Skip to main content
Erschienen in: Forensic Science, Medicine and Pathology 1/2021

12.11.2020 | Case Report

A fatal case after an intravenous injection of levamisole

verfasst von: Bénédicte Lelièvre, Benoit Suply, François Schmitt, Pascale Marcorelles, Guillaume Drevin, Clotilde Rougé Maillart

Erschienen in: Forensic Science, Medicine and Pathology | Ausgabe 1/2021

Einloggen, um Zugang zu erhalten

Abstract

Levamisole is a drug originally prescribed as an antihelmintic. Because of the occurrence of severe cases of agranulocytosis and leukoencephalitis it was removed from the French market in 1998 for human use, while it remains available for veterinary use. Nowadays in France its only use in humans is regulated by authorization for temporary use for its immunomodulatory properties in the treatment of nephritic syndrome.
A 52-year-old man was found dead at his farm. Injection points were observed on his arm and a syringe containing a dark orange-brown liquid was found near the body. At his home, the discovery of a letter highlighted suicidal intent. Analysis of the aforementioned liquid, peripheral blood and urine confirmed the unique presence of levamisole. The femoral blood concentration of levamisole was of 25 mg/L whereas the femoral blood concentrations reported in cases of fatalities after cocaine use do not exceed 0.0056 mg/L. In humans, levamisole can be detected in biological samples after cocaine use as this drug is also an adulterant and one of its metabolites (aminorex) seems to have amphetamine-like properties. In this case, the man consumed levamisole from time to time for its stimulant and strengthening effects.
Cases of fatal poisoning using levamisole are very rare and poorly documented, which makes the interpretation of postmortem blood levamisole concentration difficult.
Literatur
2.
Zurück zum Zitat Hsu WH. Toxicity and drug interactions of levamisole. JAVMA. 1980;176:1166–9. PubMed Hsu WH. Toxicity and drug interactions of levamisole. JAVMA. 1980;176:1166–9. PubMed
5.
Zurück zum Zitat Raymon LP, Isenschmid DS. Letter to the editor: The possible role of levamisole in illicit cocaine preparations. J Anal Toxicol. 2009;33:620–2. CrossRef Raymon LP, Isenschmid DS. Letter to the editor: The possible role of levamisole in illicit cocaine preparations. J Anal Toxicol. 2009;33:620–2. CrossRef
6.
Zurück zum Zitat Brunt TM, van den Berg J, Pennings E, Venhuis B. Adverse effects of levamisole in cocaine users: a review and risk assessment. Arch Toxicol. 2017;91:2303–13. CrossRef Brunt TM, van den Berg J, Pennings E, Venhuis B. Adverse effects of levamisole in cocaine users: a review and risk assessment. Arch Toxicol. 2017;91:2303–13. CrossRef
7.
Zurück zum Zitat Turcant A, Prémel-Cabic A, Cailleux A, Allain P. Toxicological screening of drugs by microbore high-performance liquid chromatography with photodiode-array detection and ultraviolet spectral library searches. Clin Chem. 1991;37:1210–5. CrossRef Turcant A, Prémel-Cabic A, Cailleux A, Allain P. Toxicological screening of drugs by microbore high-performance liquid chromatography with photodiode-array detection and ultraviolet spectral library searches. Clin Chem. 1991;37:1210–5. CrossRef
8.
