Erivedge
Generic
Name: vismodegib
Dosage Form: capsule
WARNING: EMBRYO-FETAL
TOXICITY
Erivedge can cause
embryo-fetal death or severe birth defects when administered to a pregnant
woman. Erivedge is embryotoxic, fetotoxic, and teratogenic in animals.
Teratogenic effects included severe midline defects, missing digits, and other
irreversible malformations.
Verify the pregnancy status of females of
reproductive potential within 7 days prior to initiating Erivedge therapy.
Advise females of reproductive potential to use effective contraception during
and after Erivedge therapy. Advise males of the potential risk of Erivedge
exposure through semen and to use condoms with a pregnant partner or a female
partner of reproductive potential. Advise pregnant women of the potential risks
to a fetus. [See Warnings and Precautions (5.1, 5.3), Use in Specific Populations (8.1, 8.3)].
Indications and Usage for Erivedge
Erivedge capsule is indicated
for the treatment of adults with metastatic basal cell carcinoma, or with
locally advanced basal cell carcinoma that has recurred following surgery or
who are not candidates for surgery, and who are not candidates for radiation.
Erivedge Dosage and Administration
The recommended dose of
Erivedge is 150 mg taken orally once daily until disease progression or until
unacceptable toxicity [see Clinical Studies (14)].
Erivedge may be taken with or
without food. Swallow capsules whole. Do not open or
crush capsules.
If a dose of Erivedge is
missed, do not make up that dose; resume dosing with the next scheduled dose.
Dosage Forms and Strengths
Erivedge (vismodegib)
capsules, 150 mg. The capsule has a pink opaque body and a grey opaque cap,
with "150 mg" printed on the capsule body and "VISMO"
printed on the capsule cap in black ink.
Contraindications
None.
Warnings and PrecautionsEmbryo-Fetal
Toxicity
Based on its mechanism of action, Erivedge
can cause embryo-fetal death or severe birth defects when administered to a
pregnant woman. In animal reproduction studies, vismodegib was embryotoxic,
fetotoxic, and teratogenic at maternal exposures lower than the human exposures
at the recommended dose of 150 mg/day.
Verify the pregnancy status of
females of reproductive potential within 7 days prior to initiating Erivedge
therapy. Advise females of reproductive potential to use effective
contraception during therapy with Erivedge and for 24 months after the final
dose. Advise male patients to use condoms, even after a vasectomy, to avoid
potential drug exposure in pregnant partners and female partners of
reproductive potential during therapy and for 3 months after the final dose of
Erivedge. Advise pregnant women of the potential risk to a fetus [see Use in
Specific Populations (8.1, 8.3) and Clinical
Pharmacology (12.1)].
Blood
Donation
Advise patients not to donate blood or
blood products while receiving Erivedge and for 24 months after the final dose
of Erivedge.
Semen
Donation
Vismodegib is present in
semen. It is not known if the amount of vismodegib in semen can cause
embryo-fetal harm. Advise male patients not to donate semen during and for 3
months after the final dose of Erivedge [see Use in Specific
Populations (8.1, 8.3)].
Premature
Fusion of the Epiphyses
Premature fusion of the epiphyses has been
reported in pediatric patients exposed to Erivedge. In some cases, fusion
progressed after drug discontinuation [see Adverse Reactions (6.2) and Use in Specific
Populations (8.4)].
Adverse ReactionsClinical
Trials Experience
Because clinical trials are
conducted under widely varying conditions, adverse reaction rates observed in
the clinical trials of a drug cannot be directly compared to rates in the
clinical trials of another drug and may not reflect the rates observed in
clinical practice.
Erivedge capsule was
administered as monotherapy at doses ≥ 150 mg orally daily in four open-label,
uncontrolled, dose-ranging or fixed single dose clinical trials enrolling a
total of 138 patients with advanced basal cell carcinoma (BCC). The median age
of these patients was 61 years (range 21 to 101), 100% were White (including
Hispanics), and 64% were male. The median duration of treatment was
approximately 10 months (305 days; range 0.7 to 36 months); 111 patients
received Erivedge for 6 months or longer.
