Rifampin with delavirdine

Saquinavir is subject to extensive first-pass metabolism by CYP3A4 and functions as a CYP3A4 inhibitor as well as a substrate thus, there are many potential drug-drug interactions (Table 49-4). A decreased dose of saquinavir is recommended when -administered with nelfinavir. Increased saquinavir levels when -administered with omeprazole necessitate close monitoring for toxicities. Digoxin levels may increase if co administered with saquinavir and should therefore be monitored. Liver function tests should be monitored if saquinavir is -administered with delavirdine or rifampin. There is no evidence of human teratogenicity from saquinavir there is short-term safety data for both mother and infant. 

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. 

C. Delavirdine Drug interactions are a major problem with delavirdine, which is metabolized by both CYP3A4 and CYP2D6. Its blood levels are decreased by antacids, ddl. phenytoin. rifampin, and nelfinavir. Conversely, the blood levels of delavirdine are increased by azole anti-fiingals and macrolide antibiotics. Delavirdine increases plasma levels of several benzodiazepines, nifedipine, protea.se inhibitors, quinidine, and warfarin. Delavirdine causes skin rash in up to 20% of patients, and the drug should be avoided in pregnancy since it is teratogenic in animals. 

Delavirdine should not be used in combination with drugs that are CYP3A4 substrates such as pimozide, midazolam, triazolam, amiodarone, propafenone and ergot derivatives. Inducers of the hepatic P-450 system, rifampin, rifabutin, pheno-barbital, phenytoin or carbamazepine, should not be used in combination with delaviridine. It also increases the plasma levels of HIV protease inhibitors. 

Clinically important, potentially hazardous interactions with amiodarone, amitriptyline, amoxapine, benzodiazepines, bepridil, clomipramine, clonazepam, clorazepate, delavirdine, desipramine, diazepam, dihydroergotamine, doxepin, ergotamine, fentanyl, flurazepam, imipramine, ixabepilone, lidocaine, lorazepam, methysergide, midazolam, nortriptyline, oxazepam, phenytoin, protriptyline, quazepam, quinidine, rifampin, ritonavir, sildenafil, St John s wort, temazepam, tricyclic antidepressants, trimipramine, vitamin E... 

Clinically important, potentially hazardous interactions with amiodarone, anabolic steroids, antithyroid agents, barbiturates, bivalirudin, cimetidine, clofibrate, clopidogrel, cyclosporine, delavirdine, dextrothyroxine, disulfiram, fluconazole, glutethimide, imatinib, itraconazole, ketoconazole, metronidazole, miconazole, penicillins, phenylbutazones, piperacillin, quinidine, quinine, rifabutin, rifampin, rifapentine, rofecoxib, salicylates, sulfinpyrazone, sulfonamides, testosterone, thyroid, zileuton... 

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 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... 

Clinically important, potentially hazardous interactions with atazanavir, clarithromycin, darunavir, delavirdine, efavirenz, erythromycin, fosamprenavir, indinavir, itraconazole, ketoconazole, rifampin, ritonavir, telithromycin, tipranavir... 

Delavirdine and efavirenz need to be increased if given with rifampin, no dose... 

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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