakes and Coral Snake Bites and Envenomation

The Eastern coral snake ( M. f. fulvius ) is found from eastern North Carolina through the tip of Florida and in the coastal plain of the Gulf of Mexico to the Mississippi River.1,8,9,23 The Texas coral snake ( M. f. tenere ) is found west of the Mississippi River in Louisiana, Arkansas, Texas, and northern Mexico.1,8,9,23,31 Coral snakes of the genus Micrurus also inhabit Mexico, Central America, and South America.9,23

M. fulvius have completely black snouts and alternating, continuous colored bands of red, yellow, and black which encircle the body without interruption.1,6,8,9 The red and yellow bands are contiguous,8,9 and the red and black bands are wider than the interposed yellow bands.1,8,9 Rarely, coral snakes may be melanistic (completely black),1,32 albino (completely white),1 or partially pigmented.1 M. f. fulvius and M. f. tenere are very similar in appearance but can be differentiated1 by the amount and arrangement of black pigment found within the red bands,8 as well as by other characteristics.31 In contrast to crotalines (rattlesnakes, copperheads, cottonmouths), coral snakes have rounded pupils and lack facial pits.1,8,9,31 Adult M. f. fulvius usually vary from approximately 50-110 cm in length1,9 but may rarely be longer.8,9,29

Coral snakes are secretive,1,8,9 diurnal9,29 snakes, and rarely bite unless disturbed or handled.1,8,9 It is estimated that fewer than 20 coral snake bites occur annually in the US.1,8,31 The fangs of coral snakes are short, erect, and, unlike the hinged fangs of crotalines, fixed to the maxilla.1,8,10,31 The venom enters the fang at an opening in its base.1,31 The small size of the fangs makes it difficult for a coral snake bite to penetrate clothing.1 Most coral snake bites are inflicted on the upper extremities, particularly the hands and fingers,1,8,10 mainly because most bites occur as a result of handling the snakes.8,10,29,31 The biting mechanism of coral snakes differs from that of crotaline snakes.1,10 Crotaline snakes usually strike and withdraw rapidly; in contrast, coral snakes usually bite, hold on, and “chew,” presumably so that a sufficient amount of venom can be introduced to immobilize its prey.1,10,31 The “chewing” action may result in more than one bite,1,10 and the victim may recall the snake “hanging on” for a “minute” or so.1,8,10

Coral snake venoms appear to be less complex than the venoms of other snakes, but they have not been as well characterized.15,16 Phospholipase A₂ is present in coral snake venom,15,16,17 but proteolytic enzymes are not.15,16 Coral snake venoms are principally paralytic and neurotoxic in action,1,5,6,8,10,13,14 although they may also exhibit other toxic actions (e.g., cardiovascular toxicity).7,10,13,21,27 The mechanism(s) of its paralytic and neurotoxic action has not been clearly elucidated, but may include a direct toxic effect on muscle27 and/or interference with neuromuscular transmission at postsynaptic receptors.27,28 Under laboratory conditions, M. f. fulvius snakes have yielded 1-28 mg of dried venom per snake.1,10,11,12 A direct relationship between the length of M. f. fulvius and its venom yield has been reported, with a limited number of snakes measuring 74-112 cm in length yielding 14-28 mg of dried venom per snake and some measuring 53-71 cm in length yielding 2-10 mg of dried venom per snake.1,11,12 The manufacturer indicates that the adult human LD₁₀₀ of M. f. fulvius venom is estimated to be 4-5 mg of dried venom,1 but some authorities believe that it may be as high as 15 mg.31 Like crotaline snakebites, coral snake bites may not result in envenomation,1,5,8,13,14,29 and it has been estimated that envenomation may occur in less than 40-50% of coral snake bites.6,8,13,14 Although bitten individuals who exhibit one or more fang punctures seem most likely to have been envenomed, there is no reliable method to predict which bitten individuals may be envenomed by a coral snake bite.1,8 Even a dependable account that the biting snake did or did not “hang on” should not be used to predict the likelihood or severity of envenomation.1