The most common adverse
reactions (≥ 10%) were muscle spasms, alopecia, dysgeusia, weight loss,
fatigue, nausea, diarrhea, decreased appetite, constipation, arthralgias,
vomiting, and ageusia (Table 1).
Table 1: Adverse Reactions Occurring in ≥ 10% of Advanced BCC
Patients
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|
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MedDRA
Preferred Term*
|
All aBCC† Patients (N = 138)
|
|
|
All Grades‡ (%)
|
Grade 3 (%)
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Grade 4 (%)
|
|
|
*
MedDRA = Medical
Dictionary for Regulatory Activities.
†
aBCC = Advanced
Basal Cell Carcinoma.
‡
Grading according to NCI-CTCAE v3.0.
|
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Gastrointestinal
disorders
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|
|
|
|
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Nausea
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42 (30.4%)
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1 (0.7%)
|
-
|
|
|
Diarrhea
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40 (29.0%)
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1 (0.7%)
|
-
|
|
|
Constipation
|
29 (21.0%)
|
-
|
-
|
|
|
Vomiting
|
19 (13.8%)
|
-
|
-
|
|
|
General
disorders and administration site conditions
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|
|
|
|
|
Fatigue
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55 (39.9%)
|
7 (5.1%)
|
1 (0.7%)
|
|
|
Investigations
|
|
|
|
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Weight
loss
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62 (44.9%)
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10 (7.2%)
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-
|
|
|
Metabolism and
nutrition disorders
|
|
|
|
|
|
Decreased
appetite
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35 (25.4%)
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3 (2.2%)
|
-
|
|
|
Musculoskeletal
and connective tissue disorders
|
|
|
|
|
|
Muscle
spasms
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99 (71.7%)
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5 (3.6%)
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-
|
|
|
Arthralgias
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22 (15.9%)
|
1 (0.7%)
|
|
|
|
Nervous system
disorders
|
|
|
|
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Dysgeusia
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76 (55.1%)
|
-
|
-
|
|
|
Ageusia
|
15 (10.9%)
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-
|
-
|
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|
Skin and
subcutaneous tissue disorders
|
|
|
|
|
|
Alopecia
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88 (63.8%)
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-
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-
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|
Amenorrhea:
In clinical trials, a total of
3 of 10 pre-menopausal women developed amenorrhea while receiving Erivedge
[see Non-Clinical Toxicology
(13.1)].
Laboratory Abnormalities:
Treatment-emergent Grade 3
laboratory abnormalities observed in clinical trials were hyponatremia in 6
patients (4%), hypokalemia in 2 patients (1%), and azotemia in 3 patients (2%).
Additionally, in a
post-approval clinical trial conducted in 1232 patients with locally advanced
or metastatic BCC treated with Erivedge, a subset of 29 patients had baseline
values for CPK reported. Within the subset of patients, 38% had a shift from
baseline, and one of the patients had a Grade 3 value. The prevalence of Grade
3/4 CPK elevation across the entire study population with any CPK measurement
was 2.4% (11 out of 453 patients).
Postmarketing
Experience
The following adverse
reactions have been identified during post-approval use of Erivedge. Because
these reactions 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.
Musculoskeletal
and connective tissue disorders: Premature
fusion of the epiphyses [see Warnings and
Precautions (5.4) and Use in
Specific Populations (8.4)].
Investigations: blood creatine phosphokinase increased
Drug Interactions
Clinically relevant
pharmacokinetic interactions are not expected between vismodegib and a
substrate, inducer or inhibitor of cytochrome 450 enzymes or an inhibitor of
P-glycoprotein (P-gp) or between vismodegib and gastric pH elevating agents
[see Clinical Pharmacology
(12.3)].
USE IN SPECIFIC POPULATIONSPregnancy
Risk Summary
Based on its mechanism of
action and animal reproduction studies, Erivedge can cause fetal harm when
administered to a pregnant woman [see Clinical Pharmacology
(12.1)]. In animal reproduction
studies, oral administration of vismodegib during organogenesis at doses below
the recommended human dose resulted in embryotoxicity, fetotoxicity, and
teratogenicity in rats [see Data]. There are no human data on the use of Erivedge in pregnant
women. Advise pregnant women of the potential risk to a fetus. Report
pregnancies to Genentech at 1-888-835-2555.
