Is valacyclovir (valacyclovir hydrochloride) safe to use during pregnancy?

Valacyclovir Safety in Pregnancy

Valacyclovir is safe to 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 and Birth Defect Risk

• 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 outcomes of 111 pregnancies with an overall major birth defect rate of 3.9% (95% CI: 1.3% to 10.7%), which is comparable to the general population background risk of 2-4% 1

• The Acyclovir Pregnancy Registry (which included 1,246 pregnancies) showed a major birth defect rate of 2.6% during any trimester exposure, providing additional reassurance for valacyclovir use 1

Clinical Indications During Pregnancy

For suppressive therapy in late pregnancy: Valacyclovir 1000 mg orally twice daily starting at 36 weeks gestation until delivery is recommended for pregnant women with a history of genital herpes 2

For acute herpes treatment: Valacyclovir 1 g orally twice daily for 7-10 days is appropriate for first episode genital herpes during pregnancy 3

Evidence of Efficacy in Pregnancy

• A randomized trial of 350 pregnant women demonstrated that valacyclovir 500 mg twice daily starting at 36 weeks significantly reduced HSV shedding at delivery (2% vs 9% in placebo, P=0.02) and recurrent genital herpes requiring cesarean delivery (4% vs 13% in placebo, P=0.009) 4

• Another randomized trial of 112 women showed valacyclovir 500 mg twice daily starting at 36 weeks reduced clinical HSV recurrences between randomization and delivery (10.5% vs 27.3% in placebo, P=0.023) 5

• No neonatal HSV infections occurred in either treatment group in these trials, and no clinical or laboratory safety concerns were identified 5, 4

Pharmacokinetic Considerations

• Valacyclovir achieves significantly higher peak acyclovir plasma concentrations than acyclovir itself (3.14 vs 0.74 mcg/mL after initial dose, P<0.0001) with better bioavailability 6

• Acyclovir concentrates in amniotic fluid but does not preferentially accumulate in the fetus, with maternal/umbilical vein plasma ratios of approximately 1.7 6

• A breastfed infant would receive approximately 0.6 mg/kg/day of acyclovir from maternal valacyclovir 500 mg twice daily, which is considered safe 1

Critical Context: Disease Risks Without Treatment

• Primary HSV infection acquired in the third trimester carries a 30-50% risk of neonatal transmission, while recurrent HSV at delivery carries only a 1-3% risk 1

• Cesarean delivery is mandatory if visible genital lesions or prodromal symptoms are present at labor onset, regardless of whether the infection is primary or recurrent 2

Dosing Regimens by Indication

Suppressive therapy (36 weeks to delivery):

• Valacyclovir 1000 mg orally twice daily OR
• Acyclovir 400 mg orally three times daily 2

Acute first episode treatment:

• Valacyclovir 1 g orally twice daily for 7-10 days OR
• Acyclovir 400 mg orally three times daily for 7-10 days 3

Life-threatening maternal HSV infection:

• Intravenous acyclovir 5 mg/kg every 8 hours is indicated for disseminated infection, encephalitis, pneumonitis, or hepatitis 7, 3

Common Pitfalls to Avoid

• Do not delay suppressive prophylaxis beyond 36 weeks gestation, as the evidence base specifically supports initiation at 36 weeks for maximum benefit 2

• 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 3

• Do not routinely treat asymptomatic neonates delivered through an infected birth canal with acyclovir—reserve treatment for symptomatic infants or those with positive cultures obtained 24-48 hours after birth 3

Special Populations

HIV-infected pregnant women: The same safety profile applies, though some experts recommend acyclovir prophylaxis for those with frequent, severe recurrences of genital HSV disease (BIII recommendation) 7

Immunocompromised patients: Higher doses may be beneficial (acyclovir 400 mg orally three to five times daily), and if lesions persist during treatment, acyclovir resistance should be suspected 7