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Deaths associated with ivermectin treatment of scabies

The Lancet v.349, 19apr97

Robert Barkwell, Suzanne Shields

Wentworth Lodge is a 210 bed fully accredited long-term care facility, affiliated as a clinical teaching unit with the Faculty of Health Sciences, McMaster University. Within the Lodge, there is a 47-bed closed unit for residents with behavioural problems or wandering tendencies: most, though not all, are demented. Residents in this unit are younger (mean age 73-4 years on admission, versus 83-8 for other areas) and physically healthier than residents in the rest of the Lodge. From June to November, 1995, there was an outbreak of scabies on this ward, which we were unable to control with any of the usual topical agents. All residents were treated with crotamiton (July 7, 1995) and lindane (Aug 7, 1995). Several individuals with symptoms subsequently had repeated topical applications of lindane and/or permethrin. Finally, on Nov 10, 1995, all residents were treated with a single oral dose of ivermectin (150-200 µg/kg of body weight). Within 5 days, all rashes and symptoms had cleared and no further treatment was needed.

Monthly number of deaths in ivermectin and control groups

Over the succeeding 6 months, there was a pattern of excess deaths among the 47 residents who had received ivermectin. We retrospectively constructed a 47-patient cohort of those who had not had scabies for comparison purposes. We matched for age and sex the 47 patients who had received ivermectin with all other residents of the Lodge. In every case in which there was more than one match, if one of the matches died in the 6 months under study that resident was added to the control cohort: ie, we deliberately maximised the number of deaths in the comparison group. Between Nov 10, 1995, and May 10, 1996, 15 of the 47 who had received ivermectin died, compared with five of the age-matched and sex-matched cohort. The figure shows the time-course of deaths in the two groups. Final causes of death showed no pattern, but ,hose in the ivermectin group developed a sudden change in behaviour with lethargy, anorexia, and listlessness which -receded death. Indeed, it was this pattern that led us to study these deaths. These data, subjected to Fisher's exact test, was significant to p=0.001, and relative risk was 3.00 (95% CI 1.19-7.59). We also analysed historical death rates for the 3-year period November, 1992, to November, 1995, compared with the 6-month period November, 1995, to May, 1996:

                                   Deaths              Deaths 

                              Nov, 92-Nov, 95     Nov, 95-May, 96

Special care units (47 beds)         28                 15

All other areas (163 beds)          144                 10

Total (210 beds)                    172                 23

The change in death rate is highly significant (p<0-0001 by both chi-square and Fisher's exact tests).

Ivermectin has been used extensively in the past against onchoceriasis and other tropical filarial diseases, with excellent results and a low incidence of reported adverse effects." More recently, ivermectin has been tested for the treatment of scabies in human beings." -Mese reports were the basis on which the drug was used in our institution. We suggest, in the face of what appears to be a significant statistical association between use of ivermectin and increased risk of death, that ivermectin should not be used for treatment of scabies in the elderly, pending clarification of whether the association is causal. In particular, confounding by an underlying medical condition or interaction with another treatment (such as lindane or psychoactive drugs) needs to be ruled out.

1.  Brown KR, Neu DC. Ivermectin: clinical trials and treatment schedules in onchocerciasis. Acta Leidensia 1990; 59: 169-75.

2.  Goa KI_ McTavish D, Clissold SP. Ivermectin: a review of its antifilarial activity, pharmacological properties, and clinical efficacy in onchoceriasis. Drugs 1990; 42: 640-58.

3.  Glazion P, Cartel JL, Alzieu P, et al. Comparison of ivermectin and benzyl benzoate for treatment of scabies. Trop Med Parasitol 1993; 44: 331-32.

4.  Meinking TL, Taplin D, Hermida J, Pardo It, Kendel F. The treatment of scabies with ivermectin. N Engl J Med 1996; 333: 26-30.

Department of Family Medicine, McMaster University, Hamilton;
Wentworth Lodge, Dundas, Ontario L9H 4C4, Canada
(R Barkwell);
Institute for Work and Health, University of Toronto, Toronto


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