Famvir
Generic Name: famciclovir
Dosage Form: tablet, film coated
INDICATIONS AND USAGE
Immunocompetent Adult
Patients
Herpes labialis (cold sores): Famvir is indicated for the
treatment of recurrent herpes labialis.
Genital herpes:
Recurrent episodes: Famvir
is indicated for the treatment of recurrent episodes of genital herpes. The
efficacy of Famvir when initiated more than 6 hours after onset of symptoms or
lesions has not been established.
Suppressive therapy: Famvir
is indicated for chronic suppressive therapy of recurrent episodes of genital
herpes. The efficacy and safety of Famvir for the suppression of recurrent
genital herpes beyond 1 year have not been established.
Herpes zoster (shingles): Famvir
is indicated for the treatment of herpes zoster. The efficacy of Famvir when
initiated more than 72 hours after onset of rash has not been established.
HIV-Infected Adult
Patients
Recurrent orolabial or genital herpes: Famvir is indicated for the treatment of
recurrent episodes of orolabial or genital herpes in HIV-infected
adults. The efficacy of Famvir when initiated more than 48 hours after
onset of symptoms or lesions has not been established.
Limitation of Use
The
efficacy and safety of Famvir have not been established for:
· Patients less than 18 years of age
· Patients with first episode of genital herpes
· Patients with ophthalmic zoster
· Immunocompromised patients other than for the
treatment of recurrent orolabial or genital herpes in HIV-infected patients
· Black and African American patients with recurrent
genital herpes
DOSAGE AND ADMINISTRATION
Famvir
may be taken with or without food.
Dosing Recommendation
in Immunocompetent Adult Patients
Herpes labialis (cold sores): The recommended dosage of Famvir for
the treatment of recurrent herpes labialis is 1500 mg as a single dose. Therapy
should be initiated at the first sign or symptom of herpes labialis (e.g.,
tingling, itching, burning, pain, or lesion).
Genital herpes:
Recurrent episodes: The
recommended dosage of Famvir for the treatment of recurrent episodes of genital
herpes is 1000 mg twice daily for 1 day. Therapy should be initiated at
the first sign or symptom of a recurrent episode (e.g., tingling, itching,
burning, pain, or lesion).
Suppressive therapy: The
recommended dosage of Famvir for chronic suppressive therapy of recurrent
episodes of genital herpes is 250 mg twice daily.
Herpes zoster (shingles): The
recommended dosage of Famvir for the treatment of herpes zoster is 500 mg every
8 hours for 7 days. Therapy should be initiated as soon as herpes zoster is
diagnosed.
Dosing Recommendation
in HIV-Infected Adult Patients
Recurrent orolabial or genital herpes: The
recommended dosage of Famvir for the treatment of recurrent orolabial or
genital herpes in HIV-infected patients is 500 mg twice daily for 7 days.
Therapy should be initiated at the first sign or symptom of a recurrent episode
(e.g., tingling, itching, burning, pain, or lesion).
Dosing Recommendation
in Patients with Renal Impairment
Dosage
recommendations for adult patients with renal impairment are provided in Table
1 [see Use in Specific Populations (8.6), Clinical
Pharmacology (12.3)].
Table 1: Dosage Recommendations for
Adult Patients with Renal Impairment
|
|
Indication andNormalDosage
Regimen
|
Creatinine Clearance
(mL/min)
|
Adjusted Dosage
Regimen
Dose (mg)
|
Dosing Interval
|
|
Single-Day Dosing Regimens
|
|
Recurrent
Genital Herpes
1000 mg every 12 hours for 1 day
|
≥ 60
|
1000
|
every 12 hours for 1 day
|
|
|
40-59
|
500
|
every 12 hours for 1 day
|
|
|
20-39
|
500
|
single dose
|
|
|
< 20
|
250
|
single dose
|
|
|
HD*
|
250
|
single dose following
dialysis
|
|
Recurrent Herpes
Labialis
1500 mg single dose
|
≥ 60
|
1500
|
single dose
|
|
|
40-59
|
750
|
single dose
|
|
|
20-39
|
500
|
single dose
|
|
|
< 20
|
250
|
single dose
|
|
|
HD*
|
250
|
single dose following
dialysis
|
|
Multiple-Day Dosing Regimens
|
|
Herpes Zoster
500 mg every 8 hours
|
≥ 60
|
500
|
every 8 hours
|
|
|
40-59
|
500
|
every 12 hours
|
|
|
20-39
|
500
|
every 24 hours
|
|
|
< 20
|
250
|
every 24 hours
|
|
|
HD*
|
250
|
following each dialysis
|
|
Suppression of
Recurrent
Genital Herpes
250 mg every 12 hours
|
≥ 40
|
250
|
every 12 hours
|
|
|
20-39
|
125
|
every 12 hours
|
|
|
< 20
|
125
|
every 24 hours
|
|
|
HD*
|
125
|
following each dialysis
|
|
Recurrent
Orolabial
or Genital Herpes
in HIV-Infected Patients
500 mg every 12 hours
|
≥ 40
|
500
|
every 12 hours
|
|
|
20-39
|
500
|
every 24 hours
|
|
|
< 20
|
250
|
every 24 hours
|
|
|
HD*
|
250
|
following each dialysis
|
*Hemodialysis
DOSAGE FORMS AND STRENGTHS
Famvir
tablets are available in 3 strengths:
· 125 mg: White, round film-coated, biconvex, beveled
edges, debossed with “Famvir” on one side and “125” on the other side
· 250 mg: White, round film-coated, biconvex, beveled
edges, debossed with “Famvir” on one side and “250” on the other side
· 500 mg: White, oval film-coated, biconvex, debossed
with “Famvir” on one side and “500” on the other side
CONTRAINDICATIONS
Famvir is
contraindicated in patients with known hypersensitivity to the product, its
components, or Denavir® (penciclovir cream).
WARNINGS AND PRECAUTIONS
Acute renal failure: Cases of acute renal failure have been reported
in patients with underlying renal disease who have received inappropriately
high doses of Famvir for their level of renal function. Dosage reduction is
recommended when administering Famvir to patients with renal impairment
[see Dosage and Administration (2.3), Use in
Specific Populations (8.6)].
ADVERSE REACTIONS
Acute
renal failure is discussed in greater detail in other sections of the label
[see Warnings and Precautions (5)].
The most
common adverse events reported in at least 1 indication by greater than 10% of
adult patients treated with Famvir are headache and nausea.
Clinical Trials
Experience in Adult Patients
Because
clinical trials are conducted under widely varying conditions, adverse reaction
rates observed in the clinical trials of a drug cannot be directly compared with
rates in the clinical trials of another drug and may not reflect the rates
observed in practice.
Immunocompetent patients: The safety of
Famvir has been evaluated in active- and placebo-controlled clinical studies
involving 816 Famvir-treated patients with herpes zoster (Famvir, 250 mg three
times daily to 750 mg three times daily); 163 Famvir-treated patients with
recurrent genital herpes (Famvir, 1000 mg twice daily); 1,197 patients with
recurrent genital herpes treated with Famvir as suppressive therapy (125 mg
once daily to 250 mg three times daily) of which 570 patients received Famvir
(open-labeled and/or double-blind) for at least 10 months; and 447
Famvir-treated patients with herpes labialis (Famvir, 1500 mg once daily or 750
mg twice daily). Table 2 lists selected adverse events.
