Posaconazole-increased vincristine neurotoxicity in a child: a case report.
A 9-year-old girl was managed according to the COPRALL 04 protocol for treatment of a relapse of acute lymphoblastic leukemia. Owing to a previous case of disseminated fusariosis, posaconazole was started 5 days before initiation of chemotherapy. Six days after the last dose of vincristine, the child reported symptoms of severe peripheral neuropathy, abdominal cramps, and constipation. After this, she developed fluctuations in her level of consciousness and seizures. After cessation of therapy with posaconazole, a complete resolution of the above occurred within 7 days. This case illustrates the possibility of vincristine toxicity exacerbated by coadministration of posaconazole. As posaconazole is an inhibitor of the isoenzyme CYP3A4, interactions with drugs that are metabolized via this pathway, such as vincristine, can be anticipated. Another possibility is that, like itraconazole, posaconazole may also inhibit P-glycoprotein-mediated vincristine efflux. Although case reports of neurotoxicity owing to possible interaction between itraconazole and vincristine exist in the literature, only 1 case report relating to the possible interaction between posaconazole and vincristine exists. Clinicians should be made aware of this possible drug-drug interaction.
Department of Medical Pharmacology and Toxicology, Arnaud de Villeneuve Hospital, CHU Montpellier, Montpellier, France.
Céline
C
Eiden
Gilles
G
Palenzuela
Dominique
D
Hillaire-Buys
Geneviève
G
Margueritte
Marylène
M
Cociglio
Sylvie
S
Hansel-Esteller
Hélène
H
Peyriere
D000935:Antifungal Agents / Q000009:adverse effects*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000633:toxicity; D002648:Child; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D005260:Female; D006801:Humans; D009181:Mycoses / Q000150:complications / Q000188:drug therapy*; D009422:Nervous System Diseases / Q000139:chemically induced; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy*; D012008:Recurrence; D014230:Triazoles / Q000009:adverse effects*; D014750:Vincristine / Q000009:adverse effects* / Q000633:toxicity
D000935:Antifungal Agents; D000972:Antineoplastic Agents, Phytogenic; D065692:Cytochrome P-450 CYP3A Inhibitors; D014230:Triazoles; D014750:Vincristine; C101425:posaconazole; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human