Cancer Investigation, 19(1), 13–22 (2001)

ORIGINAL ARTICLE
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A Randomized, Double-Blind Trial of

Famciclovir Versus Acyclovir for the
Treatment of Localized Dermatomal
Herpes Zoster in Immunocompromised
Patients
Stephen Tyring, M.D., Ph.D.,1 Robert Belanger, M.D.,2
For personal use only.

Werner Bezwoda, M.D.,3 Per Ljungman, M.D.,4

Ron Boon,5 and Robin L. Saltzman, M.D.,6 for the
Collaborative Famciclovir Immunocompromised
Study Group
1
University of Texas Medical Branch, Galveston, Texas
2
Hospital Maisonneuve-Rosemont, Montreal, Quebec, Canada
3
Johannesburg Hospital, Parktown, Johannesburg, South Africa
4
Department of Hematology, Huddinge University Hospital,
Karolinska Institute, Huddinge, Sweden
5
SmithKline Beecham Pharmaceuticals, New Frontiers Science Park,
Harlow, Essex, UK
6
SmithKline Beecham Pharmaceuticals, Collegeville, Pennsylvania

ABSTRACT

In this randomized, double-blind, multicenter, acyclovir-controlled study, the efficacy

and safety of famciclovir were evaluated for the treatment of herpes zoster in patients
who were immunocompromised following bone marrow or solid organ transplantation
or oncology treatment. A total of 148 patients, 12 years or older with clinical evidence
of localized herpes zoster, received either oral famciclovir, 500 mg three times
daily, or acyclovir, 800 mg five times daily, for 10 days. Famciclovir was equivalent to

Corresponding author: Stephen Tyring, M.D., Ph.D., Route 1070, University of Texas Medical Branch, Galveston, TX 77555.
Fax: 281-335-4605; E-mail: styring@utmb.edu

13

Copyright 
C 2001 by Marcel Dekker, Inc. www.dekker.com
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14 Tyring et al.

acyclovir with respect to the numbers of patients reporting new lesion formation while
on therapy (77% vs. 73%, respectively). There were no significant differences between
the groups in the time to cessation of new lesion formation, full crusting, complete
healing of lesions, or loss of acute phase pain. Treatment with famciclovir was well
tolerated, with a safety profile comparable to that of acyclovir. Thus oral famciclovir is
a convenient, effective, and well-tolerated regimen for immunocompromised patients
with herpes zoster.

INTRODUCTION ceral dissemination and treatment failures in patients with

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zoster (7,8). Oral acyclovir has been shown to have similar

Varicella-zoster virus (VZV) is a common cause of in-
fection in humans and can result in a spectrum of illness
ranging from asymptomatic to life-threatening disease. In-
fection results from reactivation of dormant VZV within
the posterior root ganglia of the spinal cord or within the
cranial nerve root ganglia. In the immunocompromised
host, including bone marrow and organ transplant (BMT)
recipients, cancer patients receiving intensive chemother-
apy and irradiation, and patients with acquired immuno-
deficiency states, VZV infection can be particularly severe
with significant morbidity and mortality.
For personal use only.
effects (9,10), but due to its low and variable bioavailabil-
ity, frequent administration of high doses (e.g., 800 mg
five times daily) are required to maintain adequate plasma
concentrations. Adherence with this regimen of oral acy-
clovir can be difficult (11–13).
Thus, as oral acyclovir is not always regarded as a reli-
able substitute for intravenous treatment outside of a clin-
ical trial setting, immunocompromised patients with her-
pes zoster are often hospitalized for intravenous therapy.
Hence there is a need for alternative oral therapies in this
indication (14).