Table 2: Selected Adverse Events (all
grades and without regard to causality) Reported by Greater Than or Equal to
2% of Patients in Placebo-Controlled Famvir Trials*
|
|
Incidence
|
|
|
Herpes Zoster†
|
Recurrent
Genital
Herpes‡
|
Genital Herpes-
Suppression§
|
Herpes Labialis‡
|
|
|
Famvir
|
Placebo
|
Famvir
|
Placebo
|
Famvir
|
Placebo
|
Famvir
|
Placebo
|
|
|
(n=273)
|
(n=146)
|
(n=163)
|
(n=166)
|
(n=458)
|
(n=63)
|
(n=447)
|
(n=254)
|
|
Events
|
%
|
%
|
%
|
%
|
%
|
%
|
%
|
%
|
|
Nervous System
|
|
Headache
|
22.7
|
17.8
|
13.5
|
5.4
|
39.3
|
42.9
|
8.5
|
6.7
|
|
Paresthesia
|
2.6
|
0.0
|
0.0
|
0.0
|
0.9
|
0.0
|
0.0
|
0.0
|
|
Migraine
|
0.7
|
0.7
|
0.6
|
0.6
|
3.1
|
0.0
|
0.2
|
0.0
|
|
Gastrointestinal
|
|
Nausea
|
12.5
|
11.6
|
2.5
|
3.6
|
7.2
|
9.5
|
2.2
|
3.9
|
|
Diarrhea
|
7.7
|
4.8
|
4.9
|
1.2
|
9.0
|
9.5
|
1.6
|
0.8
|
|
Vomiting
|
4.8
|
3.4
|
1.2
|
0.6
|
3.1
|
1.6
|
0.7
|
0.0
|
|
Flatulence
|
1.5
|
0.7
|
0.6
|
0.0
|
4.8
|
1.6
|
0.2
|
0.0
|
|
Abdominal Pain
|
1.1
|
3.4
|
0.0
|
1.2
|
7.9
|
7.9
|
0.2
|
0.4
|
|
Body as a Whole
|
|
Fatigue
|
4.4
|
3.4
|
0.6
|
0.0
|
4.8
|
3.2
|
1.6
|
0.4
|
|
Skin and Appendages
|
|
Pruritus
|
3.7
|
2.7
|
0.0
|
0.6
|
2.2
|
0.0
|
0.0
|
0.0
|
|
Rash
|
0.4
|
0.7
|
0.0
|
0.0
|
3.3
|
1.6
|
0.0
|
0.0
|
|
Reproductive (Female)
|
|
Dysmenorrhea
|
0.0
|
0.7
|
1.8
|
0.6
|
7.6
|
6.3
|
0.4
|
0.0
|
*Patients may have entered into more than one clinical
trial.
†7 days of treatment
‡1 day of treatment
§daily treatment
Table 3
lists selected laboratory abnormalities in genital herpes suppression trials.
Table 3: Selected Laboratory
Abnormalities in Genital Herpes Suppression Studies*
|
|
Parameter
|
Famvir
(n=660)†
%
|
Placebo
(n=210)†
%
|
|
Anemia (<0.8
x NRL)
|
0.1
|
0.0
|
|
Leukopenia
(<0.75 x NRL)
|
1.3
|
0.9
|
|
Neutropenia
(<0.8 x NRL)
|
3.2
|
1.5
|
|
AST (SGOT)
(>2 x NRH)
|
2.3
|
1.2
|
|
ALT (SGPT)
(>2 x NRH)
|
3.2
|
1.5
|
|
Total Bilirubin
(>1.5 x NRH)
|
1.9
|
1.2
|
|
Serum Creatinine
(>1.5 x NRH)
|
0.2
|
0.3
|
|
Amylase (>1.5
x NRH)
|
1.5
|
1.9
|
|
Lipase (>1.5
x NRH)
|
4.9
|
4.7
|
*Percentage of patients with laboratory abnormalities
that were increased or decreased from baseline and were outside of specified
ranges.
†n values represent the minimum number of patients
assessed for each laboratory parameter.
NRH=NormalRange High.
NRL=NormalRangeLow.
HIV-infected patients: In HIV-infected patients, the most
frequently reported adverse events for Famvir (500 mg twice daily; n=150) and
acyclovir (400 mg, 5x/day; n=143), respectively, were headache (17% vs. 15%),
nausea (11% vs. 13%), diarrhea (7% vs. 11%), vomiting (5% vs. 4%), fatigue (4%
vs. 2%), and abdominal pain (3% vs. 6%).
Postmarketing
Experience
The
adverse events listed below have been reported during post-approval use of
Famvir. Because these events are reported voluntarily from a population of
uncertain size, it is not always possible to reliably estimate their frequency
or establish a causal relationship to drug exposure:
Blood and lymphatic system disorders: Thrombocytopenia
Hepatobiliary disorders: Abnormal liver function tests, cholestatic jaundice
Immune system disorders: Anaphylactic shock, anaphylactic reaction
Nervous system disorders: Dizziness, somnolence, seizure
Psychiatric disorders: Confusion (including delirium, disorientation, and confusional
state occurring predominantly in the elderly), hallucinations
Skin and subcutaneous tissue disorders: Urticaria, erythema multiforme, Stevens-Johnson
syndrome, toxic epidermal necrolysis, angioedema (e.g., face, eyelid,
periorbital, and pharyngeal edema), hypersensitivity vasculitis
Cardiac disorders: Palpitations
DRUG INTERACTIONS
Potential for Famvir to
Affect Other Drugs
The
steady-state pharmacokinetics of digoxin were not altered by concomitant
administration of multiple doses of famciclovir (500 mg three times daily). No
clinically significant effect on the pharmacokinetics of zidovudine, its
metabolite zidovudine glucuronide, or emtricitabine was observed following a
single oral dose of 500 mg famciclovir coadministered with zidovudine or
emtricitabine.
An in
vitro study using human liver microsomes suggests that
famciclovir is not an inhibitor of CYP3A4 enzymes.
Potential for Other
Drugs to Affect Penciclovir
No
clinically significant alterations in penciclovir pharmacokinetics were
observed following single-dose administration of 500 mg famciclovir after
pretreatment with multiple doses of allopurinol, cimetidine, theophylline,
zidovudine, promethazine, when given shortly after an antacid (magnesium and
aluminum hydroxide), or concomitantly with emtricitabine. No clinically
significant effect on penciclovir pharmacokinetics was observed following
multiple-dose (three times daily) administration of famciclovir (500 mg) with
multiple doses of digoxin.
Concurrent
use with probenecid or other drugs significantly eliminated by active renal tubular
secretion may result in increased plasma concentrations of penciclovir.
The
conversion of 6-deoxy penciclovir to penciclovir is catalyzed by aldehyde
oxidase. Interactions with other drugs metabolized by this enzyme and/or
inhibiting this enzyme could potentially occur. Clinical interaction studies of
famciclovir with cimetidine and promethazine, in vitro inhibitors
of aldehyde oxidase, did not show relevant effects on the formation of
penciclovir. Raloxifene, a potent aldehyde oxidase inhibitor in
vitro, could decrease the formation of penciclovir. However,
a clinical drug-drug interaction study to determine the magnitude of
interaction between penciclovir and raloxifene has not been conducted.
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy category B. After
oral administration, famciclovir (prodrug) is converted to penciclovir (active
drug). There are no adequate and well-controlled studies of famciclovir or
penciclovir use in pregnant women. No adverse effects on embryofetal
development were observed in animal reproduction studies using famciclovir and
penciclovir at doses higher than the maximum recommended human dose (MRHD) and
human exposure. Because animal reproduction studies are not always predictive
of human response, famciclovir should be used during pregnancy only if
needed.
