What can be recommended today concerning the use of acyclovir during pregnancy?/nA woman is in her

Fråga: What can be recommended today concerning the use of acyclovir during pregnancy? A woman is in her 12th week of pregnancy and has recurrent episodes of genital herpes. When not pregnant she has been treated with acyclovir (Zovirax) with good results.

Sammanfattning: In large studies congenital malformations have been reported in infants exposed to acyclovir during pregnancy. However, these do not appear to be related to the drug. In literature there is little support for avoiding acyclovir treatment during pregnancy. In addition, women treated with acyclovir due to recurrent herpes at the time of delivery seem to have great clinical benefit in reducing the number of caesarean sections, although not statistically significant compared to placebo.

Svar: The principal clinical use of acyclovir during pregnancy is for treatment of primary genital herpes simplex virus (HSV) type 2 and for the prophylaxis against recurrent genital HSV infection (1). Acyclovir is categorised B:3 in the Swedish desk reference. In 500 women with acyclovir exposure during the first trimester no increased rate of congenital abnormalities could be seen (2). In earlier Drugline documents the numbers of exposed pregnancies are insufficient to draw any conclusions about the safety of acyclovir during pregnancy (3,4).

For exposures during the first trimester excluding spontaneous losses and abortions, the rate of birth defects was 3.4 per cent, an incidence not different from that of the general population (1). Combining data from all trimesters, the rate of anomalies was 2.7 per cent, thus not different from expected in a non exposed population (1). These updated data include exposures through December 31, 1996.

Data summary of accumulated prospective reports until December 31, 1997 (1129 acyclovir exposures) from the company give about the same figures. In first trimester acyclovir exposure 19 birth defects out of 559 outcomes are reported and for all trimesters of exposure combined, 27 birth defects out of 973 outcomes are reported, not differing from the expected proportion in the general population (5).

It should be pointed out that systemic intravenous treatment of life-threatening maternal HSV infections (eg disseminated infection, encephalitis, pneumonitis or hepatitis) have reduced the maternal, fetal and infant mortality for these infections. In contrast, oral acyclovir treatment of primary genital HSV infections to prevent adverse fetal outcomes, such as prematurity, intrauterine growth retardation and neonatal HSV infection, as well as therapy to prevent recurrent genital HSV infection to reduce the need for caesarean section, have been discussed as less justifiable indications (1).

However, in a double-blind, randomised placebo controlled trial, 31 received acyclovir and 32 received placebo against recurrent genital herpes infection in late pregnancy. In total, four had caesarean section for herpes simplex virus in the acyclovir group compared to eight in the placebo group. The odds ratio for delivery by caesarean section in women taking acyclovir compared with those taking placebo was 0.44 (6). Treatment during early pregnancy is not common practise. However, in the presence of genital HSV blisters in late pregnancy before a planned delivery, there may be an indication for acyclovir treatment due to an increased risk for neonatal infection (7).