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REFERENCIAS  BIBLIOGRÁFICAS / BIBLIOGRAPHICAL REFERENCES 

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A.- Valaciclovir to prevent vertical transmission of cytomegalovirus after maternal primary infection during pregnancy: a randomised, double-blind, placebo-controlled trial.

C.-Herpes Zoster and Postherpetic Neuralgia: Prevention and Management.

D- Herpes Zoster: A Brief Definitive Review.

E.-Advances and Perspectives in the Management of Varicella-Zoster Virus.

F.-Valaciclovir for Epstein-Barr Virus Suppression in Moderate-to-Severe COPD: A Randomized Double-Blind Placebo-Controlled Trial

G.- Effectiveness and safety of prenatal valacyclovir for congenital cytomegalovirus infection: systematic review and meta-analysis.

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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 

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1.)Aciclovir. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. 

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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. 

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2.) Acyclovir. An updated review of its antiviral activity, pharmacokinetic  properties and therapeutic efficacy. 

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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. 

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3.) Acyclovir. A review of its pharmacodynamic properties and therapeutic  efficacy. 

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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. 

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4.) Uses and safety of acyclovir in pregnancy. 

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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. 

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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. 

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6.) Systemic acyclovir in pregnancy: a case report. 

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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. 

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7.) Treatment of disseminated herpes simplex virus in pregnancy with  parenteral acyclovir. A case report. 

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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. 

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8.) [Recurrent cutaneous herpes in the newborn and acyclovir]. 

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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. 

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9.) Oral acyclovir and recurrent genital herpes during late pregnancy. 

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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. 

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10.) Acyclovir therapy during pregnancy. 

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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. 

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11.) Herpes simplex virus hepatitis in pregnancy. A case report. 

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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. 

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12.) Disseminated herpes simplex infection in an immunocompromised  pregnancy: treatment with intravenous acyclovir. 

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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. 

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13.) Acyclovir for disseminated herpes simplex virus in pregnancy. A case  report. 

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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. 

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14.) Acyclovir for the prevention and treatment of varicella zoster in  children, adolescents and pregnancy. 

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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. 

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15.) Treatment with acyclovir of varicella pneumonia in pregnancy. 

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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. 

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16.) Varicella pneumonia during pregnancy. Treatment of two cases with  acyclovir. 

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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. 

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17.) Use of acyclovir for varicella pneumonia during pregnancy. 

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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. 

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18.) Varicella during pregnancy. Maternal and fetal effects. 

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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. 

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

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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. 

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20.) Varicella and pregnancy. 

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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. 

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21.) Intrauterine infection with varicella-zoster virus after maternal  varicella. 

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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. 

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22.) [Varicella in pregnancy after the 20th week of amenorrhea]. 

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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. 

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23.) Varicella in pregnancy. 

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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. 

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24.) [Chickenpox and pregnancy. Perinatal aspects and prevention]. 

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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. 

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25.) Use of acyclovir for varicella pneumonia during pregnancy. 

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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. 

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26.) Fatal disseminated herpes simplex in pregnancy with maternal and  neonatal death. 

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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. 

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27.) Connatal herpes zoster. 

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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. 

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28.) Pregnancy outcomes following systemic prenatal acyclovir  exposure--June 1, 1984-June 30, 1993. 

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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. 

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29.) Severe pneumonia in pregnancy three months after resolution of  cutaneous zoster. 

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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. 

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30.) Disseminated herpes zoster in a pregnant woman positive for human  immunodeficiency virus. 

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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. 

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31.) Early-second-trimester use of acyclovir in treating herpes zoster in a 

bone marrow transplant patient. A case report. 

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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. 

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32.) [Acyclovir and pregnancy: current aspects]. 

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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. 

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33.) [A case of delayed cerebral infarction occurring in puerperium  preceded by herpes zoster ophthalmicus in late pregnancy]. 

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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. 

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34.) Congenital varicella-zoster virus infection and Barrett's esophagus. 

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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. 

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35.) Antibodies to varicella zoster virus in the cerebrospinal fluid of  neonates with seizures. 

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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. 