The background risk of major
birth defects and miscarriage for the indicated population is unknown. In the
U.S. general population, the estimated background risk of major birth defects
and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%,
respectively.
Data
Animal Data
In an embryo-fetal
developmental toxicity study, pregnant rats were administered vismodegib orally
at doses of 10, 60, or 300 mg/kg/day during the period of organogenesis. Pre-
and post-implantation loss were increased at doses of ≥ 60 mg/kg/day
(approximately ≥ 2 times the systemic exposure (AUC) in patients at the
recommended human dose), which included early resorption of 100% of the
fetuses. A dose of 10 mg/kg/day (approximately 0.2 times the AUC in patients at
the recommended dose) resulted in malformations (including missing and/or fused
digits, open perineum and craniofacial anomalies) and retardations or
variations (including dilated renal pelvis, dilated ureter, and incompletely or
unossified sternal elements, centra of vertebrae, or proximal phalanges and
claws).
Lactation
No data are available
regarding the presence of vismodegib in human milk, the effects of the drug on
the breastfed infant, or the effects of the drug on milk production. Because of
the potential for serious adverse reactions in breastfed infants from Erivedge,
advise a nursing woman that breastfeeding is not recommended during therapy
with Erivedge and for 24 months after the final dose.
Females and
Males of Reproductive Potential
Pregnancy Testing
Verify the pregnancy status of
females of reproductive potential within 7 days prior to initiating Erivedge
therapy.
Contraception
Females
Based on its mechanism of
action and animal data, Erivedge can cause fetal harm when administered to a
pregnant woman [see Use in Specific
Populations (8.1)]. Advise females of
reproductive potential to use effective contraception during therapy and for 24
months after the final dose of Erivedge.
Males
Vismodegib is present in semen
[see Clinical Pharmacology
(12.3)]. It is not known if the
amount of vismodegib in semen can cause embryo-fetal harm. Advise male patients
to use condoms, even after a vasectomy, to avoid drug exposure to pregnant
partners and female partners of reproductive potential during therapy with and
for 3 months after the final dose of Erivedge. Advise males of the potential
risk to an embryo or fetus if a female partner of reproductive potential is
exposed to Erivedge. Advise males not to donate semen during therapy with and
for 3 months after the final dose of Erivedge.
Infertility
Females
Amenorrhea can occur in
females of reproductive potential. Reversibility of amenorrhea is unknown
[see Adverse Reactions (6)].
Pediatric Use
The safety and effectiveness
of Erivedge capsule have not been established in pediatric patients.
Premature fusion of the
epiphyses has been reported in pediatric patients exposed to Erivedge. In some
cases, fusion progressed after drug discontinuation. [see Warnings
and Precautions (5.4) and Adverse Reactions (6.2)].
In repeat-dose toxicology
studies in rats, administration of oral vismodegib resulted in toxicities in
bone and teeth. Effects on bone consisted of closure of the epiphyseal growth
plate when oral vismodegib was administered for 26 weeks at ≥ 50 mg/kg/day
(approximately ≥ 0.4 times the systemic exposure (AUC) in patients at the
recommended human dose). Abnormalities in growing incisor teeth (including
degeneration/necrosis of odontoblasts, formation of fluid-filled cysts in the
dental pulp, ossification of the root canal, and hemorrhage resulting in
breakage or loss of teeth) were observed after administration of oral
vismodegib at ≥ 15 mg/kg/day (approximately ≥ 0.2 times the AUC in patients at the
recommended human dose).
Geriatric Use
Clinical studies of Erivedge
capsule did not include sufficient numbers of patients aged 65 and over to
determine whether they respond differently from younger patients.
Hepatic
Impairment
No dose adjustment is required
in patients with hepatic impairment [see Clinical Pharmacology
(12.3)].
Renal
Impairment
No dose adjustment is required
in patients with renal impairment [see Clinical Pharmacology
(12.3)].
Overdosage
There is no information on
overdosage in humans. In clinical trials, Erivedge capsule was administered at
540 mg orally once daily; exposure did not increase between 150 mg and 540 mg
daily.
Erivedge Description
Vismodegib is an inhibitor of
the hedgehog (Hh) signaling pathway, which is described chemically as 2-Chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide.
