Zidovudine Abacavir

NRTIs are water soluble, and are mainly eliminated by the kidneys (di-danosine, lamivudine, stavudine, and zalcitabine) or undergo hepatie glu-curonidation (abacavir, zidovudine). The few important interactions with these drugs primarily involve altered renal clearance. For zidovudine (and possibly abacavir) some interactions occur via altered glucuronidation, but the clinical relevance of these are less clear (e.g. rifampicin , (p.792)). Cytochrome P450-mediated interactions are not important for this class of drugs. 

At present there are seven NRTIs, which have been formally approved for the treatment of AIDS 3 -azido-2, 3 -dideoxythymidine (AZT, zidovudine), 2, 3 -dideoxyinosine (ddl, didanosine), 2, 3 -dideoxycytidine (ddC, zalcitabine), 2, 3 -didehydro-2, 3 -dideoxythymidine (d4T, stavudine), (—)-L-3 -thia-2, 3 -dideoxycytidine (3TC, lamivudine), cyclopentenyl V -cyclopropylaminopurine (abacavir, ABC), and (—)-L-5-fluoro-3 -thia-2, 3 -dideoxycytidine ((—)FTC, emtricitabine) (De Clercq 2004a) (Fig. 3). 

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... 

Atazanavir or fosamprenavir or nelfinavir or saquinavir/ ritonavir, and zidovudine or stavudine or tenofovir or abacavir or didanosine, and lamivudine or emtricitabine... 

Triple NRTI therapy is recommended only when a first-line or alternative first-line therapy with either an NNRTI-based or Pi-based regimen cannot be used. Abacavir plus zidovudine plus lamivudine is the only regimen approved by the DHHS. The following triple nucleoside therapy combinations have shown poor or limited efficacy, and should be avoided abacavir plus tenofovir plus lamivudine (or emtricitabine), and didanosine plus tenofovir plus lamivudine (or emtricitabine). 

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. 

Only as an alternative to NNRTI- or Pl-based regimens when these cannot be used as preferred therapy) Alternative Abacavir plus lamivudinep/us zidovudine (CM) See above... 

Current recommendations for treating HIV infection advocate a minimum of three antiretroviral agents. The typical regimen consists of two NtRTIs and either a ritonavir-boosted PI or NNRTI. The dual NtRTI backbone should include tenofovir plus emtricitabine (coformulated as Truvada) or zidovudine plus lamivudine (coformulated as Combivir). Abacavir plus lamivudine is an alternative. Recommended initial NtRTIs include atazana-vir-ritonavir, lopinavir-ritonavir, or fosamprenavir-ritonavir. Efavirenz is the recommended NNRTI except for women who plan to become pregnant or who do not have adequate contraception. 

GlaxoSmithKline recalled in May 2002 three lots of Combivir (Lamivudine/zidovudine, used in treatment of HIV infection) due to the fact that it actually contained a drug known as Ziagen (abacavir sulfate). 

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. 

Combination therapy Lamivudine/zidovudine and abacavir/lamivudine/zidovudine are combination product tablets that contain zidovudine as one of their components. Do not administer zidovudine concomitantly with lamivudine/zidovudine or abacavir/lamivudine/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. 

Consult the complete prescribing information for each agent, abacavir. lamivudine. and zidovudine, prior to administration of abacavir/lamivudine/zidovudine combination tablets. 

This product contains 3 nucleoside analogs (abacavir sulfate, lamivudine, and zidovudine) and is intended only for patients whose regimen would otherwise include these 3 components. 

Severe or fatal hypersensitivity reactions can occur within hours after reintroduction of abacavir in patients who have no identified history or unrecognized symptoms of hypersensitivity to abacavir therapy (see Warnings and Adverse Reactions). Zidovudine has been associated with hematologic toxicity, including neutropenia and severe anemia, particularly in patients with advanced HIV disease (see Warnings). Prolonged use of zidovudine has been associated with symptomatic myopathy. 

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination, including abacavir, lamivudine, zidovudine, and other antiretrovirals (see Warnings). 

Pharmacology The combination tablets contain the following 3 synthetic nucleoside analogs Abacavir sulfate, lamivudine, and zidovudine. Abacavir is a carbocyclic synthetic nucleoside analog. Lamivudine and zidovudine are synthetic nucleoside analogs. 

Pharmacokinetics Following oral administration, abacavir, lamivudine, and zidovudine are rapidly absorbed and extensively distributed. Binding of abacavir to human plasma proteins is about 50% binding of lamivudine and zidovudine to plasma proteins is low. 

Abacavir/lamivudine/zidovudine tablets are contraindicated in patients with previously demonstrated hypersensitivity to any of the components of the product (see Warnings). 

The present NRTIs available for the treatment of HIV are zidovudine (azidothymidine, AZT), stavu-dine (d4T), didanosine (ddl), lamivudine (3TC), dideoxycytidine (ddC, zalcitabine) and abacavir, emtricitabine and tenofovir disoproxil. Combination formulations are abcavir combined with zidovudine and lamivudine and the abacavir-lamivudine combination. 

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... 

Zidovudine (ZDV or AZT) is a nucleoside reverse transcriptase inhibitor (NRTI) and it was the first anti-HIV agent to be introduced. Other NRTIs include stavudine (d4T), lamivudine (3TC), didano-sine (ddl), abacavir (ABC) and zalcitabine (ddC). Recent additions to this class are emtricitabine (FTC) which has a molecular structure similar to 3TC and tenofovir (TDF) a nucleotide reverse transcriptase inhibitor. 

Lamivudine (3TC, Epivir) is a cytosine nucleoside analogue with activity against HIV-1, HIV-2, and hepatitis B virus. It is approved as part of a multidrug regimen for the therapy of HIV infection in adults and children and has been used for HIV postexposure prophylaxis. Combination products contain lamivudine with either zidovudine (Combivir) or zidovudine and abacavir (Trizivir). The use of low-dose lamivudine in the treatment of chronic hepatitis B is described in Chapter 50. 

Lamivudine is the best-tolerated NRTI. Its most common adverse effects include headache, malaise, fatigue, and insomnia. Pancreatitis is rare. Gastrointestinal complaints are common with lamivudine-zidovudine therapy but are probably mainly due to the zidovudine component. Lamivudine resistance sometimes occurs early in treatment. Cross-resistance to zal-citabine, didanosine, and abacavir can occur simultaneously. Withdrawal of lamivudine in patients infected with both hepatitis B virus and HIV can cause a flare-up of hepatitis symptoms. 

Abacavir (Ziagen) is a guanosine nucleoside analogue indicated for the therapy of HIV-1 infection in adults and children. It is used as part of a multidrug regimen and is available in a fixed-dose combination with zidovudine and lamivudine (Trizivir). It is also used for postexposure HIV infection prophylaxis. 

Abacavir is associated with side effects such as anorexia, nausea, vomiting, malaise, headache, and insomnia. A potentially fatal hypersensitivity reaction develops in approximately 5% of patients, usually early in the course of treatment. Fever and rash are the most common symptoms of this reaction malaise, respiratory symptoms, and gastrointestinal complaints may also occur. Resistance to abacavir may be associated with resistance to zidovudine, didanosine, and lamivudine. 

Rx with abacavir (Epzicom) with zidovudine (Combivir)... 

NRTIs) abacavir sulfate didanosine (ddl) lamivudine (3TC) stavudine (d4T) zalcitabine (ddC) zidovudine (AZT)... 

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