Isoniazid Chlorzoxazone

E1 Chlorzoxazone, isoniazid, acetaminophen, halothane, enflurane, methoxyflurane Dimethylnitrosamine, benzene, halogenated alkanes (eg, CCLj) acylonitrile, alcohols, aniline, styrene, vinyl chloride Chlorzoxazone (6-OH), [p-nitrophenol]... 

Drugs that may interact with disulfiram include alcohol, benzodiazepines, caffeine, chlorzoxazone, cocaine, hydantoins, isoniazid, metronidazole, theophylline, tricyclic antidepressants, and warfarin. 

Drugs that may interact with isoniazid include acetaminophen, carbamazepine, chlorzoxazone, disulfiram, enflurane, hydantoins, ketoconazole, rifampin, and theophylline. 

E1 Acetaminophen, chlorzoxazone, enflurane, halothane, ethanol (a minor pathway) Ethanol, isoniazid 4-Methylpyrazole, disulfiram... 

Isoniazid Isoniazid is incompatible with sugars. Isoniazid overdose may be severe to fatal, and treatment is symptomatic and supportive, including stomach wash for control of convulsions and treating metabolic acidosis. Administration of pyridoxine and hemodialysis may be needed. Isoniazid interacts with carba-mazepine, phenytoin, diazepam, triazolam, chlorzoxazone, theophylline, ethosux-imide, enflurane, cycloserine, and warfarin. 

CYP2E1 Ethanol Acetaminophen Ethanol Isoniazid Disulfiram (Yes)" Chlorzoxazone... 

E1 Chlorzoxazone 6-hydroxylation" p-Nitrophenol hydroxylation"" iV-N itrosodimethylamine A -demethylationP Ethanol Isoniazid 4-Methylpyrazole "" Diethyldithiocarbamate"" Chlorzoxazone... 

CYP2E1 chlorzoxazone, ethanol, paracetamol ethanol, isoniazid diethyldithiocarbamate... 

The adverse effects of chlorzoxazone may be increased in some patients (particularly slow-acetylators of isoniazid) if they also take isoniazid. 

Five out of 10 healthy slow acetylators of isoniazid experienced an increase in the adverse effects of a 750-mg dose of chlorzoxazone (sedation, headache, nausea) after taking isoniazid 300 mg daily for 7 days. These symptoms disappeared within 2 days of withdrawing the isoniazid. Pharmacokinetic analysis showed that the clearance of chlorzoxazone was reduced by 56% when given on the last day of isoniazid administration, then increased by 56% when given 2 days after stopping isoniazid. Similar findings were reported in another study in slow acetylators of isoniazid chlorzoxazone clearance was reduced by 78% when subjects had taken isoniazid 300 mg daily for 14 days, at which point the isoniazid was stopped. Two days later chlorzoxazone clearance was increased by 58%, and it had returned to normal 2 weeks later. Rapid acetylators of isoniazid also had a 60% reduction in chlorzoxazone clearance on the last day of isoniazid administration, but did not have any increase 2 days later. ... 

Isoniazid appears to cause a dual interaction. During administration, it inhibits the activity of cytochrome P450 isoenzyme CYP2E1, the enzyme involved in the metabolism of chlorzoxazone. Shortly after stopping isoniazid, the metabolism of chlorzoxazone is increased, possibly because of induction of CYP2E1, although this effect was only evident in the slow acetylators. ... 

The increase in chlorzoxazone levels is established, and occurs in both slow and fast acetylators of isoniazid, although the increase in levels is slightly greater in slow acetylators. In practical terms this means that it may be necessary to reduce the chlorzoxazone dosage in some patients if they take isoniazid. Monitor concurrent use carefully. The rebound increase in chlorzoxazone clearance in slow acetylators on stopping isoniazid was short-lived and is probably of little clinical importance. 

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