The largest trial to date has offered reassurance to women who require antiviral drugs to treat herpes infections in early pregnancy that the drugs do not cause birth defects. (1)
Among 837 795 live births over 13 years, 1804 pregnancies were exposed to aciclovir, valaciclovir or famciclovir in the first trimester.
Major birth defects were found in 2.2% of infants exposed to the antivirals (aciclovir, 2% [32 defects/1561 infants]; valaciclovir, 3.1% [7/229]; and famciclovir 3.8% [1/26]) and 2.4% in the control group.
The Danish study findings should prompt Australian regulators to reconsider the current B3 classification of aciclovir and valaciclovir according to an expert on medication use in pregnancy, Dr Debra Kennedy, director of Mothersafe at the Royal Hospital for Women in New South Wales.
Dr Kennedy said the drugs’ B3 categorisation should be re-evaluated based on the findings.
The current Australian Therapeutic Goods Administration’s B3 category means the drugs have been taken by a limited number of pregnant women without an increase in harm, but teratogenic effects have been seen in animal models, the significance of which is considered uncertain in humans.
More than 1% of susceptible women acquire herpes simplex in the first trimester of pregnancy, with antiviral treatment indicated for a significant number. Yet to date, data on antiviral use in early pregnancy have been scarce.
However, the study authors cautioned that the findings were based on records of filled prescriptions, with no confirmation that the drugs were actually used by the pregnant mothers.
An accompanying editorial in JAMA said the findings provided fairly strong reassurance that aciclovir was not a major cause of birth defects.
“However, this study leaves a key question unanswered – is acyclovir a teratogen?”, the editorial said.
“The authors note they are not able to exclude an increased risk for any individual defect because of the small number of exposed cases in each defect group.”
Based on previous studies, Dr Kennedy said Mothersafe was already comfortable with the use of these antiviral drugs in pregnancy and the latest findings offered added reassurance.
“We tell people there is a baseline risk of 3% of having a baby with a major birth defect – that’s been shown and that’s what they are seeing in the [study] control,” Dr Kennedy said.
“If someone has a significant herpes infection, then clearly you have got to treat the infection,” she said.
A limitation of the study was that it did not look at any effect on fetal growth, neurodevelopment and birth weight and did not extend beyond the first year of life, she said.
A spokeswoman for GlaxoSmithKline, which manufactures Zovirax (aciclovir) and Valtrex (valaciclovir), said any new data needed to be considered by doctors on a patient-by-patient basis. “At this stage GSK is not looking to pursue for the label to be reviewed,” she said.
JAMA 2010; 304: 905-906
Posted 30 August 2010