Data-Medicos 
Dermagic/Express No. 70 
25 Agosto 1.999. 25 August 1.999. 

~ Aciclovir y Embarazo, ~ 
~ Aciclovir and Pregnancy ~ 


EDITORIAL ESPANOL 
================= 
Hola amigos de la red, DERMAGIC de nuevo con ustedes. El tema, el ACICLOVIR, y EMBARAZO. Esta popular medicina con unos cuantos años en el mercado se le ha encontrado efectividad contra los virus del herpes simple, varicela zoster,(VZB), Epstein Barr (EBV), citomegalovirus (CMV) y herpes virus 6 (HHV-6), y todavia en nuestros dias resulta de gran utilidad contra algunas de estas enfermedades virales sobre todo en el embarazo donde ha mostrado ser bastante segura para la madre y feto y con una buena efectividad en casos de herpes simple, zoster y varicella. De modo que aun con la aparición de nuevas drogas contra estos virus como el: famciclovir, valaciclovir ganciclovir y cidofovir, el ACICLOVIR ocupa todavia un lugar importante como arma terapeutica contra estos agentes virales. Algunos Dermatologos tambien han utilizado el ACICLOVIR, en la pitiriasis rosada de Gibert pensando en una posible causa viral (herpes virus), y otros en la pitiriasis liquenoide varioliforme aguda (Enfermedad de Mucha-Habermann). En estas 36 referencias queda plasmada su efectividad en el embarazo. Al final una monografia del producto 

Bienvenido a DERMAGIC/EXPRESS Dr: B.Mehta (Bahrain), Arie Y. Lifshitz (Israel), Joe Bark (Lexinton) 

Saludos a todos !!! 
Dr. Jose Lapenta R.,,, 

EDITORIAL ENGLISH 
================= 
Hello friends of the net, DERMAGIC again with you. The topic, the ACICLOVIR, and PREGNANCY. This popular medicine with some years in the market has been found effectiveness against the herpes simplex viruses, varicella-zoster virus,(VZB), Epstein Barr Virus (EBV), cytomegalovirus (CMV) and herpes virus 6 (HHV-6), and still in our days it is mainly of great utility against some of these viral illnesses in the pregnancy where it has shown to be quite safe for the mother and fetus and with a good effectiveness in cases of herpes simplex, zoster and varicella. So that even with the appearance of new drugs against these viruses like the one: famciclovir, valaciclovir ganciclovir and cidofovir, the ACICLOVIR still occupies an important place as weapon therapy against these viral agents. Some Dermatologist the ACICLOVIR has also used, in the pityriasis rosea of Gibert thinking of a possible viral cause (herpes virus), and others in the pityiriasis lichenoid et varioliformis acuta. (Mucha Haberman' disease). In these 36 references their effectiveness is captured in the pregnancy. At the end a monograph of the product. 

Welcome to DERMAGIC/EXPRESS Dr: B.Mehta (Bahrain), Arie Y. Lifshitz (Israel), Joe Bark (Lexinton) 

Greetings to ALL, !! 
Dr. Jose Lapenta R.,,, 
=================================================================== 
REFERENCIAS BIBLIOGRAFICAS / BIBLIOGRAPHICAL REFERENCES 
=================================================================== 
1.)Aciclovir. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. 
2.) Acyclovir. An updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. 
3.) Acyclovir. A review of its pharmacodynamic properties and therapeutic efficacy. 
4.) Uses and safety of acyclovir in pregnancy. 
5.) Pharmacokinetics of acyclovir in the term human pregnancy and neonate. 
6.) Systemic acyclovir in pregnancy: a case report. 
7.) Treatment of disseminated herpes simplex virus in pregnancy with parenteral acyclovir. A case report. 
8.) [Recurrent cutaneous herpes in the newborn and acyclovir]. 
9.) Oral acyclovir and recurrent genital herpes during late pregnancy. 
10.) Acyclovir therapy during pregnancy. 
11.) Herpes simplex virus hepatitis in pregnancy. A case report. 
12.) Disseminated herpes simplex infection in an immunocompromised pregnancy: treatment with intravenous acyclovir. 
13.) Acyclovir for disseminated herpes simplex virus in pregnancy. A case report. 
14.) Acyclovir for the prevention and treatment of varicella zoster in children, adolescents and pregnancy. 
15.) Treatment with acyclovir of varicella pneumonia in pregnancy. 
16.) Varicella pneumonia during pregnancy. Treatment of two cases with acyclovir. 
17.) Use of acyclovir for varicella pneumonia during pregnancy. 
18.) Varicella during pregnancy. Maternal and fetal effects. 
19.) Perinatal outcome of pregnancies complicated with varicella 
20.) Varicella and pregnancy. 
21.) Intrauterine infection with varicella-zoster virus after maternal varicella. 
22.) [Varicella in pregnancy after the 20th week of amenorrhea]. 
23.) Varicella in pregnancy. 
24.) [Chickenpox and pregnancy. Perinatal aspects and prevention]. 
25.) Use of acyclovir for varicella pneumonia during pregnancy. 
26.) Fatal disseminated herpes simplex in pregnancy with maternal and neonatal death. 
27.) Connatal herpes zoster. 
28.) Pregnancy outcomes following systemic prenatal acyclovir exposure--June 1, 1984-June 30, 1993. 
29.) Severe pneumonia in pregnancy three months after resolution of cutaneous zoster. 
30.) Disseminated herpes zoster in a pregnant woman positive for human immunodeficiency virus. 
31.) Early-second-trimester use of acyclovir in treating herpes zoster in a bone marrow transplant patient. A case report. 
32.) [Acyclovir and pregnancy: current aspects]. 
33.) [A case of delayed cerebral infarction occurring in puerperium preceded by herpes zoster ophthalmicus in late pregnancy]. 
34.) Congenital varicella-zoster virus infection and Barrett's esophagus. 
35.) Antibodies to varicella zoster virus in the cerebrospinal fluid of neonates with seizures. 
36.) ACYCLOVIR (Systemic), The product 
=================================================================== 
1.)Aciclovir. A reappraisal of its antiviral activity, pharmacokinetic 
properties and therapeutic efficacy. 
=================================================================== 
Drugs 1994 Jan;47(1):153-205 

Wagstaff AJ, Faulds D, Goa KL 
Adis International Limited, Auckland, New Zealand. 

Aciclovir (acyclovir) is a nucleoside analogue with antiviral activity in 
vitro against the herpes simplex viruses (HSV), varicella zoster virus 
(VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human 
herpesvirus 6 (HHV-6). Topical, oral or intravenous aciclovir is well 
established in the treatment of ophthalmic, mucocutaneous and other HSV 
infections, with intravenous aciclovir the accepted treatment of choice in 
herpes simplex encephalitis. The efficacy of aciclovir is increased with 
early (preferably during the prodromal period) initiation of treatment but, 
despite significant clinical benefit, viral latency is not eradicated, and 
pretreatment frequencies of recurrence usually continue after episodic 
acute treatment is completed. Intravenous administration has also shown 
benefit in the treatment of severe complications of HSV infection in 
pregnancy, and neonatal HSV infections. Recurrence of HSV has been 
completely prevented or significantly reduced during suppressive therapy 
with oral aciclovir in immunocompetent patients. Use of oral aciclovir is 
effective but controversial in the treatment of otherwise healthy 
individuals with varicella (chickenpox), and in some countries it has been 
recommended for use only in cases which may be potentially severe. The 
development of rash and pain associated with herpes zoster (shingles) is 
attenuated with oral or intravenous aciclovir therapy, ocular involvement 
is prevented, and post-herpetic neuralgia appears to be decreased. 
Similarly, in a few patients with zoster ophthalmicus, oral aciclovir has 
reduced the frequency and severity of long term ocular complications and 
post-herpetic neuralgia, and herpes zoster oticus is improved with 
intravenous aciclovir. Oral aciclovir has prevented recurrence of HSV 
genital or orofacial infections during suppressive therapy in > 70% of 
immunocompetent patients in most clinical trials. Suppression of latent 
HSV, VZV and CMV infections has been achieved in many immunocompromised 
patients receiving the oral or intravenous formulations. Aciclovir also 
appears to offer partial protection from invasive CMV disease in 
CMV-seropositive bone marrow transplant recipients. The few comparative 
trials published have shown aciclovir to be at least as effective as other 
investigated antivirals in the treatment of HSV infections in 
immunocompetent patients, and more effective than inosine pranobex in the 
prophylaxis of genital herpes. Similarly, in isolated clinical trials, oral 
aciclovir appears as effective as topical idoxuridine and oral brivudine in 
some parameters in immunocompetent patients with VZV infections, and the 
intravenous formulation appears at least as effective as oral brivudine and 
intravenous vidarabine in treating these infections in immunocompromised 
patients. 

=================================================================== 
2.) Acyclovir. An updated review of its antiviral activity, pharmacokinetic 
properties and therapeutic efficacy. 
=================================================================== 
Drugs 1989 Mar;37(3):233-309 

O'Brien JJ, Campoli-Richards DM 
ADIS Drug Information Services, Auckland, New Zealand. 

Acyclovir (aciclovir) is a nucleoside antiviral drug with antiviral 
activity in vitro against members of the herpes group of DNA viruses. As an 
established treatment of herpes simplex infection, intravenous, oral and to 
a lesser extent topical formulations of acyclovir provide significant 
therapeutic benefit in genital herpes simplex and recurrent orofacial 
herpes simplex. The effect of acyclovir therapy is maximised by early 
initiation of treatment, especially in non-primary infection which tends to 
have a less protracted course than the primary episode. Long term 
prophylactic oral acyclovir, in patients with frequent episodes of genital 
herpes simplex, totally suppresses recurrences in the majority of subjects; 
as with other infections responding to acyclovir, viral latency is not 
eradicated and pretreatment frequencies of recurrence return after 
discontinuation of treatment. Caution should accompany the prophylactic use 
of acyclovir in the general population, due to the theoretical risk of the 
emergence of viral strains resistant to acyclovir and other agents whose 
mechanism of action is dependent on viral thymidine kinase. Intravenous 
acyclovir is the treatment of choice in biopsy-proven herpes simplex 
encephalitis in adults, and has also been successful in the treatment of 
disseminated herpes simplex in pregnancy and herpes neonatorium. 
Intravenous and oral acyclovir protect against dissemination and 
progression of varicella zoster virus infection, but do not protect against 
post-herpetic neuralgia. In immunocompromised patients, intravenous, oral 
and topical acyclovir shorten the clinical course of herpes simplex 
infections while prophylaxis with oral or intravenous dosage forms 
suppresses reactivation of infection during the period of drug 
administration. Ophthalmic application of 3% acyclovir ointment rapidly 
heals herpetic dendritic corneal ulcers and superficial herpetic keratitis. 
Thus, despite an inability to eradicate latent virus, acyclovir 
administered in therapeutic or prophylactic fashion is now the standard 
antiviral therapy in several manifestations of herpes simplex virus 
infection, and indeed represents a major advance in this regard. With the 
exception of varicella zoster virus infections, early optimism concerning 
the use of the drug in diseases due to other herpes viruses has generally 
not been supported in clinical investigations. 

