Phenobarbital with delavirdine

Delavirdine is extensively metabolized to inactive metabolites by the CYP3A and CYP2D6 enzymes. However, it also inhibits CYP3 A and thus inhibits its own metabolism. In addition to its interactions with other antiretroviral agents (see Table 49 1), delavirdine will result in increased levels of numerous agents (Table 49-3). Dose reduction of indinavir and saquinavir should be considered if they are administered concurrently with delavirdine. Delavirdine plasma concentrations are reduced in the presence of antacids, phenytoin, phenobarbital, carbamazepine, rifabutin, and rifampin concentrations are increased during coadministration with clarithromycin, fluoxetine, dexamethasone, and ketoconazole. 

Since indinavir is a substrate as well as an inhibitor of CYP3 A4, numerous and complex drug interactions can occur as described above. Indinavir levels decrease with concurrent use of rifabutin, fluconazole, St. John s wort, and rifampin. Caution is advised with other 3 A4 inducers also, including phenobarbital, phenytoin, carbamezepine, and dexamethasone. Dose reduction of indinavir should be considered if coadministered with delavirdine, ketoconazole, or itraconazole, while an increase in the dose of indinavir is indicated if the drug is coadministered with efavirenz or rifabutin. 

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 allopurinol, amiodarone, amobarbital, anabolic steroids, anti-thyroid agents, aprobarbital, aspirin, barbiturates, bivalirudin, butabarbital, butalbital, cimetidine, clofibrate, clopidogrel, cyclosporine, delavirdine, disulfiram, fenofibrate, fluconazole, gemfibrozil, glutethimide, imatinib, itraconazole, ketoconazole, levothyroxine, liothyronine, mephobarbital, methimazole, metronidazole, miconazole, penicillins, pentobarbital, phenobarbital, phenylbutazones, piperacillin, prednisone, primidone, propylthiouracil, quinidine, quinine, rifabutin, rifampin, rifapentine, rofecoxib, salicylates, secobarbital, sulfinpyrazone, sulfonamides, testosterone, thyroid, zileuton... 

Clinically important, potentially hazardous interactions with amiodarone, atorvastatin, bepridil, carbamazepine, delavirdine, dihydroergotamine, etravirine, flecainide, itraconazole, ketoconazole, lidocaine, lopinavir, lovastatin, midazolam, phenobarbital, phenytoin, pimozide, propafenone, quinidine, rifabutin, rifampin, sildenafil, simvastatin, St John s wort, triazolam, vardenafil, warfarin... 

Clinically important, potentially hazardous interactions with amprenavir, aprepitant, atazanavir, carbamazepine, chlorpheniramine, cimetidine, clarithromycin, clorazepate, CNS depressants, darunavir, delavirdine, dexamethasone, efavirenz, erythromycin, esomeprazole, fluconazole, fluoxetine, fosamprenavir, grapefruit juice, griseofulvin, imatinib, indinavir, itraconazole, ivermectin, ketoconazole, lopinavir, nelfinavir, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, ritonavir, roxithromycin, saquinavir, St John s wort, telithromycin, tipranavir... 

Delavirdine Due to its shorter tj, d rapid emergence of resistance, delavirdine is the least used of the NNRTIs. Its absorption is best at acid pH and may be decreased by histamine Hj receptor antagonists or proton pump inhibitors. It is cleared predominantly by CYP3A4 and has an elimination tj 6 hours. It should be avoided with CYP3A4 substrates with a narrow therapeutic index and not combined with potent inducers of CYP3A4 (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, and rifampin). 

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