Brands, Medical Use, Clinical Data
- Anti-HIV Agents
- Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
Brands / Synonyms
Apo-Zidovudine; Azidothymidine; AZT; Aztec; Combivir; Compound S; Novo-Azt; Retrovir; Trizivir; Zidovudine EP III
For the treatment of human immunovirus (HIV) infections.
Zidovudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Zidovudine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.
Mechanism of Action
Zidovudine, a structural analog of thymidine, inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.
Rapid and nearly complete absorption from the gastrointestinal tract following oral administration; however, because of first-pass metabolism, systemic bioavailability of zidovudine capsules and solution is approximately 65% (range, 52 to 75%). Bioavailability in neonates up to 14 days of age is approximately 89%, and it decreases to approximately 61% and 65% in neonates over 14 days of age and children 3 months to 12 years, respectively. Administration with a high-fat meal may decrease the rate and extent of absorption.
Symptoms of overdose include fatigue, headache, nausea, and vomiting. LD50 is 3084 mg/kg (orally in mice).
Biotrnasformation / Drug Metabolism
Hepatic. Metabolized by glucuronide conjugation to major, inactive metabolite, 3′-azido-3′-deoxy-5′- O-beta-D-glucopyranuronosylthymidine (GZDV).
RETROVIR Tablets, Capsules, and Syrup are contraindicated for patients who have potentially
life-threatening allergic reactions to any of the components of the formulations.
Antiretroviral Agents: Concomitant use of zidovudine with stavudine should be avoided since an antagonistic relationship has been demonstrated in vitro.
Some nucleoside analogues affecting DNA replication, such as ribavirin, antagonize the in vitro antiviral activity of Zidovudine against HIV; concomitant use of such drugs should be avoided.
Doxorubicin: Concomitant use of zidovudine with doxorubicin should be avoided since an antagonistic relationship has been demonstrated in vitro.
Phenytoin: Phenytoin plasma levels have been reported to be low in some patients receiving Zidovudine, while in one case a high level was documented. However, in a pharmacokinetic interaction study in which 12 HIV-positive volunteers received a single 300-mg phenytoin dose alone and during steady-state zidovudine conditions (200 mg every 4 hours), no change in phenytoin kinetics was observed. Although not designed to optimally assess the effect of phenytoin on zidovudine kinetics, a 30% decrease in oral zidovudine clearance was observed with phenytoin.
Overlapping Toxicities: Coadministration of ganciclovir, interferon-alpha, and other bone marrow suppressive or cytotoxic agents may increase the hematologic toxicity of zidovudine.