Valacyclovir Safety in Pregnancy
Yes, valacyclovir is safe for use during pregnancy, with clinical data over several decades showing no increased risk of major birth defects compared to the general population. 1
Safety Profile
The FDA drug label confirms that clinical data over several decades with valacyclovir and its metabolite acyclovir in pregnant women have not identified a drug-associated risk of major birth defects. 1
The Valacyclovir Pregnancy Registry documented 111 pregnancies with exposure, showing a major birth defect rate of 4.5% (95% CI: 0.24% to 24.9%) for first-trimester exposure and 3.9% (95% CI: 1.3% to 10.9%) for any trimester exposure—rates consistent with the general population background risk of 2-4%. 1
The larger Acyclovir Registry (valacyclovir's active metabolite) documented 1,246 pregnancies with a major birth defect rate of 3.2% for first-trimester exposure and 2.6% for any trimester exposure, further supporting safety. 1
Clinical Indications During Pregnancy
Treatment of Acute Herpes Infection
For first episode genital herpes during pregnancy, valacyclovir 1 g orally twice daily for 7-10 days is a recommended treatment option. 2
Acyclovir 400 mg orally three times daily for 7-10 days is an alternative first-line option. 2
For life-threatening maternal HSV infection (disseminated infection, encephalitis, pneumonitis, or hepatitis), intravenous acyclovir 5 mg/kg every 8 hours is definitively indicated, as benefits clearly outweigh any theoretical risks. 2
Suppressive Prophylaxis in Late Pregnancy
The American College of Obstetricians and Gynecologists recommends initiating suppressive therapy with valacyclovir 1000 mg orally twice daily starting at 36 weeks gestation and continuing until delivery for pregnant women with a history of genital herpes. 3
This suppressive regimen significantly reduces HSV shedding and recurrent genital herpes requiring cesarean delivery—from 13% in placebo to 4% with valacyclovir treatment. 4
The alternative regimen is acyclovir 400 mg orally three times daily from 36 weeks until delivery. 3
Recurrent Herpes Management
For pregnant women with frequent, severe recurrences of genital HSV disease, acyclovir or valacyclovir prophylaxis is indicated. 5
No pattern of adverse pregnancy outcomes has been reported after acyclovir exposure. 5
Pharmacokinetic Considerations
Valacyclovir produces higher peak acyclovir plasma concentrations (3.14 ± 0.7 μg/mL) compared to acyclovir (0.74 ± 0.6 μg/mL) in pregnant women, with better bioavailability. 6
Acyclovir concentrates in amniotic fluid but shows no evidence of preferential fetal drug accumulation, with maternal/umbilical vein plasma ratios of 1.7 for valacyclovir and 1.3 for acyclovir. 6
Valacyclovir at standard doses is extremely well tolerated with no significant laboratory or clinical evidence of toxicity. 6
Critical Context: Disease Risks Without Treatment
The risk of neonatal HSV transmission is 30-50% for primary genital HSV acquired in the third trimester, compared to only 1-3% for recurrent HSV at term. 3, 1
Primary herpes during the first trimester has been associated with neonatal chorioretinitis, microcephaly, and skin lesions. 1
In very rare cases, transplacental transmission can cause congenital infection with microcephaly, hepatosplenomegaly, intrauterine growth restriction, and stillbirth. 1
Management Algorithm at Delivery
Cesarean delivery is mandatory if visible genital lesions or prodromal symptoms are present at labor onset, regardless of whether this represents primary or recurrent disease. 3
Women without symptoms or signs of genital herpes at labor onset may deliver vaginally. 2
Cesarean delivery reduces transmission risk by approximately 85% when lesions are present. 3
Common Pitfalls to Avoid
Do not delay suppressive prophylaxis beyond 36 weeks gestation—the evidence base specifically supports initiation at 36 weeks. 3
Do not use topical antivirals for suppression; systemic oral therapy is required. 3
Do not assume viral cultures during pregnancy predict shedding at delivery—they are not routinely indicated. 2
Do not routinely treat asymptomatic infants delivered through an infected birth canal with acyclovir; reserve treatment for symptomatic infants or those with positive cultures obtained 24-48 hours after birth. 2
Special Populations
HIV-Infected Pregnant Women
HIV-infected pregnant women have the same safety profile for valacyclovir. 2
Some experts recommend acyclovir prophylaxis for those with frequent, severe recurrences of genital HSV disease. 5