The molecular formula is C19H14Cl2N2O3S. The molecular weight is 421.30 g/mol and the structural
formula is:
Vismodegib is a crystalline
free base with a pKa (pyridinium cation) of 3.8, appearing as a white to tan
powder. The solubility of vismodegib is pH dependent with 0.1 μg/mL at pH 7 and
0.99 mg/mL at pH 1. The partition coefficient (log P) is 2.7.
Each Erivedge (vismodegib)
capsule for oral administration contains 150 mg vismodegib and the following
inactive ingredients: microcrystalline cellulose, lactose monohydrate, sodium
lauryl sulfate, povidone, sodium starch glycolate, talc, and magnesium stearate
(non-bovine). The capsule shell contains gelatin, titanium dioxide, red iron
oxide, and black iron oxide. The black printing ink contains shellac and black
iron oxide.
Erivedge - Clinical PharmacologyMechanism of
Action
Vismodegib is an inhibitor of
the Hedgehog pathway. Vismodegib binds to and inhibits Smoothened, a
transmembrane protein involved in Hedgehog signal transduction.
Pharmacodynamics
Cardiac Electrophysiology
The QTc interval was not
affected by therapeutic doses of Erivedge in a thorough QTc trial.
Pharmacokinetics
Absorption
The single dose absolute
bioavailability of vismodegib is 31.8%. Absorption is saturable as evidenced by
the lack of dose proportional increase in exposure after a single dose of 270
mg or 540 mg vismodegib. Erivedge capsule may be taken without regard to meals
because the systemic exposure of vismodegib at steady state is not affected by
food.
Distribution
The volume of distribution of
vismodegib ranges from 16.4 to 26.6 L. Vismodegib plasma protein binding in
patients is greater than 99%. Vismodegib binds to both human serum albumin and
alpha-1-acid glycoprotein (AAG) and binding to AAG is saturable.
In a pharmacokinetic study,
male patients (n=3) had an average concentration of vismodegib in semen on day
8 that was 6.5% of the average steady state concentration (Css) observed in plasma.
Metabolism
Greater than 98% of the total
circulating drug-related components are the parent drug. Metabolic pathways of
vismodegib in humans include oxidation, glucuronidation, and pyridine ring
cleavage. The two most abundant oxidative metabolites recovered in feces are
produced in vitro by recombinant
CYP2C9 and CYP3A4/5.
Elimination
Vismodegib and its metabolites
are eliminated primarily by the hepatic route with 82% of the administered dose
recovered in the feces and 4.4% recovered in urine. The estimated elimination
half-life (t1/2) of vismodegib is 4 days after continuous once-daily dosing and
12 days after a single dose.
Specific Populations
Hepatic Impairment: In
a dedicated clinical study, the mean systemic exposure (AUC 0-24hr) of vismodegib was increased
by 24% in patients with mild (n=8), 31% in patients with moderate (n=6) and
decreased 14% in patients with severe (n=3) hepatic impairment when compared to
patients with normal hepatic function (n=9) after 8 days of daily Erivedge
administration. The NCI Organ Dysfunction Working Group criteria for hepatic
impairment were used in the study. Mild hepatic impairment was defined as
normal total bilirubin and aspartate transaminase (AST) > upper limit of
normal (ULN) or total bilirubin > 1.0 to 1.5 times ULN, moderate hepatic
impairment as total bilirubin > 1.5 to 3.0 times ULN, and severe hepatic impairment
as total bilirubin > 3.0 to 10.0 times ULN.
Renal Impairment: Renal
excretion of vismodegib after oral administration of Erivedge is low (<5%).
The population pharmacokinetic analysis suggested no clinically relevant effect
of renal impairment on the systemic exposure of vismodegib, based on
pharmacokinetic data from patients with mild (CLcr 50 to 79 mL/min, n=58), and
moderate (CLcr 30 to 49 mL/min, n=16) renal impairment.
Weight, Age, and Sex: The
results of a population pharmacokinetic analysis suggested no clinically
relevant effect of weight (range: 41-140 kg), age (range: 26-89 years), and sex
on the systemic exposure of vismodegib.