Zurück zum Zitat Lelievre B, Richeval C, Coulon A, Ivanikow D, Brofferio M, Deguigne M, et al. Case report on two-cathinones abuse: MPHP and N-ethyl-4’methylnorpentedrone, with a fatal outcome. Forensic Toxicol. 2020;38:243–54. CrossRef Lelievre B, Richeval C, Coulon A, Ivanikow D, Brofferio M, Deguigne M, et al. Case report on two-cathinones abuse: MPHP and N-ethyl-4’methylnorpentedrone, with a fatal outcome. Forensic Toxicol. 2020;38:243–54. CrossRef
9.
Zurück zum Zitat Gruson A, groupe “accréditation” SFTA. Aide à la validation des méthodes en toxicologie et suivi thérapeutique pharmacologique. Ann Toxicol Anal. 2005;S1:1–20. Gruson A, groupe “accréditation” SFTA. Aide à la validation des méthodes en toxicologie et suivi thérapeutique pharmacologique. Ann Toxicol Anal. 2005;S1:1–20.
10.
Zurück zum Zitat Maude RJ, Silamut K, Plewes K, Charuwatthana P, Ho M, Abul Faiz M, et al. Randomized controlled trial of levamisole hydrochloride as adjunctive therapy in severe falciparum malaria with high parasitemia. J Infect Dis. 2014;209:120–9. CrossRef Maude RJ, Silamut K, Plewes K, Charuwatthana P, Ho M, Abul Faiz M, et al. Randomized controlled trial of levamisole hydrochloride as adjunctive therapy in severe falciparum malaria with high parasitemia. J Infect Dis. 2014;209:120–9. CrossRef
11.
Zurück zum Zitat Luyckx M, Rousseau F, Cazin M, Brunet C, Cazin JC, Haguenoer JM, et al. Pharmacokinetics of Levamisole in healthy subjects and cancer patients. Eur J Drug Metab Pharmacokinet. 1982;7:247–54. CrossRef Luyckx M, Rousseau F, Cazin M, Brunet C, Cazin JC, Haguenoer JM, et al. Pharmacokinetics of Levamisole in healthy subjects and cancer patients. Eur J Drug Metab Pharmacokinet. 1982;7:247–54. CrossRef
12.
Zurück zum Zitat Kouassi E, Caillé G, Léry L, Larivière L, Vézina M. Novel assay and pharmacokinetics of levamisole and p-hydroxylevamisole in human plasma and urine. Biopharm Drug Dispos. 1986;7:71–89. CrossRef Kouassi E, Caillé G, Léry L, Larivière L, Vézina M. Novel assay and pharmacokinetics of levamisole and p-hydroxylevamisole in human plasma and urine. Biopharm Drug Dispos. 1986;7:71–89. CrossRef
13.
Zurück zum Zitat Hess C, Ritke N, Broecker S, Maeda B, Musshoff F. Metabolism of levamisole and kinetics of levamisole and aminorex in urine by means of LC-QTOF-HRMS and LC-QqQ-MS. Anal Bioanal Chem. 2013;405:4077–88. CrossRef Hess C, Ritke N, Broecker S, Maeda B, Musshoff F. Metabolism of levamisole and kinetics of levamisole and aminorex in urine by means of LC-QTOF-HRMS and LC-QqQ-MS. Anal Bioanal Chem. 2013;405:4077–88. CrossRef
14.
Zurück zum Zitat Hess C, Ritke N, Sydow K, Mehling LM, Ruehs H, Maeda B, et al. Determination of levamisole, aminorex, and pemoline in plasma by means of liquid chromatography-mass spectrometry and application to a pharmacokinetic study of levamisole. Drug Test Anal. 2014;6:1049–54. CrossRef Hess C, Ritke N, Sydow K, Mehling LM, Ruehs H, Maeda B, et al. Determination of levamisole, aminorex, and pemoline in plasma by means of liquid chromatography-mass spectrometry and application to a pharmacokinetic study of levamisole. Drug Test Anal. 2014;6:1049–54. CrossRef
15.
Zurück zum Zitat Schulz M, Iwersen-Bergmann S, Andresen H, Schmoldt A. Therapeutic and toxic blood concentrations of nearly 1,000 drugs and other xenobiotics. Crit Care. 2012;16:R136. CrossRef Schulz M, Iwersen-Bergmann S, Andresen H, Schmoldt A. Therapeutic and toxic blood concentrations of nearly 1,000 drugs and other xenobiotics. Crit Care. 2012;16:R136. CrossRef
16.
