Isoniazid toxicity - Revision history

Danbot: Add MedicationDose SMW entries for pyridoxine (adult + pediatric); doses verified against standard toxicology references

2026-03-20T17:39:36Z

Add MedicationDose SMW entries for pyridoxine (adult + pediatric); doses verified against standard toxicology references

← Older revision		Revision as of 17:39, 20 March 2026
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	*Patient will likely require admission and potentially ICU care for continued monitoring and evaluation		*Patient will likely require admission and potentially ICU care for continued monitoring and evaluation
	*If the patient has active [[TB]] also keep in respiratory isolation		*If the patient has active [[TB]] also keep in respiratory isolation


			==Medication Dosing==
			*{{MedicationDose\|drug=Pyridoxine\|dose=Gram-for-gram of INH ingested (empiric: 5 g)\|route=IV at 1 g/min\|context=Specific antidote\|indication=Isoniazid toxicity\|population=Adult\|notes=Infuse at 1 g/min until seizures stop; remainder over 4-6 hr}}
			*{{MedicationDose\|drug=Pyridoxine\|dose=70 mg/kg\|route=IV at 1 g/min\|context=Specific antidote\|indication=Isoniazid toxicity\|population=Pediatric\|max_dose=5 g\|notes=1:1 ratio with INH if known quantity ingested}}

	==See Also==		==See Also==

Ostermayer: /* Management */

2022-01-19T00:58:31Z

Management

← Older revision		Revision as of 00:58, 19 January 2022
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	==Management==		==Management==
	*Focus on aggressive supportive care and hemodynamic stabilization with early pyridoxine administration		*Focus on aggressive supportive care and hemodynamic stabilization with early pyridoxine administration
	*Pyridoxine does not reverse hepatic injury that can result from chronic toxicity.		*Pyridoxine does not reverse hepatic injury that can result from chronic toxicity.<ref>Farrell G. Drug induced hepatic injury. J. Gastroenterol. Hepatat. 1997; 12:S242l-S50</ref>
	===[[Activated Charcoal]]===		===[[Activated Charcoal]]===
	*If ingestion occurred within an hour of presentation, activated charcoal with cathartics may be necessary to restrict absorption and to facilitate excretion via the GI tract		*If ingestion occurred within an hour of presentation, activated charcoal with cathartics may be necessary to restrict absorption and to facilitate excretion via the GI tract

Ostermayer: /* Management */

2022-01-19T00:54:35Z

Management

← Older revision		Revision as of 00:54, 19 January 2022
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	==Management==		==Management==
	*Focus on aggressive supportive care and hemodynamic stabilization		*Focus on aggressive supportive care and hemodynamic stabilization with early pyridoxine administration
			*Pyridoxine does not reverse hepatic injury that can result from chronic toxicity.
	===[[Activated Charcoal]]===		===[[Activated Charcoal]]===
	*If ingestion occurred within an hour of presentation, activated charcoal with cathartics may be necessary to restrict absorption and to facilitate excretion via the GI tract		*If ingestion occurred within an hour of presentation, activated charcoal with cathartics may be necessary to restrict absorption and to facilitate excretion via the GI tract

Ostermayer: /* Pyridoxine */

2022-01-19T00:53:25Z

Pyridoxine

← Older revision		Revision as of 00:53, 19 January 2022
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	*May not be effective but will activate the GABA receptors and halt seizure activity		*May not be effective but will activate the GABA receptors and halt seizure activity
	==='''[[Pyridoxine]]'''===		==='''[[Pyridoxine]]'''===
	*'''Known INH quantity''' ingested treat with with a '''1:1 ingested isoniazid:administered pyridoxine''' dose ratio		*'''Known INH quantity''' ingested - treat with with a '''1:1 ingested isoniazid:administered pyridoxine''' dose ratio
	*'''Unknown INH quantity''' ingested treat with empiric 5g of pyridoxine ~~can be administered~~		*'''Unknown INH quantity''' ingested - treat with empiric 5g of pyridoxine

	*'''Children''' - start 70mg/kg (max 5 gm)<ref>Minns, A. et al. Isoniazid-Induced Status Epilepticus in a Pediatric Patient After Inadequate Pyridoxine Therapy. Pediatric Emergency Care. 2010:26(5)380-381</ref>		*'''Children''' - start 70mg/kg (max 5 gm)<ref>Minns, A. et al. Isoniazid-Induced Status Epilepticus in a Pediatric Patient After Inadequate Pyridoxine Therapy. Pediatric Emergency Care. 2010:26(5)380-381</ref>