Signs and Symptoms of Coral Snake Envenomation

Local effects of a coral snake bite may include scratch marks or fang puncture wounds (which may often be obscure);1,6,8,10,13,29,32 minimal to moderate edema or tissue reaction;1,6,8,10,13,14,19,29,32 erythema;1,8 and pain.1,6,8,10,13,14,32 If present, pain is usually minor and confined to the bite site,1,6,8,10,13,14,19 but may radiate throughout a bitten extremity.13,29 Paresthesia1,5,6,8,29,32 and weakness5,6 of a bitten extremity may occur occasionally. In contrast to crotaline bites, in which moderate to severe envenomation usually can be predicted by rapid onset of local effects (e.g., pain, discoloration, edema), severe and even fatal envenomation from a coral snake bite can be present without signs and/or symptoms of a substantial local tissue reaction.1,8,10,13,14,29

Systemic signs and symptoms usually begin 1-7 hours after envenomation,1,8,10,14,18 although they may not occur for as long as 18 or more hours.1,19 Once evident, systemic signs and symptoms may progress rapidly and precipitously .1,8,10,14 Paralysis has occurred within 2.5 hours after a bite1,18 and appears to be a bulbar-type paralysis, involving cranial motor nerves.1,8,10,19 Death from respiratory paralysis has occurred within 4 hours after a bite.1,8 Systemic signs and symptoms of envenomation may include euphoria;1,10,18 anxiety or apprehension;10,13 lethargy;1,19 drowsiness;6,7,13,14,32 headache;7,8,14 weakness;1,6,7,13,20 nausea;1,7,8,10,13,14,19,20,29 vomiting;1,7,10,13,14,19 bulbar signs such as fasciculations of the tongue,7,18 dysphagia,7,13,18,20 and paresis of the extraocular muscles;1,6,8,10,13,14,20,29 diplopia7 or blurring of vision;14 excessive salivation1,8,10,13,14,18,20 (in part because of dysphagia);14 dysphonia;7,14,18,19,20 dyspnea;1,8,10,14,19 abnormal reflexes;1,8,10 seizures;1,10 motor weakness or paralysis,1,6,8,10,13,14,18,19,20,29 including complete respiratory paralysis;1,18,19 and weak and irregular pulse and occasional hypotension.7,13 Cardiac failure has also been noted.7,10 Hemoglobinuria1 and cardiovascular shock21 have been observed in envenomed experimental animals. With vigorous supportive therapy and close observation, patients with complete respiratory paralysis have recovered, indicating that respiratory paralysis is reversible.1,18,19 Death is usually associated with respiratory and cardiac failure.6,8,10,13,29

Management of Coral Snake Envenomation

Suspected coral snake envenomation should be considered a medical emergency requiring prompt evaluation and appropriate management.1,5,6,7,8,10,13,14,22,25 A regional poison control center (at 800-222-1222) and/or other qualified expert (e.g., a herpetologist at a large zoo or university) should be consulted for recommendations regarding management of envenomation; however, inability to obtain professional advice should not preclude appropriate use of antivenin (Micrurus fulvius) (equine).1,5,6,7,30,31 Administration of the antivenom does not obviate other measures used in the management of envenomation.1,5,6,7,13,14 Clinicians responsible for the treatment of an envenomed patient should be familiar with the signs and symptoms of coral snake envenomation and current methods of first aid and general supportive therapy for venomous snakebites.1

After a coral snake bite, the bitten extremity and, preferably the bitten individual if practical, should be immediately immobilized to limit the spread of venom.1,7,14 The bitten individual should be kept warm and transported to the nearest hospital as soon as possible;1,7 rings and/or other constrictive items should be removed.7 If the biting snake was killed, it should also be brought to the hospital for use in identification.1,6 Any individual who has been bitten by a coral snake and has any evidence of a break in the skin caused by the snake's teeth or fangs should be hospitalized for observation and/or treatment.1,8,13 The bite area should be cleansed with soap and water to remove any venom that may be present on the skin.1,7,8,13 Although there is no evidence to indicate that incision and suction are of value in removing coral snake venom, the manufacturer states that if fang puncture wounds are present, application of a tourniquet and incision and suction over the fang punctures is recommended.1 The bitten individual should be closely observed for at least 24 hours,1,14,22 including monitoring of respiratory rate every 30 minutes,1 vital signs,13,31 and neurologic status.8,10,13,14 Some clinicians suggest that it may be useful to monitor vital capacity as a means to detect incipient respiratory paralysis.31 Since respiratory difficulties and/or paralysis can occur, facilities and personnel necessary for administration of oxygen, assisted or controlled respiration, and endotracheal intubation (or possibly tracheostomy) should be immediately and readily available, as well as an adequate supply of antivenom.1,25,31 Since hemoglobinuria has been observed in experimental animals envenomed by coral snakes, continuous bladder drainage with careful attention to urinary output and serum electrolyte balance is recommended in symptomatic individuals.1,31 Appropriate tetanus prophylaxis should be administered.1,7,8,13,14 For information on postexposure prophylaxis of tetanus, including ACIP recommendations, see Uses: Postexposure Prophylaxis of Tetanus in Diphtheria and Tetanus Toxoids Adsorbed/ Tetanus and Diphtheria Toxoids Adsorbed for Adult Use 80:08.

