Utah Poison Control Center

The monthly tox case, from Dr. Mike Moss! A 28 year-old male was inadvertently given 9 tabs of 300 mg INH (2700 mg) instead of 9 tabs of 100 mg INH (900 mg) for weekly treatment of latent tuberculosis. About 1-2 hours later, he suffered a single seizure and was transported to a local emergency department. The treating team administered 2700 mg pyridoxine IV, and the patient suffered no further seizures. He was admitted overnight for observation without further ill effects. He did not have any hepatotoxicity. He was discharged in good condition. Isoniazid Toxicity Isoniazid (or isonicotinic hydrazide – INH) is indicated for active and latent tuberculosis treatment. Typical doses are 5 mg/kg (up to 300 mg) daily or 15 mg/kg (up to 900 mg) once or twice weekly. It uniquely causes toxicity in mycobacteria after conversion to an active form which irreversibly binds to NADH, inhibiting a key enzyme for cell wall mycolic acid synthesis. While single therapeutic 600 mg doses of INH have been associated with seizures (Puri 2012), toxic doses are usually in excess of 20 mg/kg and lethal doses may be as low as 40 mg/kg (Brown 1972, Holdiness 1987, Terman 1970). Signs and symptoms of toxicity begin with 1-2 hours of ingestion. Patients may initially have vomiting, drowsiness, tachycardia, and hyperreflexia before developing refractory seizures. The metabolic acidosis and elevated lactate classically associated with INH (one of the “I”s in MUDPILES) is simply due to generalized seizures. Without GABA, benzodiazepines are unable to independently open GABA chloride channels making them ineffective at terminating seizures. Traditional antiepileptics targeting sodium channels are also ineffective. Levetiracetam could potentially be effective as it decreases glutamate release. Additionally, direct GABA agonists such as phenobarbital or propofol would likely be effective. However, the most effective and rapid treatment for INH induced seizures is simply pyridoxine. Recommended doses included 1) empiric dosing of 5 g pyridoxine 2) 1:1 quantities of pyridoxine to INH and 3) 1:5 ratio of pyridoxine to INH.

Dr. Mike Moss recently helped with an article on Microdosing candy injuries, the newest concern around the use of synthetic psychedelics- check it out here! https://buff.ly/3XbHtoa