Drug Interaction Studies
Effect of Drugs on Vismodegib: Coadministration of Erivedge with fluconazole (a moderate
CYP2C9 inhibitor and moderate CYP3A4 inhibitor) increased mean AUC0-24hr and steady-state
concentrations of vismodegib by 1.3-fold in healthy subjects. A strong
inhibitor of CYP3A4 and P-gp (itraconazole) or a proton pump inhibitor
(rabeprazole) had no effect on the steady-state systemic exposure of vismodegib
when coadministered with Erivedge in healthy subjects.
Effects of Vismodegib on Other Drugs: Results of a drug interaction study conducted in cancer
patients demonstrated that the systemic exposure of rosiglitazone (a CYP2C8
substrate) or oral contraceptives (ethinyl estradiol and norethindrone) is not
altered when either drug is coadministered with vismodegib.
In vitro studies suggest that
vismodegib is an inhibitor of CYP2C8, CYP2C9, CYP2C19 and the transporter BCRP
and that vismodegib is not an inducer of CYP1A2, CYP2B6, or CYP3A.
Nonclinical ToxicologyCarcinogenesis,
Mutagenesis, Impairment of Fertility
Carcinogenicity studies were
performed in mice and rats. No carcinogenic potential was identified in either
species.Vismodegib was not mutagenic in the in
vitro bacterial reverse mutation (Ames) assay and was not
clastogenic in the in vitro human
chromosomal aberration assay in human peripheral blood lymphocytes or in
the in vivo rat bone marrow
micronucleus assay.
In a dedicated 26-week rat
fertility study, no effects on male reproductive organs or fertility endpoints
were observed at vismodegib doses of 100 mg/kg/day (approximately 1.3-times the
steady-state AUC0-24h at the recommended human dose) either at the end of dosing
or following a 16 week recovery phase. While there were increased numbers of
degenerating germ cells and hypospermia in sexually immature dogs observed at ≥
50 mg/kg/day in the 4-week general toxicity study, there were no effects on
male reproductive organs in sexually mature rats and dogs, in the vismodegib
general toxicity studies of up to 26-weeks.
In a female fertility study,
treatment of rats with vismodegib at 100 mg/kg/day (approximately 1.2-fold of
the steady-state AUC0-24h at the recommended human dose) for 26-weeks prior to
mating resulted in decreased implantations, increased percent preimplantation
loss, and decreased numbers of dams with viable embryos. No vismodegib-related
changes in fertility were observed following a 16-week recovery period. In a
26-week general toxicity study in rats, decreased numbers of corpora lutea were
observed at 100 mg/kg/day; the effect was not reversed by the end of an 8-week
recovery period.
Animal
Toxicology
Neurologic effects
characterized as limb or body tremors or twitching were observed in rats
administered oral vismodegib for 4 weeks or longer at ≥ 50 mg/kg/day
(approximately ≥ 0.4 times the AUC in patients at the recommended human dose).
These observations resolved upon discontinuation of dosing and were not
associated with microscopic findings.
Clinical Studies
A single, international,
single-arm, multi-center, open-label, 2-cohort trial was conducted in 104
patients with either metastatic basal cell carcinoma (mBCC) (n = 33) or locally
advanced BCC (laBCC) (n = 71). Patients with laBCC were required to have
lesions that had recurred after radiotherapy, unless radiotherapy was
contraindicated or inappropriate (e.g. Gorlin syndrome; limitations because of
location of tumor or cumulative prior radiotherapy dose), and where the lesions
were either unresectable or surgical resection would result in substantial
deformity. Patients were to receive 150 mg vismodegib per day orally until
disease progression or unacceptable toxicity.
The major efficacy outcome
measure of the trial was objective response rate (ORR) as assessed by an
independent review facility (IRF). In the mBCC cohort, tumor response was
assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST)
version 1.0. In the laBCC cohort, tumor response evaluation included
measurement of externally assessable tumor (including scar) and assessment for
ulceration in photographs, radiographic assessment of target lesions (if
appropriate), and tumor biopsy. An objective response in laBCC required at
least one of the following criteria and absence
of any criterion for disease progression: (1) ≥ 30% reduction in lesion size
[sum of the longest diameter (SLD)] from baseline in target lesions by
radiographic assessment; (2) ≥ 30% reduction in SLD from baseline in externally
visible dimension of target lesions; (3) complete resolution of ulceration in
all target lesions. Complete response was defined as objective response (as
defined above) with no residual BCC on sampling tumor biopsy. Disease
progression was defined as any of the following: (1) ≥ 20% increase in the SLD
from nadir in target lesions (either by radiography or by externally visible
dimension); (2) new ulceration of target lesions persisting without evidence of
healing for at least 2 weeks; (3) new lesions by radiographic assessment or
physical examination; (4) progression of non-target lesions by RECIST.