=================================================================== 
3.) Acyclovir. A review of its pharmacodynamic properties and therapeutic 
efficacy. 
=================================================================== 
Drugs 1983 Nov;26(5):378-438 

Richards DM, Carmine AA, Brogden RN, Heel RC, Speight TM, Avery GS 

Acyclovir (aciclovir) is a nucleoside analogue antiviral drug related to 
cytarabine, idoxuridine, trifluridine and vidarabine. In common with these 
earlier antivirals, acyclovir is active against some members of the 
herpesvirus group of DNA viruses. The efficacy of topical acyclovir has 
been convincingly demonstrated in ocular herpetic keratitis, and in initial 
and primary initial genital herpes infection, but little or no clinical 
benefit was seen when non-primary initial genital infections were assessed 
separately. Acyclovir ointment demonstrated little benefit in recurrent 
genital herpes but topical acyclovir cream decreased the course of the 
infection by 1 to 2 days. Orally and intravenously administered acyclovir 
were beneficial in initial genital herpes infections, and oral therapy 
shortened the duration of recurrent infections by 1 to 2 days but did not 
ameliorate pain. In non-immunocompromised patients with recurrent herpes 
simplex labialis, generally little clinical benefit was seen with the use 
of topical acyclovir ointment even when therapy was initiated during the 
prodromal phase, while topical acyclovir cream effected small but 
significant improvements in the clinical but not the symptomological course 
of the disease. However, in immunocompromised patients, both intravenous 
and topical acyclovir shortened the clinical course of herpes simplex virus 
infections occurring mainly on the lips, oral mucosa and face, and 
prophylaxis with either oral or intravenous acyclovir suppressed the 
appearance of recurrent lesions from latent virus for the period of drug 
administration, but acyclovir did not eradicate latent herpesviruses. In 
non-immunocompromised patients, intravenous acyclovir was shown to decrease 
the acute pain of zoster, especially in the elderly, but postherpetic 
neuralgia was not ameliorated. When immunocompromised patients were 
studied, intravenous acyclovir inhibited the progression of zoster 
infections and shortened the healing time and duration of viral shedding in 
patients with cutaneous disseminated zoster. However, acute and 
post-herpetic pain were not significantly affected. Well designed 
controlled studies are underway to establish the efficacy of acyclovir in 
herpes simplex encephalitis and cytomegalovirus infections in 
immunocompromised patients, infections due to Epstein-Barr virus, and 
neonatal herpesvirus infections. Despite some aspects of the drug's use 
which require further clarification, acyclovir will make a major impact on 
the treatment of herpesviral infections. Barring unexpected findings with 
wider clinical use, it will become the agent of choice in several conditions. 

=================================================================== 
4.) Uses and safety of acyclovir in pregnancy. 
=================================================================== 
J Fam Pract 1994 Feb;38(2):186-91 

Spangler JG, Kirk JK, Knudson MP 
Department of Family and Community Medicine, Bowman Gray School of Medicine 
of Wake Forest University, Winston-Salem, NC 27157-1084. 

Acyclovir, an antiviral nucleoside analogue, is a widely used agent highly 
specific for herpes simplex and varicella-zoster viruses. Unintended 
exposure to acyclovir early in pregnancy, which is not uncommon, may cause 
excessive maternal and physician anxiety. This drug has not been studied 
prospectively in large numbers of pregnant women and lacks the Food and 
Drug Administration's approval for gestational use unless benefits clearly 
outweigh potential fetal harm. However, data published since acyclovir 
became available do not indicate increased adverse effects related to its 
use in pregnancy, especially if prescribed in selected situations, such as 
disseminated primary herpes simplex infections or maternal varicella 
pneumonia. This article reports the impact of inadvertent acyclovir 
exposure on a woman during the first trimester of pregnancy and reviews the 
literature on acyclovir's pharmacology, safety profile, and potential uses 
during pregnancy. 

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5.) Pharmacokinetics of acyclovir in the term human pregnancy and neonate. 
=================================================================== 
Am J Obstet Gynecol 1991 Feb;164(2):569-76 

Frenkel LM, Brown ZA, Bryson YJ, Corey L, Unadkat JD, Hensleigh PA, Arvin 
AM, Prober CG, Connor JD 
Department of Pediatrics, University of California, Los Angele Center for 
Health Sciences 90024-1752. 

Concern about neonatal herpes often leads to cesarean delivery of infants 
in women with a history of genital herpes. The antiviral drug acyclovir has 
been used effectively to suppress genital herpes simplex virus recurrences 
in nonpregnant adults. Its administration to pregnant women with recurrent 
genital herpes may reduce herpes simplex virus recurrences and thus may 
decrease the cesarean section rate among this population. To study the 
pharmacokinetics, safety, and patient tolerance of suppressive oral 
acyclovir, either 200 mg (n = 7) or 400 mg (n = 8) was administered orally 
every 8 hours to pregnant women with a history of recurrent herpes simplex 
virus, from 38 weeks' gestation until delivery. The mean +/- SD plasma 
levels for the 200 and 400 mg groups, respectively, were: first dose peak, 
1.7 +/- 0.6 and 2.3 +/- 1.0 mumol/L; steady-state trough, 0.7 +/- 0.3 and 
0.8 +/- 0.6 mumol/L; steady-state peak, 1.9 +/- 1.0 and 3.3 +/- 1.0 
mumol/L. In late gestation maternal acyclovir pharmacokinetics were similar 
to those of nonpregnant adults from other studies. Acyclovir was 
concentrated in the amniotic fluid; however, there was no accumulation in 
the fetus (mean maternal/infant plasma ratio at delivery was 1.3). 
Acyclovir was well tolerated, and no toxicity was seen in the mothers or 
infants. The administration of acyclovir, 400 mg every 8 hours, appears 
appropriate for use in an efficacy and safety study regarding suppression 
of herpes simplex virus recurrences during the last weeks of pregnancy. 

=================================================================== 
6.) Systemic acyclovir in pregnancy: a case report. 
=================================================================== 
Obstet Gynecol 1985 Feb;65(2):284-7 

Grover L, Kane J, Kravitz J, Cruz A 
Disseminated herpes simplex infection in pregnancy presents serious risk to 
mother and fetus. Although an uncommon problem, the high maternal and fetal 
mortality and morbidity accompanying disseminated herpes infection warrants 
aggressive new treatment. Specific antiviral chemotherapy is now possible 
for selected cases. The present report describes the use of acyclovir 
during the third trimester for disseminated herpes simplex infection. The 
treatment protocol used and pregnancy outcome are described for this case. 
Acyclovir therapy and potential toxicities are described. 

=================================================================== 
7.) Treatment of disseminated herpes simplex virus in pregnancy with 
parenteral acyclovir. A case report. 
=================================================================== 
J Reprod Med 1986 Oct;31(10):1005-7 

Cox SM, Phillips LE, DePaolo HD, Faro S 
Disseminated herpes simplex virus infection in a pregnant woman was 
successfully treated with acyclovir. Similar reported cases have suggested 
that acyclovir may be suitable for the treatment of disseminated or severe 
primary herpes in pregnant women. 

=================================================================== 
8.) [Recurrent cutaneous herpes in the newborn and acyclovir]. 
=================================================================== 
Pediatrie 1993;48(5):381-3 

Haddad J, Pierrat V, Langer B, Rousseau S, Astruc D, Messer J, Lequien P 
Service de neonatologie, CHU de Hautepierre, Strasbourg, France. 

The authors report two cases of cutaneous recurrent herpes occurring after 
a neonatal herpes simplex virus type 2 (HSV2) infection and comment on the 
role of acute or suppressive therapy by aciclovir (ACV). The two infants 
were not treated by ACV after the neonatal period. None of the recurrent 
cutaneous herpes episodes was followed by viral widespread. One case 
reported by Bergstrom et al on a relapse of HSV2 encephalitis occurring 
after a cutaneous herpes in a child argues for the use of ACV in recurrent 
herpes. However, ACV might alter host defense response to HSV2 infection in 
neonates and children. Thus, it seems not yet recommended to use ACV either 
as acute or suppressive therapy in recurrent cutaneous herpes unless a 
progression of the viral disease is noted. 

=================================================================== 
9.) Oral acyclovir and recurrent genital herpes during late pregnancy. 
=================================================================== 
Obstet Gynecol 1993 Jul;82(1):102-4 

Haddad J, Langer B, Astruc D, Messer J, Lokiec F 
Service de Neonatologie, Hospital University of Strasbourg, France. 

OBJECTIVE: To assess plasma acyclovir levels in pregnant women given oral 
acyclovir during late gestation and to determine the role and effect of 
oral acyclovir on asymptomatic shedding of virus in cases of recurrent 
genital herpes. METHODS: Five pregnant women with proven genital herpes 
isolate (herpes simplex virus [HSV] 2) after 37 weeks' gestation were 
studied. Oral acyclovir was administered every 8 hours at dosages of 300, 
400, and 300 mg in two subjects, and 200 mg five times daily in the other 
three until delivery. Plasma acyclovir peak and trough levels were 
determined. Viral cultures were obtained from both the mothers and neonates 
at delivery. RESULTS: There was no difference in acyclovir plasma levels 
among the patients. Furthermore, acyclovir levels were comparable to those 
of nonpregnant adults. The drug failed to suppress asymptomatic shedding of 
virus and transmission of HSV 2 to the neonate in one of five of the 
patients. CONCLUSION: Our study suggests that asymptomatic shedding of 
virus is not prevented by use of oral acyclovir during late gestation in 
proven recurrent genital herpes even though plasma acyclovir levels were 
within the normal range. 

=================================================================== 
10.) Acyclovir therapy during pregnancy. 
=================================================================== 
Obstet Gynecol 1989 Mar;73(3 Pt 2):526-31 

Brown ZA, Baker DA 
Department of Obstetrics and Gynecology, University of Washington, Seattle. 

