To the Editor: During a national multicentre study of snake bites — the Australian Snakebite Project (ASP), involving over 40 hospitals — we have recently noted a high rate of early allergic reactions following the administration of tiger snake antivenom in Australia. People with suspected or definite snake envenoming are recruited to ASP, and laboratory and clinical data and serial blood samples are collected to measure venom and antivenom concentrations.

From 1 November 2005 to 31 January 2006, 14 patients who had been given tiger snake antivenom (CSL Limited, Parkville, VIC) were recruited. These patients are briefly described in the Box, and include bites from several different groups of snakes. Of the 14 patients, 11 exhibited immediate systemic hypersensitivity reactions to antivenom infusion. Reactions were mild in five patients, moderate in three, and severe in three, according to the grading system by Brown.1 The six patients in the moderate and severe groups fulfilled the criteria for anaphylaxis according to a recent consensus definition.2 All patients required specific treatment in addition to ceasing antivenom therapy, and nine were treated with adrenalin. Antivenom was recommenced in all patients at a slower rate, although an adrenalin infusion was required in four of these and repeat doses of intramuscular or subcutaneous adrenalin in another four while the antivenom infusion continued.

Over the same period, there were seven administrations of brown snake antivenom (over 30 vials of antivenom) reported to ASP without any hypersensitivity reactions.

There has been a previous report of allergic reactions to tiger snake antivenom in a single hospital,3 and we are concerned that there may be a particular problem with tiger snake antivenom. The reaction rate in this series is similar to reported rates in parts of the world where high reaction rates have been attributed to relatively impure antivenom preparations.4,5 The reactions here were traced to at least four different batches of tiger snake antivenom.

We have informed CSL of this high rate of reactions and the antivenom batch numbers, and we have encouraged the treating doctors to make formal reports of each adverse reaction to CSL and the Adverse Drug Reactions Advisory Committee.

Health care professionals treating patients with tiger snake antivenom need to be aware of the possible higher risk of anaphylaxis with tiger snake antivenom and be prepared to treat with adrenalin. Recommendations for the diagnosis and treatment of anaphylaxis have recently been reviewed.6 However, this current problem with CSL tiger snake antivenom should not cause health professionals to reduce or cease its use. In all patients described here, control of the adverse reaction and continuation of antivenom was possible. The rapid identification of this problem over a short period was only possible because of our large multicentre collaborative study, and supports such studies for recognising uncommon envenoming syndromes.

Comment: Thank you for the opportunity to comment on the letter by Isbister et al regarding hypersensitivity reactions to tiger snake antivenom.

CSL has been notified about the cases of hypersensitivity reactions to tiger snake antivenom in general, but has only received two individual case reports. We have been in contact with the study investigators and have requested more detailed information on the other patients so that we can further our investigations.

A thorough check of product manufacturing records revealed no deviations from approved specifications for tiger snake antivenom.

It is important to note Isbister et al have advised health professionals not to reduce or cease the use of tiger snake antivenom. We would like to draw physicians’ attention to the approved Product Information before use of the product. The tiger snake (and other antivenom) Product Information lists the possibility of both anaphylactic and anaphylactoid reactions. Hypersensitivity and skin reactions (including urticaria, rash, hypotension, bronchospasm, anaphylaxis and delayed serum sickness) are listed as common, and are more likely to occur in people who have had previous exposure to equine-based products.

In addition, the Product Information describes an anaphylactoid reaction which can occur because the antivenom has the ability to bind complement. The risk of this reaction can be minimised by adequate dilution of the antivenom (1 : 10 for adults and 1 : 5 in small children) before infusion. Further, the Product Information states that a syringe already loaded with 1 : 1000 adrenalin must be available during antivenom therapy.

CSL is continuing to monitor this situation closely and is awaiting further details on the patients from the reporting physicians. In the meantime, we encourage users of all antivenom products to report any untoward reaction to CSL so that these can be fully evaluated.