Erleada
Generic Name: apalutamide
Dosage Form: tablet, film coated
Medically reviewed by
Drugs.com. Last updated on Sep 1, 2019.
Indications
and Usage for Erleada
Erleada is indicated for the treatment
of patients with
Metastatic castration-sensitive
prostate cancer (mCSPC)Non-metastatic castration-resistant
prostate cancer (nmCRPC)Erleada
Dosage and AdministrationRecommended Dosage
The recommended dose of
Erleada is 240 mg (four 60 mg tablets) administered orally once daily. Swallow
the tablets whole. Erleada can be taken with or without food.
Patients should also receive
a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had
a bilateral orchiectomy.
Dose Modification
If a patient experiences a
greater than or equal to Grade 3 toxicity or an intolerable side effect, hold
dosing until symptoms improve to less than or equal to Grade 1 or original
grade, then resume at the same dose or a reduced dose (180 mg or 120 mg), if
warranted.
Dosage
Forms and Strengths
Tablets (60 mg): slightly
yellowish to greyish green oblong film-coated tablets, debossed with "AR
60" on one side.
Contraindications
None.
Warnings
and PrecautionsIschemic Cardiovascular Events
Ischemic cardiovascular events,
including events leading to death, occurred in patients receiving Erleada.
Monitor for signs and symptoms of ischemic heart disease. Optimize management
of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia.
Consider discontinuation of Erleada for Grade 3 and 4 events.
In a randomized study (SPARTAN) of
patients with nmCRPC, ischemic cardiovascular events occurred in 4% of patients
treated with Erleada and 3% of patients treated with placebo. In a randomized
study (TITAN) in patients with mCSPC, ischemic cardiovascular events occurred
in 4% of patients treated with Erleada and 2% of patients treated with placebo.
Across the SPARTAN and TITAN studies, 6 patients (0.5%) treated with Erleada
and 2 patients (0.2%) treated with placebo died from an ischemic cardiovascular
event. Patients with current evidence of unstable angina, myocardial
infarction, or congestive heart failure within six months of randomization were
excluded from the SPARTAN and TITAN studies.
Fractures
Fractures occurred in patients receiving
Erleada. Evaluate patients for fracture risk. Monitor and manage patients at
risk for fractures according to established treatment guidelines and consider
use of bone-targeted agents.
In a randomized study (SPARTAN) of
patients with non-metastatic castration-resistant prostate cancer, fractures
occurred in 12% of patients treated with Erleada and in 7% of patients treated
with placebo. Grade 3-4 fractures occurred in 3% of patients treated with Erleada
and in 1% of patients treated with placebo. The median time to onset of
fracture was 314 days (range: 20 to 953 days) for patients treated with
Erleada. Routine bone density assessment and treatment of osteoporosis with
bone-targeted agents were not performed in the SPARTAN study.
In a randomized study (TITAN) of
patients with metastatic castration-sensitive prostate cancer, fractures
occurred in 9% of patients treated with Erleada and in 6% of patients treated
with placebo. Grade 3-4 fractures were similar in both arms at 2%. The median
time to onset of fracture was 56 days (range: 2 to 111 days) for patients
treated with Erleada. Routine bone density assessment and treatment of
osteoporosis with bone-targeted agents were not performed in the TITAN study.
Falls
Falls occurred in patients receiving
Erleada with increased frequency in the elderly [See Use in Specific Populations (8.5)]. Evaluate patients for fall risk.
In a randomized study (SPARTAN), falls
occurred in 16% of patients treated with Erleada compared to 9% of patients
treated with placebo. Falls were not associated with loss of consciousness or
seizure.
Seizure
Seizure occurred in patients
receiving Erleada. Permanently discontinue Erleada in patients who develop a
seizure during treatment. It is unknown whether anti-epileptic medications will
prevent seizures with Erleada. Advise patients of the risk of developing a
seizure while receiving Erleada and of engaging in any activity where sudden
loss of consciousness could cause harm to themselves or others.
In two randomized studies (SPARTAN and
TITAN), five patients (0.4%) treated with Erleada and one patient treated with
placebo (0.1%) experienced a seizure. Seizure occurred from 159 to 650 days
after initiation of Erleada. Patients with a history of seizure, predisposing
factors for seizure, or receiving drugs known to decrease the seizure threshold
or to induce seizure were excluded. There is no clinical experience in
re-administering Erleada to patients who experienced a seizure.
Embryo-Fetal Toxicity
The safety and efficacy of Erleada have
not been established in females. Based on its mechanism of action, Erleada can
cause fetal harm and loss of pregnancy when administered to a pregnant
female [see Clinical Pharmacology (12.1)]. Advise males with female partners
of reproductive potential to use effective contraception during treatment and
for 3 months after the last dose of Erleada [see Use in Specific Populations (8.1, 8.3)].
Adverse
Reactions
The following are discussed
in more detail in other sections of the labeling:
Ischemic Cardiovascular
Events
[see Warnings and Precautions (5.1)].Fractures
[see Warnings and Precautions (5.2)].Falls
[see Warnings and Precautions (5.3)].Seizure
[see Warnings and Precautions (5.4)].Clinical Trial 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
practice.
The most common adverse
reactions (≥ 10%) that occurred more frequently in the Erleada-treated patients
(≥ 2% over placebo) from the randomized placebo-controlled clinical trials
(TITAN and SPARTAN) were fatigue, arthralgia, rash, decreased appetite, fall,
weight decreased, hypertension, hot flush, diarrhea, and fracture.