Of the 104 patients enrolled,
96 patients were evaluable for ORR. Twenty-one percent of patients carried a
diagnosis of Gorlin syndrome. The median age of the efficacy evaluable
population was 62 years (46% were at least 65 years old), 61% male and 100%
White. For the mBCC cohort (n = 33), 97% of patients had prior therapy
including surgery (97%), radiotherapy (58%), and systemic therapies (30%). For
the laBCC cohort (n = 63), 94% of patients had prior therapies including
surgery (89%), radiotherapy (27%), and systemic/topical therapies (11%). The
median duration of treatment was 10.2 months (range 0.7 to 18.7 months).
The key outcome measures are
presented in Table 2, below.
Table 2: Objective Response Rate: Efficacy-Evaluable Patients*
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mBCC
(n = 33)
|
laBCC
(n = 63)
|
|
*
Patients who
received at least one dose of Erivedge with independent pathologist-confirmed
diagnosis of BCC
†
IRF =
Independent Review Facility
‡
For laBCC,
complete response was defined as objective response with no residual BCC on
sampling tumor biopsy.
§
CI = Confidence
Interval
¶
NE = Not estimable
|
|
IRF†-Confirmed ORR, n (%)
|
10 (30.3)
|
27 (42.9)
|
|
(95% CI)
|
(15.6, 48.2)
|
(30.5, 56.0)
|
|
Complete response‡
|
0 (0.0)
|
13 (20.6)
|
|
Partial response
|
10 (30.3)
|
14 (22.2)
|
|
Median Response Duration (months)
|
7.6
|
7.6
|
|
(95% CI§)
|
(5.6, NE¶)
|
(5.7, 9.7)
|
How Supplied/Storage and Handling
Each Erivedge (vismodegib)
capsule has a pink opaque body and a grey opaque cap with "150 mg"
printed on the capsule body and "VISMO" printed on the capsule cap in
black ink. Erivedge capsules are available in bottles of 28 capsules (NDC
50242-140-01).
Store at room temperature 20°C
to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to
86°F) [see USP Controlled Room Temperature].
Keep the bottle tightly closed
in order to protect from moisture.
Patient Counseling Information
See FDA-approved
patient labeling (Medication Guide).
Administration Instructions
Advise patients to swallow Erivedge capsules whole
and not to crush or open the capsules.
Embryo-Fetal Toxicity
Advise pregnant women of the potential risk to a
fetus [see Warnings
and Precautions (5.1) and Use
in Specific Populations (8.1)].Advise females of reproductive potential to use
effective contraception during therapy with and for 24 months after the
final dose of Erivedge [see Warnings
and Precautions (5.1) and Use
in Specific Populations (8.1, 8.3)].Advise males, even those with prior vasectomy, to
use condoms to avoid potential drug exposure in both pregnant partners and
female partners of reproductive potential during therapy with and for 3
months after the final dose of Erivedge [see Warnings
and Precautions (5.1) and Use
in Specific Populations (8.1, 8.3)].Advise female patients and female partners of male
patients to contact their healthcare provider with a known or suspected
pregnancy. Report pregnancies to Genentech at 1-888-835-2555 [see Warnings
and Precautions (5.1) and Use
in Specific Populations (8.1, 8.3)].
Semen Donation
Advise males not to donate semen during therapy
with and for 3 months after the final dose of Erivedge.
Lactation
Advise women that breastfeeding is not recommended
during therapy with Erivedge and for 24 months after the final dose
[see Use
in Specific Populations (8.2)].
Blood Donation
Advise patients not to donate blood or blood
products while taking Erivedge and for 24 months after the final dose of
Erivedge.
