Professional Information
Antivenin (Chironex Fleckeri Systemic)
VA CLASSIFICATION
Primary: AD500
Some commonly used names are
box jellyfish antivenom and sea wasp antivenom .
Note: Antivenin Chironex fleckeri is available in Australia via Commonwealth Serum Laboratories, Melbourne.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
*Not commercially available in the U.S.
†Not commercially available in Canada.
Category:
Antivenin—
Indications
General considerations
There are two species of box jellyfish indigenous to the southern Pacific Ocean: Chironex fleckeri , native to Australia, and Chiropsalmus quadrigatus , native to the Philippines {01} {02} {07}. C. fleckeri , the most studied of the two species, has been described as the “world's most venomous animal” {02}. There have been approximately 60 to 70 documented deaths from C. fleckeri envenomation in Australia {02} {04}. Extracts of the tentacles of the box jellyfish have been reported to possess lethal, hemolytic, myotoxic, and dermatonecrotic activities {04}. The extent of distribution of C. fleckeri in the waters north of Australia is unknown, as is the southern and lateral distribution of C. quadrigatus , which has caused many fatalities in the Philippines {02}.
Envenomation by C. fleckeri is dramatic and often severe {02}. Unlike snake or spider envenomations, the box jellyfish applies its venom in multiple tiny injected doses over a wide area. Rapid absorption and high blood levels of toxins are thus achieved, and are enhanced by any muscular exertion of the distraught victim in the first few minutes {09}. During the first 15 minutes, pain increases in mounting waves, despite removal of the tentacle. Areas of contact are linear and multiple, presenting as purple or brown lines often compared to the marks made by a whip {01}. A pattern of transverse bars usually is visible. Wealing is prompt and massive. Edema, erythema, and vessication soon follow, and, when these subside (after about 10 days), patches of full-thickness necrosis are revealed {01}. Healing is by granulation and cicatrization, taking a month or more, and leaving permanent scars, perhaps with pigment changes {01}. In fatal cases, death may occur within a few minutes and usually within 20 minutes of the sting {02}.
Accepted
Envenomation, box jellyfish (treatment)—Antivenin (Chironex fleckeri ) is indicated in the treatment of life-threatening envenomation by the box jellyfish (C. fleckeri , commonly known as the sea wasp) in an unconscious patient or in patients with cardiac or respiratory complications, severe pain from the skin lesions, or cosmetic concerns about skin scarring caused by the stings {01} {02}. Antivenin (C. fleckeri ) may also neutralize the venom of Chiropsalmus quadrigatus , which is the other of the two species of box jellyfish common in tropical waters surrounding the Philippines {01}. However, the antivenin is unlikely to give pain relief in damaged skin when administered more than 4 hours after envenomation {02}.
Unaccepted
Antivenin (C. fleckeri ) will not neutralize the venoms of Physalia physalis or Chrysaora quinquecirrha , two other jellyfish species that have toxic effects similar in some respects to those of the box jellyfish {11}. Antivenin (C. fleckeri ) should not be used in the treatment of envenomation caused by the stings of these jellyfish {11}.
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Source—
Antivenin (Chironex fleckeri ) is prepared by hyperimmunizing sheep with venom of box jellyfish (C. fleckeri ) {01} {15}. The preparation contains concentrated immunoglobulins that have the ability to bind to {20} the toxins present in venoms of C. fleckeri and Chiropsalmus quadrigatus {01}. The antivenin is standardized by its ability to neutralize the lethal action of C. fleckeri venom in a biological assay in mice. One dose of antivenin neutralizes approximately 20,000 mouse median lethal doses of C. fleckeri venom {01} {11} {12} {15}.
Mechanism of action/Effect:
Antivenin (C. fleckeri ) specifically binds to and neutralizes the venom of the box jellyfish, C. fleckeri {11}.
Onset of action:
Effect is rapid after intravenous administration, which is the preferred route of administration {01}. However, the antivenin is unlikely to give pain relief in damaged skin when administered more than 4 hours after envenomation {02}.
Precautions to Consider
Pregnancy/Reproduction
Fertility—
Studies on the effects of antivenin (Chironex fleckeri ) on fertility have not been performed.
Pregnancy—
Studies in humans have not been done. It is not known whether antivenin (C. fleckeri ) can cause fetal harm when administered to a pregnant woman. However, a case report shows that a pregnant woman was successfully treated and had a healthy infant nine weeks later {09}. The risks to the mother of severe or life-threatening envenomation outweigh any possible, and never demonstrated, risks to the fetus {16}.
Breast-feeding
It is not known whether antivenin (C. fleckeri ) is distributed into breast milk. However, problems in humans have not been documented.
Pediatrics
Appropriate studies on the relationship of age to the effects of antivenin (C. fleckeri ) have not been performed in the pediatric population. However, no pediatrics-specific problems have been documented to date {10}. Because of lower body mass, small children may receive a higher concentration of venom. Antivenin may be even more crucial to survival from severe stings in children than in adults {16}.
