A Case of Severe Toxicity During Coadministration of Vincristine and Piperacillin

Abstract

Neurotoxicity is frequent with vincristine treatment, but severe autonomic neuropathy is rare. A decreased activity of drug transporters in the presence of an interacting drug may favor such events by increasing systemic or tissue exposure to the drug. We encountered severe autonomic neuropathy and cholestasis in a child receiving vincristine, after the introduction of piperacillin-tazobactam. A causality assessment of the adverse reaction identified the antibiotic as the most probable cause of the observation. The patient was heterozygous for several common polymorphisms of ABCC2 (multidrug-related protein-2), CYP3A5, and ABCB1 (multidrug-related protein-1, P-glycoprotein), but their role in the toxicity cannot be ascertained.

Involvement of Cannabinoid Signaling in Vincristine-Induced Gastrointestinal Dysmotility in the Rat

“…Importantly, gastrointestinal ileus induced by vincristine, in contrast to sensory neuropathy, seems to be transient and is reverted soon after treatment discontinuation (Sharma, 1988 ; Chae et al, 1998 ; Peixoto Júnior et al, 2009 ). However, in addition to reducing quality of life, vincristine-induced gastrointestinal dysmotility may be problematic and even fatal, particularly under certain circumstances (liver failure, concomitant condition predisposing to constipation, drug interactions, or even accidental overdose: (Toghill and Burke, 1970 ; Leker et al, 1997 ; Bermúdez et al, 2005 ; Uner et al, 2005 ; Levêque et al, 2009 ; Diezi et al, 2010 ; Le Guellec et al, 2012 ; Essa et al, 2014 ; Yasu et al, 2016 ). This justifies the search for anti-ileus treatments.…”