Clinical Pharmacology and Therapeutics
Clinical Pharmacology and Therapeutics
5 years ago

Syndrome of inappropriate antidiuretic hormone secretion from concomitant use of itraconazole and vindesine

Syndrome of inappropriate antidiuretic hormone secretion from concomitant use of itraconazole and vindesine
L. Li, H. Zhou, Y. Zhou, Y. Han
What is known and objective Several studies have reported that itraconazole-induced inhibition of vincristine (VCR) metabolism might result in neurological impairment and syndrome of inappropriate antidiuretic hormone (SIADH). However, there are few reports concerning adverse drug reactions (ADRs) resulting from concomitant use of vindesine (VDS) and itraconazole. Here, we report the first case of adverse drug interactions (ADIs) between itraconazole and VDS in a Chinese child with acute lymphocytic leukaemia (ALL). Case summary A 4-year-old boy was diagnosed with standard-risk ALL and was receiving VDS (3 mg/m2) for maintenance therapy and itraconazole for IFI recurrence. Severe neurotoxicity, consisting mainly of trismus and SIADH, was noticed after 7 days of VDS administration. After discontinuation of itraconazole and its replacement with caspofungin, the patient recovered from neurological signs and symptoms. The ADIs can be explained by VDS accumulation owing to inherent loss of CYP3A5 (*3/*3) function, and inhibition of CYP3A4 activity by itraconazole. What is new and conclusion Syndrome of inappropriate antidiuretic hormone from co-administration of itraconazole and VDS has not previously been reported to our knowledge. We suggest that the concomitant use of these drugs should be avoided if possible. The use of alternative antifungal drugs (AFDs) should be considered, and ADRs should be closely monitored when the combination of itraconazole and VDS is unavoidable. This is the first case report of adverse drug interactions (ADIs) between itraconazole and VDS in a Chinese child with acute lymphocytic leukaemia (ALL). We paid more attention on the management of severe neurotoxicity, especially SIADH. The mechanism of ADIs can be explained by inhibition of itraconazole on both CYP3A and P-gp, which results in decreased VDS clearance and aggravated toxicity.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/jcpt.12598

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