Drugs 2011; 71 (5): 603-610

ADIS DRUG PROFILE 0012-6667/11/0005-0603/$55.55/0

ª 2011 Adis Data Information BV. All rights reserved.

Ganciclovir Ophthalmic Gel 0.15%

In Acute Herpetic Keratitis (Dendritic Ulcers)
Jamie D. Croxtall
Adis, a Wolters Kluwer Business, Auckland, New Zealand

Contents
Abstract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 603
1. Pharmacodynamic Profile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605
2. Pharmacokinetic Profile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605
3. Therapeutic Efficacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 606
4. Tolerability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 607
5. Dosage and Administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 608
6. Ganciclovir Ophthalmic Gel 0.15%: Current Status in Acute Herpetic Keratitis . . . . . . . . . . . . . . . . . . . 609

Abstract
Features and properties of ganciclovir ophthalmic gel
Dendritic epithelial keratitis is most commonly 0.15% (Zirgan®)
caused by infections of herpes simplex virus (HSV)
type 1 (HSV-1), and less frequently by HSV type 2
Featured indication
(HSV-2). Ganciclovir, a guanosine nucleoside ana-
logue, is a well established broad-spectrum antiviral
agent that inhibits replication of viral DNA and is Treatment of acute herpetic keratitis (dendritic ulcers)
active against both HSV-1 and -2 and several other
viruses. Ganciclovir ophthalmic gel 0.15% is a five- Mechanism of action
times-daily topical preparation that is indicated for
the treatment of acute herpetic keratitis (dendritic Inhibits replication of viral DNA
ulcers).
A randomized, open-label, phase III trial in im-
Dosage and administration
munocompetent patients with acute herpetic kera-
titis showed that ganciclovir ophthalmic gel 0.15%
applied five times daily provided effective clinical Route of administration Topical ocular
resolution of dendritic ulcers following 7 days of
treatment (primary endpoint). Moreover, a retro- Dose One drop in the affected
spective analysis of noninferiority showed that eye(s)
ganciclovir ophthalmic gel 0.15% was no less effec-
tive than aciclovir (acyclovir) ointment 3%. Frequency of administration Five times daily (≈ every 3 h
A pooled analysis of three randomized, single- while awake) until cornea
heals, then three times daily
masked, phase II multinational trials also showed for 7 days
high rates of dendritic ulcer healing at day 7 for
eyes treated with ganciclovir ophthalmic gel 0.15%
Pharmacokinetic profile of topical ganciclovir ophthalmic
and aciclovir ointment 3%. Furthermore, in the in- gel 0.15% five times daily
dividual phase II trials, most patients showed evi-
dence of healed dendritic and geographic ulcers at
day 14 in either treatment arm. Median healing times Systemic exposure to ganciclovir is expected to be minimal
with either treatment ranged from 6 to 10 days.
Ganciclovir ophthalmic gel 0.15% was generally Most frequent adverse events (incidence ≥5%)
well tolerated and was associated with a significant-
ly lower incidence of visual disturbances than aci- Blurred vision, eye irritation, punctate keratitis and conjunctival
clovir ointment 3% in the phase III trial. hyperaemia
604
Infection with herpes simplex virus (HSV) is a
major health concern, which is virtually endemic
in the human population.[1] HSV type 1 (HSV-1)
is generally transmitted by nonsexual contact
(often during childhood) and is most often the
cause of herpetic keratitis. HSV type 2 (HSV-2)
infection is one of the most prevalent sexually
transmitted diseases and is most often the cause
of genital herpes. However, both types of HSV
can cause herpetic keratitis with apparently in-
distinguishable characteristics.[2] For the period
1999–2004, the seroprevalence rate of HSV-1
within the overall US population was estimated
to be 58% and for HSV-2, 17%.[3]
Herpetic keratitis is a common cause of ocular
morbidity and in the US is considered to be the
most common cause of infectious corneal blind-
ness.[4,5] In the US, an estimated 400 000 in-
dividuals have experienced some form of ocular
infection with HSV.[5] The condition initially
manifests as a cluster of small vesicles in the cor-
neal epithelium that coalesce to form branching
epithelial defects (termed dendrites) which may
be visualized using a fluorescein stain.[1,6] If un-
treated, dendritic ulcers can progress to large,
amoeboid epithelial defects (termed geographic
ulcers).[1,6]
Following resolution of the primary infection,
which may be mild in intensity, HSV remains life-
long in latent form within the trigeminal ganglion
as a reservoir for future outbreaks.[7] Subsequent
recurring keratitis eventually leads to scarring,
thinning and neovascularization of the cornea,
which may require corneal transplantation.[7] Re-
current keratitis in the corneal graft may result in
rejection of the transplant.[8]
Pharmacological treatment options for acute
herpetic keratitis were initially hampered by a
lack of antiviral agents that selectively targeted
HSV-infected cells.[4,9] However, the availability
of agents such as aciclovir (acyclovir), a purine
nucleoside, has greatly improved treatment out-
comes.[10] Aciclovir is initially selectively phos-
phorylated by viral thymidine kinase and is
subsequently further phosphorylated by both viral
and cellular thymidine kinases to aciclovir tri-
phosphate, the active metabolite.[10] This leads to
