Amprenavir Abacavir

Lalezari JP, DeJesus E, Northfelt DW, Richmond G, Wolfe P, Haubrich R, Henry D, Powderly W, Becker S, Thompson M, Valentine E, Wright D, Carlson M, Riddler S, Haas FF, DeMasi R, Sista PR, Salgo M, Delehanty J (2003a) A controlled Phase II trial assessing three doses of enfuvirtide (T-20) in combination with abacavir, amprenavir, ritonavir and efavirenz in nonnucleoside reverse transcriptase inhibitor-naive HIV-infected adults. Antivir Ther 8 279-287... 

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 might affect amprenavir include abacavir, aldesleukin, antacids, anticonvulsants, azole antifungals, clarithromycin, cyclosporine, dexamethasone, buffered didanosine, disulfiram, ethanol, indinavir, methadone, metronidazole, nelfinavir, nonnucleoside reverse transcriptase inhibitors, oral contraceptives, rifamycins, ritonavir, saquinavir, St. John s wort, tacrolimus, and 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. 

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... 

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. 

A syndrome of drug hypersensitivity has been described in patients receiving NNRTIs as well as in those receiving amprenavir or abacavir. Serious rashes, including Stevens-Johnson syndrome, have occurred. 

Amprenavir Abacavir, delavirdine, indinavir, lopinavir, ritonavir, zidovudine Didanosine, efavirenz, nevirapine, saquinavir... 

Preferred Pl-based regimens are lopinavir/ritonavir plus lamivudine or emtricitabine plus another NRTI, usually zidovudine, stavudine or abacavir. Alternative combinations include other Pis with or without ritonavir, and two NRTIs. The combination of a protease inhibitor with ritonavir provides inhibition of cytochrome p450 enzymes and permits less frequent dosing of amprenavir, indinavir, lopinavir and saquinavir. Use of ritonavir in this setting is also known as boosting. ... 

Fosamprenavir is a prodrug of amprenavir with better systemic availability. In large clinical trials the most common adverse events in patients taking fosamprenavir, with or without ritonavir, plus abacavir and lamivudine were diarrhea, nausea, vomiting, abdominal pain, drug hypersensitivity, and skin rashes (3). 

Kost RG, Hurley A, Zhang L, Vesanen M, Talal A, Furlan S, Caldwell P, Johnson J, Smiley L, Ho D, Markowitz M. Open-label phase II trial of amprenavir, abacavir, and fixed-dose zidovudine/lamivudine in newly and chronically HIV-l-infected patients. J Acquir Immune Defic Syndr 2001 26(4) 332-9. 

Bart PA, Rizzardi PG, Gallant S, Golay KP, Baumann P, Pantaleo G, Eap CB. Methadone blood concentrations are decreased by the administration of abacavir plus amprenavir. Ther Drug Monit 2001 23(5) 553-5. 

In an open, 48-week, single-arm, multicenter phase II study in 99 patients abacavir 300 mg bd, amprenavir 1200 mg bd, and efavirenz 600 mg/day were associated with rashes in 50 patients, possibly because of abacavir hjrpersensitivity 17 permanently discontinued one or more drugs as a result (5). Other adverse effects included nausea (n = 41), diarrhea (n = 27), sleep disorders (n = 27), dizziness (n = 25), fatigue (n = 23), hypertriglyceridemia (n = 18), neutropenia (n = 8), hyperamylasemia (n = 4), leukopenia (n = 3), hypercholesterolemia (n = 2), raised alkaline phosphatase (n = 1), and raised aspartate transaminase (n = 1). 

A study involving 16 opioid-dependent subjects found that amprenavir 1.2 g twice daily for 10 days decreased the AUCs for both f -methadone (active enantiomer) and 5-methadone (inactive enantiomer) by 13% and 40%, respectively. No clinically significant changes were noted in opioid effects and there was no evidence of opioid withdrawal. However, in another study methadone levels were reduced by 35% (range 28% to 87%) in 5 patients within 17 days of starting to take amprenavir 1.2 g twice daily and abacavir 600 mg twice daily. Two patients reported nausea before their daily methadone dose, which can be a sign of opiate withdrawal. Note that abacavir , (p.l75), may modestly reduce methadone levels, and could therefore have contributed to this effect. 

Falloon J, Piscitelli S, Vogel S, Sadler B, Mitsuya H, KavUck MF, Yoshimura K, Rogers M, LaFon S, Manion DJ, Lane HC, Masur H. Comhination therapy with amprenavir, abacavir, and efavirenz in human immunodeficiency virus (HIV) infected patients failing a protease-inhibitor regimen pharmacokinetic drug interactions and antiviral activity. Clin bfect Dis (2000) 30, 313-18. 

Amprenavir A phase I study in HIV-positive patients given amprenavir 900 mg twice daily with abacavir 300 mg twice daily for 3 weeks found that neither drug had any clinically significant effect on the pharmacokinetics of the other. The manufacturer of amprenavir notes that its AUC, and minimum and maximum levels were increased by 29%, 27%, and 47%, respectively, by abacavir, without any change in abaeavir pharmacokinetics, but no dosage adjustments are considered necessary. ... 

Combination of 16 ARVs seven HIV protease inhibitors (amprenavir, atazanavir, indinavir, lopinavir, nelfmavir, ritonavir, and saquinavir), seven nucleoside reverse transcriptase inhibitors (abacavir, didanosine, emtricitabine, lamivudine, stavudine, zalcitabine, and zidovudine), and two nonnucleoside reverse transcriptase inhibitors (efavirenz and nevirapine)... 

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]... 

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