Although there are as yet no established indications for acyclovir use in 
pregnancy, the most reasonable uses are for maternal infections such as 
disseminated herpes simplex, varicella pneumonia, and severe primary 
genital herpes. Other potential, but more problematic, uses during 
pregnancy are for uncomplicated primary genital herpes infections, maternal 
varicella, and for prophylaxis against the recurrence of genital herpes 
near term. We review each of these potential uses and the pharmacokinetics 
of acyclovir in pregnancy while emphasizing that at the present time, 
safety, efficacy, and appropriate dosage of the drug have not been 
established for any use in pregnancy. 

=================================================================== 
11.) Herpes simplex virus hepatitis in pregnancy. A case report. 
=================================================================== 
J Reprod Med 1994 Jul;39(7):544-6 

Johnson LG, Saldana LR 
Department of Obstetrics and Gynecology, Bethesda Hospital, Cincinnati, Ohio. 

Hepatitis is a rare but serious complication of a herpes simplex viral 
infection. Pregnancy is a risk factor and has been associated with a high 
maternal and fetal mortality rate. Acyclovir appears to improve the outcome. 

=================================================================== 
12.) Disseminated herpes simplex infection in an immunocompromised 
pregnancy: treatment with intravenous acyclovir. 
=================================================================== 
Am J Perinatol 1987 Oct;4(4):363-4 

Chazotte C, Andersen HF, Cohen WR 
Department of Obstetrics and Gynecology, Bronx Municipal Hospital Center, 
Albert Einstein College of Medicine, New York. 

In this article, we report a case of third-trimester disseminated herpes 
simplex virus (HSV) infection in an immunocompromised gravida who was 
treated with parenteral acyclovir. Rapid resolution of lesions occurred, 
and the fetus was delivered at term without evident abnormalities. Of the 
four previous reports on this therapy, there has been one maternal death 
and survival of all neonates. Acyclovir should be considered in the 
treatment of disseminated HSV infection in pregnancy. 

=================================================================== 
13.) Acyclovir for disseminated herpes simplex virus in pregnancy. A case 
report. 
=================================================================== 
J Reprod Med 1994 Apr;39(4):311-7 

Greenspoon JS, Wilcox JG, McHutchison LB, Rosen DJ 
Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los 
Angeles, CA 90048. 

Seventeen cases of disseminated herpes simplex virus (HSV) infection have 
occurred during pregnancy. Acyclovir therapy was associated with 
prolongation of the time from admission until spontaneous rupture of the 
membranes or delivery and an improved maternal outcome. This 
life-threatening condition has a typical presentation, which includes a 
nonspecific viral prodrome. During pregnancy, fever and anicteric hepatitis 
unresponsive to empiric antibiotics should prompt an evaluation for 
disseminated herpes simplex. Pharyngitis or skin lesions with a positive 
herpes simplex culture are common, specific signs associated with 
dissemination. The fever resolves within 48 hours in response to acyclovir 
therapy. One case of maternal disseminated HSV occurred at 22 weeks' 
gestation and resolved with acyclovir therapy; a healthy neonate was 
delivered vaginally at term. 

=================================================================== 
14.) Acyclovir for the prevention and treatment of varicella zoster in 
children, adolescents and pregnancy. 
=================================================================== 
J Paediatr Child Health 1996 Jun;32(3):211-7 

Kesson AM, Grimwood K, Burgess MA, Ferson MJ, Gilbert GL, Hogg G, Isaacs D, 
Kakakios A, McIntyre P 
Australasian Society for infectious Diseases, Sydney, New South Wales, 
Australia. 

Varicella causes a mild, self-limiting childhood disease that may 
reactivate years later as shingles. In immunocompromised patients with 
altered cell mediated immunity, and rarely in healthy individuals, 
varicella results in a life-threatening infection. The antiviral drug, 
acyclovir, substantially reduces the mortality and risk of severe disease 
in these groups of patients. Early commencement of acyclovir is recommended 
for children with both varicella and altered cell mediated immunity, 
newborns during the first 2 weeks of life, preterm infants in the neonatal 
nursery, and severe varicella or shingles (including ocular zoster) in any 
patient, as well as during pregnancy. Acyclovir may be considered in 
children with serious cardiopulmonary disease or chronic skin disorders 
where varicella may exacerbate the underlying disease or increase the risk 
of secondary bacterial sepsis. Acyclovir, however, is not recommended for 
healthy individuals without severe disease, as a prophylactic agent against 
varicella, for asthmatics receiving aerosolized or low-dose oral steroids 
and/or as treatment of the post-varicella syndromes. When acyclovir is 
prescribed it should be given intravenously to those with severe disease, 
those at risk of dissemination and in children younger than 2 years of age. 

=================================================================== 
15.) Treatment with acyclovir of varicella pneumonia in pregnancy. 
=================================================================== 
Chest 1991 Apr;99(4):1045-7 

Broussard RC, Payne DK, George RB 
Department of Medicine, Louisiana State University School of Medicine, 
Shreveport. 

Varicella pneumonia during pregnancy carries a significant mortality for 
both mother and fetus. The antiviral drug, acyclovir, appears to have 
decreased mortality in reported cases. We present a case report and review 
of the literature summarizing the experience to date with acyclovir in the 
treatment of varicella pneumonia during pregnancy. 


=================================================================== 
16.) Varicella pneumonia during pregnancy. Treatment of two cases with 
acyclovir. 
=================================================================== 
Am J Perinatol 1988 Jan;5(1):16-8 

Eder SE, Apuzzio JJ, Weiss G 
Department of Obstetrics and Gynecology, University of Medicine and 
Dentistry of New Jersey, New Jersey Medical School, Newark 07103. 

Pneumonia is a rare but serious complication of varicella during pregnancy. 
Maternal mortality has been reported to be 41% with fetal and neonatal 
mortality at 65%. Treatment has included respiratory support and 
prophylactic antibiotics. Acyclovir has been prescribed with the intent to 
decrease the impact of the infection. It was added to the treatment 
protocol of two cases of varicella pneumonia in pregnancy. Despite the high 
maternal and perinatal mortality both pairs of patients and infants 
survived. Acyclovir did not appear to adversely influence the fetus, and 
may have contributed to the survival of mother and child. 

=================================================================== 
17.) Use of acyclovir for varicella pneumonia during pregnancy. 
=================================================================== 
Obstet Gynecol 1991 Dec;78(6):1112-6 

Smego RA Jr, Asperilla MO 
Section of Infectious Diseases, West Virginia University Health Sciences 
Center, Morgantown. 

Twenty-one cases (five new and 16 literature) of varicella pneumonia of 
pregnancy were retrospectively reviewed to evaluate the benefits and risks 
of intravenous acyclovir on maternal and fetal outcomes. All women were in 
their second (12 cases) or third (nine cases) trimester. Mean gestational 
ages at the onset of pneumonia and time of delivery were 27 and 36 weeks, 
respectively. Twelve patients required mechanical ventilation. The mean 
duration of treatment was 7 days. No definite adverse drug effects were 
noted. Three women (14%) died of uncontrolled infection or complications. 
Two infants died (whose mothers also died): One was stillborn at 34 weeks' 
gestation, and the other died from prematurity shortly after birth at 26 
weeks. No child was born with features of congenital varicella syndrome, 
and none developed active perinatal varicella infection. Onset of pneumonia 
during the third trimester was a risk factor associated with fatal maternal 
outcome. Intravenous acyclovir may reduce maternal morbidity and mortality 
associated with varicella pneumonia occurring during pregnancy, and appears 
to be safe for the developing fetus when given during the latter trimesters. 

=================================================================== 
18.) Varicella during pregnancy. Maternal and fetal effects. 
=================================================================== 
West J Med 1995 Nov;163(5):446-50 

Katz VL, Kuller JA, McMahon MJ, Warren MA, Wells SR 
Dept of Obstetrics and Gynecology, University of North Carolina Hospital, 
Chapel Hill 27599-7570, USA. 

To determine the characteristics of maternal varicella at our institution, 
we reviewed all cases of primary varicella in pregnancy. Using a perinatal 
database that summarizes all obstetric admissions, we reviewed the medical 
records of women with varicella infections during pregnancy. Over a 5 
1/2-year period, 31 pregnancies were affected by varicella infection among 
11,753 deliveries. The mean age of those patients was 19.6 years, 
significantly different from our overall population of 25.3 years (P < 
.05). The racial composition of 35% Hispanic, 35% white, and 29% African 
American was different from that of our general population of 55% white, 
38% African American, and 6% Hispanic (P = .023). The mean gestational age 
of the eruption of vesicles was 25 weeks. Of the 31 women, 7 had preterm 
labor within a week of their varicella, 3 delivered prematurely, and 3 
infants had a birth weight of less than 2,700 grams. Respiratory symptoms 
developed in 6 women, and pneumonia developed in 4, 2 of whom required 
ventilatory support, 1 for 5 days, the other for 49 days. Eight women 
received acyclovir during gestation, and none suffered sequelae. In all, 6 
infants had lesions and anomalies noted at birth, 5 possibly associated 
with varicella. Varicella infection is associated with a 
greater-than-expected level of both maternal and fetal morbidity. The fetal 
disease may occur due to maternal infection at any gestation and is most 
likely a spectrum of complications. The maternal disease appears to be 
worse in the latter half of pregnancy. Programs of prevention through 
vaccination must account for a possibly decreased level of immunity in 
different populations. 

=================================================================== 
19.) Perinatal outcome of pregnancies complicated with varicella 
=================================================================== 
infection during the first 20 weeks of gestation. 

Am J Perinatol 1997 Aug;14(7):411-4 

Figueroa-Damian R, Arredondo-Garcia JL 
Infectious Diseases Department, National Institute of Perinatology, Mexico, 
D.F., Mexico. 

Varicella-Zoster (V-Z) virus infection during pregnancy is uncommon. 
Nevertheless, it has importance due to the risk of vertical transmission of 
the infection and also because of a higher morbidity rate among pregnant 
women. The cases of varicella infection that occur in the first and second 
trimesters of pregnancy are occasionally associated to the development of 
congenital varicella syndrome. We studied 22 women whose pregnancy was 
complicated with varicella during the first 20 weeks of gestation. The 
average age of these patients was 20 +/- 3.6 years with a range of 16 to 20 
years. None of the patients presented complications due to the V-Z virus 
infection. Two pregnancies finalized in preterm labor. None of the newborns 
had congenital anormalies; one presented microcephaly, and another low 
birth weight. There was no significant difference between the infants of 
women with varicella and those of the controls in birth weight, size, and 
head circumference. We concluded that varicella infection during the first 
20 weeks of gestation was not associated with serious maternal morbidity, 
and has low repercussion in the pregnancy outcome and the fetus. 

=================================================================== 
20.) Varicella and pregnancy. 
=================================================================== 
Eur J Obstet Gynecol Reprod Biol 1996 Jun;66(2):119-23 

Dufour P, de Bievre P, Vinatier D, Tordjeman N, Da Lage B, Vanhove J, 
Monnier JC 
Service of Gynecology-Obstetrics, Pr. J.C. Monnier, CHRU de Lille, France. 

