Acyclovir Safety in Pregnancy
Acyclovir is safe to use during pregnancy, with decades of clinical data showing no increased risk of major birth defects compared to the general population. 1, 2
Safety Evidence
The FDA pregnancy registries (completed in 1999) documented 1,246 pregnancies exposed to acyclovir, with birth defect rates of 3.2% in first-trimester exposures and 2.6% across all trimesters—rates comparable to the general population background risk of 2-4%. 1, 2
- Valacyclovir (acyclovir prodrug) showed similar safety, with 4.5% birth defects in first-trimester exposures and 3.9% across all trimesters in 111 documented pregnancies. 2
- No consistent pattern of abnormalities has emerged from registry data, providing reassurance for inadvertent prenatal exposure. 3, 4
Clinical Indications for Treatment
Life-Threatening Maternal Infections (Definitive Indication)
Intravenous acyclovir is definitively indicated for life-threatening maternal HSV infections including disseminated infection, encephalitis, pneumonitis, or hepatitis—the benefits clearly outweigh any theoretical risks. 3, 4
First Episode Genital Herpes During Pregnancy
The CDC and ACOG recommend treating first episode genital herpes during pregnancy with oral acyclovir 400 mg three times daily for 7-10 days OR valacyclovir 1 g twice daily for 7-10 days. 4
- This is critical because primary HSV infection near delivery carries a 30-50% neonatal transmission risk, compared to only 1-3% with recurrent disease. 4, 5, 2
- Treatment of first episodes is justified to reduce viral shedding and potentially decrease transmission risk. 4
Suppressive Prophylaxis at Term
For women with a history of genital herpes during the current pregnancy, initiate suppressive therapy at 36 weeks gestation with acyclovir 400 mg orally three times daily OR valacyclovir 1000 mg orally twice daily, continuing until delivery. 4, 5
- This recommendation is supported by ACOG and CDC guidelines to reduce clinical recurrences at delivery and potentially decrease cesarean delivery rates. 4, 5
- Clinical data shows only 1-4% clinical recurrence rates at delivery with suppressive therapy, compared to 18-37% in historical controls without treatment. 6
- Suppressive therapy is cost-effective, saving approximately $20 per person while preventing cesarean deliveries. 7
Pharmacokinetics in Pregnancy
- Acyclovir crosses the placenta with maternal/infant plasma ratios of approximately 1.3 at delivery, but does not accumulate in the fetus. 8
- Peak and trough plasma concentrations in pregnant women are similar to non-pregnant adults and remain therapeutically effective. 9, 8
- The drug concentrates in amniotic fluid but maintains safe fetal levels. 8
Important Caveats and Pitfalls
Do NOT use systemic acyclovir for routine suppression of recurrent herpes earlier in pregnancy (before 36 weeks) in women without life-threatening disease, per older CDC guidance, though this has evolved with current recommendations supporting 36-week initiation. 3, 4
- Viral cultures during pregnancy do not predict shedding at delivery and are not routinely indicated. 3, 4
- Cesarean delivery remains mandatory if visible genital lesions or prodromal symptoms are present at labor onset, regardless of suppressive therapy. 4, 5
Neonatal Management
- Infants delivered through an infected birth canal should be followed carefully with viral cultures obtained 24-48 hours after birth. 3, 4, 5
- Do NOT routinely treat asymptomatic infants with acyclovir—reserve treatment only for those who develop clinical disease or have positive cultures. 3, 4, 5