Is it safe for a pregnant woman in her first trimester to take valgancyclovir (Valcyte)?

Valganciclovir Use in First Trimester

Valganciclovir should be avoided in the first trimester when possible, with local therapy (intraocular implants or intravitreous injections) preferred for CMV retinitis, and systemic therapy delayed until after the first trimester. 1

Clinical Context and Indications

Treatment is only indicated for maternal CMV end-organ disease (such as CMV retinitis in HIV-infected patients), not for preventing congenital infection in asymptomatic maternal infection. 2

• The indications for treating CMV infection during pregnancy are identical to those for non-pregnant HIV-infected adults, primarily focusing on end-organ disease like CMV retinitis 1
• Treatment of asymptomatic maternal CMV infection during pregnancy solely to prevent infant infection is not indicated 1
• The risk of symptomatic fetal infection is low since >90% of HIV-infected pregnant women are CMV antibody positive 1

First Trimester Management Strategy

Preferred Approach: Local Therapy

For retinal disease requiring treatment in the first trimester, intraocular implants or intravitreous injections should be used to limit fetal exposure to systemically administered antiviral drugs. 1

• Systemic antiviral therapy should then be started after the first trimester 1
• This approach minimizes fetal exposure during organogenesis (first 10-12 weeks), when the embryo is most susceptible to potential teratogenic effects 1

When Systemic Therapy Cannot Be Delayed

If systemic therapy is absolutely necessary during the first trimester, valganciclovir is recognized as the treatment of choice during pregnancy based on limited data, toxicity reports, and ease of use compared to alternatives. 1, 2

Safety Profile and Concerns

Animal Toxicity Data

• Ganciclovir (the active metabolite of valganciclovir) is embryotoxic in rabbits and mice and teratogenic in rabbits, causing cleft palate, anophthalmia, aplastic kidney and pancreas, and hydrocephalus 1
• No experience has been reported with valganciclovir use in human pregnancy during the first trimester, but concerns are expected to be the same as with ganciclovir 1, 2

Human Experience

• Safe use of ganciclovir in human pregnancy after organ transplantation has been reported, though primarily in later pregnancy 1
• The FDA label warns that valganciclovir may cause birth defects, as it causes birth defects in animals, though it is not known if it causes birth defects in humans 3

Maternal Safety

• Valganciclovir can affect blood cells and bone marrow, causing serious and life-threatening problems including lowering white blood cells, red blood cells, and platelets 3
• Valganciclovir can affect kidneys, including serious problems such as kidney failure 3
• In recent studies of prenatal use, acute renal failure occurred in 1.71% of women but resolved after discontinuation 4, 5

Contraception Requirements

Effective contraception is mandatory for women of childbearing potential during and for at least 30 days after valganciclovir treatment. 3

• Pregnancy testing should be performed before starting valganciclovir 3
• Males should use barrier contraception during and for at least 90 days following treatment 3
• Valganciclovir may cause temporary or permanent female and male infertility 3

Monitoring Requirements If Treatment Is Initiated

If valganciclovir is used during pregnancy, close fetal monitoring is essential:

• Fetal movement counting in the third trimester 1, 2
• Periodic ultrasound monitoring after 20 weeks of gestation to look for evidence of hydrops fetalis indicating substantial anemia 1, 2
• Regular blood tests to check maternal blood cell counts and kidney function 3

Alternative Agents (All Have Worse Safety Profiles)

• Foscarnet: Associated with increased skeletal anomalies in rats and rabbits; only one case report in third trimester with normal outcome 1, 2
• Cidofovir: Embryotoxic and teratogenic (meningomyelocele and skeletal abnormalities) in rats and rabbits; use in pregnancy is not recommended 1, 2

Critical Pitfalls to Avoid

• Do not use systemic valganciclovir in the first trimester when local therapy options exist for CMV retinitis 1
• Do not treat asymptomatic maternal CMV infection during pregnancy solely to prevent infant infection 1, 2
• Do not take valganciclovir concurrently with Cytovene-IV (ganciclovir IV), as this could cause overdose 3
• Do not ignore the need for effective contraception before and during treatment 3