Regardless of the bitten individual's clinical history,1 an intradermal sensitivity test should be performed prior to administration of the antivenom.1,7,13,14,22,25,31 (See Dosage and Administration: Sensitivity Testing and Desensitization.) Because the effects of envenomation may be delayed and difficult or impossible to further prevent or reverse once present, it is generally recommended that individuals with one or more fang punctures (particularly if pain is present)13 receive the antivenom as soon as possible, even before the onset of signs and symptoms of envenomation.1,8,13,14,22 Although coral snake bites do not necessarily result in envenomation, it is also generally recommended that bitten individuals receive the antivenom if the biting snake is positively identified as M. f. fulvius or M. f. tenere , since there is no reliable method to predict whether envenomation has occurred.6,14,22

Specialized references should be consulted for more specific information on coral snake envenomation and its management.6,7,13,14

Reconstitution and Administration

Antivenin (Micrurus fulvius) (equine) is preferably7,13,14,22 administered by IV infusion,1,7,13,14,22 but may also be administered by slow IV injection into the tubing of a freely flowing IV solution of 0.9% sodium chloride injection.1 The antivenom must not be injected into a finger or toe .13,14,22,25

The possibility of severe hypersensitivity reactions (anaphylaxis) exists since antivenin (Micrurus fulvius) (equine) is prepared using horse serum, and intradermal skin sensitivity testing should be performed in all patients prior to administration of the antivenom .1,7,13,14,22,25,31(See Dosage and Administration: Sensitivity Testing and Desensitization.)

Antivenin (Micrurus fulvius) (equine) is reconstituted by adding 10 mL of sterile water for injection to the vial labeled as containing the antivenom and gently agitating the vial.1 In order to ensure that the lyophilized pellet of antivenom is saturated with diluent during reconstitution, the stream of diluent should be directed toward the center of the pellet; otherwise, if the diluent stream is directed toward the side of the vial, the pellet may float to the top of the vial and adhere to the rubber septum or dry pellet fragments may become trapped in foam resulting in reconstitution difficulties and delay.1 To avoid foaming, solutions of the antivenom should be mixed by gentle swirling and should not be shaken.1 During reconstitution the vial should be swirled for 1-minute increments at 5-minute intervals; generally, reconstitution requires at least 30 minutes.1 The vacuum in the antivenom vial will pull the diluent out of the syringe into the vial; however, delivery of the diluent may not completely replenish the negative pressure.1 The presence of a vacuum in the vial may impede reconstitution of the lyophilized antivenom; therefore, any vacuum remaining after adding the supplied diluent should be exhausted by injecting additional air into the vial with the syringe and needle or by disconnecting the syringe from the needle and allowing room air to enter the vial until the negative pressure is extinguished.1

The reconstituted antivenom should be inspected visually for particulate matter and/or discoloration whenever solution and container permit and should be discarded if either is present.1

For IV infusion, the dose of reconstituted antivenom may be added to 250-500 mL of 0.9% sodium chloride injection; the solution should be gently swirled again immediately prior to administration.1 Some clinicians dilute each reconstituted vial of the antivenom in 50 or 25 mL of 0.9% sodium chloride injection for administration to adults or children, respectively.31

Whether the antivenom is administered by IV infusion or slow IV injection, the initial 1-2 mL should be administered over 3-5 minutes with careful observation of the patient; if no signs or symptoms of an immediate systemic reaction occur, administration of the antivenom is continued.1 The rate of administration should be based on the severity of the signs and symptoms of envenomation and the patient's tolerance to the antivenom; however, until 3-5 vials of antivenom (diluted or undiluted) have been given, administration should be at the maximum safe rate of IV fluid administration.1 Methods for administering the antivenom to sensitive patients are described in Dosage and Administration: Sensitivity Testing and Desensitization .