Metastatic Castration-sensitive Prostate Cancer (mCSPC)
TITAN, a randomized (1:1),
double-blind, placebo-controlled, multi-center clinical study, enrolled
patients who had mCSPC. In this study, patients received either Erleada at a
dose of 240 mg daily or placebo. All patients in the TITAN study received a
concomitant gonadotropin-releasing hormone (GnRH) analog or had prior bilateral
orchiectomy. The median duration of exposure was 20 months (range: 0 to 34
months) in patients who received Erleada and 18 months (range: 0.1 to 34
months) in patients who received placebo.
Ten patients (2%) who were
treated with Erleada died from adverse reactions. The reasons for death were
ischemic cardiovascular events (n=3), acute kidney injury (n=2), cardio-respiratory
arrest (n=1), sudden cardiac death (n=1), respiratory failure (n=1),
cerebrovascular accident (n=1), and large intestinal ulcer perforation (n=1).
Erleada was discontinued due to adverse reactions in 8% of patients, most
commonly from rash (2%). Adverse reactions leading to dose interruption or
reduction of Erleada occurred in 23% of patients; the most frequent (>1%)
were rash, fatigue, and hypertension. Serious adverse reactions occurred in 20%
of Erleada-treated patients and 20% in patients receiving placebo.
Table 1 shows adverse
reactions occurring in ≥10% on the Erleada arm in TITAN that occurred with a
≥2% absolute increase in frequency compared to placebo. Table 2 shows
laboratory abnormalities that occurred in ≥15% of patients, and more frequently
(>5%) in the Erleada arm compared to placebo.
Table 1: Adverse Reactions in TITAN
(mCSPC)
|
|
|
Erleada
N=524
|
Placebo
N=527
|
|
System/Organ
Class
Adverse reaction
|
All Grades
%
|
Grade 3–4
%
|
All Grades
%
|
Grade 3–4
%
|
|
*
Includes fatigue and asthenia
†
Per the Common Terminology Criteria for Adverse
Reactions (CTCAE), the highest severity for these events is Grade 3
‡
Includes rash, rash maculo-papular, rash
generalized, urticaria, rash pruritic, rash macular, conjunctivitis, erythema
multiforme, rash papular, skin exfoliation, genital rash, rash erythematous,
stomatitis, drug eruption, mouth ulceration, rash pustular, blister, papule,
pemphigoid, skin erosion, dermatitis, and rash vesicular
|
|
General disorders and administration site conditions
|
|
|
|
|
|
Fatigue*,†
|
26
|
3
|
25
|
2
|
|
Musculoskeletal and connective tissue disorders
|
|
|
|
|
|
Arthralgia†
|
17
|
0.4
|
15
|
0.9
|
|
Skin and subcutaneous tissue disorders
|
|
|
|
|
|
Rash‡
|
28
|
6
|
9
|
0.6
|
|
Pruritus
|
11
|
<1
|
5
|
<1
|
|
Vascular disorders
|
|
|
|
|
|
Hot
flush
|
23
|
0
|
16
|
0
|
|
Hypertension
|
18
|
8
|
16
|
9
|
Additional adverse reactions
of interest occurring in 2%, but less than 10% of patients treated with Erleada
included diarrhea (9% versus 6% on placebo), muscle spasm (3% versus 2% on
placebo), dysgeusia (3% versus 1% on placebo), and hypothyroidism (4% versus 1%
on placebo).
Table 2: Laboratory Abnormalities
Occurring in ≥ 15% of Erleada-Treated Patients and at a Higher Incidence
than Placebo (Between Arm Difference > 5% All Grades) in TITAN (mCSPC)
|
|
|
Erleada
N=524
|
Placebo
N=527
|
|
Laboratory
Abnormality
|
All Grades
%
|
Grade 3–4
%
|
All Grades
%
|
Grade 3–4
%
|
|
*
Does not reflect fasting values
|
|
Hematology
|
|
|
|
|
|
White
blood cell decreased
|
27
|
0.4
|
19
|
0.6
|
|
Chemistry
|
|
|
|
|
|
Hypertriglyceridemia*
|
17
|
3
|
12
|
2
|
Non-metastatic Castration-resistant Prostate Cancer (nmCRPC)
SPARTAN, a randomized (2:1),
double-blind, placebo-controlled, multi-center clinical study, enrolled patients
who had nmCRPC. In this study, patients received either Erleada at a dose of
240 mg daily or a placebo. All patients in the SPARTAN study received a
concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral
orchiectomy. The median duration of exposure was 16.9 months (range: 0.1 to 42
months) in patients who received Erleada and 11.2 months (range: 0.1 to 37
months) in patients who received placebo.
Eight patients (1%) who were
treated with Erleada died from adverse reactions. The reasons for death were
infection (n=4), myocardial infarction (n=3), and cerebral hemorrhage (n=1).
One patient (0.3%) treated with placebo died from an adverse reaction of
cardiopulmonary arrest (n=1). Erleada was discontinued due to adverse reactions
in 11% of patients, most commonly from rash (3%). Adverse reactions leading to
dose interruption or reduction of Erleada occurred in 33% of patients; the most
common (>1%) were rash, diarrhea, fatigue, nausea, vomiting, hypertension,
and hematuria. Serious adverse reactions occurred in 25% of Erleada-treated
patients and 23% in patients receiving placebo. The most frequent serious
adverse reactions (>2%) were fracture (3%) in the Erleada arm and urinary
retention (4%) in the placebo arm.
