Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy

Prolonged, continuous, high-dose zidovudine administration to adult rodents is associated with the development of nonmetastasizing vaginal squamous tumors in 13 percent of female rodents (at estimated drug concentrations three and 24 times that of human therapeutic exposure in mice and rats, respectively) (1). In rodents, unmetabolized zidovudine is concentrated in urine with reflux into the vaginal vault. Therefore, vaginal tumors could be a topical effect of chronic zidovudine exposure on the vaginal mucosa. The observation that vaginal squamous cell carcinomas were observed in rodents exposed to 20 mg/mL zidovudine intravaginally is consistent with this hypothesis (1). In humans, only metabolized zidovudine is excreted in the urine. No increase in tumors in other organ sites has been seen in adult rodent studies.