Odomzo
Generic
Name: sonidegib
Dosage Form: capsule
Medically reviewed by
Drugs.com. Last updated on May 1, 2019.
WARNING: EMBRYO-FETAL TOXICITY
·
Odomzo can cause embryo-fetal death or severe birth
defects when administered to a pregnant woman. Odomzo is embryotoxic,
fetotoxic, and teratogenic in animals [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)].
·
Verify the pregnancy status of females of reproductive
potential prior to initiating therapy. Advise females of reproductive potential
to use effective contraception during treatment with Odomzo and for at least 20
months after the last dose [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3)].
·
Advise males of the potential risk of exposure through
semen and to use condoms with a pregnant partner or a female partner of
reproductive potential during treatment with Odomzo and for at least 8 months
after the last dose [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3)].
Indications
and Usage for Odomzo
Odomzo (sonidegib) is
indicated for the treatment of adult patients with locally advanced basal cell
carcinoma (BCC) that has recurred following surgery or radiation therapy, or
those who are not candidates for surgery or radiation therapy.
Odomzo
Dosage and AdministrationImportant Safety Information
Verify the pregnancy status
of females of reproductive potential prior to initiating Odomzo [see Use in Specific Populations (8.1, 8.3)].
Recommended Dosage
The recommended dosage of
Odomzo is 200 mg taken orally once daily on an empty stomach, at least 1 hour
before or 2 hours after a meal, administered until disease progression or
unacceptable toxicity [see Clinical Pharmacology (12.3)].
Obtain serum creatine kinase
(CK) levels and renal function tests prior to initiating Odomzo in all
patients [see Dosage and Administration (2.2) and Warnings and Precautions (5.2)].
If a dose of Odomzo is
missed, resume dosing with the next scheduled dose.
Dosage Modifications for Adverse Reactions
Interrupt Odomzo for
Severe or intolerable
musculoskeletal adverse reactions.First occurrence of serum CK
elevation between 2.5 and 10 times upper limit of normal (ULN).Recurrent serum CK elevation
between 2.5 and 5 times ULN.
Resume Odomzo at 200 mg
daily upon resolution of clinical signs and symptoms.
Permanently discontinue
Odomzo for
Serum CK elevation greater
than 2.5 times ULN with worsening renal function.Serum CK elevation greater
than 10 times ULN.Recurrent serum CK elevation
greater than 5 times ULN.Recurrent severe or
intolerable musculoskeletal adverse reactions.Dosage
Forms and Strengths
Capsules: 200 mg, opaque
pink colored with ‘SONIDEGIB 200MG’ printed on the body and ‘NVR’ printed on
the cap in black ink (equivalent to 281 mg of diphosphate salt of sonidegib).
Contraindications
None.
Warnings
and PrecautionsEmbryo-Fetal Toxicity
Odomzo can cause
embryo-fetal death or severe birth defects when administered to a pregnant
woman. In animal reproduction studies, sonidegib was embryotoxic, fetotoxic,
and teratogenic at maternal exposures below the recommended human dose of 200
mg [see Use in Specific Populations (8.1)].
Females
of Reproductive Potential
Verify pregnancy status of
females of reproductive potential prior to initiating Odomzo treatment. Advise
pregnant women of the potential risk to a fetus. Advise females to use
effective contraception during treatment with Odomzo and for at least 20 months
after the last dose [see Use in Specific Populations (8.3)].
Males
Advise male patients with
female partners to use condoms, even after a vasectomy, during treatment with
Odomzo and for at least 8 months after the last dose to avoid potential drug
exposure in pregnant females or females of reproductive potential [see Use in Specific Populations (8.3)].
Blood
Donation
Advise patients not to
donate blood or blood products while taking Odomzo and for at least 20 months
after the last dose of Odomzo, because their blood or blood products might be
given to a female of reproductive potential.
Musculoskeletal Adverse Reactions
Musculoskeletal adverse
reactions, which may be accompanied by serum creatine kinase (CK) elevations,
occur with Odomzo and other drugs which inhibit the hedgehog (Hh) pathway.
In a pooled safety analysis
of 12 clinical studies involving 571 patients with various advanced cancers
treated with Odomzo at doses ranging from 100 mg to 3000 mg, rhabdomyolysis
(defined as serum CK increase of more than ten times the baseline value with a
concurrent 1.5-fold or greater increase in serum creatinine above baseline
value) occurred in one patient (0.2%) treated with Odomzo 800 mg.
