Rifampicin Diazepam

The interaction of rifampicin with diazepam has been reviewed (54). The mean half-life of diazepam fell from 58 to 14 hours in seven patients who took isoniazid, rifampicin, and ethambutol (55). 

BZDs, NOT LORAZEPAM, OXAZEPAM, TEMAZEPAM RIFAMPICIN 1 BZD levels Induction of CYP3A4-mediated metabolism Watch for poor response to these BZDs consider increasing the dose, e.g. diazepam or nitrazepam 2-3-fold... 

Rifampicin Diazepam Ethosuximide Phenobarbital Phenytoin Valproate Reduced effect of the object drugs Induction of metabolism of the object drugs... 

Cronqvist, J. Nilsson-Ehle, I. Determination of acyclovir in human serum hy hi -performance liquid chromatography. J.Liq.Chromatogr., 1988, 11, 2593-2601 [serum non-interfering acetaminophen, allopurinol, baclofen, carbacholine, cefuroxime, chlorpropamide, cilastatin, cloxacillin, diazepam, di-cumarol, digoxin, flucloxacillm, furosemide, fusidic acid, fusidic, glipizide, heparin, hydrochlorothiazide, imipenem, insulin, isoniazid, ketoprofen, metronidazole, naproxen, perphenazine, phenytoin, prednisolone, propranolol, p3razinamide, p3ridoxine, ranitidine, rifampicin, rifampin, spironolactone, streptomycin, sulfamethoxazole, trimethoprim, warfarin]... 

CYP2C19 CYP2D6 diazepam, imipramine, 5-mephenytoin, omeprazol, proguanil, propranolol codeine, debrisoquine, dextromethorphan, flecainide, paroxetine, perphenazine, thioridazine carbamazepine, rifampicin cimetidine, felbamate fluoxetine, paroxetine, quinidine... 

As parecoxib is rapidly metabolised to valdecoxib, the interactions are usually considered to be due to the effects of valdecoxib. The manufacturer of parecoxib cautions the concurrent use with carbamazepine, dexamethasone and rifampicin as their effects on parecoxib have not been studied. Valdecoxib increases the levels of dextromethorphan and omeprazole. Because of these interactions, caution is advised with drugs that are metabolised by the same isoenzymes, nameiy flecainide, metoprolol, propafenone, omeprazoie, diazepam, imipramine and phenytoin. No interaction appears to occur between parecoxib and midazolam. 

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. 

The mean half-life of diazepam was redueed from 58 to 14 hours and the elearanee was inereased fourfold in 7 patients with tuberculosis who were given daily doses of isoniazid 500 mg to 2.2 g, rifampicin 450 to 600 mg and ethambutol 25 mg/kg, when eompared with healthy control subjects. In 21 healthy subjeets rifampiein 600 mg or 1.2 g daily for 7 days inereased the elearanee of diazepam by about threefold. ... 

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). 

Boyd has examined the delivery profile from cubosomes of various hydrophobic drugs, including griseofulvrn, rifampicin, diazepam and propofol [39]. In each case only burst release was found and the release reached a plateau within 20 min (Figure 15.6). 

Figure 15.6 Release of lipophilic drugs from cubosome dispersions by pressure ultrafiltration. Dispersions were loaded with griseofulvin ( ), rifampicin (B), diazepam ( ) and propofol (A). (Reprinted with permission from Ref [39].)...

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