Dosage

When indicated, antivenin (Micrurus fulvius) (equine) should be administered as soon as possible, even before the onset of signs and symptoms of envenomation .1,7,13,14,22

Dosage of antivenin (Micrurus fulvius) (equine) is expressed in terms of the number of vials of the antivenin.1

The usual recommended initial IV dose of antivenin (Micrurus fulvius) (equine) in children and adults30,31 is 3-5 vials.1,7,13,22 Higher initial doses may be indicated in some individuals, depending on the nature and severity of the signs and symptoms of envenomation.13,22,31 Some clinicians suggest that 5-6 vials be given to coral snake bite victims if pain or neurologic signs or symptoms (e.g., paresthesia) are evident13,22 and that 8-10 vials may be given if bulbar signs of paralysis are present.31 Envenomation by large snakes may require relatively high doses, particularly in children or small adults.14,22,25,30,31 The dose of antivenom administered to children is not based on weight.30,31

The need for additional doses of antivenom is based on the clinical response to the initial dose and continuing assessment of the patient and severity of poisoning.1,7,13,22 If necessary, additional antivenom may be administered,1,7,22,31 usually in doses of 1-5 vials.7,13,22,31 Venom yields determined under laboratory conditions suggest that some envenomed patients might require administration of a total dose of 10 or more vials of the antivenom to neutralize the venom injected by a biting snake.1,11,12

Sensitivity Testing and Desensitization

Because of the risk of a severe sensitivity reaction (e.g., anaphylaxis), an intradermal skin test is recommended prior to administration of antivenin (Micrurus fulvius) (equine).1,7,13,14,22,25,31 The skin test procedure consists of intradermal injection of 0.02-0.03 mL of a 1:10 dilution of antivenin (Micrurus fulvius) (equine) or normal equine serum in 0.9% sodium chloride injection.1,13,22,25,30 Use of larger amounts of diluted antivenom increases the likelihood of a false-positive reaction and, in extremely sensitive patients, increases the risk of a systemic reaction.1 When the patient has a history of sensitivity to equine serum, a 1:100 or greater dilution should be used for preliminary skin testing.1 A control test on the opposite extremity using an equal volume of 0.9% sodium chloride injection facilitates interpretation of the results.1,13,22,25 The test site is read after 5-30 minutes.1,13,22 A positive reaction consists of an urticarial wheal, with or without pseudopods, and surrounding edema.1 The possibility of false negative reactions should be considered; although false-negative skin test reactions have not been reported with antivenin (Micrurus fulvius) (equine) to date, such reactions have been reported in 10% of patients tested with another equine antivenom (antivenin [Crotalidae] polyvalent [equine]).1

In general, the shorter the interval between intradermal injection of the diluted antivenom and the beginning of a positive reaction, the greater the degree of sensitivity.1 If the individual does not have a history of allergy and the skin test is negative, the antivenom may be administered; however, a negative history of allergy and the absence of a reaction to a properly performed skin test do not preclude the possibility of an immediate sensitivity reaction.1,13,14,22 A negative skin test also does not indicate whether serum sickness will occur after administration of full doses of the antivenom.1 If the individual has a history of allergy and the skin test is strongly positive, administration of the antivenom may be hazardous (particularly if the positive skin test reaction is accompanied by systemic allergic manifestations) and the risk of administering the antivenom must be weighed against the risk of withholding it, taking into consideration that severe envenomation may be fatal.1,22 If the antivenom is to be administered to such an individual, desensitization should be performed1,14,25 or an alternative procedure for administration should be considered.13,22,24,25 If the individual does not have a history of allergy and the skin test is mildly or questionably positive, desensitization should be performed1,14 or an alternative procedure for administration should be considered.13,22,24,25

The procedure for desensitization suggested by the manufacturer consists of subcutaneous injection of 0.1, 0.2, and 0.5 mL of a 1:100 dilution of antivenom (Micrurus fulvius) (equine) at 15-minute intervals; the procedure is repeated with a 1:10 dilution, and then with undiluted antivenom.1 If a systemic immediate sensitivity reaction occurs at any time during the desensitization procedure, a tourniquet should be loosely applied proximal to the sites of injection and epinephrine administered proximal to the tourniquet or into another extremity.1 After at least 30 minutes, the procedure may be continued by injecting the last dose of antivenom that did not produce a reaction.1 If no reaction occurs after 0.5 mL of undiluted antivenom has been administered, the usual dose may be administered IV; alternatively, the antivenom can be administered IM with the dose doubled at 15-minute intervals until the entire dose has been given.1