In the BOLT study,
musculoskeletal adverse reactions occurred in 68% (54/79) of patients treated
with Odomzo 200 mg daily with 9% (7/79) reported as Grade 3 or 4. The most
frequent manifestations of musculoskeletal adverse reactions reported as an
adverse event were muscle spasms (54%), musculoskeletal pain (32%), and myalgia
(19%). Increased serum CK laboratory values occurred in 61% (48/79) of patients
with 8% (6/79) of patients having Grade 3 or 4 serum CK elevations.
Musculoskeletal pain and myalgia usually preceded serum CK elevation. Among
patients with Grade 2 or higher CK elevations, the median time to onset was
12.9 weeks (range: 2 to 39 weeks) and the median time to resolution (to ≤ Grade
1) was 12 days (95% CI: 8 to 14 days). Odomzo was temporarily interrupted in 8%
of patients or permanently discontinued in 8% of patients for musculoskeletal
adverse reactions. The incidence of musculoskeletal adverse reactions requiring
medical intervention (magnesium supplementation, muscle relaxants, and
analgesics or narcotics) was 29%, including four patients (5%) who received
intravenous hydration or were hospitalized.
Obtain baseline serum CK and
creatinine levels prior to initiating Odomzo, periodically during treatment,
and as clinically indicated (e.g., if muscle symptoms are reported). Obtain
serum creatinine and CK levels at least weekly in patients with musculoskeletal
adverse reactions with concurrent serum CK elevation greater than 2.5 times ULN
until resolution of clinical signs and symptoms. Depending on the severity of
symptoms, temporary dose interruption or discontinuation may be required for
musculoskeletal adverse reactions or serum CK elevation [see Dosage and Administration (2.2)].
Advise patients starting therapy with Odomzo of the risk of muscle-related
adverse reactions. Advise patients to report promptly any new unexplained
muscle pain, tenderness or weakness occurring during treatment or that persists
after discontinuing Odomzo.
Premature Fusion of the Epiphyses
Premature fusion of the epiphyses has
been reported in pediatric patients exposed to Odomzo and other Hh pathway
inhibitors. Despite discontinuation of drug, cases of progressive of epiphyseal
fusion have been reported in pediatric patients receiving other Hh pathway
inhibitors. Odomzo is not indicated for use in pediatric patients.
Adverse
Reactions
The following clinically
significant adverse reactions are described elsewhere in the labeling:
Musculoskeletal Adverse
Reactions
[see Warnings and Precautions (5.2)].Clinical 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.
The safety of Odomzo was
evaluated in BOLT, a randomized, double-blind, multiple cohort trial in which
229 patients received Odomzo at either 200 mg (n=79) or 800 mg (n=150) daily.
The frequency of common adverse reactions including muscle spasms, alopecia,
dysgeusia, fatigue, nausea, decreased weight, decreased appetite, myalgia,
pain, and vomiting was greater in patients treated with Odomzo 800 mg as
compared to 200 mg.
The data described below
reflect exposure to Odomzo 200 mg daily in 79 patients with locally advanced
BCC (laBCC; n=66) or metastatic BCC (mBCC; n=13) enrolled in BOLT. Patients
were followed for at least 18 months unless discontinued earlier. The median
duration of treatment with Odomzo was 11.0 months (range 1.3 to 33.5 months).
The study population
characteristics were: median age of 67 years (range 25 to 92; 59% were ≥65
years), 61% male, and 90% white. The majority of patients had prior surgery
(75%), radiotherapy (24%), systemic chemotherapy (4%), or topical or
photodynamic therapies (18%) for treatment of BCC. No patient had prior
exposure to a Hh pathway inhibitor.
Odomzo was permanently
discontinued in 34% of patients or temporarily interrupted in 20% of patients
for adverse reactions. Adverse reactions reported in at least two patients that
led to discontinuation of the drug were: muscle spasms, and dysgeusia (each
5%), asthenia, increased lipase, and nausea (each 4%), fatigue, decreased
appetite, alopecia, and decreased weight (each 3%). Serious adverse reactions
occurred in 18% of patients.
The most common adverse
reactions occurring in ≥10% of patients treated with Odomzo 200 mg were muscle
spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea,
decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain,
vomiting, and pruritus (Table 1).
The key laboratory
abnormalities are described in Table 2.
