Professional Information
Antivenin (Enhydrina Schistosa Systemic)
VA CLASSIFICATION
Primary: AD500
Note: Antivenin ( Enhydrina schistosa ) is available in Australia via Commonwealth Serum Laboratories, Melbourne {01} {15}.
Another commonly used name is
sea snake antivenom {01} {15}.
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
Snake venom poisoning is a medical emergency {14}. If snakebite envenomation is known or suspected in a patient, it is very important that the attending physician contact a poison control center immediately, before treatment is attempted. Snake venoms are complex substances, and there may be multiple organ, system, or tissue effects {17}. As an additional measure it is also very important to consult experts who have successfully treated snakebite poisoning {18}. Physicians responsible for the treatment of such patients should be familiar with the signs and symptoms of snakebite envenomation and current methods of first aid and general supportive therapy for venomous snakebites {10}.
It is also very important to differentiate between sea snake bites and fish stings. Fish stings are much more common than sea snake bites, especially among swimmers {01} {03}. Differential diagnosis usually is easy since severe local pain follows a fish sting, whereas a sea snake bite is painless {01}. A sea snake bite usually is felt by the patient. Small but distinct teeth marks, which may be multiple, usually are visible and are caused mostly by nonfang teeth. Pain at the bite site is not a major feature, nor is swelling. The important effects, paralysis and myolysis, are systemic and are seen only in some cases {15}. If envenomation has occurred, paralysis and/or myolysis may be expected within 6 hours in most cases, manifested as either early paralysis (e.g., ptosis, ophthalmoplegia, limb or respiratory weakness) or myolysis (e.g., myoglobinuria, muscle pain and weakness). Secondary kidney damage may occur if there is major myolysis; severe hyperkalemia may also occur. Coagulopathy is not seen {15}.
There are 31 species of sea snake in northern Australian waters alone. All may be dangerous to humans, but relatively few of these have caused bites of significance {15}. Severe envenomation occurs in approximately 25% of humans bitten by sea snakes. As the bite is a defensive act, the dose of venom injected is usually small. Antivenin (Enhydrina schistosa ) is, therefore, only indicated in the 25% of victims who show signs of severe envenomation {01}.
Signs of severe envenomation following a sea snake bite include generalized muscle aches, pain, and stiffness on movement developing within 30 minutes to 1 hour after the bite; moderate or severe pain on passive movement of arm, thigh, neck, or trunk muscles developing 1 to 2 hours after the bite; and myoglobinuria becoming evident on inspection of urine 3 to 6 hours after the bite. Dusky yellow urine with positive protein and occult blood tests precedes by approximately an hour the red-brown color of myoglobinuria {01}.
If 1 hour has elapsed since the bite and distinct muscle groups are not painful on passive movement, severe poisoning with myolysis is unlikely {20}. Signs and symptoms of paralysis may take several hours to develop {20}. Clinical trials have shown that antivenin (E. schistosa ) is effective in severe poisoning even when given 7 to 8 hours after the bite. Therefore, it is very important to wait until there is evidence of systemic poisoning before giving antivenin (E. schistosa ) {01}.
Accepted
Envenomation, sea snake (treatment)—Antivenin (E. schistosa ) is indicated for the treatment of severe envenomation caused by the bites of sea snakes (family Hydrophiidae ) native to the Indian and the Pacific Oceans, including olive sea snake (Aipysurus laevis ), Stoke's sea snake (Astrotia stokesii ), beaked sea snake (E. schistosa ), banded sea snake (Hydrophis cyanocinctus ), elegant sea snake (H. elegans ), olive headed sea snake (H. [Disteira] major ), Daudin's sea snake (H. nigrocinctus ), narrow banded sea snake (H. spiralis ), Gunther's sea snake (H. stricticollis ), spine-bellied sea snake (Lapemis hardwickii ), banded sea krait (Laticauda semifasciata ), and needle-headed sea snake (Microencephalophis gracilis ) {01} {02} {15}.
—Antivenin (E. schistosa ) may also neutralize the venoms of Laticauda laticaudata , Pelamis platurus , and Praescutata viperina {01} {04} {05} {06}.
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Source—
Antivenin (Enhydrina schistosa ) is a sterile, nonpyrogenic, refined, and concentrated preparation of venom-neutralizing globulins obtained from the serum of healthy horses immunized with the venoms of the beaked sea snake (E. schistosa ), and the Australian tiger snake (Notechis scutatus ). The antivenin is standardized by its ability to neutralize the lethal action of E. schistosa venom in a biological assay in mice. One dose of antivenin neutralizes approximately 10 mg of E. schistosa venom {01} {15}.
Mechanism of action/Effect:
Antivenin (E. schistosa ) specifically binds to and neutralizes the venom of sea snakes {13}, but does not reverse local injury {13}.