In animal
reproduction studies, pregnant rats and rabbits received oral famciclovir at
doses (up to 1000 mg/kg/day) that provided 2.7 to 10.8 times (rats) and 1.4 to
5.4 times (rabbits) the human systemic exposure based on AUC. No adverse
effects were observed on embryo-fetal development. In other studies, pregnant
rats and rabbits received intravenous famciclovir at doses (360 mg/kg/day) 1.5
to 6 times (rats) and (120 mg/kg/day) 1.1 to 4.5 times (rabbits) or penciclovir
at doses (80 mg/kg/day) 0.3 to 1.3 times (rats) and (60 mg/kg/day) 0.5 to
2.1 times (rabbits) the MRHD based on body surface area comparisons. No adverse
effects were observed on embryo-fetal development.
Pregnancy exposure reporting. To
monitor maternal-fetal outcomes of pregnant women exposed to Famvir, Novartis
Pharmaceuticals Corporation maintains a Famvir Pregnancy Reporting system.
Physicians are encouraged to report their patients by calling 1-888-NOW-NOVA
(669-6682).
Nursing Mothers
It is not
known whether famciclovir (prodrug) or penciclovir (active drug) are excreted
in human milk. Following oral administration of famciclovir to lactating rats,
penciclovir was excreted in breast milk at concentrations higher than those
seen in the plasma. There are no data on the safety of Famvir in infants.
Famvir should not be used in nursing mothers unless the potential benefits are
considered to outweigh the potential risks associated with treatment.
Pediatric Use
The
efficacy of Famvir has not been established in pediatric patients. The
pharmacokinetic profile and safety of famciclovir (experimental granules mixed
with OraSweet® or tablets) were studied in 3 open-label studies.
Study 1
was a single-dose pharmacokinetic and safety study in infants 1 month to less
than 1 year of age who had an active herpes simplex virus (HSV) infection or
who were at risk for HSV infection. Eighteen
subjects were enrolled and received a single dose of famciclovir experimental
granules mixed with OraSweet based on the patient’s body weight (doses ranged
from 25 mg to 175 mg). These doses were selected to provide penciclovir
systemic exposures similar to the penciclovir systemic exposures observed in
adults after administration of 500 mg famciclovir. The efficacy and safety of
famciclovir have not been established as suppressive therapy in infants
following neonatal HSV infections. In addition, the efficacy cannot be extrapolated
from adults to infants because there is no similar disease in adults.
Therefore, famciclovir is not recommended in infants.
Study 2
was an open-label, single-dose pharmacokinetic, multiple-dose safety study of
famciclovir experimental granules mixed with OraSweet in children 1 to less
than 12 years of age with clinically suspected HSV or varicella zoster virus
(VZV) infection. Fifty-one subjects were enrolled in the pharmacokinetic part
of the study and received a single body weight adjusted dose of famciclovir
(doses ranged from 125 mg to 500 mg). These doses were selected to provide penciclovir
systemic exposures similar to the penciclovir systemic exposures observed in
adults after administration of 500 mg famciclovir. Based on the pharmacokinetic
data observed with these doses in children, a new weight-based dosing algorithm
was designed and used in the multiple-dose safety part of the study.
Pharmacokinetic data were not obtained with the revised weight-based dosing
algorithm.
A total
of 100 patients were enrolled in the multiple-dose safety part of the study; 47
subjects with active or latent HSV infection and 53 subjects with chickenpox.
Patients with active or latent HSV infection received famciclovir twice a day
for 7 days. The daily dose of famciclovir ranged from 150 mg to 500 mg
twice daily depending on the patient’s body weight. Patients with chickenpox
received famciclovir three times daily for 7 days. The daily dose of
famciclovir ranged from 150 mg to 500 mg three times daily depending on the
patient’s body weight. The clinical adverse events and laboratory test
abnormalities observed in this study were similar to these seen in adults. The
available data are insufficient to support the use of famciclovir for the
treatment of children 1 to less than 12 years of age with chickenpox or
infections due to HSV for the following reasons:
Chickenpox: The
efficacy of famciclovir for the treatment of chickenpox has not been
established in either pediatric or adult patients. Famciclovir is approved for
the treatment of herpes zoster in adult patients. However, extrapolation of
efficacy data from adults with herpes zoster to children with chickenpox would
not be appropriate. Although chickenpox and herpes zoster are caused by the
same virus, the diseases are different.
Genital herpes: Clinical information on genital herpes in children is
limited. Therefore, efficacy data from adults cannot be extrapolated to this
population. Further, famciclovir has not been studied in children 1 to less
than 12 years of age with recurrent genital herpes. None of the children in
Study 2 had genital herpes.
Herpes labialis: There are no pharmacokinetic and safety data in
children 1 to less than 12 years of age to support a famciclovir dose that
provides penciclovir systemic exposures comparable to the penciclovir systemic
exposures in adults after a single dose administration of 1500 mg. Moreover, no
efficacy data have been obtained in children 1 to less than 12 years of age
with recurrent herpes labialis.
Study 3
was an open-label, single-arm study to evaluate the pharmacokinetics, safety,
and antiviral activity of a single 1500 mg dose (three 500 mg tablets) of
famciclovir in children 12 to less than 18 years of age with recurrent herpes
labialis. A total of 53 subjects were enrolled in the study; 10 subjects in the
pharmacokinetic part of the study and 43 subjects in the non-pharmacokinetic
part of the study. All enrolled subjects weighed greater than or equal to 40
kg. The 43 subjects enrolled in the non-pharmacokinetic part of the study had
active recurrent herpes labialis and received a single 1500 mg dose of
famciclovir within 24 hours after the onset of symptoms (median time to
treatment initiation was 21 hours). The safety profile of famciclovir observed
in this study was similar to that seen in adults. The median time to healing of
patients with non-aborted lesions was 5.9 days.
In a
phase 3 trial in adults in which patients received a single 1500 mg dose of
famciclovir or placebo, the median time to healing among patients with
non-aborted lesions was 4.4 days in the famciclovir 1500 mg single-dose group
and 6.2 days in the placebo group. Of note, in the adult study treatment
was initiated by patients within 1 hour after the onset of symptoms
[see Clinical Studies (14.1)].
Based on the efficacy results in Study 3, famciclovir is not recommended in
children 12 to less than 18 years of age with recurrent herpes labialis.
Geriatric Use
Of 816
patients with herpes zoster in clinical studies who were treated with Famvir,
248 (30.4%) were greater than or equal to 65 years of age and 103 (13%) were
greater than or equal to 75 years of age. No overall differences were observed
in the incidence or types of adverse events between younger and older patients.
Of 610 patients with recurrent herpes simplex (type 1 or type 2) in clinical
studies who were treated with Famvir, 26 (4.3%) were greater than 65 years of
age and 7 (1.1%) were greater than 75 years of age. Clinical studies of Famvir in
patients with recurrent genital herpes did not include sufficient numbers of
subjects aged 65 years and over to determine whether they respond differently
compared to younger subjects.
No
famciclovir dosage adjustment based on age is recommended unless renal function
is impaired [see Dosage and
Administration (2.3), Clinical
Pharmacology (12.3)]. In general, appropriate caution
should be exercised in the administration and monitoring of Famvir in elderly
patients reflecting the greater frequency of decreased renal function and
concomitant use of other drugs.