Table
1: Adverse Reactions Occurring in ≥10% of Patients in BOLT
|
a No Grade 4 adverse reactions were
reported.
|
|
Adverse Reaction
|
Odomzo 200 mg
(N=79)
|
|
All Gradesa
%
|
Grade 3
%
|
|
Musculoskeletal and connective
tissue
|
|
Muscle spasms
|
54
|
3
|
|
Musculoskeletal pain
|
32
|
1
|
|
Myalgia
|
19
|
0
|
|
Skin and subcutaneous tissue
|
|
Alopecia
|
53
|
0
|
|
Pruritus
|
10
|
0
|
|
Nervous system
|
|
Dysgeusia
|
46
|
0
|
|
Headache
|
15
|
1
|
|
General
|
|
Fatigue
|
41
|
4
|
|
Pain
|
14
|
1
|
|
Gastrointestinal
|
|
Nausea
|
39
|
1
|
|
Diarrhea
|
32
|
1
|
|
Abdominal pain
|
18
|
0
|
|
Vomiting
|
11
|
1
|
|
Investigations
|
|
Decreased weight
|
30
|
3
|
|
Metabolism and nutrition
|
|
Decreased appetite
|
23
|
1
|
Table
2: Key Laboratory Abnormalitiesa in
BOLT
|
a Based on worst post-treatment
laboratory value regardless of baseline; grading by CTCAE v4.03.
b The serum creatinine level remained
within normal range in 76% (60/79) of patients.
|
|
Laboratory Test
|
Odomzo 200 mg
(N=79)
|
|
|
|
|
All Grades
%
|
Grades 3-4
%
|
|
|
|
|
Chemistry
|
|
|
|
|
Increased serum
creatinine
|
92b
|
0
|
|
|
|
|
Increased serum
creatine kinase (CK)
|
61
|
8
|
|
|
|
|
Hyperglycemia
|
51
|
4
|
|
|
|
|
Increased lipase
|
43
|
13
|
|
|
|
|
Increased alanine
aminotransferase
|
19
|
4
|
|
|
|
|
Increased aspartate
aminotransferase
|
19
|
4
|
|
|
|
|
Increased amylase
|
16
|
1
|
|
|
|
|
Hematology
|
|
|
|
|
Anemia
|
32
|
0
|
|
|
|
|
Lymphopenia
|
28
|
3
|
|
|
|
Amenorrhea
Amenorrhea lasting for at
least 18 months occurred in two of 14 pre-menopausal women treated with Odomzo
200 mg or 800 mg once daily.
Drug
InteractionsEffects of Other Drugs on Odomzo
Strong and Moderate CYP3A Inhibitors
Avoid concomitant
administration of Odomzo with strong CYP3A inhibitors [see Clinical Pharmacology (12.3)].
Avoid concomitant
administration of Odomzo with moderate CYP3A inhibitors. If a moderate CYP3A
inhibitor must be used, administer the moderate CYP3A inhibitor for less than
14 days and monitor closely for adverse reactions particularly musculoskeletal
adverse reactions [see Clinical Pharmacology (12.3)].
Strong
and Moderate CYP3A Inducers
Avoid concomitant administration
of Odomzo with strong and moderate CYP3A inducers [see Clinical Pharmacology (12.3)].
USE IN
SPECIFIC POPULATIONSPregnancy
Risk Summary
Based on its mechanism of
action and data from animal reproduction studies, Odomzo can cause fetal harm
when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There
are no available data on the use of Odomzo in pregnant women. In animal
reproduction studies, oral administration of sonidegib during organogenesis at
doses below the recommended human dose of 200 mg resulted in embryotoxicity,
fetotoxicity, and teratogenicity in rabbits (see
Data). Teratogenic effects observed included severe midline
defects, missing digits, and other irreversible malformations. Advise pregnant
women of the potential risk to a fetus. Report pregnancies to Sun
Pharmaceutical Industries, Inc. at 1-800-406-7984.
In theU.S.general
population, the estimated background risk of major birth defects is 2-4% and of
miscarriage in clinically recognized pregnancies is 15-20%.
Data
Animal
Data
Daily oral administration of
sonidegib to pregnant rabbits resulted in abortion, complete resorption of
fetuses, or severe malformations at ≥ 5 mg/kg/day (approximately 0.05 times the
recommended human dose based on AUC). Teratogenic effects included vertebral,
distal limb and digit malformations, severe craniofacial malformations, and
other severe midline defects. Skeletal variations were observed when maternal
exposure to sonidegib was below the limit of detection.
Lactation
No data are available
regarding the presence of sonidegib 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, advise women
not to breastfeed during treatment with Odomzo and for 20 months after the last
dose.
Females and Males of Reproductive Potential
Based on its mechanism of
action and animal data, Odomzo can cause fetal harm when administered to a
pregnant woman [see Use in Specific Populations (8.1)].
