Signs and Symptoms:

Isoniazid overdosage produces signs and symptoms within 30 minutes to 3 hours after ingestion. Nausea, vomiting dizziness, slurring of speech, blurring of vision, and visua hallucinations (including bright colors and strange designs are among the early manifestations. With marked overdosage, respiratory distress and CNS depression progressing rapidly from stupor to profound coma, are to be expected, along with severe, intractable seizures Severe metabolic acidosis, acetonuria, and hyperglycemia are typical laboratory findings.

Treatment:

Untreated or inadequately treated cases of gross isoniazid overdosage, 80 mg/kg-150 mg/kg, can cause neurotoxicity and terminate fatally, but good response has been reported in most patients brought under adequate treatment within the first few hours after drug ingestion.

For the Asymptomatic Patient: Absorption of drugs from the Gl tract may be decreased by giving activated charcoal. Gastric emptying should also be employed in the asymptomatic patient. Safeguard the patient's airway when employing these procedures. Patients who acutely ingest > 80 mg/kg should be treated with intravenous pyridoxine on a gram per gram basis equal to the isoniazid dose. If an unknown amoun of isoniazid is ingested, consider an initial dose of 5 grams of pyridoxine given over 30 to 60 minute in adults, or 80 mg/kg of pyridoxine in children.

For the Symptomatic Patient: Ensure adequate ventilation lation, support cardiac output, and protect the airway while treating seizures and attempting to limit absorption. If the dose of isoniazid is known, the patient should be treated initially with a slow Intravenous bolus of pyridoxine, over 3 to 5 minutes, on a gram per gram basis, equal to the isoniazid dose. If the quantity of isoniazid ingestion is unknown, then consider an initial intravenous bolus of pyridoxine of 5 grams in the adult or 80 mg/kg in the child. If seizures continue, the dosage of pyridoxine may be repeated. It would be rare that more 10 grams of pyridoxine would need to be given. The maximum safe dose for pyridoxine in isoniazid intoxication is not known. If the patient does not respond to pyridoxine, diazepam may be administered. Phenytoin should be used cautiously, because isoniazid interferes with the metabolism of phenytoin.

General

Obtain blood samples for immediate determination o gases, electrolytes, BUN, glucose, etc.; type and cross match blood in preparation for possible hemodialysis Rapid control of metabolic acidosis: Patients with this degree of INH intoxication are likely to have hypoventilation. The administration of sodium bicarbonate under these circumstances can cause exacerbation of hypercarbia. Ventilation must be monitored carefully, by measuring blo od carbon dioxide levels, and supported mechanically, if there is respiratory insufficiency.

Dialysis

Both peritoneal and hemodialysis have been used in the management of isoniazid overdosage. These procedures are probably not required if control of seizures and acidosis is achieved with pyridoxine, diazepam and bicarbonate.

Along with measures based on initial and repeated determination of blood gases and other laboratory tests as needed, utilize meticulous respiratory and other intensive care to protect against hypoxia, hypotension, aspiration pneumonitis, etc.

Isoniazid is contraindicated in patients who develop severe hypersensitivity reactions, including drug -induced hepatitis; previous isoniazid-associated hepatic injury; severe adverse reactions to isoniazid such as drug fever, chills, arthritis; and acute liver disease of any etiology.

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