Zidovudine agents

In addition to the three anti-HIV agents [AZT (zidovudine), DDI (dida-nosine) and DDC (zalcitabine)] that have been formally approved by the U.S. Food and Drug Administration for the treatment of HIV infections, several other 2, 3 -dideoxynucleoside (ddN) analogues (Fig. 5), including 3 -fluoro-2, 3 -didcoxy-5-chlorouridine (FddClUrd) and 2, 3 -didehydro-... 

A patient with AIDS is treated with a combination of agents, which includes zidovudine. What is the mechanism of action of zidovudine ... 

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. 

Other applications include bioequivalent measurements of bromazepam, an anticonvulsant, in human plasma. The lower limit of quantitation (LLOQ) was 1 ng/mL (Gongalves et al. 2005). Kuhlenbeck et al. (2005) studied antitussive agents (dextromethorphan, dextrophan, and guaifenesin) in human plasma LLOQ values were 0.05, 0.05, and 5 ng/mL, respectively. Other compounds studied were nucleoside reverse transcriptase inhibitors, zidovudine (AZT) and lamivudine (3TC) (de Cassia et al. 2004) and stavudine (Raices et al. 2003) in human plasma, and paclitaxel, an anticancer agent, in human serum (Schellen et al. 2000). 

Zidovudine, azidothymidine, AZT (Retrovir, Combivir) Antiretroviral agent Inhibits HIV replication by blocking reverse transcriptase... 

Ueno, R. and Kuno, S. Dextran sulfate, a potent anti-HIV agent in vitro having synergism with zidovudine. Lancet, 1987, 1379. 

Drugs that may affect zidovudine include acetaminophen, atovaquone, bone marrow suppressive/cytotoxic agents (eg, adriamycin, dapsone), clarithromycin, doxorubicin, fluconazole, ganciclovir, methadone, nelfinavir/ritonavir, phenytoin, probenecid, ribavirin, rifamycins, stavudine, trimethoprim, and valproic acid. 

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

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. 

Ganciclovir interacts with a number of medications, some of which are used to treat HIV or transplant patients. Ganciclovir may cause severe neutropenia when used in combination with zidovudine. Ganciclovir increases serum levels of didanosine, whereas probenecid decreases ganciclovir elimination. Nephrotoxicity may result if other nephrotoxic agents (e.g., amphotericin B, cyclosporine, NSAIDs) are administered in conjunction with ganciclovir. 

Zidovudine should be used cautiously with any other agent that causes bone marrow suppression, such as interferon-a, trimethoprim-sulfamethoxazole, dap-sone, foscarnet, flucytosine, ganciclovir, and valganci-clovir. Probenecid and interferon-p inhibit the elimination of zidovudine therefore, a dosage reduction of zidovudine is necessary when the drugs are administered concurrently. Ribavirin inhibits the phosphorylation reactions that activate zidovudine, and zidovudine similarly inhibits the activation of stavudine thus, the coadministration of zidovudine with ribavirin or stavudine is contraindicated. 

Zidovudine was the first agent to be used to prevent the transmission of HIV from a pregnant woman to her child. It was given to the mother at 14 to 34 weeks gestation and to the child for the first 6 weeks of life. Current combination therapies employ zidovudine with another NRTI and a protease inhibitor. 

Drug Interactions According to the product label, interactions between Intron A and other drugs have not been fully evaluated. Caution should be exercised when administering Intron A therapy in combination with other potentially myelo-suppressive agents such as zidovudine. Concomitant use of alfa interferon and theophylline decreases theophylline clearance, resulting in a 100% increase in serum theophylline levels. 

Concurrent use of nephrotoxic agents may enhance the potential for nephrotoxicity. Probenecid and cimetidine decrease acyclovir clearance and increase exposure. Somnolence and lethargy may occur in patients receiving zidovudine and acyclovir. 

Richman DD, Rosenthal AS, Skoog M, Echner RJ, Chou T-C, Sabo JP, et al. BIRG-587 is active against zidovudine-resistant human immunodeficiency virus type 1 and synergistic with zidovudine. Antimicrob Agents Chemother 1991 35 305-308. 

Drug Interactions Antineoplastlc agents Corticosteroids and corticotropin Cyclosporine-A Digitalis glycosides Flucytosine Imidazoles Leukocyte transfusions Nephrotoxic medications Skeletal muscle relaxants Zidovudine... 

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