Table 3 shows adverse reactions
occurring in ≥10% on the Erleada arm in SPARTAN that occurred with a ≥2%
absolute increase in frequency compared to placebo. Table 4 shows laboratory
abnormalities that occurred in ≥15% of patients, and more frequently (>5%)
in the Erleada arm compared to placebo.
Table 3: Adverse Reactions in SPARTAN
(nmCRPC)
|
|
|
Erleada
N=803
|
Placebo
N=398
|
|
System/Organ
Class
Adverse reaction
|
All Grades
%
|
Grade 3–4
%
|
All Grades
%
|
Grade 3–4
%
|
|
*
Includes fatigue and asthenia
†
Per the Common Terminology Criteria for Adverse
Reactions (CTCAE), the highest severity for these events is Grade 3
‡
Includes rash, rash maculo-papular, rash
generalized, urticaria, rash pruritic, rash macular, conjunctivitis, erythema
multiforme, rash papular, skin exfoliation, genital rash, rash erythematous,
stomatitis, drug eruption, mouth ulceration, rash pustular, blister, papule,
pemphigoid, skin erosion, dermatitis, and rash vesicular
§
Includes appetite disorder, decreased appetite,
early satiety, and hypophagia
¶
Includes peripheral edema, generalized edema, edema,
edema genital, penile edema, peripheral swelling, scrotal edema, lymphedema,
swelling, and localized edema
#
Includes rib fracture, lumbar vertebral fracture,
spinal compression fracture, spinal fracture, foot fracture, hip fracture,
humerus fracture, thoracic vertebral fracture, upper limb fracture, fractured
sacrum, hand fracture, pubis fracture, acetabulum fracture, ankle fracture,
compression fracture, costal cartilage fracture, facial bones fracture, lower
limb fracture, osteoporotic fracture, wrist fracture, avulsion fracture,
fibula fracture, fractured coccyx, pelvic fracture, radius fracture, sternal
fracture, stress fracture, traumatic fracture, cervical vertebral fracture,
femoral neck fracture, and tibia fracture
|
|
General disorders and administration site conditions
|
|
|
|
|
|
Fatigue*,†
|
39
|
1
|
28
|
0.3
|
|
Musculoskeletal and connective tissue disorders
|
|
|
|
|
|
Arthralgia†
|
16
|
0
|
8
|
0
|
|
Skin and subcutaneous tissue disorders
|
|
|
|
|
|
Rash‡
|
25
|
5
|
6
|
0.3
|
|
Metabolism and nutrition disorders
|
|
|
|
|
|
Decreased
appetite§
|
12
|
0.1
|
9
|
0
|
|
Peripheral
edema¶
|
11
|
0
|
9
|
0
|
|
Injury, poisoning and procedural complications
|
|
|
|
|
|
Fall†
|
16
|
2
|
9
|
0.8
|
|
Fracture#
|
12
|
3
|
7
|
0.8
|
|
Investigations
|
|
|
|
|
|
Weight
decreased†
|
16
|
1
|
6
|
0.3
|
|
Vascular disorders
|
|
|
|
|
|
Hypertension
|
25
|
14
|
20
|
12
|
|
Hot
flush
|
14
|
0
|
9
|
0
|
|
Gastrointestinal disorders
|
|
|
|
|
|
Diarrhea
|
20
|
1
|
15
|
0.5
|
|
Nausea
|
18
|
0
|
16
|
0
|
Additional clinically
significant adverse reactions occurring in 2% or more of patients treated with
Erleada included hypothyroidism (8.1% versus 2% on placebo), pruritus (6.2%
versus 2% on placebo), and heart failure (2.2% versus 1% on placebo).
Table 4: Laboratory Abnormalities
Occurring in ≥ 15% of Erleada-Treated Patients and at a Higher Incidence
than Placebo (Between Arm Difference > 5% All Grades) in SPARTAN (nmCRPC)
|
|
|
Erleada
N=803
|
Placebo
N=398
|
|
Laboratory
Abnormality
|
All Grades
%
|
Grade 3–4
%
|
All Grades
%
|
Grade 3–4
%
|
|
*
Does not reflect fasting values
|
|
Hematology
|
|
|
|
|
|
Anemia
|
70
|
0.4
|
64
|
0.5
|
|
Leukopenia
|
47
|
0.3
|
29
|
0
|
|
Lymphopenia
|
41
|
2
|
21
|
2
|
|
Chemistry
|
|
|
|
|
|
Hypercholesterolemia*
|
76
|
0.1
|
46
|
0
|
|
Hyperglycemia*
|
70
|
2
|
59
|
1
|
|
Hypertriglyceridemia*
|
67
|
2
|
49
|
0.8
|
|
Hyperkalemia
|
32
|
2
|
22
|
0.5
|
Rash
In the combined data of two
randomized, placebo-controlled clinical studies, rash associated with Erleada
was most commonly described as macular or maculo-papular. Adverse reactions of
rash were reported for 26% of patients treated with Erleada versus 8% of
patients treated with placebo. Grade 3 rashes (defined as covering > 30%
body surface area [BSA]) were reported with Erleada treatment (6%) versus
placebo (0.5%).
The onset of rash occurred
at a median of 83 days of Erleada treatment. Rash resolved in 78% of patients
within a median of 78 days from onset of rash. Rash was commonly managed with
oral antihistamines, topical corticosteroids, and 19% of patients received
systemic corticosteroids. Dose reduction or dose interruption occurred in 14%
and 28% of patients, respectively. Of the patients who had dose interruption,
59% experienced recurrence of rash upon reintroduction of Erleada.
