HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
LAMPRENE
safely and effectively. See full prescribing information for
LAMPRENE
.
LAMPRENE
�
(clofa
zimine)
capsules
, for oral
use
Initial U.S. Approval
:
1986
----------------------
------RECENT MAJOR CHANGES
-------------------------�
Dosage and A
dministration (
2)
7/201
6
Contraindications (
4)
7/2016
Warning
s and P
recautions (
5)
7/201
6
--------------------------INDICATIONS AND USAG
E----------------------�
LAMPRENE
is a
n antimycobacterial
indicated for
the treatment
of
lepromatous leprosy, including dapsone
-resistant lepromatous leprosy
and
lepromatous leprosy complicated by erythema nodosum leprosum
. ( 1.1
)
To
prevent
the development of drug
-resistance, LAMPRENE
should be used
only
as a part of combination therapy for initial treatment of
lepromatous
leprosy
. ( 1.2
)
------------------------DOSAGE AND ADMINISTRATION---------------------�
�
For
dapsone
-sensitive
lepromatous
leprosy,
100
mg daily
with meals
as
a part of
a combination regimen
for at
least 2 years is recommended.
(2 .1)
�
For
dapsone
-resistant
lepromatous
leprosy,
100 mg
daily with meals in
combination
with one or more
other agents
for
3 years.
(2 .1)
�
For
lepromatous leprosy complicated by
erythema nodosum leprosum
,
100 mg to 200 mg
daily
for up
to
3 months
. Taper dose to 100
mg as
quickly as possible
. (2.1)
-----------------------DOSAGE
FORMS AND STRENGTHS
-------------------�
50 mg soft gelatin
capsules.
(3)
-----------------------------CONTRAINDICATIONS
-------------------------------�
Known hypersensitivity to clofazimine or to any of the
excipients of
LAMPRENE
. ( 4)
-----------------------WARNINGS AND PRECAUT
IONS
-----------------------�
�
Abdominal obstruction and
other gastrointestinal adverse reactions
:
LAMPRENE
may
deposit
in intestinal mucosa causing
intestinal
disturbances
, including
abdominal obstruction, bleeding, splenic
infarction
and death
. Reduce dose or discontinue LAMPRENE if patient
complains of
pain in abdomen
or other gastrointestinal
symptoms
. ( 5. 1)
�
QT pr
olongation
: QT prolongation and Torsades de Pointes
may
occur
with
LAMPRENE. Coadministration with other QT prolonging drugs
or
with
bedaquiline
may cause additive QT prolongation. Monitor ECG
s
and discontinue LAMPRENE if significant ventricu
lar arrhythmia or
QTcF interval
greater than or equal to
500 ms develop
. (
5.2
)
�
Skin and
body fluid dis
coloration
and other skin reactions
: Advise
patients that s
kin
and body fluid
discoloration
frequently occur
with
use
of
LAMPRENE
. ( 5. 3)
�
Depression and s
uicide
due to skin discoloration
. Monitor patients for
psychological effects of skin discoloration
. ( 5. 4)
--------------------------------
ADVERSE REACTIONS
----------------------------�
Most common adverse
reactions
reported in 40%
to
50% of patients are
skin
and body fluid
discoloration,
abdominal and epigastric pain, diarrhea, nausea,
vomiting,
gastrointestinal intolerance.
(6)
To report SUSPECTED ADVERSE REACTIONS, contact Novartis
Pharmaceuticals Corporation
at 1
-888
-669
-6682
or FDA at 1
-800
-FDA�
1088 or
www.fda.
gov/medwatch
.
