Isoniazid reduces clearance of both diazepam and triazolam
A study in 9 healthy subjects found that isoniazid 90mg twice daily for 3 days increased half-life of a single 5- or 7.5mg dose of diazepam from about 34 to 45 hours, and reduced total clearance by 26 % (See reference number 1). A study in 6 healthy subjects found that isoniazid 90mg twice daily for 3 days, increased half-life of a single 500 microgram dose of triazolam from 2.5 to 3.3 hours, increased AUC by 46 % and reduced clearance by 43 % (See reference number 2).
A study in 9 healthy subjects found that isoniazid 90mg twice daily for 3 days had no effect on pharmacokinetics of a single 30mg oral dose of oxazepam (See reference number 2). Similarly, in another study, pharmacokinetics of clotiazepam were not altered by isoniazid (See reference number 3).
What is known suggests that isoniazid acts as an enzyme inhibitor, decreasing metabolism and loss of diazepam and triazolam from body, thereby increasing and prolonging their effects. Oxazepam which is metabolised by glucuronidation would be unlikely to interact.
Information is limited but interactions appear to be established. Their clinical importance is uncertain but be alert for need to decrease dosages of diazepam and triazolam if isoniazid is started. There seems to be no direct information about other benzodiazepines,but those undergoing high first-pass extraction and/or liver microsomal metabolism may interact similarly. Oxazepam and clotiazepam appear not to interact.
Ochs HR,Greenblatt DJ, Roberts G-M, Dengler HJ. Diazepam interaction with antituberculosis drugs. Clin Pharmacol Ther (1981) 29, 671–8.
Ochs HR,Greenblatt DJ, Knüchel M. Differential effect of isoniazid on triazolam oxidation and oxazepam conjugation. Br J Clin Pharmacol (1983) 16, 743–6.
Ochs HR,Greenblatt DJ, Verburg-Ochs B, Harmatz JS, Grehl H. Disposition of clotiazepam:influence of age, sex, oral contraceptives, cimetidine, isoniazid and ethanol. Eur J Clin Pharmacol (1984) 26, 55–9.