Hypothyroidism
In the combined data of two
randomized, placebo-controlled clinical studies, hypothyroidism was reported
for 8% of patients treated with Erleada and 2% of patients treated with placebo
based on assessments of thyroid-stimulating hormone (TSH) every 4 months.
Elevated TSH occurred in 25% of patients treated with Erleada and 7% of
patients treated with placebo. The median onset was at the first scheduled
assessment. There were no Grade 3 or 4 adverse reactions. Thyroid replacement
therapy was initiated in 5% of patients treated with Erleada. Thyroid
replacement therapy, when clinically indicated, should be initiated or
dose-adjusted [see Drug Interactions (7.2)].
Drug
InteractionsEffect of Other Drugs on Erleada
Strong CYP2C8 or CYP3A4 Inhibitors
Co-administration of a
strong CYP2C8 or CYP3A4 inhibitor is predicted to increase the steady-state
exposure of the active moieties (sum of unbound apalutamide plus the
potency-adjusted unbound N-desmethyl-apalutamide). No initial dose adjustment
is necessary however, reduce the Erleada dose based on tolerability [see Dosage and Administration (2.2)].
Mild or moderate inhibitors of CYP2C8 or CYP3A4 are not expected to affect the
exposure of apalutamide.
Effect of Erleada on Other Drugs
CYP3A4, CYP2C9, CYP2C19 and UGT Substrates
Erleada is a strong inducer
of CYP3A4 and CYP2C19, and a weak inducer of CYP2C9 in humans. Concomitant use
of Erleada with medications that are primarily metabolized by CYP3A4, CYP2C19,
or CYP2C9 can result in lower exposure to these medications. Substitution for
these medications is recommended when possible or evaluate for loss of activity
if medication is continued. Concomitant administration of Erleada with
medications that are substrates of UDP-glucuronosyl transferase (UGT) can
result in decreased exposure. Use caution if substrates of UGT must be
co-administered with Erleada and evaluate for loss of activity [see Clinical Pharmacology (12.3)].
P-gp, BCRP or OATP1B1 Substrates
Apalutamide was shown to be
a weak inducer of P-glycoprotein (P-gp), breast cancer resistance protein
(BCRP), and organic anion transporting polypeptide 1B1 (OATP1B1) clinically. At
steady-state, apalutamide reduced the plasma exposure to fexofenadine (a P-gp
substrate) and rosuvastatin (a BCRP/OATP1B1 substrate). Concomitant use of
Erleada with medications that are substrates of P-gp, BCRP, or OATP1B1 can
result in lower exposure of these medications. Use caution if substrates of
P-gp, BCRP or OATP1B1 must be co-administered with Erleada and evaluate for
loss of activity if medication is continued [see Clinical Pharmacology (12.3)].
USE IN
SPECIFIC POPULATIONSPregnancy
Risk Summary
The safety and efficacy of
Erleada have not been established in females. Based on its mechanism of action,
Erleada can cause fetal harm and loss of pregnancy [see Clinical Pharmacology (12.1)]. There
are no human data on the use of Erleada in pregnant women. Erleada is not
indicated for use in females, so animal embryo-fetal developmental toxicology
studies were not conducted with apalutamide.
Lactation
Risk Summary
The safety and efficacy of
Erleada have not been established in females. There are no data on the presence
of apalutamide or its metabolites in human milk, the effect on the breastfed
child, or the effect on milk production.
Females and Males of Reproductive Potential
Contraception
Males
Based on the mechanism of
action and findings in an animal reproduction study, advise male patients with
female partners of reproductive potential to use effective contraception during
treatment and for 3 months after the last dose of Erleada. [see Use in Specific Populations (8.1)].
Infertility
Males
Based on animal studies,
Erleada may impair fertility in males of reproductive potential [see Nonclinical Toxicology (13.1)].
Pediatric Use
Safety and effectiveness of
Erleada in pediatric patients have not been established.
Geriatric Use
Of the 1327 patients who
received Erleada in clinical studies, 19% of patients were less than 65 years,
41% of patients were 65 years to 74 years, and 40% were 75 years and over.
No overall differences in
effectiveness were observed between older and younger patients.
Of patients treated with
Erleada (n=1073), Grade 3–4 adverse reactions occurred in 39% of patients
younger than 65 years, 41% of patients 65–74 years, and 49% of patients 75
years or older. Falls in patients receiving Erleada with androgen deprivation
therapy was elevated in the elderly, occurring in 8% of patients younger than
65 years, 10% of patients 65-74 years, and 19% of patients 75 years or older.
Overdosage
There is no known specific
antidote for apalutamide overdose. In the event of an overdose, stop Erleada,
undertake general supportive measures until clinical toxicity has been
diminished or resolved.
Erleada
Description
Apalutamide, the active
ingredient of Erleada, is an androgen receptor inhibitor. The chemical name is
(4-[7-(6-Cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide).
Apalutamide is a white to slightly yellow powder. Apalutamide is practically
insoluble in aqueous media over a wide range of pH values.
The molecular weight is
477.44 and molecular formula is C21H15F4N5O2S. The structural formula is:
Erleada (apalutamide) is
supplied as film-coated tablets for oral administration containing 60 mg of
apalutamide. Inactive ingredients of the core tablet are: colloidal anhydrous
silica, croscarmellose sodium, hydroxypropyl methylcellulose-acetate succinate,
magnesium stearate, microcrystalline cellulose, and silicified microcrystalline
cellulose.
