Fertility: There are no data on the effect of RETROVIR on human female fertility. In men, zidovudine has been shown to have no effect on sperm count, morphology or motility.
Pregnancy: Zidovudine has been evaluated in the Antiretroviral Pregnancy Registry (APR) in over 13,000 women during pregnancy and postpartum. Available human data from the APR do not show an increased risk of major birth defects for zidovudine compared to the background rate (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
The safe use of zidovudine in human pregnancy has not been established in adequate and well-controlled trials investigating congenital abnormalities. Therefore administration of RETROVIR in pregnancy should be considered only if the expected benefit outweighs the possible risk to the foetus.
Zidovudine has been shown to cross the placenta in humans (see Pharmacology: Pharmacokinetics under Actions). Zidovudine has been associated with findings in animal reproductive studies (see Pharmacology: Toxicology: Pre-Clinical Safety Data under Actions). Pregnant women considering using RETROVIR during pregnancy should be made aware of these findings.
There have been reports of mild, transient elevations in serum lactate levels, which may be due to mitochondrial dysfunction, in neonates and infants exposed in utero or peri-partum to nucleoside reverse transcriptase inhibitors (NRTIs). The clinical relevance of transient elevations in serum lactate is unknown. There have also been very rare reports of developmental delay, seizures and other neurological disease. However, a causal relationship between these events and NRTI exposure in utero or peri-partum has not been established. These findings do not affect current recommendations to use antiretroviral therapy in pregnant women to prevent vertical transmission of HIV.
Maternal-foetal transmission: In ACTG 076 the use of RETROVIR in pregnant women over 14 weeks of gestation, with subsequent treatment of their newborn infants, has been shown to significantly reduce the rate of maternal-foetal transmission of HIV (23% infection rate for placebo versus 8% for RETROVIR). Oral RETROVIR therapy began between weeks 14 and 34 of gestation and continued until onset of labour. During labour and delivery RETROVIR was administered intravenously. The newborn infants received RETROVIR orally until 6 weeks old. Infants unable to receive oral dosing were given the intravenous formulation.
It is unknown whether there are any long-term consequences of in utero and infant exposure to zidovudine. Based on the animal carcinogenicity/mutagenicity findings a carcinogenic risk to humans cannot be excluded (see Pharmacology: Toxicology: Preclinical Safety Data under Actions). The relevance of these findings to both infected and uninfected infants exposed to zidovudine is unknown. However, pregnant women considering using RETROVIR during pregnancy should be made aware of these findings.
Syrup: In the 1998 Thailand CDC study, use of oral RETROVIR therapy only, from week 36 of gestation until delivery, significantly reduced the rate of maternal-foetal transmission of HIV (19% infection rate for placebo versus 9% for RETROVIR). No mothers in this study breast fed their infants.
Lactation: Health experts recommend that where possible women infected with HIV do not breast feed their infants in order to avoid the transmission of HIV. In settings where formula feeding is not feasible, local official lactation and treatment guidelines should be followed when considering breast-feeding during antiretroviral therapy.
After administration of a single dose of 200 mg RETROVIR to HIV-infected women, the mean concentration of zidovudine was similar in human milk and serum. In other studies following repeat oral dose of 300 mg zidovudine twice daily (given either as a single entity or as COMBIVIR or TRIZIVIR) the maternal plasma:breast milk ratio ranged between 0.4 and 3.2. Zidovudine median infant serum concentration was 24 ng/mL in one study and was below assay limit of quantification (30 ng/mL) in another study. Intracellular zidovudine triphosphate (active metabolite of zidovudine) levels in breastfed infants were not measured therefore the clinical relevance of the serum concentrations of the parent compound measured is unknown.