The temporal occurrence of herpes zoster in transplant
and oncology patients is predictable with the highest prob-
ability of recurrence reported in patients with Hodgkin’s
disease and in those undergoing BMT. Between 30–50%
of BMT recipients surviving 6 months or longer are likely
to experience herpes zoster (1–3). Reported incidences
following renal and heart transplantation are between 8%
and approximately 20% (4–6). Most cases of herpes zoster
occur within 1 year after marrow transplantation and
within the first 2 years after initial treatment for Hodgkin’s
disease (1,3).
Dermatomal zoster is the usual presentation, although
fever, abdominal pain, nausea, and vomiting may pre-
cede cutaneous manifestations of infection. In one study
in BMT patients who did not receive antiviral therapy at
the time of onset of herpes zoster, significant morbidity
was reported for 30% of patients with 25% developing
severe post herpetic neuralgia (all patients were less than
55 years of age). Disseminated disease developed in 37%
of patients with an associated mortality of 10% (3). Dis-
semination of VZV may lead to visceral manifestations
such as pneumonia, hepatitis, or encephalitis, which may
be fatal.
Acyclovir (Zovirax; Glaxo Wellcome) has been the
most extensively used therapy for VZV infection in
immunocompromised patients. Intravenous acyclovir has
been shown to reduce the incidence of cutaneous and vis-
Famciclovir is the oral prodrug of penciclovir (BRL
39123), a novel nucleoside analogue that shares the same
antiviral spectrum against the herpes viruses as acyclovir
and has similar potency and selectivity. The favorable bi-
ological properties of penciclovir (15–17) (i.e., prolonged
intracellular half-life, persistent antiviral activity in vitro),
the consistent and high bioavailability of famciclovir, and
the proven efficacy in the treatment of herpes zoster in-
fection in immunocompetent patients (18), highlight the
potential therapeutic value of famciclovir in the immuno-
compromised host.
The current multicenter, randomized, double-blind,
acyclovir-controlled trial was therefore conducted to de-
termine the efficacy and safety of famciclovir at a dose
of 500 mg three times a day (tid) for 10 days for the
treatment of herpes zoster infection in immunocompro-
mised patients.
METHODS
Study Sites
The study was conducted at 29 centers located in
Belgium (1), Canada (5), Finland (1), France (7), Hol-
land (1), Italy (4), South Africa (2), Spain (3), Sweden
(2), Switzerland (2), and the United States (1). The pro-
tocol and statement of informed consent were approved
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Famciclovir Vs. Acyclovir in Herpes Zoster
by an Institutional Review Board (or Ethics Committee)
prior to each center’s initiation.
Study Population
Patients aged 12 years or older who were immunosup-
pressed due to either BMT or solid organ transplant, or
due to chemotherapy/radiotherapy for cancer or leukemia
were eligible for inclusion. Patients with HIV infection
were excluded. Patients were required to have clear clini-
cal evidence of a herpes zoster infection and to start study
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medication within 72 hours of rash onset. Written in-
formed consent was obtained from each patient, and their
guardian where applicable, prior to entry into the study.
Female patients of childbearing potential were required to
have a negative result from the screening pregnancy test
prior to participation.
Patients with complications of herpes zoster includ-
ing ophthalmic or visceral involvement, disseminated
zoster, motor neuropathies, encephalitis, and cerebrovas-
cular complications were excluded because this might
warrant intravenous antiviral therapy. In addition, patients
with evidence of renal dysfunction, gastrointestinal ab-
For personal use only.
sorption problems, allogeneic BMT recipients who were
transplanted within 3 months prior to screening, and pa-
tients with primary VZV infection indicated by negative
VZV-IgG serology were also excluded.
Study Design
This was a double-blind, acyclovir-controlled study.
Patients were enrolled within 72 hours of first vesicle
formation, and the clinical diagnosis of herpes zoster
was confirmed by direct immunofluorescence antigen
(DFA) staining. Eligible patients were sequentially allo-
cated a unique patient number at each center according
to a computer-generated randomization code; the patient
number determined their assignment to either famciclovir
500 mg tid or to acyclovir 800 mg five times daily. Each
day, patients took 10 capsules of acyclovir 400 mg or
matching placebo, and 6 tablets of famciclovir 250 mg or
matching placebo. Medication was blister packed so pa-
tients were able to see clearly which capsules and tablets
were to be taken at each dose. Patients were requested to
take tablets at the times and in the sequence presented on
the blister packs and to record in a diary the date and time
that each dose of study medication was taken. Tablets and
capsules containing placebo were identical to those con-
taining famciclovir and acyclovir respectively, and there
were no reports of compromised blinding by vision or
taste. Treatment was continued for a period of 10 days.
REPRINTS
15
Lesion assessments were conducted by the investigator
every day for the first 5 days or until 24 hours after the
cessation of new lesion formation (whichever was longer).
Patients were then assessed every other day until full crust-
ing had occurred, and thereafter weekly until complete
healing had occurred.
Patients were not followed up after healing; therefore
the effect of treatment on post herpetic neuralgia could not
be determined.
Efficacy Assessments
Data for the analysis of efficacy parameters were pro-
vided from investigator assessment of new lesion forma-
tion and lesion staging (macules, papules, vesicles, crusts).
Patient diary cards were used to determine the presence
and severity (none, mild, moderate, or severe, as assessed
subjectively by the patient) of pain each day, and to deter-
mine the time at which the last crust was lost.
Safety Assessments
Adverse experiences were identified by the investiga-
tor or elicited from the patient in response to the question
“Have you felt different in any way since starting the treat-
ment, or since your last assessment?”
Blood and urine samples were taken prior to the first
dose, on day 4 or 5 during treatment, at the end of the treat-
ment period (day 9–12) and 1 week following the end of
treatment (day 16–20) for measurement of hematological
and clinical chemistry parameters and urinalysis.
Sample Size
The study was designed to demonstrate equivalence to
acyclovir with respect to the proportion of patients who de-
velop new lesions while on study medication. Sample size
was calculated using a confidence interval (CI) approach
(19). The treatments would be regarded as equivalent if
the upper limit of the two-sided confidence interval for
the difference (famciclovir minus acyclovir) was less than
20%. Assuming famciclovir was at least as effective as
acyclovir and with similar rates of new lesion formation
within each group (expected to be 80–85%), a sample size
of 51 to 63 patients per treatment group was required to
demonstrate equivalence with 80% power.
Statistical Methods
All analyses were performed on an intent-to-treat pop-
ulation (i.e., those patients who were randomized and
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16
received at least one dose of study medication). All sta-
tistical tests were carried out using two-tailed tests and an
overall significance level of 5%.
The key efficacy parameters included the proportion of
patients with new lesion formation while on study medi-
cation; time to complete healing of all lesions, time to full
crusting of all lesions; time to loss of acute phase pain; and
the change in mean pain intensity scores from baseline.
Equivalence testing was performed for the proportion of
patients with new lesion formation while on study med-
ication, and superiority testing was performed for all the
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remaining efficacy parameters. Center effect was assessed
using graphical presentation of confidence intervals for the
difference in proportion of patients with new lesion for-
mation during therapy to assure that data could be pooled
across centers.
For personal use only.
Figure 1. Trial profile.
REPRINTS
Tyring et al.
Assessment of equivalence (i.e., as good as or bet-
ter than acyclovir) for “the proportion of patients with
new lesion formation while on study medication” was
prospectively defined using a confidence interval ap-
proach, based on standard, validated statistical method-
ology (19–21), as previously discussed (see Sample
Size).
For additional endpoints where proportions were an-
alyzed, confidence intervals for the difference in propor-
tions (famciclovir minus acyclovir) were used to assess
treatment effects. The treatment differences were consid-
ered to be statistically significant if the 95% CI lay entirely
above or below zero. If confidence intervals for the differ-
ences spanned zero it was concluded that the comparison
of famciclovir and acyclovir was not statistically signifi-
cantly different.
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Famciclovir Vs. Acyclovir in Herpes Zoster 17