Pregnancy
Testing
Verify the pregnancy status
of females of reproductive potential prior to initiating Odomzo treatment.
Contraception
Females
Advise females of
reproductive potential to use effective contraception during treatment with
Odomzo and for at least 20 months after the last dose.
Males
It is not known if sonidegib
is present in semen. Advise male patients to use condoms, even after a
vasectomy, to avoid potential drug exposure to pregnant partners and female
partners of reproductive potential during treatment with Odomzo and for at
least 8 months after the last dose.
Advise males not to donate
semen during treatment with Odomzo and for at least 8 months after the last
dose.
Infertility
Based on findings from
animal studies, female fertility may be compromised with Odomzo [see Nonclinical Toxicology (13.1)].
Pediatric Use
The safety and effectiveness
of Odomzo have not been established in pediatric patients.
Epiphyseal disorders,
including premature fusion of the epiphyses, have been reported in pediatric
patients exposed to Odomzo in a clinical trial. In some cases, pediatric
patients treated with other Hh pathway inhibitors have experienced progression
of epiphyseal fusion despite discontinuation of the Hh pathway inhibitor.
Juvenile
Animal Data
In a 5-week juvenile rat
toxicology study, effects of sonidegib were observed in bone, teeth,
reproductive tissues, and nerves at doses ≥10 mg/kg/day (approximately 1.2
times the recommended human dose based on AUC). Bone findings included
thinning/closure of bone growth plate, decreased bone length and width, and
hyperostosis. Findings in teeth included missing or fractured teeth, and
atrophy. Reproductive tissue toxicity was evidenced by atrophy of testes, ovaries,
and uterus, partial development of the prostate gland and seminal vesicles, and
inflammation and aspermia of the epididymis. Nerve degeneration was also noted.
Geriatric Use
Of the 229 patients who
received Odomzo (79 patients receiving 200 mg daily and 150 patients receiving
800 mg daily) in BOLT, 54% were 65 years and older, while 28% were 75 years and
older. No overall differences in effectiveness were observed between these
patients and younger patients. There was a higher incidence of serious adverse
reactions, Grade 3 and 4 adverse reactions, and adverse reactions requiring
dose interruption or discontinuation in patients ≥65 years compared with
younger patients; this was not attributable to an increase in any specific
adverse event.
Odomzo
Description
Sonidegib is a Hh pathway
inhibitor. The molecular formula for sonidegib phosphate is C26H26 F3N3O3• 2H3PO4. The molecular weight is
681.49 daltons. The chemical name is
N-[6-(cis-2,6-dimethylmorpholin-4-yl)pyridine-3-yl]-2-methyl-4’-(trifluoromethoxy)
[1,1’-biphenyl]-3-carboxamide diphosphate. The molecular structure is shown
below:
Sonidegib phosphate is a
white to off-white powder. Sonidegib freebase is practically insoluble.
Odomzo (sonidegib) capsules
for oral use contain 200 mg of sonidegib as the freebase (equivalent to 281 mg
of diphosphate salt of sonidegib) and the following inactive ingredients:
colloidal silicon dioxide, crospovidone, lactose monohydrate, magnesium
stearate, poloxamer and sodium lauryl sulfate. The opaque pink hard gelatin
capsule shell contains gelatin, red iron oxide, and titanium dioxide. The black
printing ink contains ammonium hydroxide, black iron oxide, propylene glycol,
and shellac.
Odomzo -
Clinical PharmacologyMechanism of Action
Sonidegib is an inhibitor of
the Hh pathway. Sonidegib binds to and inhibits Smoothened, a transmembrane
protein involved in Hh signal transduction.
Pharmacodynamics
Cardiac Electrophysiology
At a dose of 800 mg once
daily, sonidegib does not prolong the QTc interval.
Pharmacokinetics
Sonidegib exhibited
dose-proportional increases in the area under the curve (AUC) and the maximal
concentration (Cmax) over the dose range of 100 mg to 400 mg, but less than
dose-proportional increases at doses greater than 400 mg. Steady-state was
reached approximately 4 months after starting Odomzo and the estimated
accumulation at steady-state was 19-fold. Following a dose of 200 mg once
daily, the estimated mean steady-state Cmax is 1030 ng/mL, AUC0-24h is 22 μg*h/mL and
minimal concentration (Cmin) is 890 ng/mL.