Since the suggested procedure for desensitization may require several hours to administer the initial dose and time is an important factor in neutralization of venom, some clinicians have recommended an alternative procedure for administering snake antivenom to patients with potential or known sensitivity in whom prompt administration of the antivenom is considered necessary.6,13,22,24,25 First, an antihistamine is administered IV (e.g., 50-100 mg of diphenhydramine hydrochloride in an adult).6,13,22,24,25 A diluted solution of the antivenom is then infused slowly IV, with close observation of the patient for signs and symptoms of an immediate sensitivity reaction (e.g., anaphylaxis);13,22,24,25 if a reaction does not occur, IV infusion of the antivenom and close observation of the patient are continued until the necessary dose has been administered.13,25 An allergist, immunologist, and/or other experts should be consulted for advice on treatment of patients who develop signs and symptoms of impending anaphylaxis in spite of desensitization or an alternative procedure for administration.13,22,25 Some clinicians suggest that these patients may be managed by administering diluted antivenom by slow IV infusion with a concomitant IV infusion of epinephrine at a different site,22,24 or by alternating and titrating separate IV infusions of diluted antivenom and epinephrine.25

Sensitivity Reactions

Immediate Sensitivity or Anaphylaxis

Immediate and potentially fatal sensitivity reactions (shock, anaphylaxis) may occur in patients receiving antivenin (Micrurus fulvius) (equine).1 If an immediate sensitivity reaction occurs, it usually occurs within 30 minutes after administration of the antivenom.1 Immediate sensitivity reactions may be most likely to occur in individuals with atopic sensitivity to horses.6 Signs and symptoms may develop within minutes after beginning, or during, administration of the antivenom1,13 and may include apprehension; flushing; itching; urticaria; edema of the face, tongue, and throat; cough; dyspnea; cyanosis; vomiting; and cardiovascular collapse.1

If a severe immediate sensitivity reaction occurs during administration of the antivenom, administration should be immediately discontinued,1,13,14,22 at least temporarily,6,13 and the patient given appropriate therapy (e.g., epinephrine, antihistamines, IV fluids, maintenance of an adequate airway, oxygen) as indicated.1,6,13,14,22,31 Immediate sensitivity reactions may usually be managed by temporarily interrupting administration of the antivenom or slowing its rate of administration, and administering an antihistamine and/or epinephrine.6,13,24 If administration of the antivenom is temporarily interrupted and then reinitiated after control of the reaction, administration should be at a slower rate.13

Delayed Hypersensitivity or Serum Reactions

Serum sickness, if it occurs, usually is evident 5-24 days after administration of the antivenom.1,14,25 The onset of serum sickness may be less than 5 days in some individuals, especially those who have received preparations containing equine serum in the past.1 Antivenom-induced serum sickness is generally dose related.6,22,25 The usual manifestations of serum sickness are malaise, fever, urticaria, lymphadenopathy, edema, arthralgia, nausea, and vomiting.1 Neurologic manifestations such as meningism or peripheral neuritis occasionally occur.1 Peripheral neuritis usually involves the shoulder and arms.1 Pain and muscle weakness are frequently present, and permanent atrophy may develop.1 Although their efficacy is not clearly established in the treatment of envenomation or venom shock, corticosteroids and antihistamines are the treatment of choice for the treatment of serious serum sickness reactions.14,25

Thimerosal Allergy

Antivenin (Micrurus fulvius) (equine) contains thimerosal, a mercury-containing preservative.1,55 (See Cautions: Precautions and Contraindications.)