ª 2011 Adis Data Information BV. All rights reserved.
Croxtall
an enhanced accumulation of aciclovir triphos-
phate in HSV-infected rather than healthy cells.[10]
Following topical administration, the drug is ac-
tivated in HSV-infected cells only, whereas
healthy cells are spared with a resultant reduction
in toxicity.[10] However, aciclovir is poorly soluble
in water and, for topical ocular applications, must
be formulated as an ointment, which may cause
severe visual blurring and thus impact upon pa-
tient adherence.[11]
Ganciclovir, a guanosine nucleoside analogue
that has a similar mechanism of action to aciclo-
vir, has a well established broad-spectrum anti-
viral activity when used as an oral or intravenous
agent.[12-14] It is active against several members of
the herpesvirus family (including HSV-1, HSV-2,
human herpesvirus 6, cytomegalovirus [CMV],
Epstein-Barr virus [EBV] and varicella zoster
virus [VZV]), hepatitis B virus and human adeno-
viruses.[12-15] However, unlike aciclovir, ganciclo-
vir is water soluble, which permits the formulation
of aqueous preparations, including a gel, that are
more suitable for ocular use.
Ganciclovir ophthalmic gel 0.15% is approved
as a topical antiviral for the treatment of acute
herpetic keratitis in numerous countries includ-
ing the EU (Virgan),[16] and recently received
approval in the US (Zirgan)[17] for the treatment
of acute herpetic keratitis (dendritic ulcers).[17]
This article, which is written from a US perspec-
tive, provides an overview of the pharmacologi-
cal profile of ganciclovir ophthalmic gel 0.15%
and reviews its clinical efficacy and tolerability in
patients with acute herpetic keratitis.
Medical literature (including published and
unpublished data) on the use of ganciclovir oph-
thalmic gel 0.15% in acute herpetic keratitis was
identified by searching databases since 1996 (in-
cluding MEDLINE, EMBASE and AdisBase,
a proprietary database), bibliographies from pub-
lished literature, clinical trial registries/databases
and websites (including those of regional regula-
tory agencies and the manufacturer). Additional
information (including contributory unpublish-
ed data) was also requested from the company
developing the drug. Searches were last updated
7 March 2011.
Drugs 2011; 71 (5)
Ganciclovir Ophthalmic Gel 0.15%: Adis Drug Profile
1. Pharmacodynamic Profile
 Ganciclovir is a guanosine nucleoside ana-
logue that is selectively phosphorylated to its
monophosphate form by viral thymidine kinases
of the herpesvirus family and other viruses and by
protein kinase of CMV.[14,18] In contrast, cellular
thymidine kinase does not phosphorylate ganci-
clovir. Ganciclovir monophosphate is subsequently
further phosphorylated by both viral and cellular
thymidine kinases of virus-infected cells to ganci-
clovir triphosphate, the active metabolite.[18] Con-
sequently, ganciclovir triphosphate concentrations
accumulate in host cells infected with virus and not
uninfected healthy cells.
 Ganciclovir triphosphate competes with deoxy-
guanosine triphosphate for binding to DNA poly-
merases, thereby inhibiting de novo viral DNA
synthesis, and its incorporation into viral strand
primer DNA results in chain termination and pre-
vention of viral replication.[17]
 Ganciclovir shows potent in vitro antiviral
activity against HSV-1 and -2. Across several
studies, the range of reported concentrations of
ganciclovir achieving 50% inhibition of viral acti-
vity (ID50) was 0.2–2.0 mmol/L for HSV-1 and
0.3–10.0 mmol/L for HSV-2.[13]
 In vitro antiviral activity of ganciclovir is also
evident against other viruses, with reported 50%
inhibitory concentrations (IC50) of 10.0 mmol/L
for human CMV,[18] 8.0 mmol/L for VZV[18]
and 1.0 mmol/L for EBV[18] and ID50 values of
26–47 mmol/L for human adenoviruses.[15]
 Proliferation of uninfected host cells in vitro is
relatively unaffected by ganciclovir. The ganci-
clovir IC50 for inhibition of proliferation of
human embryonic lung cells is 110 mmol/L and
250 mmol/L for human embryonic tonsil cells.[18]
The exception appears to be bone marrow cells,
the proliferation of which were inhibited by
ganciclovir with an IC50 of 39 mmol/L.[18]
 On a molar basis, ganciclovir exhibits similar
in vitro antiviral activity to aciclovir against
HSV-1 and -2 but is a less effective inhibitor of
CMV DNA polymerase.[13,14] However, intracellu-
lar concentrations of ganciclovir triphosphate are
10-fold higher than aciclovir triphosphate in CMV-
infected cells.[14]
ª 2011 Adis Data Information BV. All rights reserved.
605
 As ganciclovir and aciclovir are structurally
related and have a similar mechanism of action,
cross-resistance between the two agents is pos-
sible.[19] Among immunocompetent patients, the
prevalence of nucleoside analogue-resistant HSV
is generally low (0.1% to 0.7%); however, among
those who are immunocompromised (i.e. patients
with HIV infection), resistance rates are higher
(4% to 7%).[20]
 Data regarding HSV resistance to nucleoside
analogues in patients with herpetic keratitis are
limited. One study of 173 immunocompetent
patients with herpetic keratitis has shown that
isolates of HSV-1 from 11 (6.4%) patients were
resistant to aciclovir in vitro.[21] Nine of the
11 patients were refractory to aciclovir treatment
and isolates from five of the nine patients were
also resistant to ganciclovir in vitro.[21] A muta-
tion in the thymidine kinase gene was found in