Onset of action:
Effect is rapid after intravenous administration, which is the preferred route of administration {01} {15}.
Precautions to Consider
Pregnancy/Reproduction
Pregnancy—
Studies have not been done in humans. However, snake venoms may precipitate spontaneous abortion {11}. Before administering antivenin (Enhydrina schistosa ) to a pregnant woman, the risk of envenomation should be weighed against the risk of maternal and fetal toxicity from the antivenin {16}.
Studies have not been done in animals.
Breast-feeding
It is not known whether antivenin (E. schistosa ) is distributed into breast milk. However, problems in humans have not been documented.
Pediatrics
Children typically have more severe reactions to envenomation because of the greater amount of venom per kg of body weight; therefore, children may require larger doses of antivenin (E. schistosa ) than do adults. Pediatric doses should not be adjusted by the weight of the patient {19}.
Geriatrics
No information is available on the relationship of age to the effects of antivenin (E. schistosa ) in geriatric patients.
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 (E. schistosa )
» Hypersensitivity to horse serum (antivenin [E. schistosa ] is obtained from the serum of healthy horses immunized with the venom of the sea snake; patients allergic to horse serum may be allergic to antivenin [E. schistosa ]; administration of the antivenin to these patients may result in severe systemic reactions {07})
Side/Adverse Effects
Note: Antivenin (Enhydrina schistosa ) may cause immediate hypersensitivity reactions, such as anaphylaxis and shock. These reactions generally become evident within 30 minutes after antivenin administration; signs and symptoms of the reactions include apprehension; flushing; itching; urticaria; edema of the face, tongue, and throat; cough; dyspnea; cyanosis; vomiting; and collapse. In the event of a systemic reaction during antivenin administration, antivenin should be discontinued and appropriate treatment initiated {07} {12} {13}. However, the incidence of such adverse reactions is poorly documented, but appears to be small {20}.
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 more frequent
Anaphylactic reaction (difficulty in breathing and 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, sudden and severe)
serum sickness (enlargement of the lymph glands; fever; generalized rash and itching; inflammation of joints)
{01}{13}{15}
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Antivenin, Sea Snake (Systemic) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before receiving this medication
» Conditions affecting use, especially:
Hypersensitivity to antivenin (Enhydrina schistosa ) or horse serum
Pregnancy—Snake venoms may precipitate spontaneous abortion
Proper use of this medication
» Proper dosing
Side/adverse effects
Signs of potential side effects, especially anaphylactic reaction and serum sickness
General Dosing Information
Anaphylaxis may occur following antivenin (Enhydrina schistosa ) administration, even in individuals with no prior history of hypersensitivity to the antivenin or to horse serum. Before antivenin (E. schistosa ) is used, appropriate measures should be taken to detect the presence of a dangerous sensitivity {01}. The patient's history (including any report of asthma, hay fever, urticaria, or other allergic manifestations; allergic reactions upon exposure to horses; and prior injections of horse serum) should be reviewed carefully {07} {12}.
Use of subcutaneous or intradermal skin test doses 30 minutes before intravenous administration of antivenin is not recommended. Such tests are unreliable and further delay treatment. They will not detect the likelihood of a reaction due to anticomplementary activity {02}. The use of premedication with subcutaneous epinephrine injection and antihistamines is the subject of controversy {20}. It is unproven as a measure to reduce the risk of anaphylaxis {20}.
Antivenin (E. schistosa ) should be diluted 1:10 in 0.9% sodium chloride injection (normal saline) or 5% dextrose injection {02} {15}. The antivenin should be infused slowly, over a period of 15 to 30 minutes {15}; pulse and blood pressure should be observed carefully {01}.
Antivenin (E. schistosa ) should never be injected into a finger or a toe {08}.
If itching of the skin, urticaria, or cough develops, or if there is an increase in oral secretion, a decrease in pulse volume, or a fall in blood pressure during antivenin infusion, administration of the antivenin should be stopped immediately and further treatment with epinephrine, antihistamine, and corticosteroids instituted {02}.
When the patient has recovered from the reaction, it is possible to continue the cautious infusion of antivenin. However, since this procedure is not without risk, the severity of the snakebite may dictate its adoption. Some patients receiving antivenins develop shivering attacks or rigors, followed by a rise in body temperature. This usually occurs within 1 hour after infusion of the antivenin {02}.
The minimum effective dose of antivenin (E. schistosa ) is in 1 ampul {01}. In severe envenomation, as shown by ptosis, weakness of external eye muscles, dilation of pupils with sluggish light reaction, and leukocytosis exceeding 20,000 cells/mm 3, 3 to 4 ampuls should be administered {01}.
