Uses and safety of acyclovir in pregnancy

Journal of Family Practice, Feb, 1994 by John G. Spangler, Julienne K. Kirk, Mark P. Knudson

Intravenous acyclovir can cause phlebitis at the injection site as a result of the drug's high pH. Acyclovir's other side effects include headache, lethargy, tremor, vomiting seizures, and delirium. Chronic suppressive therapy of genital herpes, with either oral or intravenous acyclovir, can cause nausea in 5% and diarrhea in approximately 2% of patients.[2,3] Skin rash has been reported in 1% to 2% of patients.[3] Patients with underlying neurologic disease or renal impairment should be monitored carefully for signs of central nervous system toxicity.[13] Generally, acyclovir is well tolerated by most patients.

Inadvertent First-Trimester Exposure

An estimated 30% to 50% of acyclovir users in the United States are women of child-bearing age who take the drug for suppression of recurrent genital herpes or complicated VZV.[1] The likelihood of inadvertent first-trimester exposure to acyclovir illustrates the need for physicians to provide patients with current data on the potential for fetal harm. The Acyclovir in Pregnancy Registry, recently summarized by Andrews et al,[1] includes early acyclovir exposures that were prospectively reported to Burroughs Wellcome. Of 239 first-trimester exposures, there were 24 spontaneous abortions, 47 elective abortions, 159 live births of normal infants, and 9 live births with congential malformations. None of these anomalies followed a consistent pattern and the authors note that the anomaly rate is similar to that of the general population. The most recent update of this registry, which includes 171 additional first-trimester exposures, confirms this trend (Burroughs Wellcome Company, written communication, June 1993).

Aside from the registry, there are few reports of first-trimester exposures to acyclovir. Five published cases[14-17] resulted in the birth of four normal infants (three at term, one at 42 weeks) and one elective termination of pregnancy. Initial exposures ranged from 1 to 13 weeks' gestation. A report from Great Britain identified 24 additional pregnant patients exposed to acyclovir during the first trimester (Inman WHW. Prescription event monitoring studies. Prescription Monitoring Event News, Sept 1988), 18 of whom gave birth to normal infants, 1 who had a spontaneous abortion, and 5 who had elective abortions.

While the total number of reported cases of first-trimester exposures to acyclovir is too small to justify conclusions regarding the drug's safety, available data do not point to a pattern of increased maternal or fetal adverse outcomes. However, as a nucleoside analogue, acyclovir is potentially teratogenic, and its use should be restricted to situations in which benefits clearly outweigh potential fetal risks. Although acyclovir lacks FDA approval for use during pregnancy, there seems to be a consensus in the literature warranting its use in some situations.

Disseminated Maternal Herpes Simplex Virus Infection

The initial episode of genital HSV infection in a pregnant woman seronegative for HSV types 1 or 2 (known as primary genital HSV) is often marked by severe, prolonged pain and fever and the appearance of distal lesions.[6] Rarely, during the second half of pregnancy, primary genital HSV infection can disseminate as a result of the normal decline in maternal cell-mediated immunity that occurs during pregnancy.[18] This dissemination can lead to encephalitis, pneumonitis, disseminated intravascular coagulation, and, most commonly, hepatitis with very high rate of maternal and fetal mortality.[19] Because of its life-threatening nature, patient with primary genital HSV infections who begin to manifest signs of dissemination (coagulopathy, encephalopathy, pneumonitis, or hepatitis) should be started on intravenous acyclovir,[19,20] with a suggested dose of 7.5mg/kg every 8 hours.[6] Reported lengths of therapy range from 5 days[21] to 11 days,[22] based on the rate of maternal response. Watts suggests continuing 7.5mg/kg intravenously every 8 hours until the mother's condition improves, then switching to oral acyclovir 200 mg every 4 hours to complete a 14-day course.[3]