Absorption
Less than 10% of an oral
dose of Odomzo is absorbed. Following the administration of a single Odomzo
dose (100 mg to 3000 mg) under fasted conditions in patients with cancer, the
median time-to-peak concentration (Tmax) was 2 to 4 hours.
Effect
of Food
A high-fat meal
(approximately 1000 calories with 50% of calories from fat) increased exposure
to sonidegib (geometric mean AUCinf and Cmax) by 7.4- to 7.8-fold [see Dosage and Administration (2.1)].
Distribution
The estimated apparent
steady-state volume of distribution (Vss/F) was 9,166 L. Sonidegib was greater than 97% bound to human
plasma proteins in vitro and the binding was concentration independent. In
vitro studies suggested that sonidegib is not a substrate of P-glycoprotein,
MRP2 or BCRP.
Elimination
The elimination half-life (t1/2) of sonidegib estimated
from population pharmacokinetic (PK) modeling was approximately 28 days.
Metabolism
Sonidegib is primarily
metabolized by CYP3A. The main circulating compound was unchanged sonidegib
(36% of circulating radioactivity).
Excretion
Sonidegib and its
metabolites are eliminated primarily by the hepatic route. Of the absorbed
dose, approximately 70% was eliminated in the feces and 30% was eliminated in
the urine. Unchanged sonidegib was not detectable in the urine.
Specific
Populations
Age, body weight, hepatic
impairment (Child-Pugh A, B and C), mild to moderate renal impairment
(creatinine clearance 30 to 89 mL/min) and sex had no clinically meaningful
effect on sonidegib steady-state exposure.
Racial
or Ethnic Groups
A cross study comparison
suggests that geometric mean AUCinf of sonidegib is 1.7-fold higher in Japanese healthy
subjects compared to Western healthy subjects (Whites and Blacks) following a
single 200 mg dose of Odomzo.
Drug
Interaction Studies
Effects
of CYP3A Inhibitors on Sonidegib
Strong
CYP3A inhibitor: The geometric mean
sonidegib AUC0-10d increased by 2.2-fold and the Cmax increased by 1.5-fold
when Odomzo at a dose of 800 mg was taken with ketoconazole compared to Odomzo
alone [see Drug Interactions (7.1)].
The geometric mean sonidegib steady-state AUC0-24h would similarly
increase in cancer patients taking Odomzo 200 mg once daily when coadministered
with a strong CYP3A inhibitor for 14 days.
Moderate
CYP3A inhibitor: The geometric mean
sonidegib steady-state AUC0-24h would increase 1.8-fold when Odomzo 200 mg once daily is
coadministered with a moderate CYP3A inhibitor (erythromycin) for 14 days and
would increase 2.8-fold when Odomzo 200 mg once daily is coadministered with a
moderate CYP3A inhibitor (erythromycin) for 4 months.
Effects
of CYP3A Inducers on Sonidegib
Strong
CYP3A inducer: The geometric mean
sonidegib AUC0-10d decreased by 72% and the Cmax decreased by 54% when
Odomzo at a dose of 800 mg was taken with rifampicin compared to Odomzo
alone [see Drug Interactions (7.1)].
Moderate
CYP3A inducer: The geometric mean
sonidegib steady-state AUC0-24h would decrease 56% in cancer patients taking Odomzo 200 mg
once daily when coadministered with a moderate CYP3A inducer (efavirenz) for 14
days and would decrease 69% when coadministered with a moderate CYP3A inducer
(efavirenz) for 4 months [see Drug Interactions (7.1)].
Effect
of Sonidegib on Cytochrome P450 Enzymes and Transporters
In vitro studies suggested
that sonidegib inhibits CYP2B6 and CYP2C9 and it does not induce CYP1A2, CYP2B6
or CYP3A expression or activity.
In vitro studies suggested
that sonidegib inhibits BCRP, but not P-glycoprotein, MRP2, OATP1B1, OATP1B3,
OAT1, OAT3, OCT1 or OCT2.
Effects
of Acid Reducing Agents on Sonidegib
No clinically meaningful
effect on sonidegib exposure was observed when Odomzo at dose of 200 mg was
coadministered with esomeprazole, a proton pump inhibitor.
Nonclinical
ToxicologyCarcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies with
sonidegib have not been performed.
Sonidegib was not mutagenic
in the in vitro bacterial reverse mutation (Ames) assay and was not clastogenic or
aneugenic in the in vitro human chromosome aberration assay or in vivo rat bone
marrow micronucleus assay.