Premature Fusion of the Epiphyses
Advise patients and caregivers that premature
fusion of the epiphyses has been reported in pediatric patients exposed to
Erivedge. In some cases, fusion progressed after drug discontinuation.
Erivedge® [vismodegib] capsule
Manufactured by:
Patheon, Inc.
Mississauga, Canada
Erivedge is a registered
trademark of Genentech, Inc.
©2017
Genentech, Inc. All rights reserved.
Distributed by:
Genentech USA, Inc.
A Member of the Roche Group
1 DNA Way
South San Francisco, CA 94080-4990
|
This
Medication Guide has been approved by the U.S. Food and Drug Administration.
Revised:
11/2016
|
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MEDICATION GUIDE
Erivedge® (EH-rih-vej)
(vismodegib)
capsule
|
|
What is the most important information I
should know about Erivedge?
Erivedge can cause your baby to die before it is born (be
stillborn) or cause your baby to have severe birth defects.
For females who can become pregnant:
|
|
· You
should talk with your healthcare provider about the risks of Erivedge to your
unborn child.
· Your
healthcare provider will do a pregnancy test before you start taking
Erivedge.
· In
order to avoid pregnancy, you should use birth control during treatment and
for 24 months after your final dose of Erivedge. Talk with your healthcare
provider about what birth control method is right for you during this time.
· Talk
to your healthcare provider right away if you have unprotected sex or if you
think that your birth control has failed.
· Tell
your healthcare provider right away if you become pregnant or think that you
may be pregnant.
|
|
For males:
Erivedge is present in semen. Do not
donate semen while you are taking Erivedge and for 3 months after your
final dose.You should always use a condom, even
if you have had a vasectomy, during sex with female partners who are
pregnant or who are able to become pregnant, during treatment with
Erivedge and for 3 months after your final dose to protect your female
partner from being exposed to Erivedge.Tell your healthcare provider right away if
your partner becomes pregnant or thinks she is pregnant while you are
taking Erivedge.
|
|
Exposure to Erivedge during pregnancy:
If you think that you or your female partner may have been exposed to
Erivedge during pregnancy, talk to your healthcare provider right away. If
you become pregnant during treatment with Erivedge, you or your healthcare
provider should report your pregnancy to Genentech at 1-888-835-2555.
|
|
What is Erivedge?
Erivedge is a prescription medicine used to treat adults with a type of skin
cancer, called basal cell carcinoma, that has spread to other parts of the
body, or that has come back after surgery or that your healthcare provider
decides cannot be treated with surgery or radiation.
It is not known if Erivedge is safe and effective in children.
|
|
What should I tell my healthcare provider before taking Erivedge?
Before taking Erivedge, tell your healthcare provider if
you:
|
|
are pregnant or
plan to become pregnant. See "What is the most important
information I should know about Erivedge?"are breastfeeding
or plan to breastfeed. It is not known if Erivedge passes into your breast milk.
You should not breastfeed during treatment and for 24 months after your
final dose of Erivedge. Talk to your healthcare provider about the best
way to feed your baby during this time.
Tell your healthcare provider about all the medicines you take, including prescription and
over-the-counter medicines, vitamins, and herbal supplements.
|
|
How should I take Erivedge?
Take Erivedge exactly as your
healthcare provider tells you.You can take Erivedge with or
without food.Swallow Erivedge capsules
whole. Do not open or crush the capsules.Take Erivedge one time each day.If you miss a dose, skip the missed dose. Just
take your next scheduled dose.
|
|
What should I avoid while taking Erivedge?
Do not donate blood or blood
products while you are taking Erivedge and for 24 months after your
final dose.Do not donate semen while you are taking
Erivedge and for 3 months after your final dose.
|
|
What are the possible side effects of Erivedge?
Erivedge can cause serious side effects, including:
See "What is the most important
information I should know about Erivedge?"Bone growth problems. Bone growth problems have
happened in children who have been exposed to Erivedge. These problems
may continue even after stopping treatment with Erivedge.
|
|
The most common
side effects of Erivedge are:
|
|
· muscle
spasms
· hair
loss
· change
in how things taste or loss of taste
· weight
loss
· tiredness
· nausea
|
· diarrhea
· decreased
appetite
· constipation
· joint
pain
· vomiting
|
|
Erivedge can
cause absence of menstrual periods (amenorrhea) in females who are able to
become pregnant. It is not known if amenorrhea is permanent. Talk to your
healthcare provider if you have concerns about fertility.