If sea snake antivenin is not available, alternatively tiger snake antivenin may be used. One ampul of sea snake antivenin is roughly equivalent to 2 to 4 ampuls of tiger snake antivenin. If neither sea snake nor tiger snake antivenin is available, polyvalent snake antivenin may be used {15}.
For treatment of adverse effects
Recommended treatment consists of the following:
• For anaphylaxis—Administering epinephrine {09}.
• For serum sickness—Administering salicylates, antihistamines, or corticosteroids {08} {09}. The risk of serum sickness generally increases with increasing antigen load {20}. Therefore, prophylaxis with oral corticoseroids for 5 to 7 days should be considered if 2 or more doses of antivenin (E. schistosa ) are administered {20}.
Parenteral Dosage Forms
ANTIVENIN (ENHYDRINA SCHISTOSA) FOR INJECTION
Note: A single dose of antivenin (Enhydrina schistosa ) usually is adequate if the intravenous route is used. However, in severe envenomations, larger doses of antivenin may be needed. After dilution, the intravenous dose should be infused over fifteen to thirty minutes and further doses titrated according to clinical effect {15}. Absorption from the intramuscular or subcutaneous route is too slow, as it may take about twelve hours for thirty to forty percent of the injected antivenin to reach the circulation, and twenty-four hours for fifty percent to be absorbed. Therefore, the intramuscular route is justified only if the antivenin is to be administered by paramedics and the patient is in a remote area far from medical aid {07}.
Usual adult and adolescent dose
Envenomation, sea snake (treatment)
Intravenous infusion, 1000 antivenin units administered over a fifteen- to thirty-minute period, or intramuscular, 3000 antivenin units {01} {15}.
Usual pediatric dose
See Usual adult and adolescent dose {01} {15}.
Strength(s) usually available
U.S.—
Not commercially available.
Canada—
Not commercially available.
Australia—
Each ampul is standardized to neutralize approximately 10 mg E. schistosa venom (Rx)[Generic]{01}{02}
Note: Each batch is standardized to contain 1000 units. One unit of antivenin (E. schistosa ) neutralizes 0.01 mg of E. schistosa venom {01}. However, the volume in each ampul may vary from 15 mL to 35 mL {15}.
Packaging and storage:
Store between 2 and 8 ºC (36 and 46 ºF), unless otherwise specified by manufacturer {01}.
Developed: 02/06/1997
References
- Sea snake antivenom package insert (Commonwealth Serum Laboratories—Australia), Rev 8/93, Rec 4/95.
- Baxter EH, Gallichio HA. Protection against sea snake envenomation: comparative studies of four antivenenes. Toxicon 1976; 14: 347-55.
- Reid HA, Edin MD. Diagnosis, prognosis, and treatment of sea snake bite. Lancet 1961; 2: 399-402.
- Reid HA. Sea snake antivenene: successful trial. BMJ 1962; 2: 576-9.
- Tu AT, Salafranca ES. Immunological properties and neutralization of sea snake venoms. Am J Trop Med Hyg 1974; 23(1): 135-8.
- Tu AT, Ganthavorn S. Immunological properties and neutralization of sea snake venoms from Southeast Asia. Am J Trop Med Hyg 1969; 18(1): 151-4.
- Treatment of snake bite in Australia and Papua New Guinea using antivenom. Package insert (Commonwealth Serum Laboratories—Australia), Rev 9/92, Rec 4/95.
- Wingert WA, Wainschel J. Diagnosis and management of envenomation by poisonous snakes. South Med J 1975; 68(8): 1015-26.
- Durand LS, Hiebert JM, Rodeheaver GT, et al. Snake venom poisoning. Compr Ther 1981; 7: 51-7.
- Oicchioni AL, Hardy DL, Russell FE, et al. Management of poisonous snakebite. Vet Hum Toxicol 1984; 26(2): 139-40.
- Parrish HM, Khan MS. Snakebite during pregnancy. Report of 4 cases. Obstet Gynecol 1966; 27(4): 468-71.
- Malasit P, Warrell DA, Chanthavanich P, et al. Prediction, prevention, and mechanism of early (anaphylactic) antivenom reactions in victims of snake bites. BMJ 1984; 292: 17-20.
- Ellenhorn MJ, Barceloux DG. Medical toxicology. Diagnosis and treatment of human poisoning. New York, NY: Elsevier, 1988: 1112-32.
- Smith TA II, Figge HL. Treatment of snake bite poisoning. Am J Hosp Pharm 1991; 48: 2190-6.
- White J. CSL antivenom handbook. National Library of Australia 1995: 57-9.
- Panel comment, 04/95.
- Panel comment, 04/95.
- Panel comment, 04/95.
- Panel comment, 04/95.
- Panel comment, 12/96.
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