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36.) ACYCLOVIR (Systemic) 

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INN: Aciclovir 

VA CLASSIFICATION (Primary/Secondary;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;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;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;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)]*: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)*:Parenteral acyclovir is indicated  in the treatment of herpes simplex encephalitis.17,18,44,46,67 

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

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

Varicella (treatment;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: 

5Acyclovir: 225.21 

Acyclovir sodium: 247.19 

pH: 

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: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; 

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: 

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: 

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: 

3.3 hours.54 

Time to peak serum concentration 

Intravenous:End of infusion (approximately 1 hour). 

Oral:1.7 hours.48 

Mean peak serum concentration (steady-state) 

Oral:Adults: 

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: 

Adults: 

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

10 mg per kg (over 1 hour) every 8 hours: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:10.3 mcg/mL (45.8 micromoles/L). 

500 mg per m2 (over 1 hour) every 8 hours: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:6.8 mcg/mL (30 micromoles/L). 

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

Elimination: 

Renal: 

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: 

Insignificant amounts (<2%).1,11 

Lungs: 

Trace amounts in exhaled CO2.1,11 

Dialysis: 

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: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: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;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:(concurrent use with  intravenous acyclovir may increase the potential for nephrotoxicity,  especially in the presence of renal function impairment) 

Probenecid1,2,54,80:(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;not  necessarily inclusive (>> = major clinical significance): 

With physiology/laboratory test values 

>> Blood urea nitrogen (BUN) and 

>> Creatinine, serum:(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;not necessarily inclusive (>> = major  clinical significance). 

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

>> Dehydration or 

>> Renal function impairment, pre-existing1:(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: 

Neurological abnormalities or 

Prior neurologic reactions to cytotoxic medications1:(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:(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:(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: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;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: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:especially with high doses 

For parenteral acyclovir 

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

Incidence less frequent: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:Acyclovir crosses the placenta 

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

Use in children: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:  Adequate hydration to prevent precipitation of acyclovir in the renal  tubules.3,28,41,42 

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: 

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: 

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

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 

[Herpes simplex, mucocutaneous (treatment)]: 

Oral, 200 to 400 mg five times a day for ten days in immunocompromised  patients.50,61 

[Herpes simplex, mucocutaneous (prophylaxis)]*: 

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: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: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.: 

200 mg (Rx)[Zovirax (lactose)]. 

Canada: 

200 mg (Rx)[Avirax].[Zovirax (lactose) (parabens)]. 

Packaging and storage: 

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

Auxiliary labeling: 

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.: 

200 mg per 5 mL (Rx)[Zovirax]. 

Canada: 

200 mg per 5 mL (Rx)[Avirax].[Zovirax]. 

Packaging and storage: 

Store between 15 and 25 ;C (59 and 77 ;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: 

Continue medicine for full time of treatment. 

Shake well. 

Take with water. 

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.: 

400 mg (Rx)[Zovirax].800 mg (Rx)[Zovirax]. 

Canada: 

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 ;C (59 and 77 ;F), in a tight container, unless  otherwise specified by manufacturer. Protect from light. 

Auxiliary labeling: 

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:  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:  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*:  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:  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:  Intravenous infusion, Infants and children up to 12 years of age: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:See Usual adult and adolescent dose. 

Herpes simplex (HSV-1 and HSV-2) infections, mucocutaneous, in  immunocompromised patients: 

Infants and children up to 12 years of age: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:See Usual adult and adolescent dose. 

Herpes simplex encephalitis*:  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:  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]*:  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.: 

500 mg (base) (Rx)[Zovirax].1 gram (base) (Rx)[Zovirax]. 

Canada: 

500 mg (base) (Rx)[Zovirax].1 gram (base) (Rx)[Avirax]. 

Packaging and storage: 

Prior to reconstitution, store between 15 and 30 ;C (59 and 86 ;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 ;C [59 to 77 ;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 ;C [59 to 77 ;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-MÉDICOS/DERMAGIC-EXPRESS No (64) 31/05/2025 DR. JOSÉ LAPENTA R. 

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Produced by Dr. José Lapenta R. Dermatologist
Venezuela 1.998-2.025

Producido por Dr. José Lapenta R. Dermatólogo Venezuela 1.998-2.025

Tlf: 0414-2976087 - 04127766810