Abstract
Coadministration of azoles and vincristine has been shown to increase vincristine neurotoxic effects due to the inhibition of cytochrome P450 (CYP) isoform 3A4, for which vincristine is a substrate. Despite the absence of any casual relationship between seizure and coadministration of azoles, few case reports of vincristine-induced seizure have been documented after coadministration of fluconazole or posaconazole in children. In this paper we are reporting the first young female adult who experienced generalized seizure after coadministration of posaconazole and vincristine. The 19-year-old female was diagnosed with acute lymphoblastic leukemia. She started induction phase of Berlin Frankfurt Muenster protocol along with posaconazole 200 mg three times daily as prophylactic antifungal therapy. Five days after the third vincristine dose, she developed generalized seizure accompanied by high blood pressure and SIADH. Her neurological exam/CT scan did not show any abnormality. In conclusion, this study reports a novel finding in the sense that all previous case reports pertaining to posaconazole-vincristine-induced seizure in literature involved children. Physicians should be made aware of this rare possible outcome to closely monitor their patients and take appropriate measures to prevent such possible adverse effect.
Highlights
Vincristine (VCR) is widely used in the treatment of acute lymphoblastic leukemia (ALL) [1]
Coadministration of azoles and VCR has been shown to increase VCR neurotoxic effects due to the inhibition of cytochrome P450 (CYP) isoform 3A4, for which VCR is a substrate [1, 5]. Those neurotoxic symptoms usually present as constipation and peripheral neurotoxicity [6, 7]
Despite the absence of any casual relationship between seizure and coadministration of azoles, few case reports of VCR-induced seizure have been documented after coadministration of fluconazole in an 11-years-old child [8] and coadministration with PSZ in 9- and 4-year-old children [9, 10]
Summary
Vincristine (VCR) is widely used in the treatment of acute lymphoblastic leukemia (ALL) [1]. Coadministration of azoles (as prophylaxis or treatment of fungal infections) and VCR has been shown to increase VCR neurotoxic effects due to the inhibition of cytochrome P450 (CYP) isoform 3A4, for which VCR is a substrate [1, 5]. Those neurotoxic symptoms usually present as constipation and peripheral neurotoxicity [6, 7]. Despite the absence of any casual relationship between seizure and coadministration of azoles, few case reports of VCR-induced seizure have been documented after coadministration of fluconazole in an 11-years-old child [8] and coadministration with PSZ in 9- and 4-year-old children [9, 10]
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