-------------------------USE IN SPECIFIC POPU
LATIONS
---------------------�
Human Immunodeficiency
Virus (HIV)
Patients
: No
dose adjustment of
LAMPRENE is needed
for HIV
-infected patients
(8.6
)
See 17 for
PATIENT COUNSELING INFORMATION
Revised:
7/ 201
6
FULL PRESCRIBING INF
ORMATION: CONTENTS*
1
INDICATIONS AND USAGE
1.1
Lepromatous Leprosy
1.2
Usage
2
DOSAGE AND ADMINISTRATION
2.1
Dosage
2.2
Important
Pre
-test Prior to Administration
3
DOSAGE FORMS AND STRENGTHS
4
CONTRAINDICATIONS
5
WARNINGS AND PRECAUTIONS
5.1
Abdominal O
bstruction and Other Gastrointestinal Adverse
Reactions
5.2
QT prolongation
5.3
Skin and Body Fluid Discoloration and Other Skin Reactions
5.4
Psychological
Effects of Skin Discoloration
6
ADVERSE REACTIONS
8
USE IN SPECIFIC POPULATIONS
8.1
Pregnancy
8.2
Lactation
8.3
Females and Males of Reproductive Potential
8.4
Pediatric Use
8.5
Geriatric Use
8.6
Patients with HIV Co
-infection
10
OVERDOSAGE
11
DESCRIPTION
12
CLINICAL PHARMACOLOGY
12.1
Mechanism of Action
12.3
Pharmacokinetics
12.4
Microbiology
13
NONCLINICAL TOXICOLOGY
13.1
Carcinogenesis, Mutagenesis, and Impairment of Fertility
16
HOW SUPPLIED/STORAGE AND HANDLING
17
PATIENT COUNSELING INFORMATION
*
Sections or subsections omitted from the full prescribing information are
not listed
.
Reference ID: 3956651
FULL PRESCRIBING INF
ORMATION
1
INDICATIONS AND USAG
E
1.1
Lepromatous Leprosy
LAMPRENE is indicated in
combination with other antileprosy
drugs for
the treatment of lepromatous leprosy, including
dapsone-
resistant lepromatous leprosy
, and lepromatous leprosy complicated by erythema nodosum leprosum.
1.2
Usage
To prevent
the development of drug-resistance, LAMPRENE should be used only as a part of combination therapy for
initial treatment of
lepromatous (
multibacillary
) leprosy
[see Do
sage and Administration (2.1)].
For further guidance on the treatment of leprosy, contact the
National Hansen�s Disease Clinical Center
, Baton Rouge,
Louisiana (LA
) at (
1-800-642-2477) or https://www.hrsa.gov/hansensdisease/clinicalcenter
.html
.
2
DOSAGE AND ADMINISTRATION
2.1
Dosage
�
Dapsone
-sensitive Lepromatous (multibacillary) L
eprosy
Administer
100 mg
LAMPRENE
daily
with meals in combination
with two other antileprosy drugs
for at least 2 years
and if possible, until negative skin smears are obtained
, followed
by monotherapy
with an appropriate antileprosy
drug.
�
Dapsone
-resistant
Lepromatous L
eprosy
Administer
100 mg
LAMPRENE
daily
with meals in combination with one or more other antileprosy drugs for 3
years, followed by monotherapy with 100 mg of
LAMPRENE daily.
�
Lepromatous Leprosy
complicated
by Erythema Nodosum Leprosum Reactions
Administer
LAMPRENE
at 100
mg
to
200 mg daily,
in conjunction with baseline antileprosy treatment
and steroids
as clinically indicated. If LAMPRENE is administered at 200 mg dose, taper to 100 mg as soon as possible after the
erythema nodosum reaction is controlled. Doses of
LAMPRENE
of more than 100 mg daily should be given for as
short a period as possible and only under close medical supervision
[see Warnings and P
recautions
(5.1)]
.
2.2
Important Pre
-test Prior to
Administration
Sexually-
active females
of reproductive potential
should
have a pregnancy test prior to LAMPRENE administration
[see
Use in Specific Populations (8.3)].
3
DOSAGE FORMS AND STRENGTHS
Each LAMPRENE capsule contains 50 mg
clofazimine in a soft gelatin capsule. The capsules are brown
and
spherical.
4
CONTRAINDICATIONS
LAMPRENE is contraindicated in patients with k
no wn
hypersensitivity to clof
azimi
ne or any of th
e excipients of
LAMPRENE.
