Conditions · Emergency medicine and toxicology
Isoniazid toxicity !
Poisoning by the tuberculosis medicine isoniazid. An overdose causes seizures that resist usual drugs, acidosis and coma; vitamin B6 is the antidote.
Updated 2026-11-01
Structures involved
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Why it happens
- Injury by therapeutic drugs: the classic examples
- The main neurotransmitters
- Vitamin B6 (pyridoxal phosphate)
- Glutamate (glutamic acid)
What it is
Toxicity of isoniazid, a first-line tuberculosis drug. Acute overdose produces the classic triad of seizures that do not respond to usual anticonvulsants, high anion gap metabolic acidosis and coma. Long-term therapy can instead cause liver injury (drug-induced hepatitis) and peripheral neuropathy.
Who gets it
Tuberculosis remains a public health problem in Colombia, and isoniazid is used widely for active disease and for preventive treatment of contacts and people living with HIV, so tablets are available in many homes. Acute poisoning occurs in intentional overdose (historically noted in Indigenous communities in North America) and in accidental ingestion by children; hepatotoxicity is far more common than overdose.
Causes
- Intentional overdose
- Accidental ingestion by a child in a household on tuberculosis treatment
- Dosing error
- Chronic therapy causing hepatotoxicity or neuropathy
Risk factors
- Access to tuberculosis medicines at home
- Depression or prior self-harm
- For hepatotoxicity: older age, alcohol use, chronic hepatitis B or C, HIV, pregnancy and the postpartum period, combination with rifampicin
- Slow acetylator status (neuropathy and some liver injury)
- Malnutrition, diabetes, alcohol use and pregnancy (neuropathy without pyridoxine)
Pathophysiology
Isoniazid depletes active vitamin B6 (pyridoxal 5'-phosphate) by inhibiting pyridoxine phosphokinase and binding pyridoxal phosphate into inactive complexes. Pyridoxal phosphate is the cofactor of glutamic acid decarboxylase, which makes GABA; with less GABA the brain becomes hyperexcitable and seizures resist benzodiazepines, which need GABA to act. Repeated seizures produce lactic acidosis, and isoniazid also blocks lactate conversion. Hepatotoxicity comes from reactive hydrazine metabolites.
Classification
- Acute overdose: seizures, metabolic acidosis, coma
- Chronic toxicity: drug-induced hepatitis
- Chronic toxicity: peripheral (sensory) neuropathy from B6 deficiency
- Other: drug-induced lupus, sideroblastic anaemia, interactions raising phenytoin and carbamazepine levels
Symptoms and signs
- Nausea, vomiting, slurred speech and dizziness within 30 minutes to 2 hours of overdose
- Recurrent generalised tonic-clonic seizures
- Deep fast breathing from acidosis
- Coma
- Chronic: loss of appetite, jaundice, dark urine and right upper quadrant pain (hepatitis)
- Chronic: tingling and burning in the hands and feet (neuropathy)
Diagnosis
- Clinical
- Suspect it in any refractory seizure in a person with access to tuberculosis medicines; ask about household members on treatment. Diagnosis is clinical; isoniazid levels are not available quickly.
- Tests
- Blood gas with anion gap and lactate; glucose; creatine kinase (rhabdomyolysis); electrolytes; liver enzymes and bilirubin; acetaminophen and salicylate levels in intentional overdose.
- Imaging
- Head CT if there is head injury or doubt about another cause of seizures.
Differential diagnosis
- Status epilepticus from epilepsy or structural brain disease
- Other toxic seizures (tricyclic antidepressants, bupropion, theophylline, cocaine)
- Hypoglycaemia
- Alcohol or benzodiazepine withdrawal seizures
- Toxic alcohol poisoning with high anion gap acidosis
Goal of treatment
Stop seizures by replacing vitamin B6, correct acidosis and protect the airway; in chronic therapy, detect liver injury early and stop the drug.
Treatment
- Acute
- Intravenous pyridoxine (vitamin B6) is the specific antidote and should be given without waiting for confirmation, together with benzodiazepines, which work better once GABA is restored. Airway protection and oxygen.
- Medical
- Sodium bicarbonate for severe acidosis that persists after seizure control; activated charcoal only when the airway is safe and the ingestion is recent; fluids for rhabdomyolysis.
- Procedure
- Haemodialysis in severe cases with refractory acidosis or seizures despite antidote, or kidney failure.
- Follow-up
- During tuberculosis therapy: baseline and periodic liver tests in at-risk patients and teaching to report symptoms of hepatitis. Pyridoxine supplementation prevents neuropathy in at-risk groups. Nursing: seizure precautions, suction at the bedside, directly observed therapy.
- Conservative
- Stop isoniazid if hepatitis develops; the tuberculosis regimen is rebuilt by the treating team.
Complications
- Status epilepticus and hypoxic brain injury
- Aspiration pneumonia
- Rhabdomyolysis and acute kidney injury
- Fulminant drug-induced hepatitis
- Persistent peripheral neuropathy
Prognosis
With prompt pyridoxine and supportive care, most acute poisonings recover without sequelae; delays can lead to death or brain injury from prolonged seizures. Drug-induced hepatitis usually resolves when isoniazid is stopped early, but severe cases can progress to liver failure.
Prevention
- Safe storage of tuberculosis medicines, limited supplies for people at risk, pyridoxine for at-risk patients and monitoring for hepatitis during treatment
Test yourself
Think of the answer, then tap the question to see it.
What is the classic triad of acute isoniazid overdose?
Seizures refractory to usual anticonvulsants, high anion gap metabolic acidosis and coma.
Why do isoniazid seizures resist benzodiazepines?
B6 depletion lowers GABA synthesis by glutamic acid decarboxylase; benzodiazepines need GABA to act.
What is the antidote for isoniazid toxicity?
Intravenous pyridoxine (vitamin B6), given empirically together with benzodiazepines.
Which patients on isoniazid need pyridoxine to prevent neuropathy?
Those with malnutrition, diabetes, HIV, alcohol use, kidney failure, pregnancy or breastfeeding.
What should a nurse teach a patient starting isoniazid?
To report loss of appetite, nausea, jaundice, dark urine or abdominal pain promptly and to avoid alcohol, because of hepatitis risk.
Related conditions
- Tuberculosis
- Pulmonary tuberculosis
- Status epilepticus
- High anion gap metabolic acidosis
- Lactic acidosis
- Rhabdomyolysis
- Acute liver failure
- Alcohol use disorder
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Seizures following Intoxication with a Common Antituberculosis Drug (Case Reports in Pediatrics (PubMed Central), 2019).
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