Rifampicin Benzodiazepines

Beta-blockers interact with a large number of other medications. The combination of beta-blockers with calcium antagonists should be avoided, given the risk for hypotension and cardiac arrhythmias. Cimetidine, hydralazine, and alcohol all increase blood levels of beta-blockers, whereas rifampicin decreases their concentrations. Beta-blockers may increase blood levels of phenothiazines and other neuroleptics, clonidine, phen-ytoin, anesthetics, lidocaine, epinephrine, monoamine oxidase inhibitors and other antidepressants, benzodiazepines, and thyroxine. Beta-blockers decrease the effects of insulin and oral hypoglycemic agents. Smoking, oral contraceptives, carbamazepine, and nonsteroidal anti-inflammatory analgesics decrease the effects of beta-blockers (Coffey, 1990). 

Benzodiazepines + smoking, rifampicin —> due to enzyme induction, plasma concentration of the benzodiazepine is reduced. 

Enzyme induction can be problematic with co-administration of benzodiazepines and rifampicin or certain anticonvulsants (phenobarbital, phenytoin, carbamaze-pine). However, despite enzyme stimulation, the net effect of adding these anticonvulsants can be augmentation of benzodiazepine-induced sedation. 

Rifampicin causes a very marked increase in the metaboiism and/or ciearance of diazepam and nitrazepam. Rifampicin aiso causes a marked increase in the ciearance of midazoiam and tria-zoiam and the non-benzodiazepine hypnotics, zaiepion, zoipidem andzopicione. Benzodiazepines and reiated drugs that are metabolised similarly are expected to interact in the same way. 

Rifampicin is a potent liver enzyme inducer, which increases the metabolism of several benzodiazepines and the non-benzodiazepine hypnotics, zaiepion, zoipidem and zopiclone, thereby decreasing their levels. The metabolism of midazolam by the cytochrome P450 isoenzyme CYP3A4 in both liver and gut is affected. The enzyme inducing effects of rifampicin seem to predominate if isoniazid (an enzyme inhibitor) is also present. Temazepam undergoes glucuronidation and is therefore unaffected by rifampicin. 

The documentation of these interactions is limited but what has been reported is consistent with the way rifampicin interacts with many other drugs. The clinical importance of some of these interactions between the benzodiazepines and related drugs and rifampicin has not yet been assessed but what is known suggests that the dosage of diazepam and nitrazepam may need to be increased if rifampicin is given. Be alert for a reduction in the effects of other similarly metabolised benzodiazepines (e.g. chlordiazepoxide, flurazepam). 

Those benzodiazepines that, like temazepam, undergo glucuronidation (e.g. lorazepam, oxazepam) are not expected to be affected by rifampicin and may be useful alternatives. 

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