Didanosine Delavirdine

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. 

Abacavir — Adefovir — Amprenavir1 — Delavirdine — Didanosine (ddl) — Efavirenz — Indinavir1 — Neirinavir — Nevirapine1 — Ritonavir — Saquinavir1 — Stavudine (d4T) — Zalcitabine (ddC) — Zidovudine (AZT)... 

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. 

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. 

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. 

Drugs that may affect delavirdine include the following Anticonvulsants, antacids, clarithromycin, didanosine, fluoxetine, histamine H2 antagonists, ketoconazole,... 

Drugs that may be affected by delavirdine include the following Clarithromycin, indinavir, amprenavir, benzodiazepines, cisapride, dihydropyridine calcium channel blockers, ergot derivatives, quinidine, sildenafil, warfarin, saquinavir, and didanosine. 

Abacavir (Ziagen) Amprenavir (Agenerase) Delavirdine (Rescriptor) Didanosine [ddl] (Videx) Efavirenz (Sustiva) Efavirenz/Emtricitabine/ Tenofovir (Atripla) Fosamprenavir (Lexiva)... 

TC Lamivudine ABC Abacavir d4T Stavudine ddC Zalcitabine ddl Didanosine TDF Tenofovir ZDV Zidovudine, also abbreviated as AZT FTC Emtricitabine NVP Nevirapine DLV Delavirdine EFV Efavirenz RTV, r Ritonavir Pl/r Ritonavir boosted protease inhibitor SQV Saquinavir IDV Indinavir LPV Lopinavir NEV Nelfinavir APV Amprenavir ATV Atazanavir DRV Darunavir... 

Buffering agents that are compounded with didanosine to counteract its degradation by gastric acid may interfere with the absorption of other drugs that require acidity (e.g., indinavir, delavirdine, ketoconazole, fluoroquinolones, tetracyclines, dapsone). An enteric-coated formulation Videx EC) that dissolves in the basic pH of the small intestine is not susceptible to these interactions. Ganciclovir and valganciclovir can increase blood levels of didanosine. The use of zalcitabine with didanosine is not recommended because that combination carries an additive risk of peripheral neuropathy. The combination of didanosine with stavudine increases the risk of pancreatitis, hepatotoxicity, and peripheral neuropa-... 

The buffer in didanosine tablets and powder interferes with absorption of indinavir, delavirdine, atazanavir, dapsone, itraconazole, and fluoroquinolone agents therefore, administration should be separated in time. Serum levels of didanosine are increased when -administered with tenofovir or ganciclovir, and are decreased by atazanavir, delavirdine, ritonavir, tipranavir, and methadone (Table 49-4). 

Delavirdine Fosamprenavir, didanosine, lopinavir, nelfinavir, ritonavir... 

Didanosine Tenofovir, ganciclovir Atazanavir, delavirdine, ritonavir, tipranavir... 

Fosamprenavir Abacavir, atazanavir, delavirdine, etravirine, indinavir, lopinavir, ritonavir, tipranavir, zidovudine Didanosine, efavirenz, nevirapine, saquinavir... 

Ritonavir Fosamprenavir, delavirdine, efavirenz, indinavir Didanosine, tenofovir, zidovudine... 

At the present time, there are at least 14 compounds that have been formally approved for the treatment of human immunodeficiency virus (HIV) infections. There are six nucleoside reverse transcriptase inhibitors (NRTIs) that, after their intracellular conversion to the 5 -triphosphate form, are able to interfere as competitive inhibitors of the normal substrates (dNTPs). These are zidovudine (AZT), didanosine (ddl), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), and abacavir (ABC). There are three nonnucleoside reverse transcriptase inhibitors (NNRTIs) — nevirapine, delavirdine, and efavirenz — that, as such, directly interact with the reverse transcriptase at a nonsubstrate binding, allosteric site. There are five HIV protease inhibitors (Pis saquinavir, ritonavir, indinavir, nelfinavir, and amprenavir) that block the cleavage of precursor to mature HIV proteins, thus impairing the infectivity of the virus particles produced in the presence of these inhibitors. 