Patients with Renal
Impairment
Apparent
plasma clearance, renal clearance, and the plasma-elimination rate constant of
penciclovir decreased linearly with reductions in renal function. After the
administration of a single 500 mg famciclovir oral dose (n=27) to healthy
volunteers and to volunteers with varying degrees of renal impairment (CLCR ranged from 6.4 to 138.8 mL/min), the following
results were obtained (Table 4):
Table 4: Pharmacokinetic Parameters of
Penciclovir in Subjects with Different Degrees of Renal Impairment
|
|
Parameter
(mean ± S.D.)
|
CLCR† ≥60
(mL/min)
(n=15)
|
CLCR 40-59
(mL/min)
(n=5)
|
CLCR 20-39
(mL/min)
(n=4)
|
CLCR <20
(mL/min)
(n=3)
|
|
CLCR (mL/min)
|
88.1 ± 20.6
|
49.3 ± 5.9
|
26.5 ± 5.3
|
12.7 ± 5.9
|
|
CLR (L/hr)
|
30.1 ± 10.6
|
13.0 ± 1.3‡
|
4.2 ± 0.9
|
1.6 ± 1.0
|
|
CL/F§ (L/hr)
|
66.9 ± 27.5
|
27.3 ± 2.8
|
12.8 ± 1.3
|
5.8 ± 2.8
|
|
Half-life (hr)
|
2.3 ± 0.5
|
3.4 ± 0.7
|
6.2 ± 1.6
|
13.4 ± 10.2
|
† CLCR is
measured creatinine clearance.
‡ n=4.
§ CL/F consists of bioavailability factor and
famciclovir to penciclovir conversion factor.
In a
multiple-dose study of famciclovir conducted in subjects with varying degrees
of renal impairment (n=18), the pharmacokinetics of penciclovir were comparable
to those after single doses.
A dosage
adjustment is recommended for patients with renal impairment [see Dosage
and Administration (2.3)].
Patients with Hepatic
Impairment
Mild or
moderate hepatic impairment (chronic hepatitis [n=6], chronic ethanol abuse
[n=8], or primary biliary cirrhosis [n=1]) had no effect on the extent of
availability (AUC) of penciclovir following a single dose of 500 mg
famciclovir. However, there was a 44% decrease in penciclovir mean maximum
plasma concentration (Cmax) and the
time to maximum plasma concentration (tmax) was
increased by 0.75 hours in patients with hepatic impairment compared to normal
volunteers. No dosage adjustment is recommended for patients with mild or
moderate hepatic impairment. The pharmacokinetics of penciclovir has not been
evaluated in patients with severe hepatic impairment. Conversion
of famciclovir to the active metabolite penciclovir may be impaired in these
patients resulting in a lower penciclovir plasma concentrations, and thus
possibly a decrease of efficacy of famciclovir [see Clinical
Pharmacology (12)].
Black and African
American Patients
In a
randomized, double-blind, placebo-controlled trial conducted in 304
immunocompetent black and African American adults with recurrent genital herpes
there was no difference in median time to healing between patients receiving
Famvir or placebo. In general, the adverse reaction profile was similar to that
observed in other Famvir clinical trials for adult patients [see Adverse
Reactions (6.1)]. The relevance of these study
results to other indications in black and African American patients is unknown
[see Clinical Studies (14.2)].
OVERDOSAGE
Appropriate
symptomatic and supportive therapy should be given. Penciclovir is removed by
hemodialysis.
DESCRIPTION
The
active ingredient in Famvir tablets is famciclovir, an orally administered
prodrug of the antiviral agent penciclovir. Chemically, famciclovir is known as
2-[2-(2-amino-9H-purin-9-yl)ethyl]-1,3-propanediol
diacetate. Its molecular formula is C14H19N5O4; its molecular weight is 321.3. It is a synthetic acyclic
guanine derivative and has the following structure
Famciclovir
is a white to pale yellow solid. It is freely soluble in acetone and methanol,
and sparingly soluble in ethanol and isopropanol. At 25°C famciclovir is freely
soluble (greater than 25% w/v) in water initially, but rapidly precipitates as
the sparingly soluble (2%-3% w/v) monohydrate. Famciclovir is not hygroscopic
below 85% relative humidity. Partition coefficients are: octanol/water (pH
4.8) P=1.09 and octanol/phosphate
buffer (pH 7.4) P=2.08.
Famvir
tablets contain 125 mg, 250 mg, or 500 mg of famciclovir, together with the
following inactive ingredients: hydroxypropyl cellulose, hydroxypropyl
methylcellulose, lactose, magnesium stearate, polyethylene glycols, sodium
starch glycolate and titanium dioxide.
CLINICAL PHARMACOLOGY
Mechanism of Action
Famciclovir
is an orally administered prodrug of the antiviral agent penciclovir [see Microbiology (12.4)].
Pharmacokinetics
Famciclovir
is the diacetyl 6-deoxy analog of the active antiviral compound penciclovir.
Following oral administration famciclovir undergoes rapid and extensive
metabolism to penciclovir and little or no famciclovir is detected in plasma or
urine. Penciclovir is predominantly eliminated unchanged by the kidney.
Therefore, the dose of Famvir needs to be adjusted in patients with different
degrees of renal impairment [see Dosage and
Administration (2.3)].
Pharmacokinetics in adults:
Absorption and Bioavailability: The absolute bioavailability of penciclovir is
77 ± 8% as determined following the administration of a 500 mg
famciclovir oral dose and a 400 mg penciclovir intravenous dose to 12 healthy
male subjects.
Penciclovir
concentrations increased in proportion to dose over a famciclovir dose range of
125 mg to 1000 mg administered as a single dose. Table 5 shows the mean
pharmacokinetic parameters of penciclovir after single administration of Famvir
to healthy male volunteers.
Table 5: Mean Pharmacokinetic Parameters
of Penciclovir in Healthy Adult Subjects*
|
|
Dose
|
AUC (0-inf)† (mcg hr/mL)
|
Cmax‡ (mcg/mL)
|
tmax§ (h)
|
|
125 mg
|
2.24
|
0.8
|
0.9
|
|
250 mg
|
4.48
|
1.6
|
0.9
|
|
500 mg
|
8.95
|
3.3
|
0.9
|
|
1000 mg
|
17.9
|
6.6
|
0.9
|
* Based on pharmacokinetic data from 17 studies
† AUC (0-inf) (mcg hr/mL) = area under
the plasma concentration-time profile extrapolated to infinity.
‡ Cmax (mcg/mL) = maximum
observed plasma concentration.
§ tmax (h) =
time to Cmax.
Following
oral single-dose administration of 500 mg famciclovir to 7 patients
with herpes zoster, the AUC (mean ± SD), Cmax,
and tmax were 12.1±1.7 mcg hr/mL, 4.0±0.7 mcg/mL, and
0.7±0.2 hours, respectively. The AUC of penciclovir was approximately 35%
greater in patients with herpes zoster as compared to healthy volunteers. Some
of this difference may be due to differences in renal function between the
2 groups.
There is
no accumulation of penciclovir after the administration of 500 mg
famciclovir three times daily for 7 days.