10 of 11 of the aciclovir-resistant isolates.[21]
 The effect of topical ocular treatment with
five-times-daily ganciclovir ophthalmic gel 0.15%
or aciclovir ointment 3% on dendritic ulcer size
was evaluated in 46 patients with herpetic
keratitis.[22] Dendritic ulcer size decreased rapidly
following treatment with either ganciclovir oph-
thalmic gel 0.15% or aciclovir ointment 3%
and was not significantly different between the
two treatment arms at all evaluable timepoints
(figure 1).[22] Mean ulcer size was reduced to
approximately half of baseline values following
2 days of either treatment; no ulceration was
visible in the ganciclovir treatment arm following
14 days’ treatment.[22]
2. Pharmacokinetic Profile
 Following topical ocular administration of
ganciclovir ophthalmic gel 0.15%, systemic ex-
posure is expected to be minimal.[17] When used
at the recommended dosage of one drop five
times daily, the maximum daily dose of ganci-
clovir is estimated to be 0.375 mg, which is ap-
proximately 0.04% of the oral and 0.1% of the
intravenous administered maintenance doses.[17]
 In studies in healthy volunteers, the mean con-
centration of ganciclovir in tears varied widely
following four instillations of ganciclovir ophthalmic
Drugs 2011; 71 (5)
606
3.5 GCV
ACV
3.0
2.5
Mean ulcer size (mm)
2.0
1.5
1.0
0.5
θ
0 mune deficiency or previous tissue transplantation
0 2 7 10 14
Day
Fig. 1. Dendritic ulcer healing in patients (pts) aged ‡18 y with
herpetic keratitis. Mean dendritic ulcer size.[22] Pts received ganci-
clovir ophthalmic gel 0.15% (GCV) [n = 24] or aciclovir ointment 3%
(ACV) [n = 22] five times daily until the ulcer healed, then three times
daily for a further 3 days. y = zero.
gel 0.15% at 3-hour intervals for 12 hours.[19]
However, all concentrations reported were greater
than the ganciclovir ID50 for HSV-1 and -2.[19]
 Several in vivo studies in rabbits have shown
that following instillation of radiolabelled ganci-
clovir ophthalmic gel 0.15%, radioactivity first
accumulates in external ocular structures followed
by the anterior and posterior internal structures.[23-25]
Concentrations of ganciclovir in the intact cornea
remained above the ID50 for HSV-1 and -2 for more
than 4 hours after instillation.[23] Plasma concentra-
tions of ganciclovir were undetectable.[25]
3. Therapeutic Efficacy
The efficacy of topical ganciclovir ophthalmic
gel 0.15% in the treatment of acute herpetic ker-
atitis (dendritic ulcers) was evaluated in four ran-
domized, multinational, single-masked, phase IIB
or open-label, phase III comparative trials, which
enrolled a total of 377 patients. Most studies are
reported in review articles.[6,11,19,26] The data from
these trials were reanalysed retrospectively in the
medical review for US FDA new drug approval,[27]
and form the primary focus of this section.
Immunocompetent patients with a clinical di-
agnosis of dendritic or geographic ulcers without
virological confirmation were eligible for inclu-
ª 2011 Adis Data Information BV. All rights reserved.
Croxtall
sion.[6,11,19,26] Ganciclovir ophthalmic gel 0.15%
is not approved for use in the US in patients with
geographic ulcers as a result of insufficient data
to establish noninferiority with aciclovir;[17,27]
therefore, discussion in this section focuses
mostly on dendritic ulcer-healing rates.
Patients with antiviral treatments within 14 days
preceding the trials, severe stromal disease, kera-
touveitis, previous keratoplasties of the affected
eye, secondary corneal of conjunctival bacterial
infection, recent ocular trauma, visual acuity <2/10
or known sensitivity to treatment, leukopenia,
anaemia, thrombocytopenia, HIV infection, im-
were excluded from the trials.[6,11,19,26] In general,
patients’ demographic and ophthalmological base-
line characteristics were comparable between treat-
ment arms within each trial.[6,11,19,26] However,
patient age range varied by study (see table I).
Eligible patients were randomized to receive
identical regimens (described in table I) of either
ganciclovir ophthalmic gel 0.15% or aciclovir
ointment 3% in each affected eye (two phase II
trials included a ganciclovir ophthalmic gel 0.05%
treatment arm and, as this dosage is not ap-
proved, these data are not discussed).[6,11,19,26]
Double-masking was not possible because of the
different nature of the two agents. The maximum
period of treatment was predefined at 21 days for
patients with dendritic ulcers and 35 days for
patients with geographic ulcers.[6,27]
In the original trials, the primary endpoint was
defined as the time to healing of the ulcer and most
efficacy data were reported for day 14.[6,11,19,26]
However, for the purpose of US approval, the pri-
mary endpoint was redefined as the proportion of
patients with corneal healing (defined by an absence
of fluorescein staining in the corneal stroma in the
phase II trials and as the clinical disappearance of
the ulcer in the phase III trial) at day 7.[27]
One trial (African phase II) reported the
number of eyes treated, whereas all other trials
reported the number of patients treated.[6,11,19,26]
All trials included an intent-to-treat (ITT) or per
protocol analysis of data, which in general
showed similar outcomes.[6,11,19,26] The ITT
population included eight eyes with protocol
violations (usually missed treatments) in the
Drugs 2011; 71 (5)
Ganciclovir Ophthalmic Gel 0.15%: Adis Drug Profile 607