Hypersensitivity reactions to thimerosal have been reported rarely in individuals receiving vaccines containing thimerosal.36,46,48 These reactions usually manifest as local, delayed-type hypersensitivity reactions (e.g., erythema, swelling),36,40,41 but a generalized reaction manifested as pruritus and an erythematous, maculopapular rash on all 4 extremities has been reported rarely.48 Even when patch or intradermal tests for thimerosal sensitivity are positive, most individuals receiving thimerosal-containing vaccines do not develop such hypersensitivity reactions.36,41

Precautions and Contraindications

Coral snake bites may cause fatal envenomation.1,8,10,13,29 If unfamiliar with appropriate management of coral snake bites, clinicians should consult a poison control center and/or other qualified expert (e.g., a herpetologist at a large zoo or university) for advice on the management of envenomation;1,5,6,7,31 however, inability to obtain professional advice should not preclude appropriate use of antivenin (Micrurus fulvius) (equine).30,31 Clinicians responsible for the treatment of an envenomed patient should be familiar with the signs and symptoms of coral snake envenomation and current methods of first aid and general supportive therapy for venomous snakebites.1 Specialized references should be consulted for specific information on coral snake envenomation and its management.6,7,13,14

Prior to administration of antivenin (Micrurus fulvius) (equine), careful inquiry should be made concerning a history of asthma, hay fever, urticaria, or other allergic manifestations; a history of allergic reactions upon exposure to horses; and prior administration of preparations containing equine serum.1,22 An intradermal skin sensitivity test should be performed prior to administration of the antivenom,1,7,13,14,22,25,31 regardless of the patient's clinical history.1 (See Dosage and Administration: Sensitivity Testing and Desensitization.)

There are no contraindications to use of antivenin (Micrurus fulvius) (equine) in individuals with coral snake envenomations threatening life or limb.1 Administration to individuals known to be allergic to horse serum, either by history or as a result of an appropriate sensitivity test, requires careful judgement and considerable experience in the use of antivenoms of equine origin.1 Appropriate equipment for maintenance of an adequate airway and other supportive measures and agents (e.g., tourniquet, epinephrine, oxygen) for the treatment of anaphylaxis or other severe systemic reactions should be immediately and readily available whenever antivenin (Micrurus fulvius) (equine) is administered.1,8,13,14,22,25

Because coral snake envenomation may result in signs and symptoms involving the nervous system,1,6,7,13,14,18,19,20 sedatives should be used with caution in bitten individuals.1 Since coral snake envenomation may also result in respiratory difficulties,1,8,10,14,19 including complete respiratory paralysis,1,18,19 the use of opiates that can depress respiration is contraindicated in bitten individuals.1,8,14

Antivenin (Micrurus fulvius) (equine) contains mercury in the form of ethyl mercury from thimerosal, a mercury-containing preservative.1,55 Prior to lyophilization, the antivenom contains 0.005% thimerosal (25 mcg of mercury per mL).1 Only limited toxicology data are available regarding ethyl mercury, but high dose and acute exposures to methyl mercury have been associated with neurologic and renal toxicities.37 Developing fetuses and young children, especially neonates and infants younger than 6 months of age, are at greatest risk of mercury toxicity.37,38,39 Although it has been suggested that thimerosal added as a preservative or used during the manufacturing process of vaccines or plasma-derived products theoretically could have adverse effects in recipients, there is no conclusive evidence that the low concentrations of thimerosal contained in vaccines cause harm in vaccine recipients.42,43,44,47,49,50,51,52,53,54 Efforts to eliminate or reduce the 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.37,38,39,41,42 For additional information on risks associated with thimerosal and mercury, see Thimerosal Precautions under Cautions: Precautions and Contraindications, in Influenza Virus Vaccine Inactivated 80:12.

Pregnancy

Pregnancy

Pregnancy does not preclude the use of snake antivenom when indicated.14,26

Analgesics

Morphine and other opiates that may cause respiratory depression should not be administered to patients being treated for coral snake envenomation.1

Sedatives

Sedatives that may cause respiratory depression should be used with extreme caution in patients being treated for coral snake envenomation.1

Beta-Adrenergic Blocking Agents

Therapy with β-adrenergic blocking agents (including cardioselective β-adrenergic blocking agents) has been associated with an increased incidence and severity of acute anaphylaxis.1,34 The fact that anaphylaxis occurring in patients receiving β-adrenergic blocking agents may be prolonged and resistant to conventional treatment should be considered34 if antivenin (Micrurus fulvius) (equine) is used in the management of envenomation in patients receiving these agents. β-Adrenergic blocking agents may alter the pharmacotherapeutic effects of epinephrine and other adrenergic agents and larger than usual doses of these drugs may be required for the treatment of anaphylaxis.1