Penciclovir
Cmax decreased approximately 50% and tmax was delayed by 1.5 hours when a capsule
formulation of famciclovir was administered with food (nutritional content was
approximately 910 Kcal and 26% fat). There was no effect on the extent of
availability (AUC) of penciclovir. There was an 18% decrease in Cmax and a delay in tmax of
about 1 hour when famciclovir was given 2 hours after a meal as compared to its
administration 2 hours before a meal. Because there was no effect on the extent
of systemic availability of penciclovir, Famvir can be taken without regard to
meals.
Distribution: The volume of distribution (Vdβ) was 1.08±0.17 L/kg in 12
healthy male subjects following a single intravenous dose of penciclovir at 400
mg administered as a 1-hour intravenous infusion. Penciclovir is less than 20% bound to plasma proteins over the
concentration range of 0.1 to 20 mcg/mL. The blood/plasma ratio of penciclovir
is approximately 1.
Metabolism: Following oral administration, famciclovir is deacetylated and
oxidized to form penciclovir. Metabolites that are inactive include 6-deoxy
penciclovir, monoacetylated penciclovir, and 6-deoxy monoacetylated penciclovir
(5%, less than 0.5% and less than 0.5% of the dose in the urine, respectively).
Little or no famciclovir is detected in plasma or urine. An in
vitro study using human liver microsomes demonstrated
that cytochrome P450 does not play an important role in famciclovir metabolism.
The conversion of 6-deoxy penciclovir to penciclovir is catalyzed by aldehyde
oxidase. Cimetidine and promethazine, in vitro inhibitors
of aldehyde oxidase, did not show relevant effects on the formation of
penciclovir in vivo [see Drug Interactions
(7.2)].
Elimination: Approximately 94% of administered radioactivity was recovered in
urine over 24 hours (83% of the dose was excreted in the first 6 hours) after
the administration of 5 mg/kg radiolabeled penciclovir as a 1-hour infusion to
3 healthy male volunteers. Penciclovir accounted for 91% of the
radioactivity excreted in the urine.
Following
the oral administration of a single 500 mg dose of radiolabeled famciclovir to
3 healthy male volunteers, 73% and 27% of administered radioactivity were
recovered in urine and feces over 72 hours, respectively. Penciclovir accounted
for 82% and 6-deoxy penciclovir accounted for 7% of the radioactivity excreted
in the urine. Approximately 60% of the administered radiolabeled dose was
collected in urine in the first 6 hours.
After
intravenous administration of penciclovir in 48 healthy male volunteers, mean ±
SD total plasma clearance of penciclovir was 36.6±6.3 L/hr (0.48±0.09 L/hr/kg).
Penciclovir renal clearance accounted for 74.5±8.8% of total plasma clearance.
Renal
clearance of penciclovir following the oral administration of a single 500 mg
dose of famciclovir to 109 healthy male volunteers was 27.7±7.6 L/hr. Active
tubular secretion contributes to the renal elimination of penciclovir.
The
plasma elimination half-life of penciclovir was 2.0±0.3 hours after intravenous
administration of penciclovir to 48 healthy male volunteers and 2.3±0.4 hours
after oral administration of 500 mg famciclovir to 124 healthy male
volunteers. The half-life in 17 patients with herpes zoster was 2.8±1.0 hours
and 2.7±1.0 hours after single and repeated doses, respectively.
Special populations:
Geriatric patients: Based
on cross study comparison, penciclovir AUC was 40% higher and penciclovir renal
clearance was 22% lower in elderly subjects (n=18, age 65 to 79 years) as
compared with younger subjects. Some of this difference may be due to
differences in renal function between the 2 groups. No famciclovir dosage
adjustment based on age is recommended unless renal function is impaired [see Dosage
and Administration (2.3), Use in Specific Populations (8.5).]
Patients with renal impairment: In
subjects with varying degrees of renal impairment, apparent plasma clearance,
renal clearance, and the plasma-elimination rate constant of penciclovir
decreased linearly with reductions in renal function, after both single and
repeated dosing [see Use in Specific
Populations (8.6)]. A
dosage adjustment is recommended for patients with renal impairment [see Dosage
and Administration (2.3)].
Patients with hepatic impairment: Mild
or moderate hepatic impairment had no effect on the extent of availability
(AUC) of penciclovir [see Use in Specific Populations (8.7)].
No dosage adjustment is recommended for patients with mild or moderate hepatic
impairment. The effect of severe hepatic impairment on the
pharmacokinetics of penciclovir has not been evaluated.
HIV-infected patients: Following oral administration of a single dose of 500 mg
famciclovir to HIV-positive patients, the pharmacokinetic parameters of
penciclovir were comparable to those observed in healthy subjects.
Gender: The pharmacokinetics of penciclovir were evaluated in 18 healthy
male and 18 healthy female volunteers after single-dose oral administration of
500 mg famciclovir. AUC of penciclovir was 9.3±1.9 mcg hr/mL and 11.1±2.1
mcg hr/mL in males and females, respectively. Penciclovir renal clearance was
28.5±8.9 L/hr and 21.8±4.3 L/hr, respectively. These differences were
attributed to differences in renal function between the 2 groups. No
famciclovir dosage adjustment based on gender is recommended.
Race: A
retrospective evaluation was performed to compare the pharmacokinetic
parameters obtained in black and Caucasian subjects after single and repeat
once-daily, twice-daily, or three times-daily administration of famciclovir 500
mg. Data from a study in healthy volunteers (single dose), a study in subjects
with varying degrees of renal impairment (single and repeat dose) and a study
in subjects with hepatic impairment (single dose) did not indicate any
significant differences in the pharmacokinetics of penciclovir between black
and Caucasian subjects.
Microbiology
Mechanism of action: Famciclovir is
a prodrug of penciclovir, which has demonstrated inhibitory activity against
herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and varicella zoster virus
(VZV). In cells infected with HSV-1, HSV-2 or VZV, the viral thymidine kinase
phosphorylates penciclovir to a monophosphate form that, in turn, is converted
by cellular kinases to the active form penciclovir triphosphate. Biochemical studies
demonstrate that penciclovir triphosphate inhibits HSV-2 DNA polymerase
competitively with deoxyguanosine triphosphate. Consequently, herpes viral DNA
synthesis and, therefore, replication are selectively inhibited. Penciclovir
triphosphate has an intracellular half-life of 10 hours in HSV-1-, 20 hours in
HSV-2- and 7 hours in VZV-infected cells grown in culture. However, the
clinical significance of the intracellular half-life is unknown.
Antiviral activity: In cell culture studies,
penciclovir is inhibitory to the following herpes viruses: HSV-1, HSV-2
and VZV. The antiviral activity of penciclovir against wild type strains grown
on human foreskin fibroblasts was assessed with a plaque reduction assay and
staining with crystal violet 3 days postinfection for HSV and 10 days
postinfection for VZV. The median EC50 values
of penciclovir against laboratory and clinical isolates of HSV-1, HSV-2, and
VZV were 2 µM (range 1.2 to 2.4 µM, n=7), 2.6 µM (range 1.6 to 11 µM, n=6), and
34 µM (range 6.7 to 71 µM, n=6), respectively.
Resistance: Penciclovir-resistant mutants of HSV and VZV can result from
mutations in the viral thymidine kinase (TK) and DNA polymerase genes.
Mutations in the viral TK gene may lead to complete loss of TK activity (TK
negative), reduced levels of TK activity (TK partial), or alteration in the
ability of viral TK to phosphorylate the drug without an equivalent loss in the
ability to phosphorylate thymidine (TK altered). The median EC50 values observed in a plaque reduction assay
with penciclovir resistant HSV-1, HSV-2, and VZV were 69 µM (range 14 to 115
µM, n=6), 46 µM (range 4 to greater than 395 µM, n=9), and 92 µM (range 51 to
148 µM, n=4), respectively. The possibility of viral resistance to penciclovir
should be considered in patients who fail to respond or experience recurrent
viral shedding during therapy.