Sonidegib resulted in a lack
of fertility when administered to female rats at ≥20 mg/kg/day (approximately
1.3 times the recommended human dose based on body surface area (BSA). A
reduction of the number of pregnant females, an increase in the number of early
resorptions, and a decrease in the number of viable fetuses was also noted at 2
mg/kg/day (approximately 0.12 times the recommended human dose based on BSA).
In addition, in a 6 month repeat-dose toxicology study in rats, effects on
female reproductive organs included atrophy of the uterus and ovaries at doses
of 10 mg/kg (approximately ≥2 times the exposure in humans at the recommended dose
of 200 mg based on AUC). No adverse effects on fertility were noted when male
rats were administered sonidegib at doses up to 20 mg/kg/day, the highest dose
tested.
Animal Toxicology and/or Pharmacology
Body tremors along with
significant increases in creatine kinase were observed in rats administered
oral sonidegib for 13 weeks or longer at ≥10 mg/kg/day (approximately ≥2 times
the recommended human dose based on AUC).
Clinical
Studies
The safety and effectiveness
of Odomzo were evaluated in a single, multicenter, double-blind, multiple
cohort clinical trial conducted in patients with locally advanced basal cell
carcinoma (laBCC) (n=194) or metastatic basal cell carcinoma (mBCC) (n=36)
(BOLT, NCT01327053). Patients were randomized (2:1) to receive either Odomzo
800 mg or 200 mg orally, once daily, until disease progression or intolerable
toxicity. Randomization was stratified by stage of disease (locally advanced or
metastatic), laBCC disease histology (aggressive vs. non-aggressive), and
geographic region. Patients with laBCC were required to have lesions for which
radiotherapy was contraindicated or inappropriate (e.g., Gorlin syndrome or
limitations because of location of tumor), that had recurred after
radiotherapy, that were unresectable or for which surgical resection would
result in substantial deformity, or that had recurred after prior surgical
resection.
The major efficacy outcome
measure of the trial was objective response rate (ORR) as determined by blinded
central review according to modified Response Evaluation Criteria in Solid
Tumors (mRECIST) for patients with laBCC or RECIST version 1.1 for patients
with mBCC. Duration of response (DoR), determined by blinded central review,
was a key secondary outcome measure.
For patients with laBCC, the
evaluation of tumor response was based on a composite assessment that
integrated tumor measurements obtained by radiographic assessments of target
lesions (per RECIST 1.1), digital clinical photography, and histopathology
assessments (via punch biopsies). All modalities used must have demonstrated
absence of tumor to achieve a composite assessment of complete response (CR).
Response by digital clinical photography was evaluated by World Health
Organization (WHO) adapted criteria [partial response (PR): ≥50% decrease in
the sum of the product of perpendicular diameters (SPD) of the lesions, CR:
disappearance of all lesions, progressive disease (PD): ≥25% increase in the
SPD of the lesions]. Multiple punch biopsies of target lesions were performed
to confirm a CR or when a response assessment was confounded by presence of
lesion ulceration, cyst, and or scarring/fibrosis.
A total of 66 patients
randomized to Odomzo 200 mg daily had laBCC. Three of these patients had a
diagnosis of Gorlin Syndrome. The demographic characteristics of the 66
patients with laBCC were: median age of 67 years (range: 25 to 92 years; 58%
were ≥65 years); 58% male, 89% white, and ECOG performance status of 0 (67%).
Seventy-six percent of patients had prior therapy for treatment of BCC; this
included surgery (73%), radiotherapy (18%), and topical/photodynamic therapies
(21%). Approximately half of these patients (56%) had aggressive histology.
Patients with laBCC
randomized to receive Odomzo 200 mg daily were followed for at least 30 months
unless discontinued earlier. The ORR was 56% (95% confidence interval: 43, 68),
consisting of 3 (5%) complete responses and 34 (52%) partial responses. A
pre-specified sensitivity analysis using an alternative definition for complete
response, defined as at least a PR according to MRI and/or photography and no
evidence of tumor on biopsy of the residual lesion, yielded a CR rate of 21%.
The median duration of response was 26.1 months (95% CI:10.1, not reached).
A total of 128 patients
randomized to Odomzo 800 mg daily had laBCC. Twelve of these patients had a
diagnosis of Gorlin Syndrome. There was no evidence of better antitumor
activity (ORR) among patients with laBCC randomized to receive Odomzo 800 mg
daily and followed for at least 30 months unless discontinued earlier.
