Erythromycin with benzodiazepines

Biotransformation of benzodiazepines occurs in the liver, where the drugs vmdergo phase I metabolism by the cytochrome P450 enzyme complex. Other drugs that may compete with benzodiazepines for liver microsomal enz)mies and result in decreased metabolism of benzodiazepines are erythromycin, ketoconazole, verapamil and... 

The route of metabolism can also be significant, particularly in those with liver disease or who are taking concomitant hepatic enzyme inhibitors, such as erythromycin (SEDA-20, 31). The complex interaction between hepatic dysfunction and benzodiazepines has been reviewed (33) these drugs more readily affect liver function in individuals with liver disease and may also directly contribute to hepatic encephalopathy, as shown by the ability of benzodiazepine antagonists to reverse coma transiently in such patients (33). Elderly people appear to be at increased risk only if they are physically unwell, and particularly if they are taking many medications. 

In a randomized, double-bhnd, pharmacokinetic-pharmacodynamic study, 12 volunteers took placebo or triazolam 0.125 mg orally, together with placebo, azithromycin, erythromycin, or clarithromycin. The apparent oral clearance of triazolam was significantly reduced by erythromycin and clarithromycin. The peak plasma concentration was correspondingly increased, and the half-life was prolonged. The effects of triazolam on dynamic measures were nearly identical when triazolam was given with placebo or azithromycin, but benzodiazepine agonist effects were enhanced by erythromycin and clarithromycin (23). 

E Itraconazole. Imatinib is primarily metabolized by the CYP3A4 hepatic enzyme system. Drugs that may inhibit this enzyme (such as ketoconazole, itraconazole, erythromycin, clarithromycin, etc.) may impair clearance of imatinib and result in increased toxicity. Imatinib itself is also a fairly potent inhibitor of the CYP3A4 enzyme and may result in toxicity due to other drugs that are substrates for this enzyme (such as simvastatin, warfarin, benzodiazepines, etc.). The other medications iisted are uniikeiy to affect the function of 0 P3A4 or interact adversely with imatinib. 

Clinically important, potentially hazardous interactions with antihistamines, azole antifungals, benzodiazepines, carbamazepine, cimetidine, delavirdine, diazepam, erythromycin, HIV protease inhibitors, ketorolac, macrolide antibiotics, neuroleptics, phenobarbital, phenytoin, rifampin, ritonavir... 

Clinically important, potentially hazardous interactions with amlodipine, anisindione, anticoagulants, aprepitant, atorvastatin, barbiturates, benzodiazepines, butabarbital, carbamazepine, chlordiazepoxide, clarithromycin, clonazepam, dorazepate, corticosteroids, cyclosporine, dexamethasone, diazepam, dicumarol, erythromycin, ethotoin, felodipine, flurazepam, fluvastatin, fosphenytoin, isradipine, itraconazole, ketoconazole, lorazepam, lovastatin, mephenytoin, mephobarbital, midazolam, nicardipine, nifedipine, nimodipine, nisoldipine, oxazepam, pentobarbital, phenobarbital, pimozide, pravastatin, primidone, quazepam, rifampin, secobarbital, simvastatin, St John s wort, temazepam, warfarin... 

With the exception of temazepam, which is eliminated by conjugation, all benzodiazepine hypnotics are metabolized by hepatic microsomal oxidation and then undergo glucuronide conjugation. Oxidation may be inhibited in patients with impaired liver function, advanced age, or concurrent use of drugs that inhibit oxidation. Drugs that inhibit the cytochrome P450 3A4 enzyme (e.g., erythromycin, nefazodone, fluvoxamine, and ketoconazole) reduce the clearance of triazolam and increase its plasma concentrations."... 

The serum levels and effects of midazolam, triazolam and zopi-clone are markedly increased and prolonged by erythromycin. The same interaction has been seen with clarithromycin, josamy-cin, or troleandomycin but not azithromycin. Alprazolam would be expected to be similarly affected. Other benzodiazepines, and the related hypnotic zaleplon, appear not to interact with the macrolides to a clinically significant extent... 

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