OBJECTIVE: To appreciate the risk of embryo-foetopathy in case of maternal 
varicella occurring before 20 weeks of gestation, as well as the maternal 
complication risk (notably pulmonary) in case of maternal varicella 
occurring the third trimester of pregnancy. METHOD: Over the period from 
January 1987 to February 1995, 20 patients were managed for maternal 
varicella confirmed during the pregnancy. From these observations, the 
authors, by studying the literature, attempt to better specify the real 
fetal and/or maternal complication risk in case of maternal varicella. 
RESULTS: In their personal series of 20 cases, including 17 before 20 weeks 
of gestation, the authors have noted no embryo-foetopathy. Similarly, no 
maternal complication (notably pulmonary complication), has been found. 
Careful study of the literature allows to specify some points. In case of 
varicella before 20 weeks, one observes an identical frequency of 
spontaneous abortions, as compared to the general population and a 
moderated increase of the frequency of premature delivery. The risk of 
congenital varicella syndrome reaches about 1.3%. Finally the risk of 
neonatal varicella consists in a maternal infection which occurs during the 
perinatal period and which is source of a high perinatal morbidity. The 
prenatal diagnosis is based essentially and currently, on the amniocentesis 
with viral research by polymerase chain reaction (PCR) in the amniotic 
fluid, completed by a ultrasound supervision. CONCLUSION: The occurrence of 
maternal varicella during the pregnancy is rare (0.7/1000) because more 
than 90% of women are immunized. The risk of congenital varicella syndrome 
is limited to the 20 first weeks and seems very weak, authorizing 
therapists to reassure patients presenting a varicella during their 
pregnancy. Nevertheless, the risk of pulmonary complications for the 
mother, in case of varicella during the third trimester, does exist and 
requires appropriated treatment. 

=================================================================== 
21.) Intrauterine infection with varicella-zoster virus after maternal 
varicella. 
=================================================================== 
N Engl J Med 1986 Jun 12;314(24):1542-6 

Paryani SG, Arvin AM 
We investigated the consequences of maternal infection with 
varicella-zoster virus in a prospective study of 43 pregnancies complicated 
by varicella and 14 pregnancies complicated by herpes zoster. Nine of 43 
pregnant women with varicella had associated morbidity--pneumonia (4 
women), death (1), premature labor (4 of 42), premature delivery (2 of 42), 
and herpes zoster (1). Intrauterine varicella infection was identified on 
the basis of clinical evidence (anomalies characteristic of the congenital 
varicella syndrome, acute varicella at birth, or herpes zoster in infancy) 
or immunologic evidence (IgM antibody to varicella-zoster in the neonatal 
period, persistent IgG antibody to varicella-zoster at one to two years of 
age, or in vitro lymphocyte proliferation in response to varicella-zoster 
virus antigen). The congenital varicella syndrome occurred in 1 of 11 
infants of women with first-trimester varicella. Immunologic evidence of 
intrauterine varicella infection was present in 7 of 33 infants tested; 4 
of these infants were asymptomatic. According to clinical or immunologic 
criteria, 8 of 33 infants had evidence of intrauterine varicella infection. 
These observations show that varicella during pregnancy was associated with 
maternal morbidity and evidence of fetal infection, but that herpes zoster 
was not. 

=================================================================== 
22.) [Varicella in pregnancy after the 20th week of amenorrhea]. 
=================================================================== 
J Gynecol Obstet Biol Reprod (Paris) 1992;21(8):935-42 

Pierre JC, Senneville E, Ajana F, Santre C, Chidiac C, Mouton Y 
Centre Hospitalier de Tourcoing, Services des Maladies Infectieuses et du 
Voyageur. 

We report five cases of varicella pneumonia among ten otherwise healthy 
pregnant women who were admitted in our hospital between 1986 and 1991 with 
chickenpox. The precise frequency of this rare complication is not well 
known actually but analysis of the literature shows that the mortality rate 
is about 20%. Beside the problem of the fetal varicella syndrome, the other 
complication is the severe varicella of the neonate which can appear when 
varicella occurs in the mother within 5 days before, and 2 days after 
delivery. When primary varicella infection occurs during pregnancy clinical 
examination must be repeated for a week after occurring of the exanthema to 
find elements of severity significance. Acyclovir is the drug of choice (10 
to 15 mg/kg every 8 hours) for 7 days when pneumonia is present. 
Varicella-zoster immunoglobulin is useful for prophylaxis and for neonates 
with high risk of severe varicella. 

=================================================================== 
23.) Varicella in pregnancy. 
=================================================================== 
Semin Perinatol 1998 Aug;22(4):339-46 

Chapman SJ 
Center for Women's Medicine, Division of Maternal-Fetal Medicine, 
Greenville Hospital System, SC 29605, USA. 

Varicella-zoster virus may cause serious infection, particularly pneumonia, 
in adult women. Women of child-bearing age should be questioned about 
immunity to varicella preconceptually, and offered serological testing, and 
VARIVAX vaccine if indicated. All pregnant patients should be questioned 
about immunity to varicella during their first prenatal appointment. 
Susceptible patients should be counseled to avoid contact with individuals 
who have chickenpox. If exposure occurs, VZIG should be administered within 
96 hours in an attempt to prevent maternal infection. Varicella embryopathy 
may occur as a result of maternal infection particularly in the first half 
of pregnancy with an incidence of 1% to 2%. Varicella of the newborn is a 
life-threatening illness that may occur when a newborn is delivered within 
5 days of the onset of maternal illness or after postdelivery exposure to 
varicella. Susceptible neonates should receive VZIG. Acyclovir is active 
against the varicella-zoster virus, and treatment is indicated in seriously 
ill adults and neonates. 

=================================================================== 
24.) [Chickenpox and pregnancy. Perinatal aspects and prevention]. 
=================================================================== 
Arch Fr Pediatr 1987 May;44(5):339-42 

Haddad J, Roth S, Simeoni U, Gut JP, Messer J, Willard D 
Five neonates born to women who had had varicella late in pregnancy or in 
the post-partum were admitted to our unit during the last year. In utero 
transmission of varicella-zoster virus occurred in 2 cases. One of them had 
no clinical eruption but specific IgM at a titer of 1/200. The mother 
presented with varicella 15 days before delivery. The other developed 
severe neonatal congenital varicella (with disseminated eruption, pneumonia 
and seizures). She was treated by Aciclovir (15 mg/kg/8 h). The mother 
presented with chickenpox 24 hours after birth. Varicella occurring in a 
pregnant woman from 4 days before to 2 days after delivery is dangerous 
because the baby will lack maternal antibodies. It may develop severe 
neonatal varicella (mortality: 20-30%). A neonate in critical condition was 
successfully given a prophylactic treatment by Aciclovir IV (15 mg/kg/8 h 
for 5 days) and varicella-zona immunoglobulins (2 ml on days 1, 2, 3). This 
approach may be the best treatment for babies at risk for severe neonatal 
varicella. 

=================================================================== 
25.) Use of acyclovir for varicella pneumonia during pregnancy. 
=================================================================== 
Obstet Gynecol 1991 Dec;78(6):1112-6 

Smego RA Jr, Asperilla MO 
Section of Infectious Diseases, West Virginia University Health Sciences 
Center, Morgantown. 

Twenty-one cases (five new and 16 literature) of varicella pneumonia of 
pregnancy were retrospectively reviewed to evaluate the benefits and risks 
of intravenous acyclovir on maternal and fetal outcomes. All women were in 
their second (12 cases) or third (nine cases) trimester. Mean gestational 
ages at the onset of pneumonia and time of delivery were 27 and 36 weeks, 
respectively. Twelve patients required mechanical ventilation. The mean 
duration of treatment was 7 days. No definite adverse drug effects were 
noted. Three women (14%) died of uncontrolled infection or complications. 
Two infants died (whose mothers also died): One was stillborn at 34 weeks' 
gestation, and the other died from prematurity shortly after birth at 26 
weeks. No child was born with features of congenital varicella syndrome, 
and none developed active perinatal varicella infection. Onset of pneumonia 
during the third trimester was a risk factor associated with fatal maternal 
outcome. Intravenous acyclovir may reduce maternal morbidity and mortality 
associated with varicella pneumonia occurring during pregnancy, and appears 
to be safe for the developing fetus when given during the latter trimesters. 

=================================================================== 
26.) Fatal disseminated herpes simplex in pregnancy with maternal and 
neonatal death. 
=================================================================== 
South Med J 1996 Jul;89(7):732-4 

Gelven PL, Gruber KK, Swiger FK, Cina SJ, Harley RA 
Department of Pathology and Laboratory Medicine, Medical University of 
South Carolina , Charleston 29425, USA. 

Disseminated herpes is rare in the adult and usually occurs in the 
immunocompromised. Twenty-one cases have been reported in which healthy 
women contracted life-threatening disseminated herpes simplex virus (HSV) 
infections in the third trimester of pregnancy. Most of these patients had 
nonspecific symptoms, and many did not have mucocutaneous lesions. On 
physical examination, they were usually febrile and anicteric and had 
markedly elevated aminotransferase values, without a corresponding 
elevation in bilirubin level. In our review of the literature, we found 
that prompt acyclovir therapy resulted in 100% survival. Those patients not 
receiving treatment or treated late in the terminal stages of their disease 
had a 63% mortality rate. We report a case of maternal disseminated HSV 
with subsequent maternal death at an estimated 31 weeks' gestation in which 
the diagnosis was made at the time of necropsy. The infant was started on 
acyclovir therapy but died of disseminated HSV. 

=================================================================== 
27.) Connatal herpes zoster. 
=================================================================== 
Cutis 1996 Sep;58(3):231-4 

Querol I, Bueno M, Cebrian A, Gonzalez-Echeverria FJ 
Department of Dermatology, Hospital Reina Sofia de Tudela, Spain. 

We describe a case of connatal herpes zoster present in a newborn girl 
whose mother had been exposed to varicella infection during the seventh 
month of pregnancy. A few minutes after delivery, the newborn was examined 
for an erythematous maculopapular rash with clear grouped vesicles 
involving the right L2-L4 dermatome. She was given varicella zoster 
immunoglobulin and oral and topical acyclovir, and all the skin lesions 
were completely healed eight days later. This report emphasizes one aspect 
of the relationship between maternal exposure to varicella zoster virus 
infection and the occurrence of connatal shingles, the benign course of the 
disease in this case, and the favorable response to acyclovir therapy in 
neonates. 