The tablets are finished
with a commercially available film-coating comprising the following excipients:
iron oxide black, iron oxide yellow, polyethylene glycol, polyvinyl alcohol,
talc, and titanium dioxide.
Erleada -
Clinical PharmacologyMechanism of Action
Apalutamide is an Androgen
Receptor (AR) inhibitor that binds directly to the ligand-binding domain of the
AR. Apalutamide inhibits AR nuclear translocation, inhibits DNA binding, and
impedes AR-mediated transcription. A major metabolite, N-desmethyl apalutamide,
is a less potent inhibitor of AR, and exhibited one-third the activity of
apalutamide in an in vitro transcriptional
reporter assay. Apalutamide administration caused decreased tumor cell
proliferation and increased apoptosis leading to decreased tumor volume in
mouse xenograft models of prostate cancer.
Pharmacodynamics
Cardiac Electrophysiology
The effect of apalutamide
240 mg once daily on the QTc interval was assessed in an open-label,
uncontrolled, multi-center, single-arm dedicated QT study in 45 patients with
CRPC. The maximum mean QTcF change from baseline was 12.4 ms (2-sided 90% upper
CI: 16.0 ms). An exposure-QT analysis suggested a concentration-dependent
increase in QTcF for apalutamide and its active metabolite.
Pharmacokinetics
Apalutamide pharmacokinetic
parameters are presented as the mean [standard deviation (SD)] unless otherwise
specified. Apalutamide Cmax and area under the concentration curve (AUC) increased
proportionally following repeated once-daily dosing of 30 to 480 mg (0.125 to 2
times the recommended dosage). Following administration of the recommended
dosage, apalutamide steady-state was achieved after 4 weeks and the mean
accumulation ratio was approximately 5-fold. Apalutamide Cmax was 6.0 mcg/mL (1.7)
and AUC was 100 mcg∙h/mL (32) at steady-state. Daily fluctuations in
apalutamide plasma concentrations were low, with mean peak-to-trough ratio of
1.63. An increase in apparent clearance (CL/F) was observed with repeat dosing,
likely due to induction of apalutamide's own metabolism. The auto-induction
effect likely reached its maximum at the recommended dosage because exposure of
apalutamide across the dose range of 30 to 480 mg is dose-proportional.
The major active metabolite
N-desmethyl apalutamide Cmax was 5.9 mcg/mL (1.0) and AUC was 124 mcg∙h/mL (23) at
steady-state after the recommended dosage. N-desmethyl apalutamide was
characterized by a flat concentration-time profile at steady-state with a mean
peak-to-trough ratio of 1.27. Mean AUC metabolite/parent drug ratio for
N-desmethyl apalutamide following repeat-dose administration was 1.3. Based on
systemic exposure, relative potency, and pharmacokinetic properties,
N-desmethyl apalutamide likely contributed to the clinical activity of
apalutamide.
Absorption
Mean absolute oral
bioavailability was approximately 100%. Median time to achieve peak plasma
concentration (tmax) was 2 hours (range: 1 to 5 hours).
Effect
of Food
Administration of
apalutamide to healthy subjects under fasting conditions and with a high-fat
meal (approximately 500 to 600 fat calories, 250 carbohydrate calories, and 150
protein calories) resulted in no clinically relevant changes in Cmax and AUC. Median time
to reach tmax was delayed approximately 2 hours with food.
Distribution
The mean apparent volume of
distribution at steady-state of apalutamide was approximately 276 L.
Apalutamide was 96% and
N-desmethyl apalutamide was 95% bound to plasma proteins with no concentration
dependency.
Elimination
The CL/F of apalutamide was
1.3 L/h after single dosing and increased to 2.0 L/h at steady-state after
once-daily dosing likely due to CYP3A4 auto-induction. The mean effective
half-life for apalutamide in patients was approximately 3 days at steady-state.
Metabolism
Metabolism is the main route
of elimination of apalutamide. Apalutamide is primarily metabolized by CYP2C8
and CYP3A4 to form active metabolite, N-desmethyl apalutamide. The contribution
of CYP2C8 and CYP3A4 in the metabolism of apalutamide is estimated to be 58%
and 13% following single dose but changes to 40% and 37%, respectively at
steady-state.
Apalutamide represented 45%
and N-desmethyl apalutamide represented 44% of the total AUC following a single
oral administration of radiolabeled apalutamide 240 mg.
Excretion
Up to 70 days following a single
oral administration of radiolabeled apalutamide, 65% of the dose was recovered
in urine (1.2% of dose as unchanged apalutamide and 2.7% as N-desmethyl
apalutamide) and 24% was recovered in feces (1.5% of dose as unchanged
apalutamide and 2% as N-desmethyl apalutamide).
Specific Populations
No clinically significant
differences in the pharmacokinetics of apalutamide or N-desmethyl apalutamide
were observed based on age (18–94 years), race (Black, non-Japanese Asian,
Japanese), mild to moderate (eGFR 30–89 mL/min/1.73m2, estimated by the
modification of diet in renal disease [MDRD] equation) renal impairment, or
mild (Child-Pugh A) to moderate (Child-Pugh B) hepatic impairment.
The effect of severe renal
impairment or end stage renal disease (eGFR ≤29 mL/min/1.73m2, MDRD) or severe hepatic
impairment (Child-Pugh C) on apalutamide pharmacokinetics is unknown.
