Combivir Use In Pregnancy & Lactation

Fertility: There are no data on the effect of lamivudine or zidovudine on human female fertility. In men, zidovudine has been shown to have no effect on sperm count, morphology or motility.
Pregnancy: Lamivudine and zidovudine have been evaluated in the Antiretroviral Pregnancy Registry (APR) in over 11,000, and 13,000 women respectively during pregnancy and postpartum. Available human data from the APR do not show an increased risk of major birth defects for lamivudine or zidovudine compared to the background rate (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
The safe use of lamivudine and zidovudine in human pregnancy has not been established in adequate and well-controlled trials investigating congenital abnormalities. Therefore administration of COMBIVIR in pregnancy should be considered only if the expected benefit outweighs the possible risk to the foetus.
Lamivudine and zidovudine have been shown to cross the placenta in humans (see Pharmacology: Pharmacokinetics under Actions). The use of zidovudine in pregnant women, with subsequent treatment of the newborn infants, has been shown to reduce the rate of maternal foetal transmission of HIV.
Lamivudine and zidovudine have been associated with findings in animal reproductive studies (see Pharmacology: Toxicology: Pre-Clinical Information under Actions). Pregnant women considering using COMBIVIR 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.
Lactation: Health experts recommend that where possible HIV infected women do not breast feed their infants in order to avoid transmission of HIV. In setting where formula feeding is not feasible, local official lactation and treatment guidelines should be followed when considering breast feeding during antiretroviral therapy.
In a study following repeat oral dose of either 150 mg lamivudine twice daily (given in combination with 300 mg zidovudine twice daily) or 300 mg lamivudine twice daily, lamivudine was excreted in human breast milk (0.5 to 8.2 micrograms/ml) at similar concentrations to those found in serum, while after administration of a single dose of 200 mg zidovudine to HIV-infected women, the mean concentration of zidovudine was similar in human milk and serum. In other studies following repeat oral administration of 150 mg lamivudine (given either in combination with 300 mg zidovudine or as Combivir) and 300 mg zidovudine twice daily (given either as a single entity or as Combivir) the maternal plasma: breast milk ratio ranged between 0.4 and 3.2 for zidovudine, and 0.6 and 3.3 for lamivudine. Lamivudine median infant serum concentrations ranged between 18 and 28 ng/mL and were not detectable in one of the studies (assay sensitivity 7 ng/mL). Zidovudine median infant serum concentration was 24 ng/mL in one study and was below assay limit of qualification (30 ng/mL) in another study. Intracellular zidovudine and lamivudine triphosphate (active metabolites of zidovudine and lamivudine) levels in breastfed infants were not measured therefore the clinical relevance of the serum concentrations of the parent compounds measured is unknown.