=================================================================== 
28.) Pregnancy outcomes following systemic prenatal acyclovir 
exposure--June 1, 1984-June 30, 1993. 
=================================================================== 
MMWR Morb Mortal Wkly Rep 1993 Oct 22;42(41):806-9 

Herpes infections are common among women of reproductive age (i.e., aged 
15-44 years). Acyclovir (Zovirax), an antiviral drug effective in the 
treatment of herpes simplex infection, was approved by the Food and Drug 
Administration (FDA) in 1984. Since its approval, the effects of acyclovir 
on human pregnancies have not been determined. However, inadvertent 
pregnancy exposures to acyclovir were expected to occur among women in whom 
treatment had been indicated for preexisting herpes simplex infections. 
Some physicians have reported intentional use of acyclovir during pregnancy 
for treatment of life-threatening herpes simplex infection. To assess the 
outcomes of pregnancies exposed to acyclovir, the Acyclovir in Pregnancy 
Registry was established on June 1, 1984, by the manufacturer, in 
collaboration with CDC. This report summarizes data on pregnancies reported 
to the registry through June 30, 1993. 

=================================================================== 
29.) Severe pneumonia in pregnancy three months after resolution of 
cutaneous zoster. 
=================================================================== 
Infection 1994 May-Jun;22(3):216-8 

Moling O, Mayr O, Gottardi H, Mian P, Zanon P, Oberkofler F, Gramegna M, 
Colucci G 
Sektion fur Infektionskrankheiten, Medizinische Abt. I, Allgemeines 
Regionalkrankenhaus Bozen, Italy. 

A 22 weeks pregnant women was affected by a life-threatening pneumonia and 
a paresis of the proximal muscles with cerebrospinal fluid pleocytosis. Her 
past medical history had been unremarkable except for recurrent episodes of 
paraumbilical herpes zoster. The clinical findings suggested a 
dissemination of varicella-zoster virus without skin lesions. Acyclovir was 
added to the therapy, and the clinical picture began to improve. 
Varicella-zoster virus DNA was detected in placental tissue by 
DNA-hybridisation analysis. 

=================================================================== 
30.) Disseminated herpes zoster in a pregnant woman positive for human 
immunodeficiency virus. 
=================================================================== 
Am J Perinatol 1993 Nov;10(6):463-4 

Petrozza JC, Monga M, Oshiro BT, Graham JM, Blanco JD 
Department of Obstetrics, Gynecology and Reproductive Sciences, Lyndon B. 
Johnson General Hospital, University of Texas Health Science Center, 
Houston 77026. 

We report a case of disseminated herpes zoster in a pregnant patient 
positive for the human immunodeficiency virus (HIV). Disseminated zoster 
was the first manifestation of HIV infection in this patient. In 
HIV-positive patients, zoster may be complicated by cutaneous 
dissemination, visceral involvement, and death. Intravenous acyclovir may 
prevent serious sequelae in both mother and fetus. 

=================================================================== 
31.) Early-second-trimester use of acyclovir in treating herpes zoster in a 
bone marrow transplant patient. A case report. 
=================================================================== 
J Reprod Med 1992 Mar;37(3):280-2 

Horowitz GM, Hankins GD 
Department of Obstetrics and Gynecology, Wilford Hall United States Air 
Force Medical Center, Lackland Air Force Base, Texas 78236-5300. 

Bone marrow transplantation from a human leukocyte antigen (HLA)-identical 
sibling for treatment of severe aplastic anemia among women of reproductive 
age is becoming more common. Successful pregnancy has been reported to 
occur in several such patients. A woman delivered a healthy, term, female 
infant 18 months after a transplant from her HLA-identical sister. Her 
pregnancy was complicated by disseminated herpes zoster, treated with 
intravenous acyclovir at 14 weeks' gestation, before the diagnosis of 
pregnancy. While there have been several case reports involving the use of 
acyclovir in the third trimester, primarily in the treatment of varicella 
infections, there have been no previous reports of such an early 
utilization of this antiviral drug. 

=================================================================== 
32.) [Acyclovir and pregnancy: current aspects]. 
=================================================================== 
J Gynecol Obstet Biol Reprod (Paris) 1989;18(5):679-83 

Haddad J, Messer J, Willard D, Ritter J 
Service de Neonatologie, CHU Hautepierre, Strasbourg. 

Acyclovir (ACV), an antiviral nucleoside analog, is active against Herpes 
simplex viruses (HSV1, HSV2) and varicella virus (VZV). These viruses seems 
to be prejudicial to the pregnant woman and to the fetus. Yet, ACV is not 
recommended for use in pregnancy. However in certain cases, this drug has 
been used. We review in this paper, the pharmacokinetics and transplacental 
passage of ACV, indications, and whether the benefits of the administration 
of ACV in pregnancy outweigh the theoretical risks. Peak and trough plasma 
concentrations of ACV in pregnant women seem to be lower as compared to 
those of non-pregnant adults but effective. This drug crosses the placenta. 
Levels of ACV in cord blood ranged from 0.5 to 3 mumol/l. In as much as in 
vitro inhibitory doses 50 (ID 50) for HSV1, HSV2 and VZV ranged from 0.1 to 
3 mumol/l, it is quite likely that levels noted above may be effective for 
in utero inhibition of viral replication. No adverse effects were noted in 
newborn exposed in utero to ACV. But one must be careful about the direct 
effects of this drug on nucleic acid metabolism despite encouraging results 
on animal fetuses. Based on these findings and from our experience, ACV can 
be administered in pregnancy in two particular situations: in cases of 
maternal severe viral infections and in order to inhibit in utero VZV 
replication. Doses required for pregnant women range from 5 to 15 mg/kg/8 
hours given intravenously, and 200 mg of oral Acyclovir 5 times daily. 

=================================================================== 
33.) [A case of delayed cerebral infarction occurring in puerperium 
preceded by herpes zoster ophthalmicus in late pregnancy]. 
=================================================================== 
No To Shinkei 1999 Jun;51(6):529-33 

Hoshino S, Hayashi A, Yoshizawa T, Tamaoka A, Shoji S 
Department of Neurology, University of Tsukuba, Japan. 

Delayed central neurological symptoms following herpes zoster ophthalmicus 
(HZO) such as "herpes zoster ophthalmicus and delayed contralateral 
hemiparesis" are considered to be due to ipsilateral intracranial 
vasculopathy. We experienced a rare case with cerebral infarction occurred 
in puerperium following HZO in late pregnancy. A healthy 30-year-old woman 
had left HZO at weeks 35 of gestation. She was given acyclovir (ACV) for 
external use and improved with small pigmentation on the left eye-lid. 
Seven weeks after the onset of HZO, she suddenly developed aphasia and 
right hemiparesis. Cerebral angiogram showed narrowing on M 1 segment of 
the ipsilateral middle cerebral artery. The occlusion was seen on 
peripheral portion of the angular artery on the same side. In cerebrospinal 
fluid (CSF), cell count was slightly elevated, but concentration of protein 
and sugar were normal. Varicella-zoster titer was increased in both serum 
and CSF. She was treated with intravenous ACV (1500 mg/day) for 10 days. On 
the next day after the treatment, the cell count was normalized and on 18th 
day, varicella-zoster titer was decreased in CSF. Higher brain function 
improved and no relapses occurred. This is a first case of delayed cerebral 
infarction occurring in puerperium preceded by herpes zoster ophthalmicus 
in late pregnancy, as far as we searched. We should treat carefully 
pregnant or lactating patients with HZO, considering delayed cerebral 
infarction. 

=================================================================== 
34.) Congenital varicella-zoster virus infection and Barrett's esophagus. 
=================================================================== 
J Infect Dis 1998 Aug;178(2):539-43 

Ussery XT, Annunziato P, Gershon AA, Reid BS, Lungu O, Langston C, 
Silverstein S, Lee KK, Baker CJ 
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, 
USA. 

Congenital varicella syndrome is a rare complication of varicella-zoster 
virus (VZV) infection during pregnancy. An infant was exposed to VZV at 
18.5 weeks of gestation and had eye and skin abnormalities at birth and 
persistent feeding difficulties, prompting esophageal biopsies at 12 days 
and 20 and 20.5 months of age. Esophageal tissues demonstrated specialized 
intestinal metaplasia (Barrett's esophagus). VZV DNA (in situ 
hybridization) and proteins (immunohistochemistry and polymerase chain 
reaction) were found in esophageal epithelial cells adjacent to the 
Barrett's lesion. Immediate-early 63 protein (IE63) of VZV was demonstrated 
in the day 12 specimen, and IE62 and the late VZV glycoprotein E (gE) were 
found in the 20-month specimen. Clinical and endoscopic improvement 
followed fundoplication and acyclovir therapy, but VZV DNA and IE62 
persisted in esophageal tissue. These findings associate VZV with 
specialized intestinal metaplasia within the esophagus and suggest a novel 
site for either latent or active VZV infection. 

=================================================================== 
35.) Antibodies to varicella zoster virus in the cerebrospinal fluid of 
neonates with seizures. 
=================================================================== 
Arch Dis Child Fetal Neonatal Ed 1998 Jan;78(1):F57-61 

Mustonen K, Mustakangas P, Smeds M, Mannonen L, Uotila L, Vaheri A, 
Koskiniemi M 
Department of Neuropediatrics, North Karelia Central Hospital, Ioensu, 
Finland. 

Four neonates with convulsions had IgG antibodies in their cerebrospinal 
fluid (CSF) to varicella zoster virus (VZV). These antibodies were found in 
the sera of two of these patients after the age of 6 months. Antibodies to 
16 different microbes were studied from the serum and CSF of 201 neonates 
with neurological problems. The presence of DNA specific to HSV-1, HSV-2, 
and VZV in the CSF was also investigated using the polymerase chain 
reaction (PCR). Antibodies to VZV were detected in the CSF of four 
neonates. Antibody indices suggested production of VZV specific antibodies 
in the central nervous system. These findings suggest that intrathecal 
production of antibodies to VZV can appear in neonates with neurological 
problems, which suggests that intrauterine VZV infection can be acquired 
without cutaneous symptoms in the mother. 

=================================================================== 
36.) ACYCLOVIR (Systemic) 
=================================================================== 
INN: Aciclovir 

VA CLASSIFICATION (Primary/Secondary)&frac34;AM800 

Commonly used brand name(s): 

Avirax; 
Zovirax. 

Note: For a listing of dosage forms and brand names by country 
availability, see Dosage Forms section(s). 

Category 

Antiviral (systemic). 

Indications 

Note: Bracketed information in the Indications section refers to uses that 
are not included in U.S. product labeling. 

