Levamisole As an Adulterant in a Cocaine Overdose Fatality

LETTERS

well as the cocaine metabolite benzoylecgo- 2 National Drug and Alcohol Research Centre, nine at a level of 3.4 mg/L. These are lethal University of New South Wales, Sydney, levels for cocaine and benzoylecgonine.1 NSW. [email protected] Cocaine was also detected in a nasal swab, and levamisole was detected in the nasal 1 Baselt RC. Disposition of toxic drugs and chemi- cals in man. 8th ed. Foster City, Mich: Biomedical swab and in the blood, as well as in a Publications, 2008. quantity of white powder found near the 2 Darke S, Degenhardt L, Mattick R. Mortality woman’s body. The cause of death was given amongst illicit drug users: epidemiology, causes as cocaine toxicity. and intervention. Cambridge: Cambridge Univer- sity Press, 2006. Illicit cocaine in Australia is generally 3 Centers for Disease Control and Prevention. diluted (“cut”) with a range of innocuous Agranulocytosis associated with cocaine use — four states, March 2008–November 2009. MMRW substances, including fructose and sucrose, Morb Mortal Wkly Rep 2009; 58: 1381-1385. and less commonly with other drugs, such 4 Wiens MO, Son WK, Ross C, et al. Cocaine adul- as lignocaine.2 In this case, levamisole was terant linked to neutropenia. CMAJ 2010; 182: 57- detected as a contaminant. Levamisole is 59. 5 Zhu NY, Legatt DF, Turner AR. Agranulocytosis primarily used as a veterinary anthelmintic, after consumption of cocaine adulterated with and used uncommonly in humans for levamisole. Ann Intern Med 2009; 150: 287-289. ❏ rheumatoid arthritis, and as adjuvant ther- apy to fluorouracil in the treatment of a variety of cancers.3,4 Agranulocytosis is a significant side effect of levamisole, and this has limited its use in humans. The clinical presentation of agranulocytosis is protean, presenting with a spectrum of abnormalities, ranging from a flu-like ill- ness to leukopenia with a potentially fatal outcome.3-5 The mechanism whereby levamisole induces agranulocytosis is unknown, although a strong link with the human leukocyte antigen HLA-B27 and rheumatoid factor positivity suggests a likely genetic predisposition.4 Recent reports from the United States and Canada have highlighted the presence of levamisole in seized illicit cocaine enter- ing these countries, with up to 69% of seized cocaine lots containing levamisole. There has been a subsequent clustering of fatal and nonfatal cases of agranulocytosis in a number of disparate locations.3-5 The Levamisole as an adulterant in reason for contaminating cocaine with a cocaine overdose fatality levamisole is unknown, although there are indications that levamisole may promote Johan A Duflou, Issabella G Brouwer the effects of cocaine by interfering with its and Shane Darke reuptake at a synaptic level.4 Although there was no evidence of agran- TO THE EDITOR: We present a case of fatal cocaine overdose in which the drug ulocytosis in the present case, we highlight was contaminated with levamisole, a thera- the apparent recent appearance of this con- peutic agent known to cause reversible taminant in the cocaine supply in Australia, agranulocytosis. because it has the potential to induce revers- The deceased, a previously well woman ible agranulocytosis in people not otherwise in her early 20s, was found dead in circum- obviously at risk for this condition. stances suspicious of a drug overdose. The Johan A Duflou, Chief Forensic Pathologist1 death was reported to the coroner and the Issabella G Brouwer, Senior Forensic autopsy findings were unremarkable, with Pathologist1 no evidence of injury or significant natural Shane Darke, Professor2 disease processes. 1 Department of Forensic Medicine, Sydney Toxicological sampling of blood revealed South West Area Health Service, Sydney, a cocaine level in the blood of 4.9 mg/L, as NSW.

724 MJA • Volume 192 Number 12 • 21 June 2010