Isoniazid poisoning: Pharmacokinetics and effect of hemodialysis in a massive ingestion

Skinner, Kirsty; Saiao, Ana; Mostafa, Ahmed; Soderstrom, Jessamine; Medley, Gregory; Roberts, Michael S.

doi:10.1111/hdi.12293

Cited by 12 publications

(8 citation statements)

References 11 publications

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“…A total of 949 articles were identified after removal of duplicates. Forty‐three articles were included for qualitative analysis: two animal experiments, 92,93 seven pharmacokinetic studies, 21,30,94–98 and 34 case reports or case series 9–14,29,36,40,99–123 . No randomized controlled trials or observational studies were identified.…”

Section: Resultsmentioning

confidence: 99%

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Extracorporeal treatments for isoniazid poisoning: Systematic review and recommendations from the EXTRIP workgroup

et al. 2021

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Isoniazid toxicity from self‐poisoning or dosing errors remains common in regions of the world where tuberculosis is prevalent. Although the treatment of isoniazid poisoning is centered on supportive care and pyridoxine administration, extracorporeal treatments (ECTRs), such as hemodialysis, have been advocated to enhance elimination of isoniazid. No systematic reviews or evidence‐based recommendations currently exist on the benefit of ECTRs for isoniazid poisoning. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup systematically collected and rated the available evidence on the effect of and indications for ECTRs in cases of isoniazid poisoning. We conducted a systematic review of the literature, screened studies, extracted data on study characteristics, outcomes, and measurement characteristics, summarized findings, and formulated recommendations following published EXTRIP methods. Forty‐three studies (two animal studies, 34 patient reports or patient series, and seven pharmacokinetic studies) met inclusion criteria. Toxicokinetic or pharmacokinetic analysis was available for 60 patients, most treated with hemodialysis (n = 38). The workgroup assessed isoniazid as “Moderately Dialyzable” by hemodialysis for patients with normal kidney function (quality of evidence = C) and “Dialyzable” by hemodialysis for patients with impaired kidney function (quality of evidence = A). Clinical data for ECTR in isoniazid poisoning were available for 40 patients. Mortality of the cohort was 12.5%. Historical controls who received modern standard care including appropriately dosed pyridoxine generally had excellent outcomes. No benefit could be extrapolated from ECTR, although there was evidence of added costs and harms related to the double lumen catheter insertion, the extracorporeal procedure itself, and the extracorporeal removal of pyridoxine. The EXTRIP workgroup suggests against performing ECTR in addition to standard care (weak recommendation, very low quality of evidence) in patients with isoniazid poisoning. If standard dose pyridoxine cannot be administered, we suggest performing ECTR only in patients with seizures refractory to GABAA receptor agonists (weak recommendation, very low quality of evidence).

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Section: Resultsmentioning

confidence: 99%

“…This can be explained by significant metabolism and elimination prior to dialysis in the latter study (perhaps by incomplete absorption as well). Toxicokinetic modeling suggests ECTR would be most beneficial within 2 h of isoniazid ingestion 121 …”

Section: Resultsmentioning

confidence: 99%

Extracorporeal treatments for isoniazid poisoning: Systematic review and recommendations from the EXTRIP workgroup

et al. 2021

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“…INH can also be cleared through hemodialysis which should be begun the earliest possible due to its rapid absorption [16, 17].…”

Section: Discussionmentioning

confidence: 99%

Seizures following Intoxication with a Common Antituberculosis Drug

Lahlou

Benlamkaddem

Berdaï

et al. 2019

Case Reports in Pediatrics

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Isoniazid is an antimycobacterial agent commonly prescribed in most tuberculosis chemotherapy regimens. Its side effects are widely known including mainly liver toxicity and peripheral neuropathy. The toxic effects of isoniazid are dose-related. Toxic doses are estimated at 35–40 mg/kg and fatal doses at 150 mg/kg. Treatment consists primarily of basic life support, antiepileptic drugs, and pyridoxine. The case is of one of the children with intentional isoniazid poisoning, the drug belonging to an uncle currently under antituberculosis treatment, resulting in tonic-clonic seizures. During her hospitalization in the paediatric intensive care unit, her neurological status as well as her lab values was closely monitored, and despite initial deterioration, the patient was discharged from critical care a week after full recovery.

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“…Hemodialysis is not necessary in mild poisoning with INH but well effective in severe intoxication and it provides rapid clinical improvement in this situation. It removes INH which did not adhere to the activated charcoal and toxic metabolites of it from circulation [2,4]. It should be kept in mind as an effective treatment option in severe INH intoxication by Emergency physicians.…”

Section: To the Editormentioning

confidence: 99%