Pharmacology

Antivenin (Micrurus fulvius) (equine) contains specific antibodies that neutralize the venom of the Eastern coral snake ( Micrurus fulvius fulvius ).1,2 Cross-neutralization tests indicate that the antivenom also neutralizes the venom of the Texas coral snake ( M. f. tenere ).1 Cross-neutralization tests also indicate that the antivenom may partially neutralize the venom of M. dumerilii carinicauda and minimally neutralize that of M. spixii .3 Antivenin (Micrurus fulvius) (equine) will not neutralize the venom of the Arizona or Sonoran coral snake ( Micruroides euryxanthus ),1 the Brazilian giant coral snake ( Micrurus frontalis ),3 or M. nigrocinctus ,3 or venoms against which antivenin (Crotalidae) polyvalent is active.30,31

Chemistry and Stability

Chemistry

Antivenin (Micrurus fulvius) (equine) is a sterile, nonpyrogenic preparation of specific venom-neutralizing immunoglobulins obtained from the serum of healthy horses immunized against the venom of the Eastern coral snake ( Micrurus fulvius fulvius ).1,2 Commercially available antivenin (Micrurus fulvius) (equine) meets standards established by the Office of Biologics of the US Food and Drug Administration.2 The commercially available antivenom is standardized by its ability to neutralize the lethal action of M. f. fulvius venom that is injected IV in mice;1,2 the reconstituted contents of each vial (10 mL) of the antivenom will neutralize not less than 250 mouse LD₅₀ units1,2 or approximately 2 mg of M. f. fulvius venom.1

Antivenin (Micrurus fulvius) (equine) occurs as a light cream-colored solid exhibiting the characteristic structure of a lyophilized solid. Prior to lyophilization, the antivenom contains phenol 0.25% and thimerosal 0.005% (25 mcg of mercury per mL) as preservatives.1 Following reconstitution as directed with sterile water for injection, the antivenom varies from clear to slightly yellow or green,1 has a pH of 6.5-7.5,30 and contains not more than 20% solids.2

Stability

Antivenin (Micrurus fulvius) (equine) should be refrigerated at 2-8°C,1 and should not be frozen1 or exposed to excessive heat.2 Reconstituted solutions of the antivenom should be used within 48 hours, and diluted solutions of the antivenom should be used within 12 hours.30

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

1. Wyeth Laboratories Inc. Antivenin (Micrurus fulvius) (equine origin) (North American Coral Snake Antivenin) prescribing information. Marietta, PA; 2001 Aug.

2. The United States pharmacopeia, 25th rev, and The national formulary, 20th ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 2002:158.

3. Cohen P, Berkeley WH. Coral snake venoms: in vitro relation of neutralizing and precipitating antibodies. Am J Trop Med Hyg . 1971; 20(4 Part 1):646-9. [PubMed 5568130]

4. Bolanos R, Cerdas L. The production and control of anti-venoms sera. In: Developments in biological standards. Vol. 41. Basel: Karger; 1978:109-16.

5. Kunkel DB, Curry SC, Vance MV et al. Reptile envenomations. J Toxicol Clin Toxicol . 1983-84; 21:503-26.

6. Anon. Treatment of snakebite in the USA. Med Lett Drugs Ther . 1982; 24:87-9. [PubMed 7110058]

7. American Association of Poison Control Centers. Management of poisonous snakebite. J Vet Hum Toxicol . 1984; 26:139-40.

8. Parrish HM. Bites by coral snakes: report of 11 representative cases. Am J Med Sci . 1967; 253:561-8. [PubMed 4960877]

9. Identification and distribution of North American venomous snakes. In: Russell FE. Snake venom poisoning. Philadelphia: JB Lippincott Company; 1980:45-86.

10. McCollough NC. Coral snake bites in the United States. J Fla Med Assoc . 1963; 49:968-77.

11. Fix JD, Minton SA Jr. Venom extraction and yields from the North American coral snake, Micrurus fulvius. Toxicon . 1976; 14:143-5.

12. Fix JD. Venom yield of the North American coral snake and its clinical significance. South Med J . 1980; 73:737-41. [PubMed 7394594]

13. Medical problems of snakebite. In: Russell FE. Snake venom poisoning. Philadelphia: JB Lippincott Company; 1980:235-343.