African phase II trial.[19,26] Two patients mis-
diagnosed with herpetic ulcer in the European
phase II trial were excluded from the efficacy
analyses.[19,26] Although the original trials were
not designed to evaluate the noninferiority, ret-
rospective analyses were conducted on the origi-
nal ITT data obtained from the open-label phase
III trial and pooled data from the phase II trials
to evaluate noninferiority of ganciclovir oph-
thalmic gel 0.15% compared with aciclovir 3%.[27]
 Ganciclovir ophthalmic gel 0.15% provided
effective treatment of acute herpetic keratitis
(dendritic ulcers) in geographically and ethnically
diverse patients with herpetic keratitis. Following
7 days’ treatment, a high proportion (77%) of
patients with dendritic ulcers in the ITT popula-
tion achieved complete corneal healing in the
open-label, randomized phase III trial (table I).[27]
 A retrospective analysis for noninferiority
showed that treatment with ganciclovir ophthalmic
gel 0.15% was no less effective than an identical
regimen with aciclovir ointment 3% in terms of
dendritic ulcer-healing rates at day 7 (table I).[27]
 Furthermore, recovery rates (the proportion
of healed ulcers at any time during the study) of
89% for recipients of ganciclovir ophthalmic gel
0.15% and 91% for recipients of aciclovir oint-
ment 3% were reported in the phase III trial, with
two patient relapses in each treatment arm.[27] The
median time to healing was 7 days in both treat-
ment arms (table I).[27]
 A pooled analysis of more than 100 evaluable
ITT patients with acute herpetic keratitis from
three single-masked, phase II trials showed den-
dritic ulcer-healing rates at day 7 of 72% for
recipients of ganciclovir ophthalmic gel 0.15%
and 69% for recipients of aciclovir ointment 3%
(table I).[27]
 Individual analysis of the individual trials
showed that at day 14 the majority of ITT patients
receiving ganciclovir ophthalmic gel 0.15% or
aciclovir ointment 3% had evidence of healed
dendritic and geographic ulcers in the phase II
trials and dendritic ulcers in the phase III trial
(figure 2).[6,11,19,26] Furthermore, ulcer-healing
rates were not significantly different between the
two treatment arms in all trials.[6,11,19,26]
 Similarly, in all trials, there were low patient
withdrawal and relapse rates for recipients of
ganciclovir ophthalmic gel 0.15% which were not
significantly different from those observed in re-
cipients of aciclovir ointment 3%.[6,11,19,26] Med-
ian healing times with either treatment ranged
from 6 to 10 days.[6,11,19,26]
4. Tolerability
The tolerability of topical ganciclovir oph-
thalmic gel 0.15% in patients with acute herpetic
keratitis was evaluated in the four random-
ized phase II and phase III trials discussed in
section 3.[6,11,19,26] However, as a result of the re-
latively small numbers of patients in each individual
trial, discussion in this section focuses on pooled
data from these trials evaluated in the medical
review for US FDA new drug approval.[27] The

