Azidothymidine - General Information
A dideoxynucleoside compound in which the 3&
Pharmacology of Azidothymidine
Azidothymidine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Azidothymidine 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.
Azidothymidine for patients
RETROVIR is not a cure for HIV infection, and patients may continue to acquire illnesses associated with HIV infection, including opportunistic infections. Therefore, patients should be advised to seek medical care for any significant change in their health status.
The safety and efficacy of RETROVIR in women, intravenous drug users, and racial minorities is not significantly different than that observed in white males.
Patients should be informed that the major toxicities of RETROVIR are neutropenia and/or anemia. The frequency and severity of these toxicities are greater in patients with more advanced disease and in those who initiate therapy later in the course of their infection. They should be told that if toxicity develops, they may require transfusions or drug discontinuation. They should be told of the extreme importance of having their blood counts followed closely while on therapy, especially for patients with advanced symptomatic HIV disease. They should be cautioned about the use of other medications, including ganciclovir and interferon-alpha, that may exacerbate the toxicity of RETROVIR. Patients should be informed that other adverse effects of RETROVIR include nausea and vomiting. Patients should also be encouraged to contact their physician if they experience muscle weakness, shortness of breath, symptoms of hepatitis or pancreatitis, or any other unexpected adverse events while being treated with RETROVIR.
RETROVIR Tablets, Capsules, and Syrup are for oral ingestion only. Patients should be told of the importance of taking RETROVIR exactly as prescribed. They should be told not to share medication and not to exceed the recommended dose. Patients should be told that the long-term effects of RETROVIR are unknown at this time.
Pregnant women considering the use of RETROVIR during pregnancy for prevention of HIV-transmission to their infants should be advised that transmission may still occur in some cases despite therapy. The long-term consequences of in utero and infant exposure to RETROVIR are unknown, including the possible risk of cancer.
HIV-infected pregnant women should be advised not to breastfeed to avoid postnatal transmission of HIV to a child who may not yet be infected.
Patients should be advised that therapy with RETROVIR has not been shown to reduce the risk of transmission of HIV to others through sexual contact or blood contamination.
Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known at this time.
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.
RETROVIR Tablets, Capsules, and Syrup are contraindicated for patients who have potentially life-threatening allergic reactions to any of the components of the formulations.
Additional information about Azidothymidine
Azidothymidine Indication: For the treatment of human immunovirus (HIV) infections.
Mechanism Of Action: Azidothymidine, 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.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Zidovudine
Synonyms: Not Available
Drug Category: Anti-HIV Agents; Antimetabolites; Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
Drug Type: Small Molecule; Approved
Other Brand Names containing Zidovudine: Apo-Zidovudine; Azidothymidine; Aztec; Compound S; Novo-Azt; Retrovir; Zidovudine EP III;
Absorption: 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.
Toxicity (Overdose): Symptoms of overdose include fatigue, headache, nausea, and vomiting. LD50 is 3084 mg/kg (orally in mice).
Protein Binding: 30-38%
Biotransformation: Hepatic. Metabolized by glucuronide conjugation to major, inactive metabolite, 3′-azido-3′-deoxy-5′- O-beta-D-glucopyranuronosylthymidine (GZDV).
Half Life: 0.5-3 hours
Dosage Forms of Azidothymidine: Liquid Intravenous
Chemical IUPAC Name: 1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
Chemical Formula: C10H13N5O4
Zidovudine on Wikipedia: http://en.wikipedia.org/wiki/Zidovudine
Organisms Affected: Human Immunodeficiency Virus