Accepted 

Herpes genitalis (treatment)&frac34;Oral acyclovir is indicated in the treatment 
of initial episodes and management of recurrent, severe herpes genitalis 
infections in immunocompromised and nonimmunocompromised patients. 
Parenteral acyclovir is indicated in the treatment of severe initial herpes 
genitalis infections in immunocompromised and nonimmunocompromised 
patients, and in patients who are unable to take (or absorb) oral 
acyclovir.2,63 

Herpes genitalis (prophylaxis)&frac34;Oral acyclovir is indicated in the 
prophylaxis of frequently recurrent (&sup3; 6 episodes per year) herpes 
genitalis infections in immunocompromised and nonimmunocompromised 
patients.2,14,26,27 

Herpes simplex (treatment)&frac34;Parenteral [and oral] acyclovir are indicated in 
the treatment of initial and recurrent mucocutaneous herpes simplex (HSV-1 
and HSV-2) infections in immunocompromised patients.1,50,59,61 

[Herpes simplex (prophylaxis)]*&frac34;Parenteral and oral acyclovir are used in 
the prophylaxis of herpes simplex virus (HSV) infections in patients who 
are immunocompromised, including transplant patients receiving 
immunosuppressant therapy, human immunodeficiency virus (HIV)-infected 
patients, and patients receiving chemotherapy.14,23,24,25,50,65,93 

Herpes simplex encephalitis (treatment)*&frac34;Parenteral acyclovir is indicated 
in the treatment of herpes simplex encephalitis.17,18,44,46,67 

Herpes zoster (treatment)&frac34;Oral acyclovir is indicated in the treatment of 
herpes zoster infections (shingles) caused by varicella-zoster virus (VZV) 
in any adult patient with herpes zoster. Therapy is most effective when 
started within 48 hours of the onset of rash.44,45,50,66 Parenteral 
acyclovir is indicated in the treatment of herpes zoster infections 
(shingles) caused by VZV in immunocompromised patients and disseminated 
herpes zoster in nonimmunocompromised patients.15,22,67 

[Herpes zoster (prophylaxis)]*&frac34;Oral acyclovir is used in the prophylaxis of 
herpes zoster infections (shingles) caused by VZV, after an initial period 
of parenteral acyclovir, in any immunocompromised patient, including 
transplant patients receiving immunosuppressant therapy, HIV-infected 
patients, and patients receiving chemotherapy.50,55 

Herpes zoster ophthalmicus (treatment)&frac34;Oral and parenteral acyclovir are 
indicated in the treatment of herpes zoster ophthalmicus.73,74,75,95 

[Herpes simplex virus, disseminated neonatal infection 
(treatment)]*&frac34;Parenteral acyclovir is used in the treatment of disseminated 
HSV in neonates.14,61,63 

Varicella (treatment)&frac34;Oral acyclovir is indicated in the treatment of 
varicella infections (chickenpox) in nonimmunocompromised patients when 
started within 24 hours of the onset of a typical chickenpox 
rash.72,88,90,92[ Parenteral acyclovir is used in the treatment of 
varicella infections (chickenpox) caused by VZV in immunocompromised 
patients.]21 
Although acyclovir is indicated for the treatment of varicella infections 
in nonimmunocompromised patients, the American Academy of Pediatrics does 
not recommend its use for the treatment of uncomplicated chickenpox in 
healthy children. It is recommended for certain groups at increased risk of 
severe varicella or its complications, such as otherwise healthy, 
nonpregnant persons 13 years of age or older; children older than 12 months 
of age with a chronic cutaneous or pulmonary disorder; and children 
receiving short, intermittent or aerosolized courses of corticosteroids. If 
possible, steroids should be discontinued after known exposure to varicella.94 

Resistance of HSV and VZV to acyclovir has been reported to develop with 
prolonged treatment or repeated therapy in severely immunocompromised 
patients. Resistance may occasionally develop as quickly as within a few 
weeks. If lesions due to herpes simplex virus fail to respond to acyclovir 
therapy, especially with continued viral shedding, viral isolates should be 
tested for susceptibility to acyclovir.2,10,63 

Unaccepted 

Oral acyclovir is not indicated in the suppression of recurrent herpes 
genitalis in patients with infrequent recurrences.2 

*Not included in Canadian product labeling. 

*Not included in Canadian product labeling. 

Pharmacology/Pharmacokinetics 

Physicochemical characteristics: 

Molecular weight&frac34; 
5Acyclovir: 225.21 
Acyclovir sodium: 247.19 
pH&frac34; 
Reconstituted acyclovir (50 mg per mL): Approximately 1149. 

Mechanism of action/Effect: 

Acyclovir is converted to acyclovir monophosphate, a nucleotide, by the 
viral thymidine kinases of herpes simplex virus (HSV) and varicella-zoster 
virus (VZV). Acyclovir monophosphate is converted to the diphosphate by 
cellular guanylate kinase and to the triphosphate by a number of cellular 
enzymes. Acyclovir triphosphate interferes with HSV and VZV DNA polymerase 
and inhibits viral DNA replication. The triphosphate can be incorporated 
into growing chains of DNA by viral DNA polymerase, resulting in 
termination of the DNA chain.1,2,44 

Absorption: 

Oral&frac34;Bioavailability 20% (range, 15 to 30%).54 Poorly absorbed from the 
gastrointestinal tract. Not significantly affected by food.2,4,44 

Distribution: 

Widely distributed to tissues and body fluids, including brain, kidneys, 
lungs, liver, aqueous humor, tears, intestines, muscle, spleen, breast 
milk, uterus, vaginal mucosa, vaginal secretions, semen, amniotic fluid, 
cerebrospinal fluid (CSF), and herpetic vesicular fluid. Highest 
concentrations are found in kidneys, liver, and intestines. CSF 
concentrations are approximately 50% of plasma concentrations. Crosses the 
placenta, also.1,4,50,76 

VolD(steady state)&frac34; 
Adults: Approximately 48 liters (L) per square meter of body surface (m2) 
(range, 37 to 57 L per m2).11,53 

Children and adolescents (1 to 18 years old): Approximately 45 L per m2.11 

Neonates (0 to 3 months old): Approximately 28 L per m2 (range, 24 to 30 L 
per m2).11,52 

End-stage renal disease: Approximately 41 L per m2.11 

Protein binding: 

Low (9 to 33%).95 

Biotransformation: 

Hepatic; only major metabolite found in urine is 
9-carboxymethoxymethylguanine, which accounts for approximately 9 to 14% of 
the dose. This metabolite has no known antiviral activity.4,47 

Half-life: 

Intravenous&frac34; 
Adults: Approximately 2.5 hours.54 

Children (1 to 18 years old): Approximately 2.6 hours.54 

Neonates (0 to 3 months old): Approximately 4 hours.48,50 

Renal impairment (adults)1,50&frac34; 



Creatinine Clearance Half-life 
(mL/min)/(mL/sec) (hr) 

>80/1.33 2.5 
50-80/0.83-1.33 3.0 
15-50/0.25-0.83 3.5 
Anuric 19.5 
During hemodialysis 5.7 
Continuous ambulatory 14-18 
peritoneal dialysis 



Oral&frac34; 
3.3 hours.54 

Time to peak serum concentration 

Intravenous&frac34;End of infusion (approximately 1 hour). 

Oral&frac34;1.7 hours.48 

Mean peak serum concentration (steady-state) 

Oral&frac34;Adults&frac34; 

200 mg every 4 hours: 
0.6 mcg/mL (2.5 micromoles/L).2 

400 mg every 4 hours: 
1.2 mcg/mL (5.3 micromoles/L).2 

800 mg every 4 hours: 
1.6 mcg/mL (6.9 micromoles/L).14 

Intravenous&frac34; 

Adults53: 
5 mg per kg (over 1 hour) every 8 hours&frac34;9.8 mcg/mL (43.5 micromoles/L). 

10 mg per kg (over 1 hour) every 8 hours&frac34;22.9 mcg/mL (101.7 micromoles/L). 

Children (1 to 18 years old)53: 
250 mg per m2 (over 1 hour) every 8 hours&frac34;10.3 mcg/mL (45.8 micromoles/L). 

500 mg per m2 (over 1 hour) every 8 hours&frac34;20.7 mcg/mL (91.9 micromoles/L). 

Neonates (0 to 3 months old)52: 
5 mg per kg (over 1 hour) every 8 hours&frac34;6.8 mcg/mL (30 micromoles/L). 

10 mg per kg (over 1 hour) every 8 hours&frac34;13.8 mcg/mL (61.2 micromoles/L). 

Elimination: 

Renal&frac34; 
Excreted by both glomerular filtration and tubular secretion.67 

Oral: Approximately 14% of total dose excreted unchanged in urine.91,95 

Intravenous: Approximately 45 to 79% excreted unchanged in urine.95 

Fecal&frac34; 
Insignificant amounts (<2%).1,11 

Lungs&frac34; 
Trace amounts in exhaled CO2.1,11 

Dialysis&frac34; 
Hemodialysis: A single 6-hour period of hemodialysis reduces plasma 
acyclovir concentrations by approximately 60%.1 

Peritoneal dialysis: Peritoneal dialysis does not substantially alter 
acyclovir clearance.51 

Precautions to Consider 

Cross-sensitivity and/or related problems 

Patients allergic to ganciclovir may also be allergic to acyclovir because 
of the chemical similarity of the two medications. 

Carcinogenicity 

Life-time bioassays in rats and mice given daily doses of 50, 150, and 450 
mg per kg of body weight (mg/kg) by gavage have not shown any evidence of 
carcinogenicity. However, in vitrocell transformation assays have given 
conflicting results, being positive at the highest dose used in one system. 
The resulting morphologically transformed cells induced tumors when 
inoculated into immunosuppressed, syngeneic, weanling mice, although 
results were negative in another transformation assay.1 

Mutagenicity 

Oral acyclovir has been shown to be mutagenic at high concentrations in 
some acute animal studies. However, no chromosomal damage was noted at 
maximum tolerated parenteral doses (100 mg/kg) in rats or Chinese hamsters. 
Higher doses (500 and 1000 mg/kg) were clastogenic in Chinese hamsters. No 
problems were reported in dominant lethal studies in mice. Also, there was 
no evidence of mutagenicity in 9 out of 11 microbial and mammalian cell 
assays. In 2 of the mammalian cell assays, a positive response for 
mutagenicity and chromosomal damage was noted, but only at concentrations 
at least 25 times the usual plasma concentrations achieved in humans.1 

Pregnancy/Reproduction 

Fertility&frac34;Impairment of spermatogenesis, sperm motility, or morphology has 
not been documented in humans.77 However, high doses of parenteral 
acyclovir have caused testicular atrophy in rats and dogs. Some evidence of 
sperm production recovery was evident 30 days post-dose. Studies in mice 
given oral doses of up to 450 mg/kg per day have shown that acyclovir does 
not impair fertility or reproduction. Studies in female rabbits given 
acyclovir subcutaneously subsequent to mating have shown a significant 
decrease in implantation efficiency, but no decrease in litter size at 
doses of 50 mg/kg per day.1 

Pregnancy&frac34;Acyclovir crosses the placenta.4 Acyclovir has been used in all 
stages of pregnancy, most commonly in the third trimester. No adverse fetal 
effects have been reported.36,81 One small, controlled study found that 
pre-partum treatment of women with recurrent genital herpes helped prevent 
symptomatic recurrences and viral shedding at the time of delivery, 
reducing the risk of the infant being exposed to the virus.82Adequate and 
well-controlled studies in humans have not been done. 