Ostermayer: /* Pyridoxine */

2022-01-19T00:52:24Z

Pyridoxine

← Older revision		Revision as of 00:52, 19 January 2022
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	*Pyridoxine administration may temporarily worsen the metabolic acidosis		*Pyridoxine administration may temporarily worsen the metabolic acidosis
	*If seizures persist repeat dosing is encouraged based on initial dosing.		*If seizures persist repeat dosing is encouraged based on initial dosing.
	*Oral tablets may be only form of pyridoxine available at many hospitals. The tablets can be crushed and administered with fluids via a nasogastric tube while arranging for transfer. <Santucci, K. et al. Acute isoniazid exposures and antidote availability. Pediatric Emergency Care. 1999;15:99-101.</ref>		*Oral tablets may be only form of pyridoxine available at many hospitals. The tablets can be crushed and administered with fluids via a nasogastric tube while arranging for transfer. <ref>Santucci, K. et al. Acute isoniazid exposures and antidote availability. Pediatric Emergency Care. 1999;15:99-101.</ref>

	===[[Hemodialysis]]===		===[[Hemodialysis]]===

Ostermayer: /* Pyridoxine */

2022-01-19T00:52:03Z

Pyridoxine

← Older revision		Revision as of 00:52, 19 January 2022
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	*Pyridoxine administration may temporarily worsen the metabolic acidosis		*Pyridoxine administration may temporarily worsen the metabolic acidosis
	*If seizures persist repeat dosing is encouraged based on initial dosing.		*If seizures persist repeat dosing is encouraged based on initial dosing.
			*Oral tablets may be only form of pyridoxine available at many hospitals. The tablets can be crushed and administered with fluids via a nasogastric tube while arranging for transfer. <Santucci, K. et al. Acute isoniazid exposures and antidote availability. Pediatric Emergency Care. 1999;15:99-101.</ref>

	===[[Hemodialysis]]===		===[[Hemodialysis]]===

Ostermayer: /* Pyridoxine */

2022-01-19T00:46:10Z

Pyridoxine

← Older revision		Revision as of 00:46, 19 January 2022
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	*'''Unknown INH quantity''' ingested treat with empiric 5g of pyridoxine can be administered		*'''Unknown INH quantity''' ingested treat with empiric 5g of pyridoxine can be administered

	*'''Children''' - start ~~70-300mg~~/kg ~~and increase until seizure resolves~~<ref>Minns, A. et al. Isoniazid-Induced Status Epilepticus in a Pediatric Patient After Inadequate Pyridoxine Therapy. Pediatric Emergency Care. 2010:26(5)380-381</ref>		*'''Children''' - start 70mg/kg (max 5 gm)<ref>Minns, A. et al. Isoniazid-Induced Status Epilepticus in a Pediatric Patient After Inadequate Pyridoxine Therapy. Pediatric Emergency Care. 2010:26(5)380-381</ref>

	*IV infusion rate is ~~0.5~~ g/min until the seizures stop or the maximum dose is reached. Remainder of dose infused over 4 to 6 hours		*IV infusion rate is 1 g/min until the seizures stop or the maximum dose is reached. Remainder of dose infused over 4 to 6 hours
	*Pyridoxine administration may temporarily worsen the metabolic acidosis		*Pyridoxine administration may temporarily worsen the metabolic acidosis
			*If seizures persist repeat dosing is encouraged based on initial dosing.

