Zidovudine is a thymidine analog in the nucleoside reverse transcriptase inhibitor class.
Zidovudine is more active against acutely infected cells as compared to chronically infected cells.
Zidovudine is phosphorylated to zidovudine-triphosphate, which competes with endogenous nucleotides for incorporation into the viral DNA and once incorporated causes chain termination due to the lack of a 3’ OH group.
Resistance to NRTIs occurs through two mechanisms; decreased incorporation of NRTIs into the viral DNA and increased excision of NRTIs from the viral DNA.
In vitro IC50 (50% inhibitory concentration) was 0.003 to 0.013mcg/mL and the IC90 (90% inhibitory concentration) was 0.03 to 0.3 mcg/mL.
Zidovudine is well absorbed and undergoes first-pass hepatic glucuronidation to zidovudine glucuronide. Peak plasma concentrations occur at 0.5-1.0 hour after dosing in the fasted state. Both zidovudine glucuronide and zidovudine are eliminated through renal excretion with tubular secretion contributing to the elimination.
Anemia, neutropenia, headache, fatigue, nausea, and myalgia are the most common toxicities.
100mg capsule (100 capsule bottle)
300mg tablet (60 tablet bottle)
Syrup 50mg/5ml (240mg bottle)
300mg twice daily
600mg once a day has been studied. This dose has been shown
to have antiviral activity. However, it is less marked and more slowly achieved
than 300mg twice a day.
Preterm Infants (<30
weeks gestational age)
Oral: 2 mg/kg
q12h IV: 1.5 mg/kg q12h (Both increased to q8h at four
weeks of age)
Preterm Infants (≥30 weeks gestational age)
Oral: 2 mg/kg q12h IV: 1.5 mg/kg q12h (Both
increased to q8h at two weeks of age)
Neonates (within
12 hours after birth through 6 weeks of age)
Oral: 2 mg/kg q6h
IV: 1.5 mg/kg, infused over 30 minutes, q6h
Pediatrics (6 weeks to 12 years)
Oral: 160 mg/m2 q8h IV intermittent: 120 mg/m2 q6h IV continuous: 20 mg/m2/hr
Take with or without food
Disease state based dosing:
Clcr >10 mL/min - 300 mg twice daily
Clcr <10 mL/min - 300 mg once daily
Hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) - 300 mg once daily
Hepatic failure – no significant data to make recommendations on dose adjustments Severe hepatic failure –the daily dose should be reduced 50% or the dosing interval should be doubled.
Contraindications/Warnings/Precautions:
Zidovudine should be used with caution in patients who have bone marrow compromise (i.e. granulocyte count <1,000 cells/mm 3 or hemoglobin <9.5 g/dL)
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of NRTIs.
The use of zidovudine and stavudine (d4T) concomitantly is contraindicated due to antagonism that occurs between these two thymidine analogues. Zidovudine plasma concentrations are decreased 25% by concurrent nevirapine use. Ritonavir induces glucuronidation and has been found to reduce the zidovudine AUC by approximately 25%.
Ganciclovir, interferon-alpha and other cytotoxic or bone marrow suppressive agents (trimethoprim-sulfamethoxazole, dapsone, pyrimethamine, flucytosine, adriamycin, vinblastine, sulfadiazine, hydroxyurea, vincristine and amphotericin B) may increase the risk of hematologic toxicity associated with zidovudine. Both doxorubicin and ribavirin have demonstrated in vitro inhibition of zidovudine phosphorylation and antagonize its antiviral activity. Probenecid increases the AUC of zidovudine by 106%.
Category C: Risk unknown. Human studies inadequate.
Zidovudine has proven effective in preventing mother to child transmission of HIV infection.
Recommended dosing regimen:
Women >14 weeks pregnant (continued until onset of labor):
100 mg orally 5 times per day OR
200 mg orally three times daily OR
300 mg orally twice daily
During labor and delivery:
2 mg/kg (using mother's total body weight) IV over 1 hour then 1 mg/kg/hour (using mother's total body weight) continuous IV infusion until clamping of the umbilical cord
Infant (start within 8 to 12 hours):
2mg/kg orally every 6 hours for the first six weeks of life
Monitoring Requirements:
Frequent blood counts in patients with advanced HIV disease, periodic blood counts in patients with asymptomatic or early HIV disease.
Brand names/Manufacturer:
Retrovir®
GlaxoSmithKline