Studies in mice given oral doses of 450 mg/kg per day and studies in rats 
and rabbits given subcutaneous doses of 50 mg/kg per day have shown that 
acyclovir does not cause adverse effects in the fetus.1 

FDA Pregnancy Category C. 

Breast-feeding 

Acyclovir passes into breast milk at concentrations from 0.6 to 4.1 times 
the corresponding plasma concentration. A very small amount of acyclovir 
has been measured in one nursing infant's urine; no toxicity was 
observed.56,57 

Pediatrics 

Limited data are available about the use of oral acyclovir in children 
younger than 2 years of age. However, no unusual toxicity or 
pediatrics-specific problems have been observed in studies done in children 
using doses of up to 3000 mg per square meter of body surface area (mg/m2) 
per day and 80 mg/kg per day.55,68,69,70,71,72Intravenous acyclovir should 
be used with greater caution in neonates due to their age-related decrease 
in clearance.51 The half-life and clearance of intravenous acyclovir in 
children older than 1 year of age is similar to that seen in adults with 
normal renal function.48 

Geriatrics 

Studies performed to date have not demonstrated geriatric-specific problems 
that would limit the usefulness of acyclovir in the elderly. However, 
elderly patients are more likely to have an age-related decrease in renal 
function, which may require an adjustment of acyclovir dosage or dosing 
interval. 

Drug interactions and/or related problems 

The following drug interactions and/or related problems have been selected 
on the basis of their potential clinical significance (possible mechanism 
in parentheses where appropriate)&frac34;not necessarily inclusive (>> = major 
clinical significance): 

Note: Combinations containing any of the following medications, depending 
on the amount present, may also interact with this medication. 

>> Nephrotoxic medications, other (See Appendix II)1&frac34;(concurrent use with 
intravenous acyclovir may increase the potential for nephrotoxicity, 
especially in the presence of renal function impairment) 

Probenecid1,2,54,80&frac34;(may decrease renal tubular secretion of intravenous 
acyclovir when used concurrently, resulting in increased acyclovir serum 
and cerebrospinal fluid [CSF] concentrations, prolonged elimination 
half-life in the serum and CSF, and, potentially, increased toxicity) 

Laboratory value alterations 

The following have been selected on the basis of their potential clinical 
significance (possible effect in parentheses where appropriate)&frac34;not 
necessarily inclusive (>> = major clinical significance): 

With physiology/laboratory test values 
>> Blood urea nitrogen (BUN) and 
>> Creatinine, serum&frac34;(concentrations may be increased because of renal 
tubular obstruction caused by intravenous acyclovir; no increase generally 
occurs with proper dosage and adequate hydration1) 

Medical considerations/Contraindications 

The medical considerations/contraindications included have been selected on 
the basis of their potential clinical significance (reasons given in 
parentheses where appropriate)&frac34;not necessarily inclusive (>> = major 
clinical significance). 

Risk-benefit should be considered when the following medical problems exist 

>> Dehydration or 
>> Renal function impairment, pre-existing1&frac34;(intravenous acyclovir may 
increase the potential for nephrotoxicity; it is recommended that acyclovir 
be administered in a reduced dosage to patients with impaired renal function) 

Hypersensitivity to acyclovir or ganciclovir&frac34; 

Neurological abnormalities or 
Prior neurologic reactions to cytotoxic medications1&frac34;(intravenous acyclovir 
may increase the potential for neurologic side effects) 

Patient monitoring 

The following may be especially important in patient monitoring (other 
tests may be warranted in some patients, depending on condition; >> = 
major clinical significance): 

Papanicolaou (Pap) test9&frac34;(although a clear association has not been shown 
to date, patients with genital herpes may be at increased risk of 
developing cervical cancer; Pap test should be done at least once a year to 
detect early cervical changes) 

>> Blood urea nitrogen (BUN) and 
>> Creatinine, serum1&frac34;(concentrations required prior to and during therapy 
since intravenous acyclovir may be nephrotoxic; if acyclovir is given by 
rapid intravenous injection or its urine solubility is exceeded, 
precipitation of acyclovir crystals may occur in renal tubules; renal 
tubular damage may occur and may progress to acute renal failure) 

Side/Adverse Effects 

Note: Acute renal insufficiency may occur due to precipitation of 
acyclovir in the renal tubules. It is most likely to occur if acyclovir is 
given by rapid intravenous injection, concurrently with known nephrotoxic 
medications, to patients who are inadequately hydrated, or to patients with 
renal function impairment without appropriate dosage reduction. However, 
acute renal failure has also been reported in patients receiving oral 
acyclovir.50,85,86 

Neuropsychiatric toxicity has been associated with high plasma acyclovir 
concentrations&frac34;which may occur when high doses are used, or when patients 
with renal function impairment are not given an appropriately lowered dose. 
Neuropsychiatric toxicity may also be more likely to occur in 
immunocompromised patients and geriatric patients.50 

The following side/adverse effects have been selected on the basis of their 
potential clinical significance (possible signs and symptoms in parentheses 
where appropriate)&frac34;not necessarily inclusive: 

Those indicating need for medical attention 

Incidence more frequent2,49,50 

For parenteral acyclovir 
Phlebitis or inflammation at the injection site (pain, swelling, or redness) 

Incidence less frequent2,49,50 

For parenteral acyclovir&frac34;more common with rapid intravenous injectionAcute 
renal failure (abdominal pain; decreased frequency of urination or 
amount of urine; increased thirst; loss of appetite; nausea; 
vomiting; unusual tiredness or weakness) 

Incidence rare 

For parenteral acyclovir only 
Encephalopathic changes (coma; confusion; hallucinations; 
seizures; tremors) 

Those indicating need for medical attention only if they continue or are 
bothersome 

Incidence more frequent&frac34;especially with high doses 

For parenteral acyclovir 
Gastrointestinal disturbances (loss of appetite; nausea or vomiting); 
lightheadedness 

Incidence less frequent&frac34;with long-term use or high doses 

For oral acyclovir 
Gastrointestinal disturbances (nausea or vomiting; diarrhea; 
abdominal pain); headache; lightheadedness 

Patient Consultation 

As an aid to patient consultation, refer to Advice for the Patient, 
Acyclovir (Systemic). 

In providing consultation, consider emphasizing the following selected 
information (>> = major clinical significance): 

Before using this medication 

>> Conditions affecting use, especially: 

Hypersensitivity to acyclovir or ganciclovir 

Pregnancy&frac34;Acyclovir crosses the placenta 

Breast-feeding&frac34;Acyclovir is distributed into breast milk at concentrations 
from 0.6 to 4.1 times the corresponding plasma concentration 

Use in children&frac34;Neonates have an age-related decrease in acyclovir clearance 

Other medications, especially nephrotoxic medications 

Other medical problems, especially dehydration or pre-existing renal 
function impairment 

Proper use of this medication 

Supplying patient information about herpes simplex or varicella-zoster 
infections 

For treatment of recurrent herpes simplex infections, initiating use of the 
medication as soon as possible after symptoms of recurrence begin to appear 

For treatment of chickenpox (varicella), initiating use of oral acyclovir 
at the earliest sign or symptom; it is most effective when started within 
24 hours of the onset of a typical chickenpox rash 

Capsules, tablets, and oral suspension may be taken with meals 

Taking with full glass of water 

Proper administration technique for oral liquids 

>> Compliance with full course of therapy; not using more often or for 
longer than prescribed 

>> Proper dosingMissed dose: Taking as soon as possible; not taking if 
almost time for next dose; not doubling doses 

>> Proper storage 

Precautions while using this medication 

>> Women with herpes genitalis may have an increased risk of developing 
cervical cancer; annual Pap tests may be required9 

Checking with physician if no improvement within a few days2 

Keeping affected areas as clean and dry as possible; wearing loose-fitting 
clothing to avoid irritation of lesions9 

>> Use of acyclovir has not been shown to prevent the transmission of 
herpes simplex virus to sexual partners 

>> Herpes genitalis may be sexually transmitted even if partner is 
asymptomatic89; sexual activity should be avoided if either partner has 
signs and symptoms of herpes genitalis; use of a condom may help prevent 
transmission of herpes; however, spermicidal jellies or diaphragms probably 
will not be adequately protective2,9 

Side/adverse effects 

Signs of potential side effects, especially phlebitis or inflammation at 
site of injection, acute renal failure, and encephalopathic changes 

General Dosing Information 

Therapy should be initiated as soon as possible following the onset of 
signs and symptoms of herpes simplex or varicella zoster infections. 

Because it may take longer for lesions to heal in immunocompromised 
patients (an average of 2 weeks of therapy for herpes simplex infections), 
the duration of therapy may need to be prolonged beyond the recommended 
number of days until the lesions are crusted over or epithelialized.50 

For oral dosage forms only 

Acyclovir capsules, tablets, and oral suspension may be taken with meals 
since absorption has not been shown to be significantly affected by food.2 

Intermittent short-term treatment of recurrent herpes genitalis infections 
may be effective for some patients, especially when treatment is 
patient-initiated during the prodrome or first sign of lesion formation.2 



For parenteral dosage forms only 

Sterile acyclovir sodium should be administered by intravenous infusion 
only. It should not be administered topically, intramuscularly, orally, 
subcutaneously, or ophthalmically.1,4 

Intravenous infusions of acyclovir should be administered at a constant 
rate over at least a 1-hour period to avoid renal tubular obstruction. 
Rapid injection must be avoided since precipitation of acyclovir crystals 
in the tubules may occur and may result in renal function impairment in up 
to 10% of patients receiving intravenous acyclovir.1 

Obese patients should be dosed based on ideal body weight.67 

Since maximum urinary concentrations of acyclovir are achieved within 2 
hours, patients receiving intravenous infusions and high oral doses must be 
adequately hydrated during this period to prevent precipitation of 
acyclovir in renal tubules.1 

The dose of acyclovir should be adjusted so that a dose is repeated after 
hemodialysis since each 6-hour hemodialysis period results in approximately 
a 60% reduction in acyclovir plasma concentrations.1 

For treatment of adverse effects 

Since there is no specific antidote, treatment of adverse effects should be 
symptomatic and supportive with possible utilization of the following: 
&middot; Adequate hydration to prevent precipitation of acyclovir in the renal 
tubules.3,28,41,42 

&middot; Hemodialysis to aid in the removal of acyclovir from the blood, 
especially in patients with acute renal failure and anuria.3,28,41,42 

Oral Dosage Forms 

Note: Bracketed uses in the Dosage Forms section refer to categories of 
use and/or indications that are not included in U.S. product labeling. 