Table I. Comparative efficacy of ganciclovir ophthalmic gel 0.15% vs aciclovir ointment 3% in adult and paediatric patients (pts) with acute
herpetic keratitis (dendritic ulcers). Results from randomized, open-label, phase III or pooled, single-masked, phase IIB, multinational trials
in the intent-to-treat population.[27] Pts were treated, in each affected eye, five times daily until healing of the ulcer and then three times daily
for 1 week (trials 1, 2 and 4) or five times daily for 10 days (trial conducted in Pakistan)
Trial (pt age) Treatment No. of pts Proportion (%) of Between-group Median time
[location] pts healed at day 7a difference [%] (95% CI) to recovery (d)
Phase III (‡18 y) Ganciclovir 0.15% 71 77b 5.8 (-9.6, 18.3)c 7
[Europe and Africa] Aciclovir 3% 67 72b 7
Pooled phase IIB (‡2 y) Ganciclovir 0.15% 57 72d 2.5 (-15.6, 20.9)
[Europe, Africa and Pakistan] Aciclovir 3% 49 69d
[27]
a Primary endpoint by composite retrospective analysis.
b Healing defined as the clinical disappearance of the ulcer.[27]
c Retrospective noninferiority analysis showed that the lower limit of the 95% CI was no greater than the noninferiority margin of 10%.[27]
d Healing defined as an absence of fluorescein staining in the corneal stroma.[27]