Drug Interactions
Effect
of Other Drugs on Erleada
Strong CYP2C8 inhibitors
Apalutamide Cmax decreased by 21% while
AUC increased by 68% following co-administration of Erleada as a 240 mg single
dose with gemfibrozil (a strong CYP2C8 inhibitor). Gemfibrozil is predicted to
increase the steady-state apalutamide Cmax by 32% and AUC by 44%. For the active moieties (sum of
unbound apalutamide plus the potency-adjusted unbound N-desmethyl apalutamide),
the predicted steady-state Cmax increased by 19% and AUC by 23%.
Strong CYP3A4 inhibitors
Apalutamide Cmax decreased by 22% while
AUC was similar following co-administration of Erleada as a 240 mg single dose
with itraconazole (a strong CYP3A4 inhibitor). Ketoconazole (a strong CYP3A4
inhibitor) is predicted to increase the single-dose apalutamide AUC by 24% but
have no impact on Cmax. Ketoconazole is predicted to increase the steady-state apalutamide
Cmax by
38% and AUC by 51%. For the active moieties, the predicted steady-state Cmax increased by 23% and
AUC by 28%.
CYP3A4/CYP2C8 inducers
Rifampin (a strong CYP3A4
and moderate CYP2C8 inducer) is predicted to decrease the steady-state
apalutamide Cmax by 25% and AUC by 34%. For the active moieties, the
predicted steady-state Cmax decreased by 15% and AUC by 19%.
Acid lowering agents
Apalutamide is not ionizable
under relevant physiological pH condition, therefore acid lowering agents (e.g.
proton pump inhibitor, H2-receptor antagonist, antacid) are not expected to affect the
solubility and bioavailability of apalutamide.
Drugs affecting transporters
In
vitro, apalutamide and N-desmethyl apalutamide are substrates for
P-gp but not BCRP, OATP1B1, and OATP1B3. Because apalutamide is completely
absorbed after oral administration, P-gp does not limit the absorption of
apalutamide and therefore, inhibition or induction of P-gp is not expected to
affect the bioavailability of apalutamide.
Effect
of Erleada on Other Drugs
CYP substrates
In
vitro studies showed that apalutamide and N-desmethyl
apalutamide are moderate to strong CYP3A4 and CYP2B6 inducers, are moderate
inhibitors of CYP2B6 and CYP2C8, and weak inhibitors of CYP2C9, CYP2C19, and
CYP3A4. Apalutamide and N-desmethyl apalutamide do not affect CYP1A2 and CYP2D6
at therapeutically relevant concentrations.
Co-administration of Erleada
with single oral doses of sensitive CYP substrates resulted in a 92% decrease
in the AUC of midazolam (a CYP3A4 substrate), 85% decrease in the AUC of
omeprazole (a CYP2C19 substrate), and 46% decrease in the AUC of S-warfarin (a
CYP2C9 substrate). Erleada did not cause clinically significant changes in
exposure to a CYP2C8 substrate.
P-gp, BCRP and OATP1B1 substrates
Co-administration of Erleada
with single oral doses of transporter substrates resulted in a 30% decrease in
the AUC of fexofenadine (a P-gp substrate) and 41% decrease in the AUC of
rosuvastatin (a BCRP/OATP1B1 substrate) but had no impact on Cmax.
UGT substrates
Apalutamide may induce UGT.
Concomitant administration of Erleada with medications that are substrates of
UGT may result in lower exposure to these medications.
OCT2, OAT1, OAT3 and MATEs substrates
In
vitro, apalutamide and N-desmethyl apalutamide inhibit organic cation
transporter 2 (OCT2), organic anion transporter 3 (OAT3) and multidrug and
toxin extrusions (MATEs), and do not inhibit organic anion transporter 1.
Apalutamide is not predicted to cause clinically significant changes in
exposure to an OAT3 substrate.
GnRH Analog
In mCSPC subjects receiving
leuprolide acetate (a GnRH analog) co-administered with apalutamide, PK data
indicated that apalutamide had no apparent effect on the steady-state exposure
of leuprolide.
Nonclinical
ToxicologyCarcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies
have not been conducted to evaluate the carcinogenic potential of apalutamide.
Apalutamide did not induce mutations in the bacterial reverse mutation (Ames)
assay and was not genotoxic in either in vitro chromosome
aberration assay or the in vivo rat bone
marrow micronucleus assay or the in vivo rat
Comet assay.
In repeat-dose toxicity
studies in male rats (up to 26 weeks) and dogs (up to 39 weeks), atrophy of the
prostate gland and seminal vesicles, aspermia/hypospermia, tubular degeneration
and/or hyperplasia or hypertrophy of the interstitial cells in the reproductive
system were observed at ≥ 25 mg/kg/day in rats (1.4 times the human exposure
based on AUC) and ≥ 2.5 mg/kg/day in dogs (0.9 times the human exposure based
on AUC).
In a fertility study in male
rats, a decrease in sperm concentration and motility, increased abnormal sperm
morphology, lower copulation and fertility rates (upon pairing with untreated
females) along with reduced weights of the secondary sex glands and epididymis
were observed following 4 weeks of dosing at ≥ 25 mg/kg/day (0.8 times the
human exposure based on AUC). A reduced number of live fetuses due to increased
pre- and/or post-implantation loss was observed following 4 weeks of 150
mg/kg/day administration (5.7 times the human exposure based on AUC). Effects
on male rats were reversible after 8 weeks from the last apalutamide
administration.
Clinical
Studies
The efficacy and safety of
Erleada was established in two randomized placebo-controlled clinical trials.
