Toxicity of Vincristine Combined With Posaconazole in Children With Acute Lymphoblastic Leukemia

Abstract

There are limited data in children with ALL for posaconazole prophylaxis. We recommend that VCR side effects should be evaluated by careful monitoring of the patients who are on this combination therapy.

High‐dose posaconazole for azole‐resistant aspergillosis and other difficult‐to‐treat mould infections

“…In our case series, we had two patients with significant interactions. Toxicity of HD‐POS in combination with vincristine was seen in a child with ALL, resulting in hepatotoxicity, convulsions and hypertension which might be attributed to the inhibition of CYP3A4 as well as P‐gp resulting in increased levels of vincristine . Another allogeneic stem cell transplant patient developed IA despite prophylaxis with voriconazole.…”

“…Toxicity of HD-POS in combination with vincristine was seen in a child with ALL, resulting in hepatotoxicity, convulsions and hypertension which might be attributed to the inhibition of CYP3A4 as well as P-gp resulting in increased levels of vincristine. 40 In conclusion, registration of new antifungals with efficacy against azole-resistant A fumigatus is expected to take several more years. Therefore, targeting high serum concentrations of POS using the tablet or IV formulation is, in our point of view, a possible step-down option in patients with azole-resistant IA as long as the POS-MIC is <1 mg/L and for patients treated for mucormycosis with L-AmB.…”

Mucormycosis diagnosed during induction chemotherapy in five pediatric patients with acute lymphoblastic leukemia

“…Most of the patients experienced feeding intolerance and/or severe abdominal pain presumably secondary to the interaction between vincristine and posaconazole. Potentiation of vincristine neurotoxicity by azole antifungals through the inhibition of CYP3A4 is well known, but the specific symptom of abdominal pain is not well described …”

“…the inhibition of CYP3A4 is well known, but the specific symptom of abdominal pain is not well described. [17][18][19] Although mucormycosis is frequently fatal, rapid diagnosis and a multidisciplinary approach to treatment can lead to excellent outcomes, even in patients undergoing intensive chemotherapy. We recommend maintaining a high index of suspicion for IFI among children receiving induction therapy for ALL along with judicious management of both the infection and the underlying leukemia to achieve the best outcomes.…”

Posaconazole aggravates vincristine-related hypertension in children with acute lymphoblastic leukemia: a case report

“…1 A variety of drugs interact with vincristine to aggravate its side effects. 2,3 This paper reports the cases of two children who received vincristine for ALL and posaconazole for fungal infections who developed vincristine-related secondary hypertension.…”