Zurück zum Zitat Pawlik E, Mahler H, Hartung B, Plässer G, Daldrup T. Drug-related death: adulterants from cocaine preparations in lung tissue and blood. Forensic Sci Int. 2015;249:294–303. CrossRef Pawlik E, Mahler H, Hartung B, Plässer G, Daldrup T. Drug-related death: adulterants from cocaine preparations in lung tissue and blood. Forensic Sci Int. 2015;249:294–303. CrossRef
17.
Zurück zum Zitat Indorato F, Romano G, Barbera N. Levamisole-adulterated cocaine: two fatal case reports and evaluation of possible cocaine toxicity potentiation. Forensic Sci Int. 2016;265:103–6. CrossRef Indorato F, Romano G, Barbera N. Levamisole-adulterated cocaine: two fatal case reports and evaluation of possible cocaine toxicity potentiation. Forensic Sci Int. 2016;265:103–6. CrossRef
18.
Zurück zum Zitat Bertol E, Mari F, Milia MG, Politi L, Furlanetto S, Karch SB. Determination of aminorex in human urine samples by GC–MS after use of levamisole. J Pharm Biomed Anal. 2011;55:1186–9. CrossRef Bertol E, Mari F, Milia MG, Politi L, Furlanetto S, Karch SB. Determination of aminorex in human urine samples by GC–MS after use of levamisole. J Pharm Biomed Anal. 2011;55:1186–9. CrossRef
19.
Zurück zum Zitat Wolford A, McDonald TS, Eng H, Hansel S, Chen Y, Bauman J, et al. Immune-mediated agranulocytosis caused by the cocaine adulterant levamisole: a case for reactive metabolite(s) involvement. Drug Metab Dispos. 2012;40:1067–75. CrossRef Wolford A, McDonald TS, Eng H, Hansel S, Chen Y, Bauman J, et al. Immune-mediated agranulocytosis caused by the cocaine adulterant levamisole: a case for reactive metabolite(s) involvement. Drug Metab Dispos. 2012;40:1067–75. CrossRef
20.
Zurück zum Zitat Spector S, Munjal I, Schmidt DE. Effects of the immunostimulant, levamisole, on opiate withdrawal and levels of endogenous opiate alkaloids and monoamine eurotransmitters in rat brain. Neuropsychopharmacology. 1998;19:417–27. CrossRef Spector S, Munjal I, Schmidt DE. Effects of the immunostimulant, levamisole, on opiate withdrawal and levels of endogenous opiate alkaloids and monoamine eurotransmitters in rat brain. Neuropsychopharmacology. 1998;19:417–27. CrossRef
21.
Zurück zum Zitat Tallarida CS, Egan E, Alejo GD, Raffa R, Tallarida RJ, Rawls SM. Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine’s action in vivo. Neuropharmacology. 2014;79:590–5. CrossRef Tallarida CS, Egan E, Alejo GD, Raffa R, Tallarida RJ, Rawls SM. Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine’s action in vivo. Neuropharmacology. 2014;79:590–5. CrossRef
22.
Zurück zum Zitat Hofmaier T, Luf A, Seddik A, Stockner T, Holy M, Freissmuth M, et al. Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters. Neurochem Int. 2014;73:32–41. CrossRef Hofmaier T, Luf A, Seddik A, Stockner T, Holy M, Freissmuth M, et al. Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters. Neurochem Int. 2014;73:32–41. CrossRef
23.
Zurück zum Zitat Scheinfeld N, Rosenberg JD, Weinberg JM. Levamisole in dermatology. Am J Clin Dermatol. 2004;5:97–104. CrossRef Scheinfeld N, Rosenberg JD, Weinberg JM. Levamisole in dermatology. Am J Clin Dermatol. 2004;5:97–104. CrossRef
24.
Zurück zum Zitat Amery WK, Butterworth BS. The dosage regimen of levamisole in cancer: is it related to efficacy and safety? Int J Immunopharmacol. 1983;5:1–9. CrossRef Amery WK, Butterworth BS. The dosage regimen of levamisole in cancer: is it related to efficacy and safety? Int J Immunopharmacol. 1983;5:1–9. CrossRef
25.