“Time to event” efficacy parameters were analyzed Table 1

using Cox proportional hazard regression methodology. Demographic Characteristics
Hazard ratios (famciclovir: acyclovir), 95% confidence
intervals for the hazard ratios, medians and quartile times Acyclovir
were calculated. Treatment differences were considered to 800 mg
be statistically significant if the confidence interval of the Famciclovir Five Times
hazard ratio lay entirely above or below 1.0. If confidence 500 mg Tid Daily
n = 71 n = 77
intervals spanned 1.0 it was concluded that the comparison
of famciclovir and acyclovir was not statistically signifi- Male 41 (57.7%) 45 (58.4%)
cantly different. Mean age (range), y 43 (13–86) 43 (13–81)
Pain was classified by the patient at both enrollment and Immunocompromised status
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on a daily basis into one of four classes: none, mild, mod- Bone marrow transplant 48 (67.6%) 52 (67.5%)
erate, or severe. For the calculation of the change in pain Autologous 21 (29.6%) 26 (33.8%)
severity these classes were given a numeric value of 0 to 3. Allogeneic 27 (38.0%) 26 (33.8%)
Clinical laboratory results were evaluated by calculat- Solid organ transplant 1 (1.4%) 2 (2.6%)
Oncology treatment 22 (31.0%) 23 (29.9%)
ing mean differences from baseline and by flagging labo-
Chemotherapy 15 (21.1%) 16 (20.8%)
ratory values that had changed from baseline by more than Radiotherapy 4 (5.6%) 3 (3.9%)
a specified amount and were outside the sponsor-defined Chemotherapy and 3 (4.2%) 4 (5.2%)
extended normal range for immunocompromised patients. radiotherapy

RESULTS
The baseline characteristics of herpes zoster infec-
tion are summarized in Table 2. The majority of patients
For personal use only.