14. Van Mierop LHS. Poisonous snakebite: a review. Part 2. Symptomatology and treatment. J Fla Med Assoc . 1976; 63:201-10. [PubMed 175130]

15. Venoms. In: Russell FE. Snake venom poisoning. Philadelphia: JB Lippincott Company; 1980:139-234.

16. Ramsey HW, Synder GK, Kitchen H et al. Fractionation of coral snake venom: preliminary studies on the separation and characterization of the protein fractions. Toxicon . 1972; 10:67-72. [PubMed 5015543]

17. Possani LD, Alagon AC, Fletcher PL Jr et al. Purification and characterization of a phospholipase A₂ from the venom of the coral snake, Micrurus fulvius microgalbineus (Brown and Smith). Biochem J . 1979; 179:603-6. [PubMed 475771] [PubMedCentral]

18. Ramsey GF. Coral snake bite: report of a case and suggested therapy. JAMA . 1962; 182:949-51. [PubMed 13990713]

19. Moseley T. Coral snake bite: recovery following symptoms of respiratory paralysis. Ann Surg . 1966; 163:943-7. [PubMed 5933807][PubMedCentral]

20. Pettigrew LC. Neurologic complications of a coral snakebite. Neurology . 1985; 35:589-92. [PubMed 3982652]

21. Ramsey HW, Taylor WJ, Boruchow IB et al. Mechanism of shock produced by an elapid snake ( Micrurus f. fulvius ) venom in dogs. Am J Physiol . 1972; 222:782-6. [PubMed 5022693]

22. Otten EJ. Antivenin therapy in the emergency department. Am J Emerg Med . 1983; 1:83-93. [PubMed 6680610]

23. Roze JA. New world coral snakes (Elapidae): a taxonomic and biologic summary. Mem Inst Butantan, Sao Paulo . 1982; 46:305-38.

24. Loprinzi CL, Hennessee J, Tamsky L et al. Snake antivenin administration in a patient allergic to horse serum. South Med J . 1983; 76:501-2. [PubMed 6836367]

25. Wingert WA. Diagnosis and management of envenomation by poisonous snakes. South Med J . 1975; 68:1015-26. [PubMed 1099653]

26. Parrish HM. Snakebite during pregnancy. Obstet Gynecol . 1966; 27:468-71. [PubMed 5907366]

27. Weis R, McIsaac RJ. Cardiovascular and muscular effects of venom from coral snake, Micrurus fulvius. Toxicon . 1971; 9:219-28.

28. Snyder GK, Ramsey HW, Taylor WJ et al. Neuromuscular blockade of chick biventer cervicis nerve-muscle preparations by a fraction from coral snake venom. Toxicon . 1973; 11:505-8. [PubMed 4762268]

29. Neill WT. Some misconceptions regarding the eastern coral snake, Micrurus fulvius. Herpetologica . 1957; 13:111-8.

30. Bierly MZ Jr (Wyeth Laboratories Inc, Philadelphia, PA): Personal communication; 1986.

31. Reviewers' comments (personal observations); 1986 Jul.

32. Gloyd HK. A case of poisoning from the bite of a black coral snake. Herpetologica . 1938; 1:121-4.

34. Lang DM. Anaphylactoid and anaphylactic reactions. Hazards of beta-blockers. Drug Saf . 1995; 12:299-304. [PubMed 7669259]

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

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

38. 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. [PubMed 10577494]

39. 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]

40. Food and Drug Administration. Thimerosal in vaccines. From FDA website ([Web]). Accessed 2008 Oct 27.

41. 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.

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

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

44. 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]

45. 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]

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

47. 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]

48. 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]

49. 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]

50. 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]

51. 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]

52. 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]

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

54. Institute of Medicine. Immunization safety review: vaccines and autism. Washington DC; National Academy Press; 2004. From IOM website ([Web]). Accessed 2008 Oct 28.

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

56. Food and Drug Administration. Information for health care professionals: anticipated short supply of coral snake antivenom (Pfizer Inc). From FDA website. Accessed 2012 Mar 16. [Web]

58. Azoulay S. Dear Health Care Provider letter regarding important product supply information for Antivenin (Micrurus fulvius) (Equine Origin) North American Coral Snake. Further extension of expiration dating to April 30, 2015 lot no. 4030024. New York, NY; Pfizer; 2014 Feb 25. From FDA website. Accessed 2014 May 1. [Web]

59. Food and Drug Administration. Expiration date extension for North American coral snake antivenin (Micrurus fulvius) (equine origin) lot 4030024 through April 30, 2017. From FDA website. Accessed 2016 Apr 19. [Web]