How
Supplied/Storage and Handling
Each Odomzo capsule has an
opaque pink color with ‘SONIDEGIB 200MG’ printed on the capsule body and ‘NVR’
printed on the cap in black ink. Odomzo capsules are supplied as follows:
Bottle of 30 capsules
NDC
47335-303-83
Store at 25°C (77°F);
excursions permitted to 15°C to 30°C (59°F to 86°F) [see
USP Controlled Room Temperature].
Patient
Counseling Information
Advise the patient to read
the FDA-approved patient labeling (Medication
Guide).
Embryo-Fetal
Toxicity [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1, 8.3)].
Females
of Reproductive Potential
Advise female patients of the
potential risk to a fetus. Advise female patients and female partners of
male patients to contact their healthcare provider with a known or
suspected pregnancy.Advise females of reproductive
potential to use effective contraception during treatment with Odomzo and
for at least 20 months after the last dose.Advise females who may have
been exposed to Odomzo during pregnancy, either directly or through
seminal fluid, to contact Sun Pharmaceutical Industries Inc. at
1-800-406-7984.
Males
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
treatment with Odomzo and for at least 8 months after the last dose.
Blood
Donation
Advise patients not to donate
blood or blood products while taking Odomzo and for 20 months after
stopping treatment.
Musculoskeletal
Adverse Reactions
Advise patients to contact
their healthcare provider immediately for new or worsening signs or symptoms of
muscle toxicity, dark urine, decreased urine output, or the inability to
urinate [see Warnings and Precautions (5.2)].
Administration
Instructions
Advise patients to take
Odomzo on an empty stomach, at least 1 hour before or 2 hours after a meal [see Dosage and Administration (2.1)].
Lactation
Advise women not to
breastfeed during treatment with Odomzo and for up to 20 months after the last
dose [see Use in Specific Populations (8.2)].
Manufactured for Sun Pharma
Global FZE by:
Patheon Inc.
Mississauga,OntarioL5N 7K9,Canada
Distributed by:
Sun Pharmaceutical
Industries, Inc.
Cranbury,NJ08512
Odomzo is a registered
trademark of Sun Pharma Global FZE.
|
This Medication
Guide has been approved by the U.S. Food and Drug Administration.
Revised
05/2019
|
|
MEDICATION GUIDE
Odomzo® (o-DOM-zo)
(sonidegib)
capsules
|
|
What
is the most important information I should know about Odomzo?
Odomzo 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 to your healthcare provider about the risks of Odomzo to
your unborn child.Your
healthcare provider will do a pregnancy test before you start taking
Odomzo.In
order to avoid pregnancy, you should use birth control during treatment,
and for at least 20 months after your final dose of Odomzo. Talk to 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 your birth control has failed.Tell
your healthcare provider right away if you become pregnant or think that
you may be pregnant.
For males:
It is
not known if Odomzo is present in semen. Do not donate semen while you
are taking Odomzo and for at least 8 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 Odomzo and for at least 8 months after
your final dose to protect your female partner from being exposed to
Odomzo.Tell
your healthcare provider right away if your partner becomes pregnant or
thinks she is pregnant while you are taking Odomzo.
Exposure to
Odomzo during pregnancy:
If you think that you or your female partner may have been exposed to Odomzo
during pregnancy, talk to your healthcare provider right away. If you become
pregnant during treatment with Odomzo, you or your healthcare provider should
report your pregnancy to Sun Pharmaceutical Industries, Inc. at
1-800-406-7984.
|
|
What
is Odomzo?
Odomzo is a prescription
medicine used to treat adults with a type of skin cancer, called basal cell
carcinoma, that has come back following surgery or radiation or that cannot
be treated with surgery or radiation.
It is not known if Odomzo is safe and effective in children.
|
|
What
should I tell my healthcare provider before taking Odomzo?
Before you
take Odomzo, tell your healthcare provider if you:
have
muscle pain or spasms, or have a history of a muscle disorder called
rhabdomyolysis or myopathyhave any
other medical conditionsare pregnant or plan to become pregnant. See “What
is the most important information I should know about Odomzo?”are breastfeeding or plan to breastfeed. It is not known if Odomzo
passes into your breast milk. Do not breastfeed during treatment and for
20 months after your final dose of Odomzo. 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 Odomzo?
Take
Odomzo exactly as your healthcare provider tells you.Take
Odomzo 1 time each day.Take
Odomzo at least 1 hour before or 2 hours after a meal.If you miss a dose, skip the missed dose. Take
your next dose as scheduled.
|
|
What
should I avoid while taking Odomzo?