A total of 149 patients were randomized to the study;

one patient failed to take any study medication and was
therefore not included in the intent-to-treat analysis. In to-
tal, 122 patients completed the study and 26 patients were
withdrawn. No famciclovir recipients withdrew while re-
ceiving study medication, compared with 7 acyclovir re-
cipients; the numbers of patients who withdrew after com-
pleting treatment were comparable for the two treatment
groups. Patient disposition, including reasons for with-
drawal, is summarized in Figure 1.
The demographic characteristics of patients partici-
pating in this study were comparable between treatment
groups (Table 1). Overall just over 40% (62/148 patients)
of the population were female, with an overall mean age
of approximately 43 years. The majority of patients were
immunocompromised as a result of BMT (100/148 pa-
tients, 68%); 47 of these patients were autologous BMT
recipients and 53 were allogeneic BMT recipients. More
than 80% of the BMT recipients initiated therapy for zoster
recurrence less than 12 months from the date of BMT.
Overall, only 3 patients were immunocompromised due
to a solid organ transplant (two kidney transplants and
one heart transplant). The remainder of the patients were
undergoing chemotherapy or radiation therapy (45/148
patients, 30%). Of the 100 BMT recipients, 31 (31/100,
31%) developed acute graft versus host disease (GVHD),
which subsequently resolved in 23 of these patients (23/31,
74%). None of the solid organ transplant recipients devel-
oped acute GVHD.
(120/148 patients, 81%) experienced prodromal symp-
toms prior to rash appearance. All patients started treat-
ment at or within 72 hours of rash onset, although there was
a tendency for more patients in the famciclovir group to
have had their rash for longer (48–72 hours) prior to start-
ing study medication. A substantial proportion of patients
in both groups (86/148 patients, 58%) were categorized
as having severe rash (>50 lesions) at enrollment. The
incidence of pain was similar at baseline in the two treat-
ment groups, with approximately 50% of patients over-
all (75/148 patients) reporting moderate or severe pain at
enrollment.
Overall, adherence with study medication was high;
only 18 patients (6 in the famciclovir group and 12 in the
acyclovir group) were less than 80% adherent over the
intended treatment course.
Efficacy Results
New Lesion Formation
A total of 55/71 famciclovir recipients (77%) and 56/77
acyclovir recipients (73%) developed new lesions while
on study medication, and famciclovir was found to be
equivalent to acyclovir (95% CI: −9.2%, 18.6%). There
were no significant differences between the two treatment
groups with respect to cessation of new lesion formation
where the median time to event was 3 days in the acyclovir
group and 4 days in the famciclovir group.
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18 Tyring et al.

Table 2 of or withdrawal from the study. The rate at which patients

Baseline Characteristics of Herpes Zoster Infection lost acute phase pain (Table 3) was similar in famciclovir
and acyclovir recipients (hazard ratio: 1.11, 95% CI: 0.71,
Acyclovir 1.75). The median time to loss of acute phase pain was 14
800 mg days for famciclovir recipients and 17 days for acyclovir
Famciclovir Five Times recipients.
500 mg Tid Daily The daily zoster pain severity scores are presented in
n = 71 n = 77
Figure 2. Lower pain severity scores were seen in the
Duration of prodrome at enrollment famciclovir 500 mg tid group compared to the acyclovir
No prodrome 17 (23.9%) 11 (14.3%) 800 mg five times daily group. However, because pain
≤96 hours 48 (67.6%) 56 (72.7%) data were only recorded until complete healing had oc-
>96 hours
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6 (8.5%) 10 (13.0%) curred, data from later time points should be interpreted
Duration of rash at enrollment with caution.
<24 hours 22 (31.0%) 24 (31.2%)
<48 hours 40 (56.3%) 54 (70.1%) Dissemination
48–72 hours 31 (43.7%) 23 (29.9%)
The number of patients developing disseminated
Number of lesions at enrollment
<25 13 (18.3%) 18 (23.4%)
zoster was low in both treatment groups, although more
25–50 15 (21.1%) 16 (20.8%) acyclovir than famciclovir recipients withdrew due to
>50 43 (60.6%) 43 (55.8%) dissemination. Four patients (all acyclovir recipients)
Pain severity prior to enrollment
withdrew while receiving study medication and 4 (2 fam-
Unknown 0 1 (1.3%) ciclovir recipients and 2 acyclovir recipients) after cessa-
None 14 (19.7%) 14 (18.2%) tion of study medication (6/77 acyclovir recipients, 8%;
For personal use only.

