eMedicine Specialties > Emergency Medicine > Toxicology
Toxicity, Isoniazid: Treatment & Medication
Updated: Mar 24, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Prehospital Care
Prehospital therapy for isoniazid poisoning is limited to supportive care and management of complications.
Emergency Department Care
- If the patient shows no signs of toxicity 4 hours following an ingestion of less than 20 mg/kg, expectant management is sufficient.
- Treatment of patients with evidence of toxicity involves managing immediate life threats, administering pyridoxine, and supportive care.
- Consider gastric lavage once the airway is secured; then administer activated charcoal at a dose 10 times that of the amount of ingested INH or 50 g if the ingested dose is unknown. Lavage and activated charcoal may not be effective if administered more than 1-2 hours after an acute ingestion.
- Control of seizures generally will correct metabolic acidosis.
- Administration of sodium bicarbonate may be beneficial in severe cases.
- While isoniazid (INH) is dialyzable, dialysis is usually unnecessary if adequate doses of anticonvulsants and pyridoxine are administered. Hemodialysis may be indicated if the patient fails to improve with standard therapy.
- Patients with clinically significant INH-associated hepatitis and progressive hepatic failure may be successfully treated with liver transplantation. INH is second only to acetaminophen among drugs resulting in hepatoxicity severe enough to warrant liver transplantation.
Consultations
- Discuss the patient's treatment with a regional poison control center or consult with a medical toxicologist.
- Obtain a psychiatric consultation in all cases of intentional overdose before discharge from hospital.
Medication
Medical management of isoniazid poisoning is directed at seizure control with pyridoxine. Benzodiazepine administration is a temporizing measure until large doses of pyridoxine are available.
Vitamin
Vitamins are involved in synthesis of GABA within the CNS.
Pyridoxine (Nestrex)
Vitamin B-6 and DOC for managing INH-induced seizures, metabolic acidosis, and mental status changes. Advisable to know in advance the availability of high doses in an institution.
Gram-for-gram dose based on the amount of INH ingested.
Adult
5 g IV over 3-5 min; repeat q5-20min until seizures resolve or patient regains consciousness
Pediatric
70 mg/kg IV; not to exceed 5 g
May decrease levodopa, phenytoin, and phenobarbital serum levels
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
>200 mg/d may precipitate withdrawal effects when medication is discontinued; may cause tachypnea, orthostatic hypotension, and seizures (rare)
Anticonvulsants
Standard anticonvulsants, when used alone, may be ineffective in controlling seizures. However, consider as first-line agents while pyridoxine is being prepared. Caution in using phenytoin because INH decreases metabolism of phenytoin, placing patients, especially slow-acetylators, at risk of phenytoin toxicity.
Lorazepam (Ativan)
DOC for status epilepticus because persists in CNS longer than diazepam. Rate of injection should not exceed 2 mg/min. May be administered IM if unable to obtain vascular access.
Adult
0.044 mg/kg (2-4 mg) IV, titrate to effect
Status epilepticus: 4 mg IV over 2-5 min; may repeat second dose in 10-15 min, if needed; not to exceed 8 mg
Pediatric
Children: 0.05 mg/kg IV (range, 0.02-0.1 mg/kg)
Adolescents: Administer as in adults
Status epilepticus:
Neonates: 0.05 mg/kg over 2-5 min; repeat in 10-15 min, if needed
Infants and children: 0.1 mg/kg over 2-5 min; repeat dose of 0.05 mg/kg IV at 10-15 min, if needed; not to exceed 4 mg
Adolescents: 0.7 mg/kg; not to exceed 4 mg, slowly over 2-5 min; repeat dose in 10-15 min, if needed
Alcohol, phenothiazines, barbiturates, and MAOIs increase CNS toxicity
Documented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor for respiratory depression with high or repeated doses; contains benzyl alcohol, which may be toxic to infants in high doses; caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, Parkinson disease, or patients who may have inhibition of benzodiazepine metabolism and clearance (eg, using nicotine, taking cimetidine)
Diazepam (Valium)
Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. Third-line agent for agitation or seizures because of shorter duration of anticonvulsive effects and accumulation of active metabolites that may prolong sedation.
Adult
5-10 mg IV q10-15min until symptoms resolve; not to exceed 30 mg
Pediatric
30 days to 5 years: 0.2-0.5 mg IV, slowly q2-5min until symptoms resolve; not to exceed 5 mg
>5 years: 1 mg IV, slowly q2-5min until symptoms resolve; not to exceed 10 mg
Increases toxicity of benzodiazepines in CNS with coadministration of phenothiazines, H1 blockers, barbiturates, alcohols, and MAOIs
Documented hypersensitivity; hypotension; acute narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution with other CNS depressants, low albumin levels, or renal and hepatic disease (may increase toxicity); monitor for respiratory depression with high or repeated doses
Midazolam (Versed)
Used as alternative in termination of refractory status epilepticus. Because water soluble, takes approximately 3 times longer than diazepam to peak EEG effects. Thus, clinician must wait 2-3 min to fully evaluate sedative effects before initiating procedure or repeating dose. Has twice the affinity for benzodiazepine receptors than diazepam. May be administered IM if unable to obtain vascular access.
Adult
0.01-0.05 mg/kg (usually 0.5-4 mg, up to 10 mg) IV, slowly over several min; may repeat q10-15min prn
Pediatric
<32 weeks: 0.5 mcg/kg/min IV infusion
>32 weeks: 1 mcg/kg/min IV infusion
Children: 0.05-0.2 mg/kg IV over 2-3 min, followed by 1-2 mcg/kg/min continuous infusion
Status epilepticus (refractory to standard therapy), >2 months and children: 0.15 mg/kg followed by continuous infusion of 1 mcg/kg/min, titrating dose upward q5min prn
Sedative effects may be antagonized by theophyllines; narcotics, cimetidine, ethanol, and erythromycin may accentuate sedative effects caused by decreased clearance; reduce dose of thiopental by 15% when using together
Documented hypersensitivity; preexisting hypotension; narrow-angle glaucoma; sensitivity to propylene glycol (diluent)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, pulmonary disease, renal impairment, hepatic failure, neuromuscular disease, hypotension, and patients >60 y; monitor for respiratory depression with high or repeated doses; consider lower dosages in organic brain syndrome and patients who may have inhibition of benzodiazepine metabolism and clearance (eg, using nicotine, taking cimetidine)
More on Toxicity, Isoniazid |
| Overview: Toxicity, Isoniazid |
| Differential Diagnoses & Workup: Toxicity, Isoniazid |
 Treatment & Medication: Toxicity, Isoniazid |
| Follow-up: Toxicity, Isoniazid |
| References |
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References
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Further Reading
Keywords
isoniazid toxicity, isoniazid poisoning, isoniazid exposure, treatment, symptoms, causes, isonicotinic acid hydrazide, INH, antituberculous medications, treatment of tuberculosis, prophylaxis of tuberculosis, isoniazid overdose, INH overdose, INH toxicity, INH poisoning, isoniazid ingestion, INH ingestion, tuberculosis treatment
