eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Toxicology

Toxicity, Isoniazid: Treatment & Medication

Author: David Tran, MD, Attending Physician, Department of Emergency Medicine, North Shore-LIJ Plainview Hospital
Coauthor(s): Binita R Shah, MD, FAAP, Professor of Clinical Pediatrics and Emergency Medicine, SUNY Health Sciences Center at Brooklyn; Director of Pediatric Emergency Medicine, Departments of Emergency Medicine and Pediatrics, Kings County Hospital Center
Contributor Information and Disclosures

Updated: Apr 15, 2009

Treatment

Medical Care

  • Therapy is mostly supportive in isoniazid (INH) toxicity and includes airway, breathing, and circulation. Provide oxygen and continuous cardiac and pulse oximetry monitoring. Obtain intravenous access. If the patient is asymptomatic after 4 hours with ingestion of less than 20 mg/kg, supportive treatment is sufficient.
  • If acute neurotoxicity (seizure, coma) occurs, administer pyridoxine immediately. Benzodiazepines and barbiturates can be used to potentiate the anticonvulsant effect of pyridoxine. Use phenytoin with caution because isoniazid inhibits the metabolism of phenytoin.
  • Ipecac syrup is contraindicated in patients with acute isoniazid neurotoxicity because it may increase the risk of aspiration secondary to seizure.
  • Perform gastric lavage and administer activated charcoal as soon as possible, preferably within 2 hours of acute ingestion.

Consultations

  • Contact regional poison control centers for assistance, if necessary.
  • Consult a psychiatrist for all suicidal cases.

Medication

Pyridoxine is the drug of choice for isoniazid (INH)-induced seizure or coma. If pyridoxine is not available, lorazepam or phenobarbital may be administered as temporary measures to control seizure while awaiting pyridoxine administration.

Vitamins

Vitamins are organic substances required by the body in small amounts for various metabolic processes. Vitamins may be synthesized in small or insufficient amounts in the body or not synthesized at all, thus requiring supplementation. They are used clinically for the prevention and treatment of specific vitamin deficiency states.


Pyridoxine (Nestrex)

Also known as vitamin B6. Involved in synthesis of GABA within the CNS. INH depletes pyridoxine, thus decreasing synthesis of GABA and increasing potential for seizures. For each gram of INH ingested, 1 g of parenteral pyridoxine should be given. If parenteral form is not available, tabs can be crushed and given as a slurry. A gram-for-gram replacement can also be used with pyridoxine tablets.

Adult

Known amount of INH ingested: 1 g pyridoxine for 1 g of INH IV/PO, initial dose not to exceed 5 g/30 min IV
Administer remaining dose in increments of 1 g/30 min until total dosage completed
Unknown amount of INH ingested: 70 mg/kg IV, not to exceed 5 g/30 min; once seizures are controlled, administer remaining dose over 4-6 h
May repeat initial IV dose q5-20 min until seizures are controlled

Pediatric

Administer as in adults

Pyridoxine may decrease levodopa, phenytoin, and phenobarbital serum levels

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

Extremely high doses may cause irreversible sensory loss

Anticonvulsants

These agents are used to prevent seizure recurrence and terminate clinical and electrical seizure activity.


Lorazepam (Ativan)

By increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation.

Adult

4 mg/dose IV slowly over 2-5 min and repeat in 10-15 min prn; not to exceed 8 mg/12 h

Pediatric

0.05-0.1 mg/kg IV infused at rate of 2 mg/min; not to exceed 4 mg/dose; may repeat once with 0.05 mg/kg IV in 10-15 min

Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAOIs

Documented hypersensitivity; preexisting CNS depression, hypotension, and narrow-angle glaucoma

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease


Diazepam (Valium)

Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA

Adult

5-15 mg IV q5min, repeat prn; not to exceed 30 mg in 8 h

Pediatric

0.2-0.3 mg/kg IV infused at rate of 1 mg/min; may repeat prn q15-30min, cumulative dose not to exceed 10 mg

Increases toxicity of benzodiazepines in CNS with coadministration of phenothiazines, barbiturates, alcohols, and MAOIs

Documented hypersensitivity; 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 hepatic disease (may increase toxicity)


Phenobarbital (Luminal)

Achieving therapeutic levels as quickly as possible is important. The IV dose may require approximately 15 min to attain peak levels in the brain. If injected continuously until convulsions stop, brain concentrations may continue to rise and can exceed that required to control seizures. Important to use minimal amount required and to wait for anticonvulsant effect to develop before giving a second dose.

Adult

15-20 mg/kg over 10-15 min IV in single or divided dose
Some patients may require 5 mg/kg/dose q15-30min until seizure is controlled or a total dose of 40 mg/kg is administered; rate of 30 mg/min

Pediatric

Administer as in adults

Coadministration with alcohol may produce additive CNS effects and death; chloramphenicol and MAOIs may increase phenobarbital effects; phenobarbital may decrease chloramphenicol effects; MAOIs may enhance sedative effects of barbiturates; rifampin may decrease effects of phenobarbital; valproic acid appears to decrease barbiturate metabolism and increase toxicity; barbiturates can decrease effects of anticoagulants, and patients stabilized on anticoagulants may require dosage adjustments if barbiturates are added to or withdrawn from their regimen; phenobarbital may decrease serum carbamazepine levels
Decreased effects of contraceptives may occur because of induction of microsomal enzymes (menstrual irregularities and pregnancy may occur); barbiturates may decrease corticosteroid effects by inducing hepatic microsomal enzymes; barbiturates may increase digitoxin metabolism; phenobarbital may decrease antimicrobial effects of metronidazole; barbiturates decrease theophylline levels, possibly resulting in decreased effects; phenobarbital may decrease bioavailability of verapamil

Documented hypersensitivity; severe respiratory disease, marked impairment of liver function, and nephritic patients

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

In prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; exercise caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia because adverse reactions can occur; exercise caution in patients with myasthenia gravis and myxedema

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References
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Further Reading

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Keywords

isoniazid, INH, INH toxicity, isoniazid poisoning, isonicotinic acid hydrazide, isoniazid-induced seizure, isoniazid seizure, tuberculosis, TB, overdose, seizure, tonic-clonic seizure, metabolic acidosis, treatment, diagnosis, hypotension, stupor tremor, mydriasis, urinary retention, ataxia, areflexia, nystagmus

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Contributor Information and Disclosures

Author

David Tran, MD, Attending Physician, Department of Emergency Medicine, North Shore-LIJ Plainview Hospital
David Tran, MD is a member of the following medical societies: American Academy of Emergency Medicine and American College of Emergency Physicians
Disclosure: Nothing to disclose.

Coauthor(s)

Binita R Shah, MD, FAAP, Professor of Clinical Pediatrics and Emergency Medicine, SUNY Health Sciences Center at Brooklyn; Director of Pediatric Emergency Medicine, Departments of Emergency Medicine and Pediatrics, Kings County Hospital Center
Binita R Shah, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Medical Editor

William T Zempsky, MD, Associate Director, Assistant Professor, Department of Pediatrics, Division of Pediatric Emergency Medicine, University of Connecticut and Connecticut Children's Medical Center
William T Zempsky, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Jeffrey R Tucker, MD, Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut and Connecticut Children's Medical Center
Jeffrey R Tucker, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Pediatrics, and Massachusetts Medical Society
Disclosure: Merck Salary Employment

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting

Chief Editor

Timothy E Corden, MD, Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin
Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, and Wisconsin Medical Society
Disclosure: Nothing to disclose.

 
 
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