Mild 19 (26.8%) 25 (32.5%)

Moderate 28 (39.4%) 20 (26.0%)
Severe 10 (14.1%) 17 (22.1%)
Table 3
Lesion Healing and Resolution of Acute Phase Pain

Lesion Healing Acyclovir

Famciclovir 800 mg Five
The results of the key healing efficacy parameters con- 500 mg Tid Times Daily
firmed the clinical efficacy of famciclovir 500 mg tid in n = 71 n = 77
the treatment of herpes zoster in immunocompromised
patients (Table 3). Time to Full Crusting
The rate at which full crusting of all zoster lesions Patients in analysis 71 77
occurred was comparable between famciclovir 500 mg Patients with event 60 60
Median (days) 8 9
tid and acyclovir 800 mg five times daily (hazard ratio:
Hazard Ratio 1.26
1.26, 95% CI: 0.88, 1.82). The median time to full crust-
95% Confidence Interval (0.88, 1.82)∗
ing was 8 days for the famciclovir group and 9 days for
Time to Complete Healing
the acyclovir group. Similarly, there were no significant
Patients in analysis 71 77
differences between the two groups with respect to the
Patients with event 56 57
time to complete healing of all lesions (hazard ratio: 0.98, Median (days) 20 21
95% CI: 0.67, 1.42); the median time to complete healing Hazard Ratio 0.98
was 20 days for famciclovir recipients and 21 days for 95% Confidence Interval (0.67, 1.42)∗
acyclovir recipients. Time to Loss of Acute Phase Pain
Patients in analysis 64 69
Resolution of Pain Patients with event 39 36
Median (days) 14 17
Overall 133 patients (90%) reported pain at some
Hazard Ratio 1.11
time during the study (64 famciclovir recipients and 69 95% Confidence Interval (0.71, 1.75)∗
acyclovir recipients). A total of 75 patients (56% of those
∗ No
reporting pain) were not experiencing pain on completion significant difference.
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Famciclovir Vs. Acyclovir in Herpes Zoster 19

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Figure 2. Mean (±SE) daily zoster pain severity scores. [∗ All time points refer to postdose assessments. Only a few patients (24/148)
recorded the severity of pain in their diary card on Day 0, after receiving double-blind study medication. In contrast, the majority of
patients participating in the study recorded the severity of pain on Day 1 (145/148) and thereafter.]
For personal use only.

