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[Antifungal azoles exacerbate vinblastine-related hyponatremia in ALL children]
Li-Ping Zhong1, Hong-Man Xue1, Dong-Bo Zhu1
1Department of Pediatrics,SUN Yat-Sen Memorial Hospital, Sun Yet-Sen University, Guangzhou 510120, Guangdong Province, China.
Insights
Vinblastine treatment for acute lymphoblastic leukemia (ALL) in children frequently causes hyponatremia. Combining vinblastine with azole antifungals significantly increases the risk and severity of this condition, necessitating avoidance of this drug combination.
Area of Science:
- Pediatric Oncology
- Clinical Pharmacology
- Nephrology
Context:
- Acute lymphoblastic leukemia (ALL) is a common childhood cancer.
- Vinblastine is a standard chemotherapeutic agent used in ALL treatment.
- Hyponatremia is a potential adverse effect of vinblastine therapy.
Purpose:
- To investigate the clinical characteristics of vinblastine-related hyponatremia in children with ALL.
- To evaluate the impact of azole antifungal agents on the incidence and severity of this hyponatremia.
- To determine optimal treatment and management strategies for vinblastine-induced hyponatremia.
Summary:
- A study of 93 children with ALL treated with vinblastine revealed a high incidence of hyponatremia (93.1%).
- The combination of vinblastine with azole antifungals significantly increased the incidence (100%) and severity of hyponatremia compared to vinblastine alone or with non-azole antifungals.
- Severe hyponatremia, manifesting as convulsions and coma, was exclusively observed in children receiving both vinblastine and azole antifungals.
Impact:
- The findings highlight the critical risk associated with co-administering azole antifungals and vinblastine in pediatric ALL patients.
- Management strategies including fluid restriction and sodium supplementation were effective in resolving hyponatremia.
- This study strongly recommends avoiding the combined use of azole antifungals with vinblastine to prevent severe hyponatremia and associated complications.
Abstract:
The purpose of this study was to investigate the clinical characteristics and the treatments of patients with vinblastine-related hyponatremia which was aggravated by azole antifungal agents in children with acute lymphoblastic leukemia(ALL). A total of 93 children treated with vinblastine in our department during April 2013 to March 2014 were enrolled in this study and were divided into 3 groups:VDLD, VDLD with azoles antifungal, VDLD with non azoles antifungal. The incidence and severity of hyponatremia were statistically analysed. The results showed that (1) the incidence of hyponatremia in VDLD group was 93.1%(67/72),100%(13/13) in VDLD with azoles antifungal group, and 75%(6/8) in VDLD with non-azoles antifungal, there was no statistically difference between these three groups. (2) Incidence of moderate to severe hyponatremia (Na<129 mmol/L) in VDLD with azoles antifungal group was(9/13,69.2%),which was significartly higher than those in VDLD group (22/72, 30.6%) and in VDLD with non azoles antifungal group (1/8, 12.5%). However, the difference between VDLD group and VDLD with non azoles antifungal group were not statistical significant. (3) the lowest serum sodium level in VDLD with azoles antifungal group (124.0 ± 8.6 mmol/L) was significantly lower than that in VDLD group (130.8 ± 3.8 mmol/L)and VDLD+non azoles antifungal group(132.9 ± 4.9 mmol/L). Otherwise, the difference was not statistically significant between VDLD group and VDLD with non azoles antifungal group. (4) four children with severe hyponatremia showed convulsions and coma which all belong to VDLD with azoles antifungal group. The children with hyponatremia were restricted intake of fluid, adjusted the liquid tension, supplied hypertonic sodium and given diuretic, the serum sodium value gradually picked up in these children. In 4-11 months' follow-up, no hyponatremia happened again in these children. It is concluded that the incident of hyponatremia in children treated with vinblastine is high, but most of them seldom showed clinical characteristics. The combination of antifungal azoles with vinblastine can increase the incidence and severity of hyponatremia. Therefore, combined administration of azole antifungals with vinblastine should be avoided.
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