TITAN (NCT02489318): Metastatic Castration-sensitive Prostate
Cancer (mCSPC)
TITAN was a randomized,
double-blind, placebo-controlled, multinational, clinical trial in which 1052
patients with mCSPC were randomized (1:1) to receive either Erleada orally at a
dose of 240 mg once daily (N = 525) or placebo once daily (N = 527). All
patients in the TITAN trial received concomitant GnRH analog or had prior
bilateral orchiectomy. Patients were stratified by Gleason score at diagnosis,
prior docetaxel use, and region of the world. Patients with both high- and
low-volume mCSPC were eligible for the study. High volume of disease was
defined as metastases involving the viscera with 1 bone lesion or the presence
of 4 or more bone lesions, at least 1 of which must be in a bony structure
beyond the vertebral column and pelvic bones.
The following patient
demographics and baseline disease characteristics were balanced between the
treatment arms. The median age was 68 years (range 43–94) and 23% of patients
were 75 years of age or older. The racial distribution was 68% Caucasian, 22%
Asian, and 2% Black. Sixty-three percent (63%) of patients had high-volume
disease and 37% had low-volume disease. Sixteen percent (16%) of patients had
prior surgery, radiotherapy of the prostate or both. A majority of patients had
a Gleason score of 8 or higher (67%). Sixty-eight percent (68%) of patients
received prior treatment with an anti-androgen (bicalutamide, flutamide, or nilutamide).
All patients except one in the placebo group, had an Eastern Cooperative
Oncology Group Performance Status (ECOG PS) score of 0 or 1 at study entry.
The major efficacy outcome
measures of the study were overall survival (OS) and radiographic progression-free
survival (rPFS). Radiographic progression-free survival was based on
investigator assessment and was defined as time from randomization to
radiographic disease progression or death. Radiographic disease progression was
defined by identification of 2 or more new bone lesions on a bone scan with
confirmation (Prostate Cancer Working Group 2 criteria) and/or progression in
soft tissue disease.
A statistically significant
improvement in OS and rPFS was demonstrated in patients randomized to receive Erleada
compared with patients randomized to receive placebo. The results for OS are
based upon a prespecified interim efficacy analysis. Efficacy results of TITAN
are summarized in Table 5 and Figures 1 and 2.
Table 5: Summary of Efficacy Results –
Intent-to-treat mCSPC Population (TITAN)
|
|
Endpoint
|
Erleada
N=525
|
Placebo
N=527
|
|
*
Interim analysis is based on 50% of the number of
events planned for the final analysis. Allocated alpha = 0.01.
†
NE=Not Estimable
‡
Hazard ratio is from stratified proportional hazards
model. Hazard ratio <1 favors Erleada.
§
p-value is from the log-rank test stratified by
Gleason score at diagnosis (≤7 vs. >7), Region (NA/EU vs. Other Countries)
and Prior docetaxel use (Yes vs. No).
|
|
Overall Survival*
|
|
|
|
Deaths
(%)
|
83 (16%)
|
117 (22%)
|
|
Median,
months (95% CI)†
|
NE (NE, NE)
|
NE (NE, NE)
|
|
Hazard
ratio (95% CI)‡
|
0.67 (0.51, 0.89)
|
|
|
p-value§
|
0.0053
|
|
|
Radiographic Progression-free Survival
|
|
|
|
Disease
progression or death (%)
|
134 (26%)
|
231 (44%)
|
|
Median,
months (95% CI)†
|
NE (NE, NE)
|
22.1 (18, 33)
|
|
Hazard
ratio (95% CI)‡
|
0.48 (0.39, 0.60)
|
|
|
p-value§
|
<0.0001
|
|
Consistent improvement in
rPFS was observed across the following patient subgroups: disease volume (high
vs low), prior docetaxel use (yes or no), and Gleason score at diagnosis (≤7
vs. >7).
Consistent improvement in OS
was observed across the following patient subgroups: disease volume (high vs
low) and Gleason score at diagnosis (≤7 vs. >7).
Treatment with Erleada
statistically significantly delayed the initiation of cytotoxic chemotherapy
(HR = 0.39, 95% CI = 0.27, 0.56; p < 0.0001).
|
Figure 1: Kaplan-Meier Plot of Overall
Survival (OS); Intent-to-treat mCSPC Population (TITAN)
|
|
|
|
Figure 2: Kaplan-Meier Plot of
Radiographic Progression-Free Survival (rPFS); Intent-to-treat mCSPC
Population (TITAN)
|
|
|
SPARTAN (NCT01946204): Non-metastatic, Castration-resistant Prostate
Cancer (nmCRPC)
SPARTAN was a multicenter,
double-blind, randomized (2:1), placebo-controlled clinical trial in which 1207
patients with nmCRPC were randomized (2:1) to receive either Erleada orally at
a dose of 240 mg once daily (N = 806) or placebo once daily (N = 401). All
patients in the SPARTAN trial received a concomitant GnRH analog or had a
bilateral orchiectomy. Patients were stratified by Prostate Specific Antigen
(PSA) Doubling Time (PSADT), the use of bone-sparing agents, and locoregional
disease. Patients were required to have a PSADT ≤ 10 months and confirmation of
non-metastatic disease by blinded independent central review (BICR). PSA
results were blinded and were not used for treatment discontinuation. Patients
randomized to either arm discontinued treatment for radiographic disease
progression confirmed by BICR, locoregional-only progression, initiation of new
treatment, unacceptable toxicity, or withdrawal.