2/71 famciclovir recipients, 3%). This difference was not Five patients died during the study (3 famciclovir recip-
statistically significant (95% CI: −12.1%, 2.1%). ients and 2 acyclovir recipients). All of the events associ-
ated with death were considered by the investigators to be
Safety Results unrelated to study medication. Four deaths resulted from
Adverse Experiences
Table 4
The proportions of patients who reported at least one
treatment-emergent adverse experience while on study Most Frequently Reported Treatment Emergent
medication, and the adverse experience profiles, were Adverse Experiences∗
comparable for famciclovir and acyclovir recipients. The Acyclovir
most frequently reported events considered by the investi- Famciclovir 800 mg Five
gator to be related or possibly related to study medication 500 mg Tid Times Daily
(or of unknown or unassessable attribution) were nausea, Adverse Experience∗ n = 71 n = 77
headache and vomiting (Table 4).
A total of 8 patients reported nonzoster adverse experi- Patients with at least 23 (32.4%) 23 (29.9%)
one event
ences during therapy that led to withdrawal from the study,
Nausea 13 (18.3%) 8 (10.4%)
3 in the famciclovir group and 5 in the acyclovir group.
Vomiting 7 (9.9%) 9 (11.7%)
All adverse experiences leading to withdrawal were re- Headache 4 (5.6%) 5 (6.5%)
ported by one patient only. Nausea and vomiting were Anorexia 2 (2.8%) 2 (2.6%)
the only adverse experiences leading to the withdrawal of Asthenia 2 (2.8%) 0
more than one patient overall (i.e., reported by one patient Dyspepsia 2 (2.8%) 0
in each treatment group). Zoster-related withdrawals are Fever 1 (1.4%) 2 (2.6%)
discussed under Dissemination. Abdominal pain 0 2 (2.6%)
Serious nonfatal adverse experiences were reported by Lactate dehydrogenase 0 2 (2.6%)
17 patients during the study (9 in the famciclovir group increased
and 8 in the acyclovir group). There were no reports of ∗ On-therapy adverse experiences classified by the investigator as related,
thrombotic thrombocytopenic purpura or hemolytic ure- possibly related, unassessable, or of unknown relationship to study med-
mic syndrome. ication.
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20
deterioration of the patient’s underlying condition (2 fam-
ciclovir recipients, 2 acyclovir recipients). The remain-
ing death resulted from visceral dissemination of herpes
zoster. This patient was randomized to famciclovir 500 mg
tid; zoster lesions failed to heal, and 3 days after com-
pleting study medication new lesions had formed in the
primary affected dermatome. The patient was withdrawn
due to lack of efficacy and adverse events, which were
described by the investigator as progressive disseminated
zoster with possible meningitis. The patient was treated
with intravenous acyclovir for 8 days but died while re-
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ceiving therapy.
Laboratory Tests
Although there were isolated differences in laboratory
variables between treatment groups, no consistent pattern
could be identified. In general, the incidence of laboratory
abnormalities was comparable for the famciclovir and acy-
clovir groups.
DISCUSSION
For personal use only.
The present study evaluated the safety and efficacy
of oral famciclovir 500 mg tid, compared with oral acy-
clovir 800 mg five times daily for 10 days in the treat-
ment of herpes zoster in patients immunocompromised
due to BMT, solid organ transplantation, chemotherapy, or
radiotherapy.
A particularly important consideration in the treatment
of immunocompromised patients with VZV infection is
the prevention of zoster progression as manifested by cu-
taneous and visceral dissemination. Intravenous acyclovir
has been shown to reduce the risk of cutaneous or visceral
dissemination compared with placebo (7). Of the patients
who had localized zoster at entry to the study, 1/28 (4%)
of those treated with acyclovir developed cutaneous or
visceral dissemination, whereas 7/24 (29%) of those re-
ceiving placebo had similar events. In our study, the num-
ber of patients developing disseminated zoster during the
course of the study was low in both treatment groups (fam-
ciclovir: 2 patients, 3%; acyclovir: 6 patients, 8%), giving
confidence in the use of an oral therapy to treat herpes
zoster in this patient population.
The results of this study demonstrate that three-times-
daily famciclovir, 500 mg, was clinically and statistically
equivalent to five-times-daily acyclovir, 800 mg, in pre-
venting new lesion formation while patients were receiv-
ing therapy, and there were no significant differences be-
tween the two treatment groups with respect to the time
to cessation of new lesion formation. The two treatments
REPRINTS
Tyring et al.
were also comparable with respect to the parameters of le-
sion healing. The median time to full crusting was 8 days
for famciclovir recipients and 9 days for acyclovir recip-
ients; the median time to complete healing of all lesions
was 20 days for famciclovir recipients and 21 days for
acyclovir recipients.
The results reported for famciclovir in our study com-
pare favorably with historical data reported for intravenous