ACYCLOVIR CAPSULES 

Usual adult and adolescent dose 

Genital herpes infections91&frac34; 
Initial therapy: Oral, 200 mg every four hours while awake, five times a 
day, for ten days. 

Recurrent infections, intermittent therapy: Oral, 200 mg every four hours 
while awake, five times a day, for five days. 

Recurrent infections, chronic suppressive therapy: Oral, 400 mg twice a 
day; or 200 mg three to five times a day.50,91 

Herpes zoster&frac34; 
Oral, 800 mg every four hours while awake, five times a day, for seven to 
ten days.44,45,58,66,78 

Varicella&frac34; 
Oral, 20 mg per kg of body weight, up to 800 mg per dose, four times a day 
for five days. Treatment should be initiated at the earliest sign or 
symptom of chickenpox.90 

[Herpes simplex, mucocutaneous (treatment)]&frac34; 
Oral, 200 to 400 mg five times a day for ten days in immunocompromised 
patients.50,61 

[Herpes simplex, mucocutaneous (prophylaxis)]*&frac34; 
Oral, 400 mg every twelve hours.93 

Note: Adults with acute or chronic renal impairment require a reduction in 
dose. 

The recommended dose for initial therapy and intermittent therapy of herpes 
infections in patients with renal function impairment is:83 



Creatinine Clearance Dose 
Dosing Interval 
(mL/min)/(mL/sec) (mg) 
(hr) 

Genital herpes: 
Initial/intermittent 
therapy 
>10/0.17 200 
4 
(5 
times daily) 
0-10/0-0.17 200 
12 
Chronic suppressive 
>10/0.17 400 
12 
0-10/0-0.17 200 
12 
Herpes zoster (shingles): 
>25/0.42 800 
4 
(5 
times daily) 
10-25/0.17-0.42 800 
8 
0-10/0-0.17 800 
12 



Usual pediatric dose 

Children up to 2 years of age&frac34;Dosage has not been established90. However, 
no unusual toxicity or pediatrics-specific problems have been observed in 
studies done in children using doses of up to 3000 mg per square meter of 
body surface area per day and 80 mg per kg of body weight per 
day.55,68,69,70,71,72 

Children 2 to 12 years old&frac34;Varicella: Oral, 20 mg per kg of body weight, up 
to 800 mg per dose, four times a day for five days. Treatment should be 
initiated at the earliest sign or symptom of chickenpox.90 

Strength(s) usually available 

U.S.&frac34; 
200 mg (Rx)[Zovirax (lactose)]. 

Canada&frac34; 
200 mg (Rx)[Avirax].[Zovirax (lactose) (parabens)]. 

Packaging and storage: 

Store between 15 and 25 &deg;C (59 and 77 &deg;F), in a tight container, unless 
otherwise specified by manufacturer. Protect from light and moisture.2,78 

Auxiliary labeling: 

&middot; Continue medicine for full time of treatment. 


ACYCLOVIR ORAL SUSPENSION 

Usual adult and adolescent dose 

See Acyclovir Capsules. 

Usual pediatric dose 

See Acyclovir Capsules. 

Strength(s) usually available 

U.S.&frac34; 
200 mg per 5 mL (Rx)[Zovirax]. 

Canada&frac34; 
200 mg per 5 mL (Rx)[Avirax].[Zovirax]. 

Packaging and storage: 

Store between 15 and 25 &deg;C (59 and 77 &deg;F), in a tight container, unless 
otherwise specified by manufacturer. Protect from light.2,78 

Stability: 

Suspension retains its potency for 24 months from date of manufacture. Does 
not require reconstitution or refrigeration.79 

Auxiliary labeling: 

&middot; Continue medicine for full time of treatment. 

&middot; Shake well. 

&middot; Take with water. 

&middot; Beyond-use date. 

Note: When dispensing, include a calibrated liquid-measuring device. 


ACYCLOVIR TABLETS 

Usual adult and adolescent dose 

See Acyclovir Capsules. 

Usual pediatric dose 

See Acyclovir Capsules. 

Strength(s) usually available 

U.S.&frac34; 
400 mg (Rx)[Zovirax].800 mg (Rx)[Zovirax]. 

Canada&frac34; 
200 mg (Rx)[Avirax].[Zovirax (lactose)].400 mg (Rx)[Avirax].[Zovirax 
(lactose)].800 mg (Rx)[Avirax].[Zovirax (lactose)]. 

Packaging and storage: 

Store between 15 and 25 &deg;C (59 and 77 &deg;F), in a tight container, unless 
otherwise specified by manufacturer. Protect from light. 

Auxiliary labeling: 

&middot; Continue medicine for full time of treatment. 

Parenteral Dosage Forms 

Note: Bracketed uses in the Dosage Forms section refer to categories of 
use and/or indications that are not included in U.S. product labeling. 

Note: The dosing and strength of the dosage forms available are expressed 
in terms of acyclovir base. 


ACYCLOVIR SODIUM STERILE 

Usual adult and adolescent dose 

Genital herpes infections, severe, initial&frac34; 
Intravenous infusion, 5 mg (base) per kg of body weight every eight hours 
for five days. Administer at a constant rate over at least a one-hour period.1 

Herpes simplex (HSV-1 and HSV-2) infections, mucocutaneous, in 
immunocompromised patients&frac34; 
Intravenous infusion, 5 to 10 mg (base) per kg of body weight every eight 
hours for seven to ten days. Administer at a constant rate over at least a 
one-hour period.1,15 

Herpes simplex encephalitis*&frac34; 
Intravenous infusion, 10 mg (base) per kg of body weight every eight hours 
for ten days. Administer at a constant rate over at least a one-hour 
period.16,17,18,67 

Varicella zoster in immunocompromised patients&frac34; 
Intravenous infusion, 10 mg (base) per kg of body weight every eight hours 
for seven days. Administer at a constant rate over at least a one-hour 
period.21,50,67 

Note: Adults with acute or chronic renal impairment require a reduction in 
dose and/or dosing interval as follows:1 


Creatinine Clearance Dose 
Dosing Interval 
(mL/min)/(mL/sec) (base) 
(hr) 

>50/0.83 100% 
8 
25-50/0.42-0.83 100% 
12 
10-25/0.17-0.42 100% 
24 
0-10/0-0.17 50% 
24 



Usual adult prescribing limits 

Up to 30 mg (base) per kg of body weight or 1.5 grams per square meter of 
body surface daily.15 

Usual pediatric dose 

Herpes genitalis infections, severe, initial&frac34; 
Intravenous infusion, Infants and children up to 12 years of age&frac34;250 mg 
(base) per square meter of body surface every eight hours for five days. 
Administer at a constant rate over at least a one-hour period.1,60 

Children 12 years of age and over&frac34;See Usual adult and adolescent dose. 

Herpes simplex (HSV-1 and HSV-2) infections, mucocutaneous, in 
immunocompromised patients&frac34; 
Infants and children up to 12 years of age&frac34;Intravenous infusion, 250 mg 
(base) per square meter of body surface every eight hours for seven days. 
Administer at a constant rate over at least a one-hour period.1,60 

Children 12 years of age and over&frac34;See Usual adult and adolescent dose. 

Herpes simplex encephalitis*&frac34; 
Intravenous infusion, 10 mg (base) per kg of body weight, or 500 mg per 
square meter, every eight hours for ten days. Administer at a constant rate 
over at least a one-hour period.19,20,67 

Varicella zoster in immunocompromised children&frac34; 
Intravenous infusion, 500 mg (base) per square meter every eight hours for 
seven days. Administer at a constant rate over at least a one-hour 
period.50,64,67 

[Disseminated HSV in neonates]*&frac34; 
Intravenous infusion, 10 mg (base) per kg of body weight every eight hours 
for ten to fourteen days. Administer at a constant rate over at least a 
one-hour period.61 

Strength(s) usually available 

U.S.&frac34; 
500 mg (base) (Rx)[Zovirax].1 gram (base) (Rx)[Zovirax]. 

Canada&frac34; 
500 mg (base) (Rx)[Zovirax].1 gram (base) (Rx)[Avirax]. 

Packaging and storage: 

Prior to reconstitution, store between 15 and 30 &deg;C (59 and 86 &deg;F), unless 
otherwise specified by manufacturer.1 

Preparation of dosage form: 

To prepare initial dilution for intravenous infusion, add 10 or 20 mL of 
sterile water for injection or bacteriostatic water for injection to each 
500-mg or 1-gram vial, respectively, to provide a concentration of 50 mg 
per mL.66 Do not use bacteriostatic water for injection containing benzyl 
alcohol.67 To ensure complete dissolution, shake vial well until solution 
is clear. The resulting solution should be further diluted with a suitable 
diluent (standard electrolyte- and dextrose-containing solutions) to at 
least 100 mL. Final concentrations of 7 mg per mL or less are recommended. 
Higher concentrations (e.g., 10 mg per mL) may cause phlebitis or 
inflammation at the injection site upon inadvertent extravasation.1 

Stability: 

After reconstitution with sterile water for injection, solutions at 
concentrations of 50 mg per mL retain their potency for 12 hours at 
controlled room temperature (15 to 25 &deg;C [59 to 77 &deg;F]). 

After further dilution with standard electrolyte- and dextrose-containing 
solutions for intravenous infusion, solutions retain their potency for 24 
hours at controlled room temperature (15 to 25 &deg;C [59 to 77 &deg;F]). 

Refrigeration of reconstituted solutions may result in the formation of a 
precipitate, which will redissolve when warmed to room temperature.1 

Incompatibilities: 

Sterile acyclovir sodium is incompatible with biological or colloidal 
solutions (e.g., blood products, protein-containing solutions). 

Parabens are incompatible with sterile acyclovir sodium and may cause 
precipitation.1,39 

*Not included in Canadian product labeling. 
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DATA-MEDICOS/DERMAGIC-EXPRESS No (64) 07/07/99 DR. JOSE LAPENTA R. 
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