Nevirapine Zidovudine

The most frequent laboratory abnormality during nevirapine treatment is an increase in serum gamma-glutamyl transpeptidase activity, usually without changes in other measures of hepatic function. However, in a randomized, placebo-controlled comparison of zidovudine plus nevirapine, zidovudine plus didanosine, and the triple... 

Zhou, X.-J. et al., Population pharmacokinetics of nevirapine, zidovudine, and didanosine in human immunodeficiency virus-infected patients, Antimicrob. Agents Chemother., 43(1) 121-128, 1999. 

Zhou XJ, Sheiner LB, D Aquila RT, Hughes MD, Hirsch MS, Fischl Johnson VA Myers M, Sommadossi JPand tfieNIAID ACTG241 Investigators. Populaticm iharmacokinetics of nevirapine, zidovudine and didanosine after combination therapy in HIV-infected patients. 

Aymard, G. Legrand, M. Trichereau, N. Diquet, B. Determination of twelve antiretroviral agents in human plasma sample using reversed-phase high-performance liquid chromatography, J.Chromatogr.B, 2000, 744, 227-240. [for amprenavir efavirenz indinavir nelflnavir ritonavir saquinavir abacavir didanosine lamivudine stavudine nevirapine zidovudine]... 

Zidovudine Didanosine Stavudine Lamivudine Abacavir Tenofovir Emtricitabine Nevirapine Efavirenz TMC125 Saquinavir Indinavir Lopinavir Fosamprenavir Atazanavir Tipranavir Darunavir Raltegravir Elvitegravir Enluvirtide Maraviroc Vicriviroc Bevirimat... 

Tenofovir + Emtricitabine Zidovudine + Lamivudine Abacavir + Lamivudine Efavirenz or Nevirapine Lopinavir/r or Atazanavir/r or Eosamprenavir/r or Saquinavir/r... 

TC, lamivudine ABC, abacavir APV, amprenavir AST, aspartate aminotransferase ALT, alanine aminotransferase ATV, atazanavir CBC, complete blood cell count D/C, discontinue ddl, didano-sine d4T, stavudine EFV, efavirenz FTC, emtricitabine P1BV, hepatitis B virus F1CV, hepatitis C vims HIV, human immunodeficiency virus IDV, indinavir IV, intravenous LFT, liver function tests LPV/r, lopinavir + ritonavir NNRTI, nonnucleoside reverse transcriptase inhibitor NRTI, nucleoside reverse transcriptase inhibitor NVP, nevirapine PI, protease inhibitor PT, prothrombin time T.bili, total bilirubin TDF, tenofovir disoproxiI fumarate TPV, tipranavir ULN, upper limit of normal ZDV, zidovudine. 

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. 

Pharmacology Abacavir is a synthetic carbocyclic synthetic nucleoside analog with inhibitory activity against HIV. Abacavir has synergistic activity in combination with amprenavir, nevirapine, and zidovudine and additive activity in combination with didanosine, lamivudine, stavudine, and zalcitabine in vitro. 

Drugs that may be affected by nevirapine include rifamycins, clarithromycin, oral contraceptives, efavirenz, ketoconazole, methadone, protease inhibitors, warfarin, zidovudine. 

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... 

One large randomised controlled trial demonstrates that nevirapine given to mothers as a single dose at the onset of labour and to babies as a single dose within 72 hours of birth is more effective than an intrapartum and post-partum regimen of zidovudine. However this regimen can cause NNRTI resistant virus in mother and child. 

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

Indinavir Delavirdine, nelfinavir, ritonavir, zidovudine, darunavir Fosamprenavir, didanosine, efavirenz, etravirine, nevirapine... 

Havlir D, Murphy R, Saag M, Kaul I, Johnson V, Richman DD. Nevirapine further dose escalation of monotherapy (600 mg/daily) and combination therapy with zidovudine. In The First National Conference on Human Retroviruses and Related Infections, Washington D.C., 1993 101. 

More recently, RTIs that are chemically distinct from zidovudine and other NRTIs have also been developed (see Table 34-3). These agents are known as nonnucleoside reverse transcriptase inhibitors (NNR-TIs), and include drugs such as delavirdine (Rescrip-tor), efavirenz (Sustiva), and nevirapine (Viramune).32 These drugs also inhibit the reverse transcriptase enzyme, but act at a different site on the enzyme than do their NRTI counterparts. 

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. 

Indinavir Delavirdine, lopinavir, nelfinavir, zidovudine Amprenavir, delavirdine, efavirenz, nevirapine, ritonavir... 

An active transport mechanism has long been suspected to account for the placental barrier that causes maternal and fetal concentrations for many drugs to differ (96 97). Studies of maternal-fetal transport of medications used during pregnancy in HIV-positive women have shown variable penetration into the fetus (98 99). Whereas the maternal-fetal drug ratios for zidovudine lamivudine/ and nevirapine (approximately 0.85 1.0/ and 0.9/ respectively) demonstrate good fetal penetration/ most protease inhibitors/ nelhnavir/ ritonavh/ saquinivir/ and lopinavir/ are known P-gp substrates and do not cross the placenta in detectable levels (98). 

A 48-year-old HIV-positive man taking indinavir, zidovudine, and lamivudine developed Herpes zoster infection, which was treated with famciclovir. Postherpetic neuralgia was treated with carbamazepine, and his plasma indinavir concentration fell substantially. The carbamazepine was withdrawn after 2.5 months and 2 weeks later HIV-RNA was detectable in his plasma (6 X 10 /ml). His circulating virus was resistant to lamivudine. With a further increase in viral load, his therapy was changed to nevirapine, didanosine, and stavudine. 

Nevirapine is a non-nucleoside reverse transcriptase inhibitor (1). Concerns about the adverse effects of nevirapine have delayed its implementation in preventing perinatal HIV. Decision analysis has been used to compare three strategies a single dose of nevirapine, a short course of zidovudine, and no intervention (2). The... 

Two patients developed grade 4 thrombocytopenia (under 25 x 10 /1) after 42 and 151 days of treatment with nevirapine (6). In the first patient, zidovudine and intravenous immunoglobulin were added to continued nevirapine, and the thrombocytopenia resolved by day 89. In the second, nevirapine was discontinued and alternative antiretroviral therapy was started, whereupon the platelet count returned to normal within 22 days. 

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