Cross-resistance: Cross-resistance has been observed among HSV DNA polymerase
inhibitors. The most commonly encountered acyclovir resistant mutants
that are TK negative are also resistant to penciclovir.
NONCLINICAL TOXICOLOGY
Carcinogenesis,
Mutagenesis, Impairment of Fertility
Carcinogenesis: Two-year dietary carcinogenicity studies with famciclovir
were conducted in rats and mice. An increase in the incidence of mammary adenocarcinoma
(a common tumor in animals of this strain) was seen in female rats receiving
the high dose of 600 mg/kg/day (1.1 to 4.5x the human systemic exposure at the
recommended total daily oral dose ranging between 500 mg and 2000 mg, based on
area under the plasma concentration curve comparisons [24 hr AUC] for
penciclovir). No increases in tumor incidence were reported in male rats
treated at doses up to 240 mg/kg/day (0.7 to 2.7x the human AUC), or in male
and female mice at doses up to 600 mg/kg/day (0.3 to 1.2x the human AUC).
Mutagenesis: Famciclovir
and penciclovir (the active metabolite of famciclovir) were tested for
genotoxic potential in a battery of in vitro and in
vivo assays. Famciclovir and penciclovir were negative
in in vitro tests for gene mutations in
bacteria (S. typhimurium and E.
coli) and unscheduled DNA synthesis in mammalian HeLa 83
cells (at doses up to 10,000 and 5,000 mcg/plate, respectively). Famciclovir
was also negative in the L5178Y mouse lymphoma assay (5000 mcg/mL), the in
vivo mouse micronucleus test (4800 mg/kg), and rat
dominant lethal study (5000 mg/kg). Famciclovir induced increases in polyploidy
in human lymphocytes in vitro in the absence
of chromosomal damage (1200 mcg/mL). Penciclovir was positive in the L5178Y
mouse lymphoma assay for gene mutation/chromosomal aberrations, with and
without metabolic activation (1000 mcg/mL). In human lymphocytes, penciclovir
caused chromosomal aberrations in the absence of metabolic activation (250
mcg/mL). Penciclovir caused an increased incidence of micronuclei in mouse bone
marrow in vivo when
administered intravenously at doses highly toxic to bone marrow (500 mg/kg),
but not when administered orally.
Impairment of fertility: Testicular
toxicity was observed in rats, mice, and dogs following repeated administration
of famciclovir or penciclovir. Testicular changes included atrophy of the
seminiferous tubules, reduction in sperm count, and/or increased incidence of
sperm with abnormal morphology or reduced motility. The degree of toxicity to
male reproduction was related to dose and duration of exposure. In male rats,
decreased fertility was observed after 10 weeks of dosing at 500 mg/kg/day (1.4
to 5.7x the human AUC). The no observable effect level for sperm and testicular
toxicity in rats following chronic administration (26 weeks) was 50 mg/kg/day
(0.15 to 0.6x the human systemic exposure based on AUC comparisons). Testicular
toxicity was observed following chronic administration to mice (104 weeks) and
dogs (26 weeks) at doses of 600 mg/kg/day (0.3 to 1.2x the human AUC) and 150
mg/kg/day (1.3 to 5.1x the human AUC), respectively.
Famciclovir
had no effect on general reproductive performance or fertility in female rats
at doses up to 1000 mg/kg/day (2.7 to 10.8x the human AUC).
Two
placebo-controlled studies in a total of 130 otherwise healthy men with a
normal sperm profile over an 8-week baseline period and recurrent genital
herpes receiving oral Famvir (250 mg twice daily) (n=66) or placebo (n=64)
therapy for 18 weeks showed no evidence of significant effects on sperm count,
motility or morphology during treatment or during an 8-week follow-up.
CLINICAL STUDIES
Herpes Labialis (Cold
Sores)
A
randomized, double-blind, placebo-controlled trial was conducted in 701
immunocompetent adults with recurrent herpes labialis. Patients self-initiated
therapy within 1 hour of first onset of signs or symptoms of a recurrent herpes
labialis episode with Famvir 1500 mg as a single dose (n=227), Famvir 750
mg twice daily (n=220) or placebo (n=254) for 1 day. The median time to healing
among patients with non-aborted lesions (progressing beyond the papule stage)
was 4.4 days in the Famvir 1500 mg single-dose group (n=152) as compared
to 6.2 days in the placebo group (n=168). The median difference in time to
healing between the placebo and Famvir 1500 mg treated groups was 1.3 days (95%
CI: 0.6–2.0). No differences in proportion of patients with aborted lesions
(not progressing beyond the papule stage) were observed between patients
receiving Famvir or placebo: 33% for Famvir 1500 mg single dose and 34% for
placebo. The median time to loss of pain and tenderness was 1.7 days in Famvir
1500 mg single dose-treated patients vs. 2.9 days in placebo-treated
patients.
Genital Herpes
Recurrent episodes: A randomized,
double-blind, placebo-controlled trial was conducted in 329 immunocompetent
adults with recurrent genital herpes. Patients self-initiated therapy within 6
hours of the first sign or symptom of a recurrent genital herpes episode with
either Famvir 1000 mg twice daily (n=163) or placebo (n=166) for 1 day.
The median time to healing among patients with non-aborted lesions (progressing
beyond the papule stage) was 4.3 days in Famvir-treated patients (n=125) as
compared to 6.1 days in placebo-treated patients (n=145). The median difference
in time to healing between the placebo and Famvir-treated groups was 1.2 days
(95% CI: 0.5 to 2.0). Twenty-three percent of Famvir-treated patients had
aborted lesions (no lesion development beyond erythema) vs. 13% in
placebo-treated patients. The median time to loss of all symptoms (e.g.,
tingling, itching, burning, pain, or tenderness) was 3.3 days in Famvir-treated
patients vs. 5.4 days in placebo-treated patients.
A
randomized (2:1), double-blind, placebo-controlled trial was conducted in 304
immunocompetent black and African American adults with recurrent genital
herpes. Patients self-initiated therapy within 6 hours of the first sign or
symptom of a recurrent genital herpes episode with either Famvir 1000 mg
twice daily (n=206) or placebo (n=98) for 1 day. The median time to healing
among patients with non-aborted lesions was 5.4 days in Famvir-treated patients
(n=152) as compared to 4.8 days in placebo-treated patients (n=78). The median
difference in time to healing between the placebo and Famvir-treated groups was
-0.26 days (95% CI: -0.98 to 0.40).
Suppressive therapy: Two randomized, double-blind,
placebo-controlled, 12-month trials were conducted in 934 immunocompetent
adults with a history of 6 or more recurrences of genital herpes episodes per
year. Comparisons included Famvir 125 mg three times daily, 250 mg twice daily,
250 mg three times daily, and placebo. At 12 months, 60% to 65% of patients
were still receiving Famvir and 25% were receiving placebo treatment.
Recurrence rates at 6 and 12 months in patients treated with the 250 mg twice
daily dose are shown in Table 6.