Delavirdine NNRTI 400 mg tid Separate dosing from didanosine or antacids by 1 hour. Rash, liver function abnormalities Teratogenic see footnote 2 for concurrent drug contraindication s... 

Administration of antacids and buffered formulations of didanosine should be separated from that of delavirdine by at least 1 hour. 

Didanosine interferes with the absorption of delavirdine and should therefore not be given concomitantly (5). 

Morse GD, Fischl MA, Shelton MJ, Cox SR, Driver M, DeRemer M, Freimuth WW. Single-dose pharmacokinetics of delavirdine mesylate and didanosine in patients with human immunodeficiency virus infection. Antimicrob Agents Chemother 1997 41(l) 169-74. 

There are currently a variety of nucleoside analogs (i.e., AZT [zidovudine] [3], DDC [zalcitabine] [4], DDI [didanosine] [4], D4T [stavudine] [5], and 3TC [lamivudine] [6] [also designated NRTIs or nucleoside RT inhibitors]) and two nonnucleoside RT inhibitors (i.e., nevirapine [viramune] and BHAP [delavirdine] [also designated NNRTIs] [7,8]) officially approved for treatment of HIV-infected individuals. It should be noted that the NNRTIs are uniquely active against HIV-1, but not HIV-2 RT, whereas the NRTIs inhibit both HIV-1 and HIV-2 RTs. In addition, several other structural classes of... 

Successful treatment of human immunodeficiency virus (HIV-1) infection has been achieved through successful implementation of highly active antiretroviral therapy, frequently referred to as HAART. This involves simultaneous administration of both nucleoside and nonnucleoside reverse transcriptase inhibitors and one or more protease inliibitors. The common nucleoside reverse transcriptase inhibitors are the thymidine analogs didanosine (ddl), lamivudine (3TC), and zalcitabine (ddC) and the non-thymidine analogs abacavir (Ziazen), stavudine (d4T), and zidovudine (AZT). The nonnucleoside reverse transcriptase inhibitors include delavirdine, efavirenz, and nevirapine. The protease inhibitors include indinavir, nelfinavir, ritonavir, and saquinavir. Response to therapy is monitored by quantification of HIV-RNA copies (viral load) and CD-4+ T-lymphocyte count. Successful therapy is indicated when viral load is reduced to <50 copies/mL and CD-4+ count >500 per mL. 

Individual Agents Delavirdine in Alphabetical Order by Generic Name Antacids/didanosine Decreased absorption of delavirdine Separate by 1 h... 

Inhibit viral reverse transcriptase Zidovudine, didanosine, zalcitabine, lamivudine, stavudine, nevirapine, delavirdine, efavirenz... 

No clinically significant interaction appears to occur between adefovir and co-trimoxazole, didanosine, delavirdine, efavirenz, ibuprofen, indinavir, lamivudine, nelfinavir, nevirapine, paracetamol, tenofovir, or zidovudine. Adefovir possibly reduces saquinavir levels. 

Delavirdine absorption is reduced by the buffered preparation of didanosine. This interaction would not be expected with the enteric-coated preparation of didanosine. Delavirdine does not affect the pharmacokinetics of zidovudine. There is no pharmacokinetic interaction between efavirenz and zidovudine or lamivudine. There is no ciinicaiiy reievant pharmacokinetic interaction between nevirapine and didanosine, iamivudine, stavudine, zaicit-abine or zidovudine. 

Cox SR, Cohn SE, Greisberger C, Reichman RC, DeUa-Coletta A Freimuth WW, Mcrse GD. Evaluation of the steady-state (SS) phannacokinetic interacticm between didanosine (ddl) and delavirdine mediate (DLV) in HIV+ patients. Intersci Corf Antnmcrab Agents ChemoOier ( 995) 35, 210. 

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