Prophylaxis and reversal of ifosfamide encephalopathy with methylene-blue.
The antineoplastic ifosfamide produces dose-dependent signs of neurotoxicity. After ifosfamide overdose in a patient, we found excessive urinary excretion of glutaric acid and sarcosine, which is compatible with glutaric aciduria type II, a defect in mitochondrial fatty acid oxidation that results from defective electron transfer to flavoproteins. We therefore used the electron-accepting drug methylene-blue as an antidote for ifosfamide encephalopathy. In one patient, ifosfamide neurotoxicity was rapidly reversed by methylene-blue 50 mg intravenously. In another patient with previous episodes of ifosfamide encephalopathy, methylene-blue was administered orally prophylactically. No symptoms of neurotoxicity were noted.
Küpfer
A
A
Department of Clinical Pharmacology, University of Berne, Switzerland.
Aeschlimann
C
C
Wermuth
B
B
Cerny
T
T
D000284:Administration, Oral; D000293:Adolescent; D000931:Antidotes; D001859:Bone Neoplasms / Q000188:drug therapy; D001927:Brain Diseases / Q000139:chemically induced / Q000517:prevention & control*; D062787:Drug Overdose; D005260:Female; D005977:Glutarates / Q000652:urine; D006801:Humans; D007069:Ifosfamide / Q000506:poisoning* / Q000627:therapeutic use; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy; D008751:Methylene Blue / Q000008:administration & dosage*; D012516:Osteosarcoma / Q000188:drug therapy; D011292:Premedication; D012521:Sarcosine / Q000652:urine
D000931:Antidotes; D005977:Glutarates; C035736:glutaric acid; D008751:Methylene Blue; D007069:Ifosfamide; D012521:Sarcosine