Valacyclovir Safety in Pregnancy
Valacyclovir is safe to use during pregnancy, with no increased risk of major birth defects compared to the general population, and is recommended by the CDC and ACOG for treatment of genital herpes infections during pregnancy. 1, 2
Safety Evidence
The FDA drug label states that clinical data over several decades with valacyclovir and acyclovir in pregnant women have not identified a drug-associated risk of major birth defects. 2
The Valacyclovir Pregnancy Registry documented outcomes of 111 pregnancies with first-trimester exposure showing a major birth defect rate of 4.5% (95% CI: 0.24%-24.9%), which is not elevated compared to the general population baseline of 3-5%. 2
Registry findings from the CDC provide reassurance that there is no consistent pattern of abnormalities or increased risk for major birth defects after valacyclovir treatment. 3, 1
Clinical Indications for Use
Valacyclovir 1 g orally twice daily for 7-10 days is recommended by the CDC for first-episode genital herpes during pregnancy. 1
Suppressive Therapy Starting at 36 Weeks
ACOG recommends initiating suppressive prophylaxis with valacyclovir 1000 mg twice daily starting at 36 weeks gestation and continuing until delivery for pregnant women with a history of genital herpes during pregnancy. 4
This suppressive regimen significantly reduces HSV shedding at delivery (2% vs 9% in placebo, P=0.02) and clinical recurrences requiring cesarean delivery (4% vs 13% in placebo, P=0.009). 5
The reduction in clinical HSV recurrences between randomization and delivery is substantial (10.5% vs 27.3% in placebo, P=0.023). 6
Pharmacokinetics and Dosing
Valacyclovir achieves higher peak acyclovir plasma concentrations (3.14 ± 0.7 μg/mL) compared to acyclovir alone (0.74 ± 0.6 μg/mL, P<0.0001) in pregnant women. 7
Acyclovir (the active metabolite) concentrates in amniotic fluid but does not preferentially accumulate in the fetus, with maternal/umbilical vein plasma ratios of 1.7 for valacyclovir. 7
Life-Threatening Maternal Infections
- For life-threatening maternal HSV infections (disseminated infection, encephalitis, pneumonitis, or hepatitis), intravenous acyclovir 5 mg/kg every 8 hours is definitively indicated, as benefits clearly outweigh any theoretical risks. 1, 2
Safety Profile and Adverse Events
The overall prevalence of severe side effects with valacyclovir in pregnancy is 2.1%, with 1.71% experiencing acute renal failure that resolves after discontinuation. 8
No significant maternal, obstetric, or neonatal complications have been identified in randomized trials of valacyclovir suppression during pregnancy. 6, 5
No cases of neonatal HSV infection were reported in infants born to mothers receiving valacyclovir suppression in clinical trials. 6, 5
Critical Context: Neonatal Transmission Risk
Primary HSV infection acquired near delivery carries a 30-50% neonatal transmission risk, while recurrent HSV at term carries only a 1-3% risk. 4, 2
Cesarean delivery is mandatory if visible genital lesions or prodromal symptoms are present at labor onset, regardless of suppressive therapy. 4
Common Pitfalls to Avoid
Do not delay suppressive prophylaxis beyond 36 weeks gestation, as the evidence base specifically supports initiation at 36 weeks. 4
Do not assume viral cultures during pregnancy predict shedding at delivery—they are not routinely indicated. 1
Do not routinely treat asymptomatic infants delivered through an infected birth canal with acyclovir; reserve treatment only for symptomatic infants or those with positive cultures. 1
Special Populations
- HIV-infected pregnant women have the same safety profile for valacyclovir, and some experts recommend prophylaxis for those with frequent, severe recurrences of genital HSV disease. 1