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Sequential randomised and double blind trial of promethazine prophylaxis against early anaphylactic reactions to antivenom for bothrops snake bites

BMJ 1999; 318 doi: (Published 29 May 1999) Cite this as: BMJ 1999;318:1451
  1. Hui Wen Fan, doctor (fhui{at},
  2. Luiz F Marcopito, associate professorb,
  3. João Luiz C Cardoso, doctora,
  4. Francisco O S França, doctora,
  5. Ceila M S Malaque, doctora,
  6. Ronnei A Ferrari, doctora,
  7. Robert David G Theakston, associate professorc,
  8. David A Warrell, associate professord
  1. a Hospital Vital Brazil, Instituto Butantan, Avenue Vital Brazil 1500, 05503-900, São Paulo, Brazil
  2. b Division of Epidemiology, Escola Paulista de Medicina, Unifesp, 04039-032, São Paulo, Brazil
  3. c Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA
  4. d Centre for Tropical Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU
  1. Correspondence to: Dr H W Fan


    Objective: To investigate the efficacy of the H1 antihistamine promethazine against early anaphylactic reactions to antivenom.

    Design: sequential randomised, double blind, placebo controlled trial.

    setting: Public hospital in a venom research institute, São Paulo, brazil.

    Participants: 101 patients requiring antivenom treatment after being bitten by bothrops snakes.

    Intervention: Intramuscular injection of promethazine (25 mg for adults and 0.5/kg for children) or placebo given 15-20 min before starting intravenous infusion of antivenom.

    Main outcome measures: Incidence and severity of anaphylactic reactions occurring within 24 hours after antivenom.

    Results: Reactions occurred in 12 of 49 patients treated with promethazine (24%) and in 13 of 52 given placebo (25%); most were mild or moderate. Continuous sequential analysis indicated that the study could be interrupted at the 22nd untied pair, without preference for promethazine or placebo.

    Conclusion: Prophylaxis with promethazine does not prevent early reactions. Patients should be observed carefully during antivenom infusion and the subsequent few hours.

    Key messages

    • Antivenom therapy may cause early anaphylactic reactions

    • Various drugs are used to prevent reactions, but none have been tested in randomised controlled studies

    • This study showed that promethazine is not better than placebo at preventing early reactions

    • Although most reactions are mild or moderate, trials of other drugs should be done to reduce frequency of anaphylaxis


    • Funding Promethazine and placebo were donated by Rhodia Farma Ltd. The study was supported by the science and Technology for Development Programme of the European Community (Contract No Ts3-CT91-0024).

    • Competing interests None declared.

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