ª 2011 Adis Data Information BV. All rights reserved. Drugs 2011; 71 (5)
608 Croxtall

100 GCV pooled analysis included data from a total of

ACV 167 recipients of ganciclovir ophthalmic gel 0.15%,
80 57 recipients of ganciclovir ophthalmic gel 0.05%
Pt withdrawal rate (%)

(which is not approved) and 167 recipients of

60 aciclovir ointment 3% in patients with both den-
dritic and geographic ulcers.[27]
 Treatment with topical ganciclovir ophthalmic
40
gel 0.15% was generally well tolerated in the
pooled analysis of phase II and phase III clinical
20 trials in patients with acute herpetic keratitis. The
most frequent (incidence ‡5%) adverse events
0 occurring in the ganciclovir and aciclovir treatment
100 groups were blurred vision, eye irritation, punctate
keratitis and conjunctival hyperaemia (figure 3).[27]
 There were no serious adverse events for
Proportion of pts healed at d 14

80
recipients of ganciclovir ophthalmic gel 0.15%
reported across all of the trials.[27] In the phase III
60
trial, two recipients of ganciclovir ophthalmic gel
0.15% discontinued treatment following an ad-
40 verse event.[27] These were a foreign body in the
eye resulting in palpebral and conjunctival dis-
20 orders and bilateral conjunctival hyperaemia
recorded 48 hours after cessation of treatment.[27]
0
 In the phase III trial, significantly (p < 0.05)
fewer patients with dendritic ulcers receiving gan-
100
ciclovir ophthalmic gel 0.15% experienced visual
Proportion of pts relapsed at d 14 (%)

disturbances at all time points (28% to 46%),

80
60
40
20
θ θ
0 red with a significantly higher frequency for
Africa Europe Pakistan
phase II
Fig. 2. Comparative efficacy of ganciclovir ophthalmic gel 0.15%
(GCV) versus aciclovir ointment 3% (ACV) in adult and paediatric
patients (pts) with acute herpetic keratitis. Results from randomized,
single-masked, phase IIB (in pts with dendritic and geographic ulcers
in Africa, Europe and Pakistan), or open-label, phase III (in pts
with dendritic ulcers in Europe and Africa), multicentre trials in the
intent-to-treat population.[6,19,26] See table I for treatment details.
Withdrawal rate was defined as the proportion of pts with
treatment-related failure due to complications, lack of efficacy or
tolerability issues. Healing was defined as an absence of fluorescein
staining in the corneal stroma in phase II trials and as the clinical
disappearance of the ulcer in the phase III trial. y = zero.
except day 14, compared with recipients of aci-
clovir ointment 3% (51% to 64%).[6] In addition,
in the phase II trial in Europe, significantly
fewer recipients of ganciclovir ophthalmic gel
0.15% experienced prolonged visual disturbances
(p < 0.05 on day 7) and tingling or burning
sensations (p < 0.05 on day 2 at all time points).[6]
 Local tolerability judged to be excellent occur-
Europe/Africa recipients of ganciclovir ophthalmic gel 0.15%
phase III
than recipients of aciclovir ointment 3% when
assessed by study investigator (79% vs 44%;
p < 0.001) and by the patient (75% vs 42%;
p < 0.001) in the phase III trial and also in the
European phase II trial (82% vs 19%; p < 0.001
and 61% vs 19%; p < 0.05, respectively).[6]
5. Dosage and Administration
The recommended dosage regimen of ganci-
clovir ophthalmic gel 0.15% in patients with acute