Table 6: Recurrence Rates at 6 and 12
Months in Adults with Recurrent Genital Herpes on Suppressive Therapy
|
|
|
Recurrence Rates
at 6 Months
|
Recurrence Rates
at 12 Months
|
|
|
Famvir
250 mg twice daily
(n=236)
|
Placebo
(n=233)
|
Famvir
250 mg twice daily
(n=236)
|
Placebo
(n=233)
|
|
Recurrence-free
|
39%
|
10%
|
29%
|
6%
|
|
Recurrences†
|
47%
|
74%
|
53%
|
78%
|
|
Lost to
follow-up‡
|
14%
|
16%
|
17%
|
16%
|
†Based on patient reported data; not necessarily
confirmed by a physician.
‡Patients recurrence-free at time of last contact
prior to withdrawal.
Famvir-treated
patients had approximately one-fifth the median number of recurrences as
compared to placebo-treated patients. Higher doses of Famvir were not
associated with an increase in efficacy.
Recurrent Orolabial or
Genital Herpes in HIV-Infected Patients
A
randomized, double-blind trial compared famciclovir 500 mg twice daily for 7
days (n=150) with oral acyclovir 400 mg 5 times daily for 7 days (n=143) in
HIV-infected patients with recurrent orolabial or genital herpes treated within
48 hours of lesion onset. Approximately 40% of patients had a CD4+ count below 200 cells/mm3, 54% of
patients had anogenital lesions and 35% had orolabial lesions. Famciclovir
therapy was comparable to oral acyclovir in reducing new lesion formation and
in time to complete healing.
Herpes Zoster
(Shingles)
Two
randomized, double-blind trials, 1 placebo-controlled and 1 active-controlled,
were conducted in 964 immunocompetent adults with uncomplicated herpes zoster.
Treatment was initiated within 72 hours of first lesion appearance and was
continued for 7 days.
In the
placebo-controlled trial, 419 patients were treated with either Famvir 500 mg
three times daily (n=138), Famvir 750 mg three times daily (n=135) or placebo
(n=146). The median time to full crusting was 5 days among Famvir 500
mg-treated patients as compared to 7 days in placebo-treated patients. The
times to full crusting, loss of vesicles, loss of ulcers, and loss of crusts
were shorter for Famvir 500 mg-treated patients than for placebo-treated
patients in the overall study population. The effects of Famvir were greater
when therapy was initiated within 48 hours of rash onset; it was also more
profound in patients 50 years of age or older. Among the 65.2% of patients with
at least 1 positive viral culture, Famvir treated patients had a shorter median
duration of viral shedding than placebo-treated patients (1 day and 2 days,
respectively).
There
were no overall differences in the duration of pain before rash healing between
Famvir- and placebo-treated groups. In addition, there was no difference in the
incidence of pain after rash healing (postherpetic neuralgia) between the
treatment groups. In the 186 patients (44.4% of total study population) who
developed postherpetic neuralgia, the median duration of postherpetic neuralgia
was shorter in patients treated with Famvir 500 mg than in those treated with
placebo (63 days and 119 days, respectively). No additional efficacy was
demonstrated with higher dose of Famvir.
In the
active-controlled trial, 545 patients were treated with 1 of 3 doses
of Famvir three times daily or with acyclovir 800 mg five times daily. Times to
full lesion crusting and times to loss of acute pain were comparable for all
groups and there were no statistically significant differences in the time to
loss of postherpetic neuralgia between Famvir and acyclovir-treated groups.
HOW SUPPLIED/STORAGE AND HANDLING
Famvir tablets
are supplied as film-coated tablets as follows: 125 mg in bottles of 30; 250 mg
in bottles of 30; 500 mg in bottles of 30, and Single Unit Packages of 50
(intended for institutional use only).
· Famvir 125 mg tablet:
White, round film-coated, biconvex, beveled edges, debossed with “Famvir” on
one side and “125” on the other.
125 mg 30’s………………………………………………………………………………………… NDC 0078-0366-15
· Famvir 250 mg tablet:
White, round film-coated, biconvex, beveled edges, debossed with “Famvir” on
one side and “250” on the other.
250 mg 30’s………………………………………………………………………………………… NDC 0078-0367-15
· Famvir 500 mg tablet:
White, oval film-coated, biconvex, debossed with “Famvir” on one side and “500”
on the other.
500 mg 30’s………………………………………………………………………………………… NDC 0078-0368-15
500 mg SUP 50’s……………………………………………………………………………...…… NDC 0078-0368-64
Store at 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86°F) [see USP
Controlled Room Temperature].
PATIENT COUNSELING INFORMATION
Advise
the patient to read the FDA-approved patient labeling (Patient Information).
There is
no evidence that Famvir will affect the ability of a patient to drive or to use
machines. However, patients who experience dizziness, somnolence, confusion or
other central nervous system disturbances while taking Famvir should refrain
from driving or operating machinery.
Because
Famvir contains lactose (Famvir 125 mg, 250 mg, and 500 mg tablets contain
lactose 26.9 mg, 53.7 mg and 107.4 mg, respectively), patients with rare
hereditary problems of galactose intolerance, a severe lactase deficiency or
glucose-galactose malabsorption should be advised to discuss with their healthcare
provider before taking Famvir.
Herpes Labialis (Cold Sores)
Patients
should be advised to initiate treatment at the earliest sign or symptom of a
recurrence of cold sores (e.g., tingling, itching, burning, pain, or lesion).
Patients should be instructed that treatment for cold sores should not exceed 1
dose. Patients should be informed that Famvir is not a cure for cold sores.
Genital Herpes
Patients
should be informed that Famvir is not a cure for genital herpes. There are no
data evaluating whether Famvir will prevent transmission of infection to
others. Because genital herpes is a sexually transmitted disease, patients
should avoid contact with lesions or intercourse when lesions and/or symptoms
are present to avoid infecting partners. Genital herpes is frequently
transmitted in the absence of symptoms through asymptomatic viral shedding.
Therefore, patients should be counseled to use safer sex practices.
If
episodic therapy for recurrent genital herpes is indicated, patients should be
advised to initiate therapy at the first sign or symptom of an episode.
There are
no data on safety or effectiveness of chronic suppressive therapy of longer
than 1-year duration.
Herpes Zoster (Shingles)
There are
no data on treatment initiated more than 72 hours after onset of zoster rash.
Patients should be advised to initiate treatment as soon as possible after a
diagnosis of herpes zoster.
T2016-77
September 2016
PATIENT
INFORMATION
Famvir® (Fam’-veer)
(famciclovir)
Tablets
Read this
Patient Information before you start taking Famvir and each time you get a
refill. There may be new information. This information does not take the place
of talking with your healthcare provider about your medical condition or
treatment.
What is Famvir?
Famvir is
a prescription antiviral medicine used to:
· treat outbreaks of cold sores (fever blisters) in
healthy adults
· treat outbreaks of genital herpes in healthy
adults
· decrease the number of outbreaks of genital herpes in
healthy adults
· treat outbreaks of herpes simplex lesions in or
around the mouth, genitals, and anal area in people infected with HIV
· treat shingles (herpes zoster) in adults with normal
immune system
It is not
known if Famvir is safe and effective in children younger than 18 years of age.
Famvir is
not a cure for herpes. It is not known if Famvir can stop the spread of herpes
to others. If you are sexually active, you can pass herpes to your partner even
if you are taking Famvir. Herpes can be transmitted even if you do not
have active symptoms. You should continue to practice safer sex to lower the
chances of spreading genital herpes to others. Do not have sexual contact with
your partner during an outbreak of genital herpes or if you have any symptoms
of genital herpes. Use a condom made of latex or polyurethane when you have a
sexual contact. Ask your healthcare provider for more information about
safer sex practices.
