The history of antiviral and antiretroviral therapy is recent compared with many other medical therapies, including traditional antibiotics in pregnancy. Given the proliferation of these recent agents, there are few long-term data on which to base decisions of management in pregnancy. Accessing up-to-date information is critical to optimizing the safety of care for mothers and their infants. The general avoidance of unnecessary medications in the first trimester is still prudent, and judicious use of these medications in later pregnancy is sensible.
Exposure to medications in pregnancy can be toxic to a fetus in a gestational age-dependent manner . Medications that are teratogenic at certain stages in the first trimester may be safe later in pregnancy, and medications later in pregnancy may have metabolic effects that interfere with neonatal function. Determination of safe medications for use in pregnancy must take into consideration the relative need for the use of certain medications and the possibility of inadvertent exposure in early pregnancy because of unplanned pregnancies.
This article reviews the most commonly used antiviral and antiretroviral agents and places particular emphasis on the issues regarding use in pregnancy.
Amantadine and rimantadine are related drugs used in the treatment of influenza A. Mechanism of action of these drugs is not well understood, but it is believed that they likely act as membrane fusion inhibitors and as RNA-dependent RNA polymerase inhibitors [2,3]. Amantadine is excreted unchanged in the urine, whereas rimantadine is metabolized in the liver. The main described side effects are central nervous system based, including insomnia, impaired thinking, and confusion . Information in pregnancy is limited, but amantadine has shown teratogenic and embryotoxic effects when given in high doses to rats. No adequate human studies have been conducted. Infants exposed to amantadine in pregnancy
Neuraminidase inhibitors are active against both influenzae A and B. Their mechanism of action involves a crucial step in the life cycle of influenzae A and B. A viral surface glycoprotein (hemagglutinin) binds to sialic acid residues on respiratory epithelial surface glycoproteins, which is necessary for the initiation of infection. After the virus replicates, it is also attached to the host cell the same way until neuraminidase cleaves this link and frees the new virions. Zanamivir and oseltamivir are sialic acid analogs that competitively inhibit the viral neuramini- dase [7,8]. Zanamivir is inhaled as a dry powder (2 x 5 mg inhalations twice daily for 5 days) and oseltamivir is an oral drug given as 75 mg orally twice a day for
5 days. The major side effects are nausea and vomiting, but there has been some concern with respiratory distress associated with zanamivir [9,10]. There are limited pregnancy data, with animal studies showing minor skeletal alterations in rats when pregnant rats are given zanamivir, and there are similar findings in pregnant rabbits given oseltamivir. These drugs are FDA category C, because there are no human data [11,12]. Given the relatively limited indications, it may be prudent to avoid these drugs in pregnancy.
The main nucleoside antiviral agents currently available are acyclovir, valacy- clovir, famciclovir, and ribaviron. Indications for the use of these medications in pregnancy included treatment of serious herpes zoster infections, primary herpes simplex infections and for prophylaxis at term for women with recurrent herpes simplex. In rare cases with HIV-infected or immunocompromised pregnant women, treatment of cytomegalovirus (CMV) infection with ganciclovir or foscarnet may be indicated. There are currently no usual indications for CMV therapy in pregnancy, even for prevention of vertical transmission .