Zurück zum Zitat Amery WK, Bruynseels JP. Levamisole, the story and the lessons. Int J Immunopharmacol. 1992;14:481–6. CrossRef Amery WK, Bruynseels JP. Levamisole, the story and the lessons. Int J Immunopharmacol. 1992;14:481–6. CrossRef
26.
Zurück zum Zitat Kimmel DW, Wijdicks EF, Rodriguez M. Multifocal inflammatory leukoencephalopathy associated with levamisole therapy. Neurology. 1995;45:374–6. CrossRef Kimmel DW, Wijdicks EF, Rodriguez M. Multifocal inflammatory leukoencephalopathy associated with levamisole therapy. Neurology. 1995;45:374–6. CrossRef
27.
Zurück zum Zitat Luppi G, Zoboli A, Barbieri F, Crisi G, Piccinini L, Silingardi V. Multifocal leukoencephalopathy associated with 5-fluorouracil and levamisole adjuvant therapy for colon cancer. A report of two cases and review of the literature. Ann Oncol. 1996;7:412–5. Luppi G, Zoboli A, Barbieri F, Crisi G, Piccinini L, Silingardi V. Multifocal leukoencephalopathy associated with 5-fluorouracil and levamisole adjuvant therapy for colon cancer. A report of two cases and review of the literature. Ann Oncol. 1996;7:412–5.
28.
Zurück zum Zitat Liu HM, Hsieh WJ, Yang CC, Wu VC, Wu KD. Leukoencephalopathy induced by levamisole alone for the treatment of recurrent aphthous ulcers. Neurology. 2006;67:1065–7. CrossRef Liu HM, Hsieh WJ, Yang CC, Wu VC, Wu KD. Leukoencephalopathy induced by levamisole alone for the treatment of recurrent aphthous ulcers. Neurology. 2006;67:1065–7. CrossRef
29.
Zurück zum Zitat Xu N, Zhou W, Li S, Zhou G, Zhang N, Liang J. Clinical and MRI characteristics of levamisole-induced leukoencephalopathy in 16 patients. J Neuroimag. 2009;19:326–31. CrossRef Xu N, Zhou W, Li S, Zhou G, Zhang N, Liang J. Clinical and MRI characteristics of levamisole-induced leukoencephalopathy in 16 patients. J Neuroimag. 2009;19:326–31. CrossRef
30.
Zurück zum Zitat González-Duarte A, Williams R. Cocaine-induced recurrent leukoencephalopathy Neuroradiol J. 2013;26:511–3. PubMed González-Duarte A, Williams R. Cocaine-induced recurrent leukoencephalopathy Neuroradiol J. 2013;26:511–3. PubMed
31.
Zurück zum Zitat Chastel C, Mabin D. Encephalopathies after levamisole therapy. Neurology. 1996;46:288. CrossRef Chastel C, Mabin D. Encephalopathies after levamisole therapy. Neurology. 1996;46:288. CrossRef
32.
Zurück zum Zitat Tseng W, Sutter ME, Albertson TE. Stimulants and the lung. Clin Rev Allergy Immunol. 2014;46:82–100. CrossRef Tseng W, Sutter ME, Albertson TE. Stimulants and the lung. Clin Rev Allergy Immunol. 2014;46:82–100. CrossRef
33.
Zurück zum Zitat Karch SB, Defraia B, Messerini L, Mari F, Vaiano F, Bertol E. Aminorex associated with possible idiopathic pulmonary hypertension in a cocaine user. Forensic Sci Int. 2014;240:e7-10. CrossRef Karch SB, Defraia B, Messerini L, Mari F, Vaiano F, Bertol E. Aminorex associated with possible idiopathic pulmonary hypertension in a cocaine user. Forensic Sci Int. 2014;240:e7-10. CrossRef
Metadaten
Titel
A fatal case after an intravenous injection of levamisole
verfasst von
Bénédicte Lelièvre
Benoit Suply
François Schmitt
Pascale Marcorelles
Guillaume Drevin
Clotilde Rougé Maillart
Publikationsdatum
12.11.2020
Verlag
Springer US
Erschienen in
Forensic Science, Medicine and Pathology / Ausgabe 1/2021
Print ISSN: 1547-769X
Elektronische ISSN: 1556-2891
DOI
https://doi.org/10.1007/s12024-020-00336-y

Weitere Artikel der Ausgabe 1/2021

Forensic Science, Medicine and Pathology 1/2021 Zur Ausgabe

Neu im Fachgebiet Pathologie