Adverse reactions with levamisole vary according to its indications and misuse: A systematic pharmacovigilance study

Levamisole was initially prescribed for the treatment of intestinal worms. Because of immunomodulatory properties, levamisole has been used in inflammatory pathologies and in cancers in association with 5‐fluorouracil. Levamisole is misused as a cocaine adulterant. Post‐marketing reports have implicated levamisole in the occurrence of adverse drug reactions (ADRs) and its use is now limited in Europe and North America. In contrast, all other parts of the World continue to use single‐dose levamisole as an anthelmintic. The aim of this study was to identify ADRs reported after levamisole exposure in VigiBase, the World Health Organisation's pharmacovigilance database, and analyse their frequency compared to other drugs and according to levamisole type of use. METHODS: All levamisole‐related ADRs were extracted from VigiBase. Disproportionality analyses were conducted to investigate psychiatric, hepatobiliary, renal, vascular, nervous, blood, skin, cardiac, musculoskeletal and general ADRs associated with levamisole and other drugs exposure. In secondary analyses, we compared the frequency of ADRs between levamisole and mebendazole and between levamisole type of use. RESULTS: Among the 1763 levamisole‐related ADRs identified, psychiatric disorders (reporting odds ratio with 95% confidence intervals: 1.4 [1.2–2.6]), hepatobiliary disorders (2.4 [1.9–4.3]), vasculitis (6.5 [4.1–10.6]), encephalopathy (22.5 [17.4–39.9]), neuropathy (4.3 [2.9–7.1]), haematological disorders, mild rashes and musculoskeletal disorders were more frequently reported with levamisole than with other drug. The majority of levamisole‐related ADRs occurred when the drug was administrated for a non–anti‐infectious indication. CONCLUSION: The great majority of the levamisole‐related ADRs concerned its immunomodulatory indication and multiple‐dose regimen. Our results suggest that single‐dose treatments for anthelmintic action have a good safety profile.