Delavirdine

C 4H2oN404 153473-24-6) see Delavirdine mesilate (l,l-dimethylethyl)[2-(28)-oxiranylethoxy]diphenylsilane (C2oH2602Si 116996-54-4) see Orlistat lV-(l,l-dimethylethyl)-3-oxo-4-aza-5a-androstane-17P-carboxamide... 

C21H24N9O3 136817-57-7) see Delavirdine inesilale (l-methylethyl)carbamic acid 2-(hydroxymethyl)-2-me-thylpentyl ester... 

CfjHftNjOj 6146-52-7) see Zafirlukast 5-nitroindole-2-carboxyllc acid (C9HftN204 16730-20-4) see Delavirdine mesilate nitromethane... 

The first lead compounds for non-nucleoside reverse transcriptase (RT) inhibitors (NNRTl) were discovered about 15 years ago (Pauwels et al. 1990 Merluzzi et al. 1990 Goldman et al. 1991 De Clercq 1993 Riibsamen-Waigmann et al. 1997). Since then they have become an important ingredient of the dmg combination schemes that are currently used in the treatment of human immunodeficiency virus type 1 (HlV-1) infections. Starting from the HEPT and TIBO derivatives, numerous classes of compounds have been described as NNRTIs. Four compounds (nevirapine, delavirdine, efavirenz and etravirine) have so far been approved for clinical use and several others are the subject of clinical trials (Balzarini 2004 Stellbrink 2007). 

Therapies not recommended for initial treatment due to poor potency or significant toxicity include delavirdine, nevirapine in patients with moderate to high CD4+ T-cell counts, indinavir or saquinavir used without ritonavir ( unboosted ), ritonavir used without another protease inhibitor, and tenofovir plus didanosine with an NNRTI. 

Delavirdine (DFV) 1 00-, 200-mg 400 mg tid (100 Use with caution in patients None Rash increased Metabolized by... 

Voorman, R.L., Payne, N.A., Wienkers, L.C., Hauer, M.J. and Sanders, P.E. (2001) Interaction of delavirdine with human liver microsomal cytochrome P450 inhibition of CYP2C9, CYP2C19, and CYP2D6. Drug Metabolism and Disposition, 29 (1), 41—47. 

Microsomal metabolism of delavirdine evidence for mechanism-based inactivation of human cytochrome P450 3A. Journal of Pharmacology and Experimental Therapeutics, 287 (1), 381-388. 

Delavirdine (4.91), a selective inhibitor of HIV-1 reverse transcriptase, also contains an amido N-atom as part of a piperazine ring. In rats and monkeys, cleavage of the amide bond constituted only a minor pathway [56]. 

Rifampin is known to induce the hepatic microsomal enzymes that metabolize various drugs such as acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta blockers, chloramphenicol, clofibrate, oral contraceptives, corticosteroids, cyclosporine, disopyramide, estrogens, hydantoins, mexiletine, quinidine, sulfones, sulfonylureas, theophyllines, tocainide, verapamil, digoxin, enalapril, morphine, nifedipine, ondansetron, progestins, protease inhibitors, buspirone, delavirdine, doxycycline, fluoroquinolones, losartan, macrolides, sulfonylureas, tacrolimus, thyroid hormones, TCAs, zolpidem, zidovudine, and ketoconazole. The therapeutic effects of these drugs may be decreased. 

Drugs that may interact with rifabutin include the following Anticoagulants, azole antifungal agents, benzodiazepines, beta blockers, buspirone, corticosteroids, cyclosporine, delavirdine, doxycycline, hydantoins, indinavir, rifamycins, losartan, macrolide antibiotics, methadone, morphine, nelfinavir, quinine, quinidine, theophylline, aminophylline, tricyclic antidepressants, and zolpidem. 

Delavirdine Consider dose reduction of indinavir to 600 mg every 8 hours when administering delavirdine 400 mg 3 times/day. 

Drugs that may affect indinavir include didanosine, aldesleukin, anticonvulsants, atazanavir, nelfinavir, nevirapine, omeprazole, rifapentine, ritonavir, clarithromycin, azole antifungals, rifamycins, delavirdine, efavirenz, St. John s wort. 

Drugs that may affect nelfinavir include anticonvulsants, azithromycin, azole antifungals, efavirenz, delavirdine, HMG-CoA reductase inhibitors, indinavir, interleukins, nevirapine, rifabutin, rifampin, ritonavir, saquinavir, St. John s wort. Drugs that may be affected by nelfinavir include amiodarone, antiarrhythmics (amiodarone, quinidine), azithromycin, benzodiazepines, efavirenz, ergot alkaloids, delavirdine, didanosine, fentanyl, indinavir, lamivudine methadone, nonsedating antihistamines, oral contraceptives, phenytoin, pimozide, quinidine, rifabutin, saquinavir, sildenafil, sirolimus, tacrolimus, zidovudine. 

Drugs that might decrease plasma concentrations of lopinavir/ritonavir include rifampin, phenobarbital, carbamazepine, phenytoin, azole antifungals, delavirdine, rifabutin, St. John s wort, efavirenz, nevirapine, and corticosteroids. 

Delavirdine tablets are indicated for the treatment of HIV-1 infection in combination with appropriate antiretroviral agents when therapy is warranted. This indication is based on surrogate marker changes in clinical studies. Clinical benefit was not demonstrated for delavirdine based on survival or incidence of AIDS-defining clinical events in a completed trial comparing delavirdine plus didanosine with didanosine monotherapy. 

Resistant virus emerges rapidly when delavirdine is administered as monotherapy. Therefore, always administer delavirdine in combination with appropriate antiretroviral therapy. 

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