5
WARNINGS AND PRECAUTIONS
5.1
Abdominal Obstruction and
Other
Gastrointestinal Adverse Reactions
Clofazimine
may accumulate in various organs as crystals, including the mesenteric lymph nodes and histiocytes at the
lamina propria of the intestinal mucosa, spleen and liver. Deposition in the intestinal mucosa may lead to intestinal
obstruction that may necessitat
e exploratory laparotomy. Splenic infarction, gastrointestinal bleeding, and death have been
reported. If a patient complains of pain in the abdomen, nausea, vomiting, or diarrhea, initiate appropriate medical
investigations and reduce
the
daily
dose
of LA
MPRENE
, or increase the dosing interval or discontinue the drug. Doses of
LAMPRENE of more than 100 mg daily should be given for as short a period as possible (
less than
3 months) and only
under close medical supervision.
5.2
QT prolongation
Cases of Torsades de Pointes with QT prolongation have been reported in patients receiving dosage regimens
containing
higher than 100 mg daily dose of LAMPRENE or in combination with QT prolonging medications. For QT prolongation
Reference ID: 3956651
and Torsades de Pointes cases, the patient must remain under medical surveillance. In all these patients, monitor
electrocardiograms (
ECGs
) for QT prolongation and cardiac rhythm disturbances
[see Dosage and Administration (2.
1)].
QT prolongation has
also been
reported
in patients who were receiving
LAMPRENE with
bedaquiline
at the
recommended dosage regimen for each drug. Monitor
ECGs
if LAMPRENE is coadministered to patients receiving
bedaquiline, and d
iscontinue LAMPRENE if
clinically significant
ventricular arrhythmia
is noted
or
if the
QTc
F inter
val
is 500 ms or
greater
. If syncope occurs, obtain an ECG to detect QT prolongation.
5.3
Skin and Body Fluid Discoloration and Other Skin Reactions
LAMPRENE cause
s orange-pink to brownish-
black discoloration of the skin, as well as discoloration of the conjunctivae,
tears, sweat, sputum, urine and feces
in 75
-100% of patients
. Advise patients that skin discoloration is likely to occur and
that it may
take several months or years to reverse after the conclusion of therapy.
Other skin reactions
associated with LAMPRENE therapy
inc
lude ic
hthyosis, dry skin and pruritu
s.
5.4
Psychological Effects of Skin Discoloration
Skin discoloration due to LAMPRENE therapy
has been
reported to
result in depression and suicide.
Advise patients
regarding skin discoloration and monitor for depression or suicidal ideation during
LAMPRENE therapy.
6
ADVERSE REACTIONS
The following serious adverse reactions are discussed in greater detail
in other sections of the label
ing
:
�
Abdominal Obstruction and Gastrointestinal Adverse Reactions
[s ee Warnings and Precautions (5.1)]
�
QT Prolongation
[s ee
Warnings and Precautions (5.2)]
�
Skin and Body Fluid Discoloration and Other Skin Reactions
[s ee
Warnings and Precautions (5.3)]
�
Psychological Effects of Skin Discoloration
[s ee Warnings and Precautions (5.4)]
The following adverse reactions associated with the use of LAMPRENE were identified. Because these adverse reactions
are reported from
different studies, these adverse reactions cannot be directly compared to rates in the clinical trials of
another drug and may not reflect the rates observed in practice.
Adverse Reactions Occurring In More Than 1% of Patients
Skin
: Pigmentation from pink
to brownish-
black in 75%
to 100% of the patients within a few weeks of treatment;
ichthyosis and dryness (8%
to 28%); rash and pruritus (1%
to 5%).
Gastrointestinal
:
Abdominal and epigastric pain, diarrhea, nausea, vomiting, gastrointestinal
intolerance
(40%
- to-50%).
Ocular
: Conjunctival and corneal pigmentation due to clofazi
mine crystal deposits; dryness;
burning; itching; irritation.
Other
: Discoloration of urine, feces, sputum, sweat;
elevated blood sugar; elevated
erythrocyte sedimentation
rate (
ESR
).
Adverse Reactions Occurring In Less Than 1% of Patients
Skin
:
Phototoxicity, erythroderma, acneiform eruptions, monilial cheilosis.