Who should not take Famvir?
Do not
take Famvir if you are allergic to any of its ingredients or to Denavir® (penciclovir
cream). See the end of this Patient Information leaflet for a complete list of
ingredients in Famvir.
What should I tell my healthcare provider before taking Famvir?
Before
you start taking Famvir, tell your healthcare provider if you:
· have kidney or liver problems
· have a rare genetic problem with galactose
intolerance, a severe lactase deficiency or you do not absorb glucose-galactose
(malabsorption)
· are pregnant or planning to become pregnant. It is
not known if Famvir will harm your unborn baby
· Pregnancy Exposure Reporting: Novartis
Pharmaceuticals Corporation collects pregnancy reports which are reported on a
voluntary basis. In case of pregnancy, talk to your healthcare provider about
reporting your pregnancy.
· are breastfeeding or plan to breastfeed
Tell your
healthcare provider about all the medicines you take, including prescription
and nonprescription medicines, vitamins, and herbal supplements. Especially
tell your healthcare provider if you take:
· any other medicines and products you use to treat
herpes outbreaks
· probenecid (Probalan)
Know the
medicines you take. Keep a list of them with you to show to your healthcare
provider and pharmacist every time you get a new medicine.
How should I
take Famvir?
· Take Famvir exactly as prescribed.
· Your healthcare provider will tell you how many
Famvir to take and when to take them. Your dose of Famvir and how often you
take it may be different depending on your condition.
· Famvir can be taken with or without food.
· It is important for you to finish all of the medicine
as prescribed, even if you begin to feel better.
· Your symptoms may continue even after you finish all
of your Famvir. This does not mean that you need more medicine, since you have
already finished a full course of Famvir and it will continue to work in your
body. Talk to your healthcare provider if you have any questions about your
condition and your treatment.
What are the possible side effects of Famvir?
The most
common side effects of Famvir include:
· headache
· nausea
Talk to
your healthcare provider if you have any side effect that bothers you or that
does not go away.
These are
not all the possible side effects of Famvir. Ask your healthcare provider or
pharmacist for more information.
Call your
healthcare provider for medical advice about side effects. You may report side
effects to FDA at 1-800-FDA-1088.
How should I store Famvir?
· Store Famvir at room temperature between 59°F and
86°F (15°C to 30°C).
Keep Famvir and all medicines out of reach from children.
General information about
Famvir
Medicines
are sometimes prescribed for purposes other than those listed in Patient
Information leaflets. Do not use Famvir for a condition for which it was not
prescribed. Do not give Famvir to other people, even if they have the same
symptoms you have. It may harm them.
This
leaflet summarizes the most important information about Famvir. If you would
like more information, talk with your healthcare provider. Your healthcare
provider or pharmacist can give you information about Famvir that is written
for health professionals. For more information, go to www.Famvir.com or call 1-888-669-6682.
What are the ingredients in Famvir?
Active ingredient: famciclovir
Inactive ingredients: hydroxypropyl cellulose, hydroxypropyl methylcellulose,
lactose, magnesium stearate, polyethylene glycols, sodium starch glycolate, and
titanium dioxide
Distributed
by:
Novartis Pharmaceuticals Corporation
East Hanover,New Jersey07936
©Novartis
T2016-77/T2016-78
September 2016/September 2016
PRINCIPAL DISPLAY PANEL
Package Label – 125 mg
Rx Only
NDC 0078-0366-15
Famvir® (famciclovir) Tablets
125 mg
per tablet
30
Tablets
PRINCIPAL DISPLAY PANEL
Package Label – 250 mg
Rx Only
NDC 0078-0367-15
Famvir® (famciclovir) Tablets
250 mg
per tablet
30
Tablets
PRINCIPAL DISPLAY PANEL
Package Label – 500 mg
Rx Only
NDC 0078-0368-15
Famvir® (famciclovir) Tablets
500 mg
per tablet
30
Tablets
|
Famvir famciclovir tablet, film coated
|
|
Product
Information
|
|
Product Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:0078-0366
|
|
Route of
Administration
|
ORAL
|
DEA Schedule
|
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
FAMCICLOVIR (PENCICLOVIR)
|
FAMCICLOVIR
|
125 mg
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
HYDROXYPROPYL CELLULOSE (TYPE H)
|
|
|
LACTOSE
|
|
|
MAGNESIUM STEARATE
|
|
|
POLYETHYLENE GLYCOLS
|
|
|
SODIUM STARCH GLYCOLATE TYPE A POTATO
|
|
|
TITANIUM DIOXIDE
|
|
|
|
Product
Characteristics
|
|
Color
|
WHITE
|
Score
|
no score
|
|
Shape
|
ROUND
|
Size
|
8mm
|
|
Flavor
|
|
Imprint Code
|
Famvir;125
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:0078-0366-15
|
30 TABLET, FILM
COATED in 1 BOTTLE
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA020363
|
06/29/1994
|
|
|
|
Famvir famciclovir tablet, film coated
|
|
Product
Information
|
|
Product Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:0078-0367
|
|
Route of
Administration
|
ORAL
|
DEA Schedule
|
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
FAMCICLOVIR (PENCICLOVIR)
|
FAMCICLOVIR
|
250 mg
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
HYDROXYPROPYL CELLULOSE (TYPE H)
|
|
|
LACTOSE
|
|
|
MAGNESIUM STEARATE
|
|
|
POLYETHYLENE GLYCOLS
|
|
|
SODIUM STARCH GLYCOLATE TYPE A POTATO
|
|
|
TITANIUM DIOXIDE
|
|
|
|
Product
Characteristics
|
|
Color
|
WHITE
|
Score
|
no score
|
|
Shape
|
ROUND
|
Size
|
10mm
|
|
Flavor
|
|
Imprint Code
|
Famvir;250
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:0078-0367-15
|
30 TABLET, FILM
COATED in 1 BOTTLE
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA020363
|
06/29/1994
|
|
|
|
Famvir famciclovir tablet, film coated
|
|
Product
Information
|
|
Product Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:0078-0368
|
|
Route of
Administration
|
ORAL
|
DEA Schedule
|
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
FAMCICLOVIR (PENCICLOVIR)
|
FAMCICLOVIR
|
500 mg
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
HYDROXYPROPYL CELLULOSE (TYPE H)
|
|
|
LACTOSE
|
|
|
MAGNESIUM STEARATE
|
|
|
POLYETHYLENE GLYCOLS
|
|
|
SODIUM STARCH GLYCOLATE TYPE A POTATO
|
|
|
TITANIUM DIOXIDE
|
|
|
|
Product
Characteristics
|
|
Color
|
WHITE
|
Score
|
no score
|
|
Shape
|
OVAL
|
Size
|
18mm
|
|
Flavor
|
|
Imprint Code
|
Famvir;500
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:0078-0368-15
|
30 TABLET, FILM
COATED in 1 BOTTLE
|
|
|
2
|
NDC:0078-0368-64
|
50 BLISTER PACK
in 1 BOX, UNIT-DOSE
|
|
|
2
|
NDC:0078-0368-61
|
1 TABLET, FILM
COATED in 1 BLISTER PACK
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA020363
|
06/29/1994
|
|
|
|
Labeler - Novartis Pharmaceuticals Corporation
(002147023)
|
Revised: 09/2016
Novartis
Pharmaceuticals Corporation
