Is acyclovir (antiviral medication) safe to use during pregnancy?

Acyclovir Safety in Pregnancy

Acyclovir is safe to use during pregnancy, with current evidence showing no increased risk of birth defects compared to the general population, and it is specifically recommended for treating acute herpes infections and as suppressive therapy starting at 36 weeks gestation in women with a history of genital herpes. 1, 2

Safety Profile and Birth Defect Risk

Registry data from 749 pregnancies with first-trimester acyclovir exposure demonstrate that birth defects occur at rates approximating the general population, with no consistent pattern of abnormalities identified. 3 The FDA classifies acyclovir as Pregnancy Category B, meaning animal studies show no fetal harm and no adequate human studies exist, though available human data are reassuring. 3

The Centers for Disease Control and Prevention confirms that current registry findings do not indicate an increased risk for major birth defects after acyclovir treatment. 1

Clinical Indications During Pregnancy

Life-Threatening Maternal Infections (Absolute Indication)

• Intravenous acyclovir is definitively indicated for life-threatening maternal HSV infections including disseminated infection, encephalitis, pneumonitis, or hepatitis. 4, 1
• This represents the clearest indication where benefits unequivocally outweigh any theoretical risks. 4

First Episode Genital Herpes (Recommended Treatment)

• Oral acyclovir 400 mg three times daily for 7-10 days is the CDC-recommended first-line treatment for acute first-episode genital herpes during pregnancy. 1
• Alternative regimen: valacyclovir 1 g orally twice daily for 7-10 days. 1
• The American College of Obstetricians and Gynecologists supports treating first clinical episodes during pregnancy with oral acyclovir. 1

Suppressive Therapy at Term (Strongly Recommended)

• Suppressive antiviral prophylaxis with acyclovir 400 mg three times daily should be initiated at 36 weeks gestation and continued until delivery for women with a history of genital herpes during the current pregnancy. 2
• Alternative suppressive regimen: valacyclovir 1000 mg twice daily starting at 36 weeks. 2
• This approach is supported by randomized controlled trial evidence showing zero recurrences at delivery in acyclovir-treated patients versus 36% recurrence in placebo (P = 0.002), eliminating cesarean deliveries for herpes indication in the treatment group. 5

What NOT to Use Acyclovir For During Pregnancy

The 1993 CDC guidelines (though older, still provide important context) stated that among pregnant women without life-threatening disease, systemic acyclovir should not be used to treat recurrences during pregnancy. 4 However, this recommendation has evolved, as more recent guidelines from ACOG and CDC now support suppressive therapy at 36 weeks. 1, 2

Pharmacokinetics in Pregnancy

• Acyclovir crosses the placenta with maternal/infant plasma ratios of approximately 1.3 at delivery. 6
• The drug concentrates in amniotic fluid but does not accumulate in the fetus. 6
• Peak plasma levels in pregnant women (1.7-3.3 μmol/L) are similar to non-pregnant adults and exceed the inhibitory concentrations needed for HSV suppression (0.1-3 μmol/L). 6
• Acyclovir is excreted in breast milk at concentrations 0.6 to 4.1 times corresponding plasma levels, potentially exposing nursing infants to up to 0.3 mg/kg/day. 3

Critical Context: Neonatal Transmission Risk

Understanding transmission risk clarifies why treatment decisions matter:

• Primary HSV infection near delivery carries 30-50% neonatal transmission risk. 2
• Recurrent HSV at delivery carries only 1-3% neonatal transmission risk. 2
• Most mothers of infants who acquire neonatal herpes lack histories of clinically evident genital herpes. 1

Delivery Management

• Cesarean delivery is mandatory if visible genital lesions or prodromal symptoms are present at labor onset, regardless of acyclovir use. 2
• Women without symptoms or signs of genital herpes at labor onset may deliver vaginally. 4
• Suppressive acyclovir reduces cesarean delivery rates by preventing recurrences at term. 5

Special Populations

Immunocompromised Pregnant Women

• Higher acyclovir doses (400 mg orally 3-5 times daily) are recommended for immunocompromised patients including those with HIV. 1
• If lesions persist during treatment, acyclovir resistance should be suspected. 1, 2

Renal Impairment

• Elderly patients and those with renal dysfunction require dose reduction, though this is less commonly an issue in pregnant women. 3

Common Pitfalls to Avoid

• Do not delay suppressive prophylaxis beyond 36 weeks gestation—the evidence base specifically supports initiation at 36 weeks. 2
• Do not use topical antivirals for suppression—systemic oral therapy is required. 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. 4, 2
• Do not assume viral cultures during pregnancy predict shedding at delivery—they do not and are not routinely indicated. 4

Neonatal Follow-Up

• Infants delivered through an infected birth canal should be followed carefully with viral cultures obtained 24-48 hours after birth. 4, 2
• Treatment should be reserved for infants who develop clinical disease or have positive postpartum cultures. 4