RETROVIR(zidovudine)IV Infusion
RETROVIR - zidovudine injection, solution 
ViiV Healthcare Company
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RETROVIR® (zidovudine)IV Infusion
FOR INTRAVENOUS INFUSION ONLY
WARNING
RETROVIR (ZIDOVUDINE) HAS BEEN ASSOCIATED WITH HEMATOLOGIC TOXICITY, INCLUDING NEUTROPENIA AND SEVERE ANEMIA, PARTICULARLY IN PATIENTS WITH ADVANCED HUMAN IMMUNODEFICIENCY VIRUS (HIV) DISEASE (SEE WARNINGS). PROLONGED USE OF RETROVIR HAS BEEN ASSOCIATED WITH SYMPTOMATIC MYOPATHY.
LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, INCLUDING FATAL CASES, HAVE BEEN REPORTED WITH THE USE OF NUCLEOSIDE ANALOGUES ALONE OR IN COMBINATION, INCLUDING RETROVIR AND OTHER ANTIRETROVIRALS (SEE WARNINGS).
DESCRIPTION
RETROVIR is the brand name for zidovudine (formerly called azidothymidine [AZT]), a pyrimidine nucleoside analogue active against HIV. RETROVIR IV Infusion is a sterile solution for intravenous infusion only. Each mL contains 10 mg zidovudine in Water for Injection. Hydrochloric acid and/or sodium hydroxide may have been added to adjust the pH to approximately 5.5. RETROVIR IV Infusion contains no preservatives.
The chemical name of zidovudine is 3′-azido-3′-deoxythymidine; it has the following structural formula:
Zidovudine is a white to beige, odorless, crystalline solid with a molecular weight of 267.24 and a solubility of 20.1 mg/mL in water at 25°C. The molecular formula is C10H13N5O4.
MICROBIOLOGY
Mechanism of Action:
Zidovudine is a synthetic nucleoside analogue. Intracellularly, zidovudine is phosphorylated to its active 5′-triphosphate metabolite, zidovudine triphosphate (ZDV-TP). The principal mode of action of ZDV-TP is inhibition of reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue. ZDV-TP is a weak inhibitor of the cellular DNA polymerases α and γ and has been reported to be incorporated into the DNA of cells in culture.
Antiviral Activity:
Activity of zidovudine against HIV-1 was assessed in a number of cell lines (including monocytes and fresh human peripheral blood lymphocytes). The EC50 and EC90 values for zidovudine were 0.01 to 0.49 µM (1 μM = 0.27 mcg/mL) and 0.1 to 9 μM, respectively. HIV from therapy-naive subjects with no mutations associated with resistance gave median EC50 values of 0.011 µM (range: 0.005 to 0.110 µM) from Virco (n = 93 baseline samples from COLA40263) and 0.02 µM (0.01 to 0.03 µM) from Monogram Biosciences (n = 135 baseline samples from ESS30009). The EC50 values of zidovudine against different HIV-1 clades (A-G) ranged from 0.00018 to 0.02 μM, and against HIV-2 isolates from 0.00049 to 0.004 μM. In cell culture drug combination studies, zidovudine demonstrates synergistic activity with the nucleoside reverse transcriptase inhibitors (NRTIs) abacavir, didanosine, lamivudine, and zalcitabine; the non-nucleoside reverse transcriptase inhibitors (NNRTIs) delavirdine and nevirapine; and the protease inhibitors (PIs) indinavir, nelfinavir, ritonavir, and saquinavir; and additive activity with interferon alfa. Ribavirin has been found to inhibit the phosphorylation of zidovudine in cell culture.
Resistance:
Genotypic analyses of the isolates selected in cell culture and recovered from zidovudine-treated patients showed mutations in the HIV-1 RT gene resulting in 6 amino acid substitutions (M41L,