Is valacyclovir (Valtrex) safe during pregnancy?

From the Guidelines

Valacyclovir is generally considered safe during pregnancy, with the most recent evidence suggesting its use can reduce the risk of viral shedding, recurrences, and cesarean deliveries when given as suppressive therapy starting at 36 weeks’ gestational age. The American College of Obstetrics and Gynecology recommends against routine screening for HSV serostatus during pregnancy, but suggests screening pregnant women for a history of genital herpes [ 1 ]. Prior randomized clinical trials have demonstrated that women with a history of genital herpes have decreased risk of viral shedding, recurrences, and cesarean deliveries when suppressive acyclovir or valacyclovir is given starting at 36 weeks’ gestational age [ 1 ].

Key points to consider when prescribing valacyclovir during pregnancy include:

• The typical dosing for herpes outbreaks during pregnancy is 1 gram twice daily for 7-10 days
• Suppressive therapy in the third trimester (to prevent outbreaks during delivery) is usually 500 mg twice daily starting at 36 weeks until delivery
• Valacyclovir works by converting to acyclovir in the body, which has been studied more extensively in pregnancy with reassuring safety data [ 1 ]
• While no medication can be guaranteed 100% safe during pregnancy, the benefits of treating herpes infections with valacyclovir typically outweigh the potential risks
• Pregnant women should discuss their specific situation with their healthcare provider before starting any medication

It's also important to note that a case-control study from the National Birth Defects Prevention Study showed a 4.7-fold increased odds for gastroschisis among women who used antiherpes medications between the month prior to conception and the third month of pregnancy [ 1 ]. However, acyclovir remains category B, and the most recent evidence suggests that valacyclovir can be safely used during pregnancy to reduce the risk of viral shedding, recurrences, and cesarean deliveries [ 1 ].

From the FDA Drug Label

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. There are insufficient data on the use of valacyclovir regarding miscarriage or adverse maternal or fetal outcomes. The Acyclovir and the Valacyclovir Pregnancy Registries, both population-based international prospective studies, collected pregnancy data through April 1999 The occurrence of major birth defects during first-trimester exposure to valacyclovir was 4.5% (95% CI: 0.24% to 24.9%) and during any trimester of exposure was 3.9% (95% CI: 1.3% to 10. 7%). Valacyclovir was administered orally to pregnant rats and rabbits (up to 400 mg/kg/day) during organogenesis (Gestation Days 6 through 15, and 6 through 18, respectively) No adverse embryo-fetal effects were observed in rats and rabbits at acyclovir exposures (AUC) of up to approximately 4 (rats) and 7 (rabbits) times the exposure in humans at the MRHD

Valacyclovir Safety in Pregnancy:

• The available data do not indicate a significant risk of major birth defects associated with valacyclovir use during pregnancy.
• However, there are insufficient data to fully assess the risk of miscarriage, adverse maternal, or fetal outcomes.
• Animal studies have shown no adverse effects at exposures up to 4 and 7 times the human exposure.
• Due to the limited data, it is recommended to use valacyclovir during pregnancy only if the potential benefit justifies the potential risk to the fetus 2.
• The decision to use valacyclovir should be made after careful consideration of the risks and benefits.
• It is essential to weigh the potential risks of valacyclovir against the risks associated with untreated herpes simplex during pregnancy.
• Close monitoring of the pregnant woman and the fetus is recommended when valacyclovir is used during pregnancy.

From the Research

Safety of Valacyclovir in Pregnancy

• The safety of valacyclovir in pregnancy is a concern, and several studies have investigated its use during pregnancy 3, 4.
• A study published in 2010 found that exposure to valacyclovir in the first trimester of pregnancy was not associated with an increased risk of major birth defects 3.
• Another study published in 2023 found that prenatal valacyclovir administration in pregnancies with maternal CMV infection reduces the risk of congenital CMV infection, but the quality of evidence was very low 4.
• The study also found that the occurrence of adverse events in pregnant individuals taking valacyclovir was 3.17%, with 1.71% experiencing acute renal failure, which resolved after discontinuation of the drug 4.
• There is limited information on the use of valacyclovir in pregnancy, and more research is needed to fully understand its safety and efficacy 3, 4.

Comparison with Acyclovir

• Acyclovir is another antiviral medication that is commonly used to treat herpes simplex virus infections, and its safety in pregnancy has been more extensively studied 5, 6, 7.
• A study published in 1984 found that oral acyclovir treatment of primary first-episode genital herpes shortened the duration of viral shedding and symptoms, but did not influence subsequent genital recurrences 6.
• Another study published in 1983 found that intravenous, oral, and topical acyclovir were effective in shortening the course of first-episode primary genital herpes, but did not delay or reduce the frequency of subsequent recurrences 7.
• The use of acyclovir in pregnancy is recommended from 36 weeks of gestation until delivery in women with a history of genital herpes 5.

Limitations of Current Evidence

• The current evidence on the safety and efficacy of valacyclovir in pregnancy is limited, and more research is needed to fully understand its effects 4, 3.
• The quality of evidence for the use of valacyclovir in pregnancy is very low, and more studies are needed to provide conclusive results 4.