acyclovir in the treatment of herpes zoster in immunocom-
promised patients. For example, in a controlled study of
intravenous acyclovir versus vidarabine (8), the median
times to full crusting and complete healing were 7 days and
17 days for intravenous acyclovir recipients and 17 days
and 28 days for vidarabine recipients, respectively.
In our study, there was also a trend toward a shorter
duration of acute phase pain for patients receiving famci-
clovir 500 mg tid, compared with acyclovir 800 mg five
times daily (median times 14 days and 17 days, respec-
tively), although the treatment comparison was not statis-
tically significant.
The safety and tolerability of famciclovir have already
been confirmed in immunocompetent patients with her-
pes zoster (18). The incidence and profile of commonly
occurring treatment emergent adverse experiences in the
immunocompromised population enrolled in our study
were similar in the famciclovir and acyclovir treatment
groups. Frequent events were either consistent with those
observed in immunocompetent patients (e.g., headache),
or were expected in this immunocompromised population
due to underlying conditions and treatments (e.g., vom-
iting and nausea). Importantly there were no reports of
thrombotic thrombocytopenic purpura or hemolytic ure-
mic syndrome (TTP/HUS). TTP/HUS, in some cases re-
sulting in death, has occurred in patients with advanced
HIV disease participating in clinical trials of valacyclovir
at high doses of 8 g per day (14).
In summary, the results of our study have demonstrated
the clear clinical benefits of famciclovir for immunocom-
promised patients with herpes zoster. In comparison to
historical data, famciclovir provides comparable efficacy
to intravenous acyclovir (8). Furthermore, the famciclovir
regimen utilized (500 mg three times daily) offers reduced
dosing frequency and therefore greater patient acceptabil-
ity compared with the recommended oral acyclovir regi-
men (800 mg five times daily). The high and consistent oral
bioavailability of famciclovir as well as its predictable and
linear pharmacokinetics are important factors when con-
sidering a substitute for intravenous treatment. Safety data
from this study confirm that famciclovir is as well tolerated
as acyclovir when administered to immunocompromised
patients and may provide patients with a safer option than
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Famciclovir Vs. Acyclovir in Herpes Zoster
the currently available alternatives to acyclovir. In conclu-
sion, oral famciclovir at a dose of 500 mg tid for 10 days
provides a convenient, effective, and well-tolerated regi-
men for immunocompromised patients with herpes zoster.
ACKNOWLEDGMENTS
Other Members of the Collaborative Famciclovir
Immunocompromised Study Group: Belgium: M. Aoun,
Institut J-Bordet, Rue Heger Bordet 1, Bruxelles; Canada:
J. Conly, The Toronto Hospital, Toronto, Ontario; A.
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McGeer, Princess Margaret Hospital, Toronto, Ontario;
S. Calderwood, Hospital for Sick Children, Toronto,
Ontario; S. Shafran, University of Alberta, Edmonton, Al-
berta; J. Parsons, K. Ford, SmithKline Beecham Pharma,
Oakville, Ontario; Finland: L. Volin, Helsinki University
Central Hospital, Helsinki; France: L. Sutton, Hôpital
Pitié-Salpêtrière, Paris; J. Cahn, Hôpital Jean Minjoz,
Besançon; J. Harousseau, Hôtel Dieu, Nantes; J. Camerlo,
Institut Paoli Calmettes, Marseille; R Herbrecht, Hôpital
de Hautepierre, Strasbourg; J. Bourhis, Institut Gustave
Roussy, Villejuif; E. Archimbaud, Hôpital Edouard
For personal use only.
Herriot, Lyon; B. Coiffier, Centre Hospitalier Lyon Sud,
Lyon; Holland: P. Van Den Broek, Academisch Zieken-
huis Leiden, Leiden; Italy: A. Bosi, Policlinico Careggi,
Firenze; P. Di Bartolomeo, Ospedale Civile, Pescara; A.
De Laurenzi, Ospedale San Camillo, Roma; M. Falda,
CTM Az Ospedale S. Giovanni, Torini; South Africa: E.
Holland, UCT Medical School, Cape; Spain: R. Cámara,
Hospital De La Princesa, Madrid; J. Perez de Oteyza,
Hospital Ramòn y Cajal, Madrid; A. Torres-Gomez,
Hospital Reina Sofia, Córdoba; Sweden: K. Pauksens,
Akademiska Hospital, Uppsala; Switzerland: A.
Gratwohl, Kantonsspital, Basel; J. Gmuer, Universi-
taetsspital, Zurich; United Kingdom: M. Poulton, J.
Taylor, R. MacDonald, H. Huntington, A. Hill, S. Rai, L.
Bannon, M. Luff, SmithKline Beecham Pharmaceuticals,
Harlow, Essex; United States: L. Locke, L. Marks, S.
Weill, D. McCarthy, K. Steide, SmithKline Beecham
Pharmaceuticals, Collegeville, Pennsylvania.
Prior publication: Presented in part at
r the 20th International Congress of Chemotherapy,
Sydney, Australia, 29 June–4 July 1997
r the 24th annual meeting of the European Group for
Blood and Marrow Transplantation, Courmayeur,
Italy, 22–26 March 1998
r American Academy of Dermatology, Orlando,
USA, 27 February–4 March 1998
r Clinical Dermatology (Derm 2000), Singapore, 17–
20 June 1998
REPRINTS
21
Financial support information: This study was funded
by SmithKline Beecham Pharmaceuticals, New Frontiers
Science Park, Harlow, Essex, UK.
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