ª 2011 Adis Data Information BV. All rights reserved. Drugs 2011; 71 (5)
Ganciclovir Ophthalmic Gel 0.15%: Adis Drug Profile
herpetic keratitis is one drop in the affected eye(s)
five times daily (approximately every 3 hours while
awake) until the corneal ulcer heals, then one drop
three times daily for 7 days.[17] Ganciclovir oph-
thalmic gel 0.15% is indicated for topical ocular
use only. Patients exhibiting signs or symptoms of
herpetic keratitis or receiving ganciclovir ophthal-
mic gel 0.15% should not wear contact lenses.[17]
6. Ganciclovir Ophthalmic Gel 0.15%:
Current Status in Acute Herpetic Keratitis
In the US, ganciclovir ophthalmic gel 0.15% is
approved for the treatment of acute herpetic
keratitis (dendritic ulcers). In the EU and various
countries worldwide, the indication does not
specify ulcer type. In one randomized, open-
label, phase III trial, a topical ocular application
of ganciclovir ophthalmic gel 0.15% five times
daily provided effective control of dendritic cor-
neal ulceration in patients with acute herpetic
keratitis and was noninferior to an identical reg-
imen of aciclovir ointment 3%. Furthermore, a
pooled analysis of three randomized, single-masked,
phase II trials showed a clinical resolution (healed
dendritic ulcers at day 7) in the majority of
GCV
ACV
Blurred vision
Eye irritation
Punctate
keratitis
Conjunctival
hyperaemia
0 20 40 60 80
Percentage of patients
Fig. 3. Tolerability of topical ganciclovir ophthalmic gel in patients
with acute herpetic keratitis (dendritic and geographic ulcers). Most
frequent adverse events that occurred with an incidence of ‡5% in
a pooled analysis of four randomized, multicentre, single-masked,
phase IIB or open-label, phase III comparative trials.[27] Patients re-
ceived ganciclovir ophthalmic gel 0.15% (n = 161) or 0.05% (n = 57)
[GCV], or aciclovir ointment 3% (ACV) [n = 167] in each affected eye
according to the treatment regimens described in table I.
ª 2011 Adis Data Information BV. All rights reserved.
609
recipients of ganciclovir ophthalmic gel 0.15%.
Ganciclovir ophthalmic gel 0.15% was generally
well tolerated and was associated with a sig-
nificantly lower incidence of visual disturbances
than aciclovir ointment 3%.
Acknowledgements and Disclosures
This manuscript was reviewed by J. Colin, Centre Hospi-
talier Universitaire Pellegrin, Bordeaux Cedex, France;
A. D. Osterhaus, Department of Virology, Erasmus Univer-
sity, Rotterdam, the Netherlands; K. R. Wilhelmus, Depart-
ment of Ophthalmology, Cullen Eye Institute, Baylor College
of Medicine, Houston, Texas, USA.
The preparation of this review was not supported by any
external funding. During the peer review process, the manu-
facturer of the agent under review was offered an opportunity
to comment on this article. Changes resulting from comments
received were made on the basis of scientific and editorial
merit.
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Correspondence: Jamie D. Croxtall, Adis, a Wolters Kluwer
Business, 41 Centorian Drive, Private Bag 65901, Mairangi
Bay, North Shore 0754, Auckland, New Zealand.
E-mail: demail@adis.co.nz
Drugs 2011; 71 (5)