Geriatrics
Appropriate studies on the relationship of age to the effects of antivenin (C. fleckeri ) have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date, and none is expected {16}.
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Risk-benefit should be considered when the following medical problems exist
Hypersensitivity to antivenin (C. fleckeri )
Hypersensitivity to sheep serum (because antivenin [C. fleckeri ] is obtained from the serum of healthy sheep immunized with the venom of box jellyfish, patients allergic to sheep serum may be allergic to antivenin [C. fleckeri ], resulting in severe systemic reactions {15})
Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):
Cardiac function and
Pulmonary function (monitoring throughout treatment is recommended {02})
Side/Adverse Effects
Note: Antivenin (Chironex fleckeri ) is made from the serum of hyperimmunized sheep and reactions in patients are rare in comparison to reactions from horse-derived antivenins. In more than 20 years of use, there has only been one published adverse reaction, a mild generalized rash 20 minutes after antivenin administration {02}. However, antivenin (C. fleckeri ) has recently been shown to possess high anticomplementary activity in vitro ; thus, there is a high theoretical risk for anaphylactoid reaction when injected into humans {09}. Therefore, appropriate precautions should be taken prior to antivenin injection to prevent allergic or other unwanted reactions. The patient's history should be revised carefully, to include any report of asthma, hay fever, urticaria, or other allergic manifestations; allergic reaction upon exposure to sheep; and prior injections of sheep serum {15}. Skin sensitivity testing has been reported to give a false positive or a false negative reaction, contribute to hypersensitizing the patient to antivenin, and itself cause an anaphylactic reaction {17}. Therefore, it is dangerous and a waste of precious time to perform skin sensitivity testing {16} {18} {22}. A tourniquet and epinephrine injection (1:1000) should be at hand to combat any unexpected anaphylactic or other allergic reactions {14}. All patients should be observed for serum sickness for an average of 7 to 14 days {15} {16}. However, no cases of serum sickness have been reported following use of this antivenin {16}.
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for medical attention
Incidence rare
Anaphylactic reaction (collapse{16}; difficulty in breathing or swallowing; hives; itching, especially of feet or hands; reddening of skin, especially around ears; swelling of eyes, face, or inside of nose; unusual tiredness or weakness{15})
serum sickness (enlargement of lymph glands; fever; generalized rash and itching; inflammation of joints)—7 to 14 days after injection
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Antivenin, Box Jellyfish (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Hypersensitivity to antivenin (Chironex fleckeri )
Hypersensitivity to sheep serum
Proper use of this medication
» Proper dosing
» Proper storage
Side/adverse effects
Signs of potential side effects, especially anaphylactic reaction and serum sickness
General Dosing Information
The object of treatment with antivenin is to neutralize the venom as quickly as possible. Therefore, the antivenin should be administered intravenously, preferably by infusion (1:10 dilution). However, if the patient is remote from medical aid and confronted with an emergency situation, intramuscular injection can be considered {01}, and has been proven effective {16}.
First aid measures are of the utmost importance if a severely affected victim is to survive {01}. This should include the application of vinegar to inactivate any pieces of tentacle adhering to the skin {01} {02} {05} {06} {07} {08}. The venom of Chironex fleckeri is located in its injector nematocysts {03}, and the importance of topical application of vinegar to box jellyfish stings is well documented {02}. Vinegar rapidly and irreversibly inactivates any adherent undischarged nematocysts and thus prevents further envenomation. However, it does not have any effect on the pain of the sting {02}. In severe stings, i.e., one covering an area of greater than 50% of one limb or causing unconsciousness, flooding the sting area with vinegar should be followed by the application of a compressive bandage {16} {18}. Equally effective substitutes for vinegar have not been identified to date {02}, but if vinegar is not available, carbonated beverages may have limited benefit as alternatives {02} {05} {06}. Attempting to remove the tentacles by rubbing with sand, a towel, or other means should be delayed until vinegar has been applied {01}. The use of any form of alcohol is not recommended since this may stimulate the discharge of nematocysts {01}. If breathing is impaired, artificial respiration, including mouth-to-mouth, should be performed {01}. In addition, external cardiac compression should be implemented if there is cardiac arrest {16}.
The administration of antivenin (C. fleckeri ) should be regarded as supplementary to first aid measures. It should be given to any victim of a suspected box jellyfish sting who, following the application of first aid measures, continues to have difficulty in breathing, swallowing, or speaking, continues to have severe pain {01}, or has significant cardiac dysfunction or arrest {16}. When indicated, early administration may {19} also prevent the severe scarring usually associated with box jellyfish stings {01} {02}.
