Management of methotrexate‐induced neurotoxicity with aminophylline plus dextromethorphan in a pediatric patient with pineoblastoma

Abstract

Methotrexate (MTX)-induced neurotoxicity is a serious adverse event associated with potentially deleterious neurological manifestations. 1-10 Proposed management of MTX-induced neurotoxicity includes supportive care, leucovorin, dextromethorphan, and aminophylline. 1,2,8-13 Dextromethorphan is a noncompetitive N-methyl-D-aspartate receptor antagonist that has been reported as a potential treatment modality at antitussive doses of 1-2 mg/kg (maximum 60 mg/dose) by mouth twice daily; however, dextromethorphan use is limited in patients unable to take enteral medications. 11-13

Dosage of Aminophylline Used for the Treatment of Neurotoxicity Caused by Methotrexate

“…5 Thus, aminophylline is used for the treatment of methotrexate-induced neurotoxicity caused by an increase in adenosine levels, which seems to act by the blockade of adenosine receptors. 3,[5][6][7][8] Liao et al 1 used high-dose aminophylline (12 mg/kg for 6 consecutive days) to treat methotrexate-induced neurotoxicity in B-cell lymphoma with brain metastasis. However, the following points should be considered regarding the dosage of aminophylline to be used for the treatment of methotrexate-induced neurotoxicity.…”

“…The dosage of aminophylline described in previous reports that used aminophylline for the treatment of methotrexate-induced neurotoxicity in chemotherapy for acute lymphoblastic leukemia and pineoblastoma, was 2.5 mg/kg or 145 mg; this is relatively lower compared with the dosage described in this case report (12 mg/kg). 1,3,7,8 In addition, other case reports have suggested that intravenous aminophylline (100 mg every 6 hours) used for the treatment of methotrexate-induced neurotoxicity improved the symptoms. 6 However, treatment using aminophylline was ceased because of tachycardia and agitation as side effects of theophylline overdoses.…”