Pyridoxine for the treatment of isoniazid-induced seizures in intentional ingestions: The experience of a national poison center

Background: Pyridoxine (vitamin B6) is used as an antidote for isoniazid (INH) overdose, especially in intentional ingestions. The active form of pyridoxine is pyridoxal 5'-phosphate (P5P), a cofactor for glutamic acid decarboxylase in gamma aminobutyric acid (GABA) synthesis. INH inhibits this enzymatic pathway causing a decrease in brain levels of GABA the major inhibitory neurotransmitter in the central nervous system, with resultant increase in susceptibility to seizures. The aim of this study was to evaluate and document the role of pyridoxine in the treatment of patients with intentional ingestion of INH and to report our experience. Methods: Medical records of affected patients were reviewed; data collected included exposure history, clinical manifestations, physical examination, laboratory values and clinical outcomes. Results: There were 16 cases of INH intoxication associated with intentional ingestions, 11 were associated with substantial ingestions with the maximum dose ingested being 15 g. In 9 cases the patients suffered seizures while other dinical manifestations included hypertension, drowsiness and vomiting. Pyridoxine was administered prophylactically in only 3 patients, none of whom developed seizures. Conclusion: Intentional ingestion of INH is one of the causes of drug-induced seizures. Early recognition and specific treatment with pyridoxine can prevent mortality. Our series suggests that patients with large-dose intentional ingestions have a substantial risk of multiple seizures that can be treated successfully with 1 g of pyridoxine intravenously or 1 g of pyridoxine per gram of isoniazid ingestion. This antidote is safe and effective. Consideration can be given to administering pyridoxine prophylactically in some circumstances. (C) 2018 Elsevier Inc. All rights reserved.