	===[[Hemodialysis]]===		===[[Hemodialysis]]===

ClaireLewis: Removed redirect to INH toxicity

2021-02-08T14:56:38Z

Removed redirect to INH toxicity

← Older revision		Revision as of 14:56, 8 February 2021
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	~~#REDIRECT~~[[INH toxicity]]		==Background==
			*[[Isoniazid]] (INH) used for latent and active [[Tuberculosis\|TB]] treatment
			===Toxicology===
			*Isoniazid’s metabolites restrict the conversion of pyridoxine to pyrodoxal-5’-phosphate and binds to pyridoxine, facilitating its excretion in the urine
			*Loss of pyridoxine leads to decreased GABA synthesis due to the decreased function of glutamic acid decarboxylase (GAD)
			*[[Anion gap acidosis]] likely results from lactic acid buildup as a consequence of persistent seizure activity
			*Finally come due to decreased catecholamine synthesis secondary to pyridoxine depletion
			===Toxic Dose===
			*2-3g ingested can lead to symptoms, 10-15g can lead to death<ref name="Haddad">Haddad and Winchester’s Clinical Management of Poisoning and Drug Overdose, 4th Ed. Chapter 55: Isoniazid.</ref>
			===Pharmacology===
			*Absorbed via GI tract (small intestine), peak concentrations at 1-2 hours after ingestion
			*Volume of Distribution: 0.6L/kg
			===Metabolism===
			*Clearance of 46mL/min, metabolized by acetylation.
			**T<sub>1/2</sub> for fast acetylators = 70 minutes
			**T<sub>1/2</sub> for slow acetylators = 3 hours
			===Excretion===
			*Via kidneys with levels successfully measured in urine<ref name="Haddad"></ref>

			==Clinical Features==
			===Signs and Symptoms===
			*[[Seizure]]
			*[[Metabolic Acidosis]]
			*[[Coma]]
			*Signs and symptoms can appear 30 minutes after ingestion, with more severe symptoms including persistent seizures, metabolic acidosis, and coma

			*[[Hepatotoxicity]]
			**Most common side effect and more frequent with slow acetylators, the elderly, and those with preexisting liver disease
			**Approximately 20% of patients on isoniazid therapy can have elevated liver enzymes
			**Treatment is stopped when levels reach three times the upper limit of normal with symptoms or five times the limit of normal without<ref name="Haddad"></ref><ref>Gent, WL et al. Factors in hydrazine formation from isoniazid by paediatric and adult tuberculosis patients. Eur J Clin Pharmacol (1992) 43: 131-136.</ref>

			==Evaluation==
			*Seizures refractory to conventional treatment are hallmarks of isoniazid toxicity
			*Clinical history is extremely important in evaluating for isoniazid toxicity (i.e. dosing history, duration of treatment, estimated dose taken)
			*Elevated anion-gap metabolic acidosis with elevated lactate in the appropriate clinical setting AND refractory seizures should raise suspicion
			*INH levels can be measured but results may not immediately be available <ref name="Haddad"></ref>

			==Management==
			*Focus on aggressive supportive care and hemodynamic stabilization
			===[[Activated Charcoal]]===
			*If ingestion occurred within an hour of presentation, activated charcoal with cathartics may be necessary to restrict absorption and to facilitate excretion via the GI tract
			===[[Benzos]]===
			*May not be effective but will activate the GABA receptors and halt seizure activity
			==='''[[Pyridoxine]]'''===
			*'''Known INH quantity''' ingested treat with with a '''1:1 ingested isoniazid:administered pyridoxine''' dose ratio
			*'''Unknown INH quantity''' ingested treat with empiric 5g of pyridoxine can be administered

			*'''Children''' - start 70-300mg/kg and increase until seizure resolves<ref>Minns, A. et al. Isoniazid-Induced Status Epilepticus in a Pediatric Patient After Inadequate Pyridoxine Therapy. Pediatric Emergency Care. 2010:26(5)380-381</ref>

			*IV infusion rate is 0.5 g/min until the seizures stop or the maximum dose is reached. Remainder of dose infused over 4 to 6 hours
			*Pyridoxine administration may temporarily worsen the metabolic acidosis

			===[[Hemodialysis]]===
			*Can clear lactate and isoniazid from the bloodstream effectively and can be used as a final measure to increase clearance if needed. <ref name="Haddad"></ref>

			==Disposition==
			*Patient will likely require admission and potentially ICU care for continued monitoring and evaluation
			*If the patient has active [[TB]] also keep in respiratory isolation

			==See Also==
			*[[Seizure (Peds)]]
			*[[Seizures]]
			*[[Antidotes]]

			==References==
			<references/>
			[[Category:Toxicology]]

Elcatracho: Redirected page to INH toxicity

2021-02-06T01:19:03Z

Redirected page to INH toxicity

New page

#REDIRECT[[INH toxicity]]