Gastrointestinal
: Bowel obstruction, gastrointestinal bleeding, anorexia, constipation, weight loss, hepatitis, jaundice,
eosinophilic enteritis, enlarged liver.
Ocular
: Diminished vision
, maculopathy
(bull�s eye retinopathy)
.
Nervous
: Dizziness, drowsiness, fatigue, headache, giddiness, neuralgia, taste disorder.
Psychiatric
: Depression and suicide secondary to skin discoloration.
Laboratory
: Elevated levels of albumin, serum bilirubin, and aspartate aminotransferase (
AST
); eosinophilia;
hypokalemia.
Other
: Splenic infarction, thromboembolism, anemia, cystitis, bone pain, edema, fever, lymphadenopathy, vascular pain.
8
USE IN SPECIFIC POPULATIONS
8.1
Pregnancy
Risk Summary
Reference ID: 3956651
There are no
data with
LAMPRENE use in pregnant women to inform associated risk. Retardation of fetal skull
ossification, increased incidences of abortions and stillbirths, and impaire
d neonatal survival were observed in mice
following prenatal exposure to LAMPRENE
at 25 mg/kg,
equivalent to the 0.6 times maximum recommended human
daily dose (200 mg), based on body surface area comparisons. Advise pregnant women of the potential risk to the fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown; however, in the U.S.
general population, the estimated background risk of major birth defects is 2-
4% and of miscarriage is 15
-20% of
clinicall
y recognized pregnancies.
Clinical Considerations
Fetal/neonatal adverse reactions
The skin of infants born to pregnant mothers who had received LAMPRENE during pregnancy is pigmented at birth.
Limited data is available regarding the reversibility of
discoloration. Based on previous observations, discoloration
gradually faded
over the first year.
Data
Human Data
There are no studies of
LAMPRENE use in pregnant women. Few cases of clofazimine use during pregnancy have been
reported in the literature. These reports
indicate that the skin of infants born to women who had received LAMPRENE
during pregnancy
was deeply pigmented at birth. LAMPRENE should be used during pregnancy
only if the potenti
al
benefit justifies the risk to the fetus.
Animal D
ata
Embryofetal toxicity studies were conducted in rats, rabbits and
mice.
In mice
LAMPRENE-induced embryotoxicity and
fetotoxicity
was evident
. Retardation of fetal skull ossification, increased incidences of abortions and stillbirths, and
impaired neonatal survival were observed
following prenatal exposure to
LAMPRENE at 25 mg/kg, equivalent to the 0.6
times maximum recommended human daily dose
[MRHD]
(200 mg), based on body surface area comparis
ons.
The skin
and fatty tissue of offspring became discolored approximately 3 days after birth, which was attributed to the presence of
clofazimine in the maternal milk
. No developmental effects were observed in rat or rabbits orally administered
clofazimi
ne during organogenesis at doses up to 50 mg/kg and 15 mg/kg,(equivalent to about 2.4 and 1.5 times the
MRHD of 200 mg based on body surface area) respectively. These animal studies were conducted according to the
standards at the time of initial drug appr
oval
(1986) and not under current regulatory standards.
8.2
Lactation
Risk summary
LAMPRENE
is excreted in
human
milk
. Skin discoloration has been observed in
breast fed
neonates
of mothers receiving
clofazimine
.
The developmental and health benefits of breastfeeding should be considered along with the mother�s clinical need for
LAMPRENE and any potential adverse effects on the breastfed infant from
LAMPRENE or from the underlying maternal
condition.
8.3
Females a
nd M
ales of
Reproductive
Potential
Pregnancy testing
Sexually-
active females of reproductive potential
should have a pregnancy test prior to starting treatment with
LAMPRENE.
Contraception
Animal studies have show
n LAMPRENE to be harmful to the developing fetus.
Advise sexually active females of
reproductive potential to use effective contraception (methods that result in less than 1 % pregnancy rates) when using
LAMPRENE during treatment and for at least 4 months
after stop
ping treatment with
LAMPRENE.
Advise males taking
LAMPRENE to use a condom during intercourse while on treatment and for at
least 4 months
after
stopping treatment with
LAMPRENE.
Infertility
Reference ID: 3956651