A single dose of antivenin (C. fleckeri ) usually is adequate if the intravenous route is used, but in severe cases three or more doses may be necessary. However, larger doses of antivenin may be needed in a critical situation in which death is imminent despite full resuscitation attempts and administration of standard antivenin therapy. In one study, it was calculated that approximately 12 doses of antivenin (C. fleckeri) may be required to counter the effects of a theoretical envenomation containing twice the lethal dose of venom. Although there are obvious concerns about adverse reactions to such large doses, antivenin (C. fleckeri ) has a relatively safe record {02} {16}.
Antivenin (C. fleckeri ) is unlikely to give pain relief to damaged skin when administered more than 4 hours after envenomation. Therefore, additional analgesic therapy such as narcotics may be required {02}. Ice-packs provide good pain relief in mild C. fleckeri stings. For cosmetic benefit and to avoid severe scarring of the skin, antivenin (C. fleckeri ) should be given as early as possible, and certainly within 4 to 6 hours of a sting {02}.
All patients should be observed for serum sickness for an average of 7 to 14 days {15}.
For treatment of adverse effects
Recommended treatment consists of the following:
• For anaphylaxis—Administering epinephrine.
• For serum sickness—Administering salicylates, antihistamines, or corticosteroids.
Parenteral Dosage Forms
ANTIVENIN (CHIRONEX FLECKERI) FOR INJECTION
Note: A single dose of antivenin (C. fleckeri ) usually is adequate if the intravenous route is used {01}. However, in severe envenomations, larger doses of antivenin may be needed {02}. The intravenous dose should be infused after dilution over ten to fifteen minutes and further doses titrated according to clinical effect {16} {18}.
Usual adult and adolescent dose
Envenomation, box jellyfish (treatment)
Intravenous, 20,000 antivenin units, or intramuscular, 60,000 antivenin units {22}.
Usual pediatric dose
Envenomation, box jellyfish (treatment)
See Usual adult and adolescent dose.
Strength(s) usually available
U.S.—
Not commercially available.
Canada—
Not commercially available.
Australia—
Each vial neutralizes approximately 20,000 mouse median lethal doses of Chironex fleckeri venom (Rx)[Generic]{22}
Note: Each batch is standardized to contain 20,000 units; however, the actual volume in the vials can vary from 1.5 mL to 4 mL {22}.
Packaging and storage:
Store between 2 and 8 ºC (35 and 46 ºF), unless otherwise specified by manufacturer {01}.
Developed: 09/23/1996
References
- Box jellyfish antivenom package insert (CSL—Australia), Rec 4/95.
- Currie B. Clinical implications of research on the box jellyfish Chironex fleckeri. Toxicon 1994; 32(11): 1305-13.
- Endean R, Monks SA, Cameron AM. Toxins from the box jellyfish Chironex fleckeri. Toxicon 1993; 31(4): 397-410.
- Collins SP, Comis A, Marshall M, et al. Monoclonal antibodies neutralizing the haemolytic activity of box jellyfish (Chironex fleckeri) tentacle extracts. Comp Biochem Physiol 1993; 106B(1): 67-70.
- Dunn S. Disarming the box jellyfish [letter]. Med J Aust 1993; 158: 647-8.
- Currie B, Ho S, Alderslade P. Box jellyfish, Coca-Cola and old wine [letter]. Med J Aust 1993; 158: 868.
- Beadnell CE, Rider TA, Williamson JA, et al. Management of major box jellyfish (Chironex fleckeri) sting—lessons from the first minute and hours. Med J Aust 1992; 156: 655-8.
- Hartwick R, Callanan VI, Williamson JA. Disarming the box jellyfish—nematocyst inhibition in Chironex fleckeri. Med J Aust 1980; 1: 15-20.
- Williamson JA, Callanan VI, Hartwick RF. Serious envenomation by the northern Australian box jellyfish (Chironex fleckeri). Med J Aust 1980; 1: 13-5.
- Sutherland SK. Response to Chironex antivenom. Med J Aust 1979; 2: 653.
- Baxter EH, Marr AGM. Sea wasp (Chironex fleckeri) antivenene: neutralizing potency against the venom of three other jellyfish species. Toxicon 1974; 12: 223-9.
- Baxter EH, Lane WR. Recent investigations on sea wasp stingings in Australia. Med J Aust 1970; 1: 508.
- Ellenhorn MJ, Barceloux DG. Medical toxicology. Diagnosis and treatment of human poisoning. New York: Elsevier Science Publishing Company Inc., 1988: 1160.
- Barach EM, Nowak RM, Lee TG, et al. Epinephrine for treatment of anaphylactic shock. JAMA 1984; 251(16): 2118-22.
- Reynolds JEF, editor. Martindale, the extra pharmacopeia. 30th ed. London: The Pharmaceutical Press, 1993: 1271, 1286.
- Panel comment, 12/95.
- Personal communication, 5/96.
- Panel comment, 12/95.
- Panel comment, 12/95.
- Panel comment, 12/95.
- Panel comment, 11/95.
- Panel comment, 01/96.
| Link to this page |  |
Printable Version |  |
Email Page |