These are not all the possible side effects of Erivedge.
Call your doctor for medical advice about side effects. You may report side
effects to FDA at 1-800-FDA-1088.
You may also report side effects to Genentech, Inc. at 1-888-835-2555.
|
|
How should I store Erivedge?
Store Erivedge at room temperature
between 68°F to 77°F (20°C to 25°C).Keep the bottle tightly closed to
protect Erivedge from moisture.
Keep Erivedge and all medicines out of the reach of children.
|
|
General information about the safe and effective use of Erivedge
Medicines are sometimes prescribed for purposes other than those listed in a
Medication Guide. Do not use Erivedge for a condition for which it was not
prescribed. Do not give Erivedge to other people, even if they have the same
symptoms that you have. It may harm them. You can ask your pharmacist or
healthcare provider for information about Erivedge that is written for health
professionals.
|
|
What are the ingredients in Erivedge?
Active ingredient: vismodegib
Inactive ingredients: microcrystalline
cellulose, lactose monohydrate, sodium lauryl sulfate, povidone, sodium
starch glycolate, talc, magnesium stearate (non-bovine). The capsule shell
contains gelatin, titanium dioxide, red iron oxide, and black iron oxide. The
black printing ink contains shellac and black iron oxide.
Manufactured by: Patheon, Inc. Mississauga, Canada
Distributed by: Genentech USA, Inc. A Member of the Roche Group 1 DNA Way
South San Francisco, CA 94080-4990
For more information, call 1-855-737-4833 or go to www.Erivedge.com
Erivedge is a registered trademark of Genentech, Inc.
©2016 Genentech, Inc.
|
Representative sample of
labeling (see the HOW SUPPLIED section for complete listing):
PRINCIPAL DISPLAY PANEL - 150 mg Capsule Bottle Carton
NDC 50242-140-01
Erivedge®
(vismodegib)
capsules
150 mg
Each capsule contains 150 mg
of vismodegib
Attention
Pharmacist:
Dispense the accompanying
Medication Guide to each
patient.
28 capsules
Rx
only
Genentech
10181780
|
Erivedge vismodegib capsule
|
|
Product
Information
|
|
Product Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:50242-140
|
|
Route of
Administration
|
ORAL
|
DEA Schedule
|
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
vismodegib (vismodegib)
|
vismodegib
|
150 mg
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
MICROCRYSTALLINE CELLULOSE
|
|
|
lactose monohydrate
|
|
|
sodium lauryl sulfate
|
|
|
POVIDONE K30
|
|
|
sodium starch glycolate type a potato
|
|
|
talc
|
|
|
magnesium stearate
|
|
|
GELATIN, UNSPECIFIED
|
|
|
titanium dioxide
|
|
|
ferric oxide red
|
|
|
ferrosoferric oxide
|
|
|
|
Product
Characteristics
|
|
Color
|
GRAY (gray
opaque) , PINK (pink opaque)
|
Score
|
no score
|
|
Shape
|
CAPSULE (hard
capsule)
|
Size
|
19mm
|
|
Flavor
|
|
Imprint Code
|
VISMO;150;mg
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:50242-140-01
|
1 BOTTLE,
PLASTIC in 1 CARTON
|
|
|
1
|
|
28 CAPSULE in 1
BOTTLE, PLASTIC
|
|
|
2
|
NDC:50242-140-86
|
1 BOTTLE,
PLASTIC in 1 CARTON
|
|
|
2
|
|
28 CAPSULE in 1
BOTTLE, PLASTIC
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA203388
|
01/30/2012
|
|
|
|
Labeler - Genentech, Inc. (080129000)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
F. Hoffmann-La
Roche Ltd
|
|
482242971
|
ANALYSIS(50242-140)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
F. Hoffmann-La
Roche Ltd
|
|
485244961
|
ANALYSIS(50242-140),
PACK(50242-140), LABEL(50242-140)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Roche Pharma AG
|
|
315009878
|
ANALYSIS(50242-140)
|
Revised:
11/2017
Genentech, Inc.