Do not
donate blood or blood products while you are taking Odomzo and for 20
months after your final dose.Do not donate semen while taking Odomzo and for
at least 8 months after your final dose.
|
|
What
are possible side effects of Odomzo?
Odomzo can
cause serious side effects, including:
See “What is the most important information I should know
about Odomzo?”Muscle Problems. Muscle spasms and muscle pain
are common with Odomzo, but can also sometimes be symptoms of serious
muscle problems. Odomzo can increase your risk of muscle pain and,
rarely a serious condition caused by injury to the muscles
(rhabdomyolysis) that can lead to kidney damage. Tell your healthcare provider
right away if you develop any new or worsening muscle spasms, pain or
tenderness, dark urine, or decreased amount of urine during treatment
with Odomzo.
Your healthcare provider should do a blood test to check for muscle
problems and to check your kidney function before you start taking
Odomzo, during treatment, and if you develop muscle problems.
|
|
The most common side effects of Odomzo include:
|
|
· hair
loss
|
· change
in taste
|
· tiredness
|
|
· nausea
|
· diarrhea
|
· weight
loss
|
|
· decreased
appetite
|
· stomach
area (abdominal) pain
|
· headache
|
|
· vomiting
|
· itching
|
|
|
Odomzo 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 of the possible side effects of Odomzo.
Call your doctor for medical advice about side effects. You may report side
effects to FDA at 1-800-FDA-1088.
|
|
How
should I store Odomzo?
Store
Odomzo at room temperature between 68°F to 77°F (20°C to 25°C).
Keep Odomzo
and all medicines out of the reach of children.
|
|
General
information about the safe and effective use of Odomzo
Medicines are sometimes
prescribed for purposes other than those listed in a Medication Guide. Do not
use Odomzo for a condition for which it was not prescribed. Do not give
Odomzo 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 Odomzo that is written for health professionals.
|
|
What
are the ingredients in Odomzo?
Active ingredient: sonidegib
Inactive ingredients: colloidal silicon
dioxide, crospovidone, lactose monohydrate, magnesium stearate, poloxamer,
and sodium lauryl sulfate. The capsule shell contains gelatin, red iron
oxide, and titanium dioxide. The black printing ink contains ammonium
hydroxide, black iron oxide, propylene glycol, and shellac.
Manufactured for Sun Pharma Global FZE by: Patheon Inc.,Mississauga,OntarioL5N 7K9,Canada.
Distributed by: Sun
Pharmaceutical Industries, Inc.,Cranbury,NJ08512.
For more information, go to www.Odomzo.com or call 1-800-818-4555.
Odomzo is a registered trademark of Sun Pharma Global FZE.
|
PRINCIPAL
DISPLAY PANEL
NDC
47335-303-83
Rx
only
Odomzo®
(sonidegib)
capsules
200
mg
Pharmacist:
Dispense with Medication Guide.
30
Capsules
SUN
PHARMA
|
Odomzo
sonidegib capsule
|
|
Product Information
|
|
Product
Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:47335-303
|
|
Route of
Administration
|
ORAL
|
DEA
Schedule
|
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
SONIDEGIB
PHOSPHATE (SONIDEGIB)
|
SONIDEGIB
|
200 mg
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
SILICON
DIOXIDE
|
|
|
CROSPOVIDONE,
UNSPECIFIED
|
|
|
LACTOSE
MONOHYDRATE
|
|
|
MAGNESIUM
STEARATE
|
|
|
POLOXAMER
188
|
|
|
SODIUM
LAURYL SULFATE
|
|
|
GELATIN,
UNSPECIFIED
|
|
|
FERRIC
OXIDE RED
|
|
|
TITANIUM
DIOXIDE
|
|
|
AMMONIA
|
|
|
FERROSOFERRIC
OXIDE
|
|
|
PROPYLENE
GLYCOL
|
|
|
SHELLAC
|
|
|
|
Product
Characteristics
|
|
Color
|
PINK (opaque
pink)
|
Score
|
no score
|
|
Shape
|
CAPSULE
|
Size
|
23mm
|
|
Flavor
|
|
Imprint
Code
|
SONIDEGIB200MG;NVR
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:47335-303-83
|
30 CAPSULE in
1 BOTTLE
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA205266
|
09/21/2017
|
|
|
|
Labeler - Sun Pharmaceutical Industries, Inc. (146974886)
|
|
Registrant - Sun Pharmaceutical Industries, Inc. (146974886)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Sun
Pharmaceutical Industries, Inc.
|
|
146974886
|
MANUFACTURE(47335-303)
|
Sun Pharmaceutical
Industries, Inc.