The following patient
demographics and baseline disease characteristics were balanced between the
treatment arms. The median age was 74 years (range 48–97) and 26% of patients
were 80 years of age or older. The racial distribution was 66% Caucasian, 12%
Asian, and 6% Black. Seventy-seven percent (77%) of patients in both treatment
arms had prior surgery or radiotherapy of the prostate. A majority of patients
had a Gleason score of 7 or higher (78%). Fifteen percent (15%) of patients had
<2 cm pelvic lymph nodes at study entry. Seventy-three percent (73%) of
patients received prior treatment with an anti-androgen; 69% of patients
received bicalutamide and 10% of patients received flutamide. All patients had
an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0
or 1 at study entry. Among the patients who discontinued study treatment (N =
279 for placebo and N = 314 for Erleada), a greater proportion (80%) of
patients treated with placebo received subsequent therapy compared to patients
treated with Erleada (56%). Locoregional-only progression occurred in 2% of patients
overall.
The major efficacy outcome
measure of the study was metastasis-free survival (MFS), defined as the time
from randomization to the time of first evidence of BICR-confirmed distant
metastasis, defined as new bone or soft tissue lesions or enlarged lymph nodes
above the iliac bifurcation, or death due to any cause, whichever occurred
first. Additional efficacy endpoints were time to metastasis (TTM),
progression-free survival (PFS) which also includes locoregional progression,
time to symptomatic progression, and overall survival (OS).
A statistically significant
improvement in MFS was demonstrated in patients randomized to receive Erleada
compared with patients randomized to receive placebo. Consistent results were
observed across patient subgroups including PSADT (≤ 6 months or > 6
months), use of a prior bone-sparing agent (yes or no), and locoregional
disease (N0 or N1). The major efficacy outcome was supported by statistically
significant improvements in TTM, PFS, and time to symptomatic progression.
Overall survival (OS) data were not mature at the time of final MFS analysis
(24% of the required number of events). The efficacy results of MFS, TTM, and
PFS from SPARTAN are summarized in Figure 3 and Table 6.
|
Figure 3: Kaplan-Meier Metastasis-Free
Survival (MFS) Curve in SPARTAN (nmCRPC)
|
|
|
|
|
Table 6: BICR-assessed Efficacy Results
(SPARTAN)
|
|
|
Endpoint
|
Number of Events (%)
|
Median [Months (95% CI)]
|
HR (95% CI)
p-value (log-rank test)*
|
|
|
Erleada
(N=806)
|
Placebo
(N=401)
|
Erleada
|
Placebo
|
|
|
NE=Not Estimable
|
|
|
*
All analyses stratified by PSA doubling time,
bone-sparing agent use, and locoregional disease status.
|
|
|
Metastasis Free
Survival
|
184 (23%)
|
194 (48%)
|
40.5
(NE, NE)
|
16.2
(15, 18)
|
0.28 (0.23, 0.35)
<0.0001
|
|
|
Time to
Metastasis
|
175 (22%)
|
191 (48%)
|
40.5
(NE, NE)
|
16.6
(15, 18)
|
0.27 (0.22, 0.34)
<0.0001
|
|
|
Progression-Free
Survival
|
200 (25%)
|
204 (51%)
|
40.5
(NE, NE)
|
14.7
(14, 18)
|
0.29 (0.24, 0.36)
<0.0001
|
|
How
Supplied/Storage and Handling
Erleada (apalutamide) 60 mg
film-coated tablets are slightly yellowish to greyish green, oblong-shaped
tablets debossed with "AR 60" on one side. Erleada 60 mg tablets are
available in bottles of 120 tablets. Each bottle contains silica gel desiccant.
Storage and Handling
Store at 20°C to 25°C (68°F
to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
Store in the original
package. Do not discard desiccant. Protect from light and moisture.
Patient
Counseling Information
Advise
the patient to read the FDA-approved patient labeling (Patient Information).
Ischemic Cardiovascular Events
Inform patients that Erleada
has been associated with ischemic cardiovascular events. Advise patients
to seek immediate medical attention if any symptoms suggestive of a
cardiovascular event occur
[see Warnings and Precautions (5.1)].
Falls and Fractures
Inform patients that Erleada
is associated with an increased incidence of falls and fractures
[see Warnings and Precautions (5.2, 5.3)].
Seizures
Inform patients that Erleada
has been associated with an increased risk of seizure. Discuss conditions
that may predispose to seizures and medications that may lower the seizure
threshold. Advise patients of the risk of engaging in any activity where
sudden loss of consciousness could cause serious harm to themselves or others.
Inform patients to contact their healthcare provider right away if they
experience a seizure
[see Warnings and Precautions (5.4)].
Rash
Inform patients that Erleada
is associated with rashes and to inform their healthcare provider if they
develop a rash
[see Adverse Reactions (6.1)].
Dosage and Administration
Inform patients receiving
concomitant gonadotropin-releasing hormone (GnRH) analog therapy that they
need to maintain this treatment during the course of treatment with
Erleada.Instruct patients to take
their dose at the same time each day (once daily). Erleada can be taken
with or without food. Each tablet should be swallowed whole.Inform patients that in the
event of a missed daily dose of Erleada, they should take their normal
dose as soon as possible on the same day with a return to the normal
schedule on the following day. The patient should not take extra tablets
to make up the missed dose
[see Dosage and Administration (2.1)].
Embryo-Fetal Toxicity
Inform patients that Erleada
can be harmful to a developing fetus. Advise male patients with female partners
of reproductive potential to use effective contraception during treatment
and for 3 months after the last dose of Erleada. Advise male patients to
use a condom if having sex with a pregnant woman
[see Warnings and Precautions (5.5)].
Infertility
Advise male patients that
Erleada may impair fertility and not to donate sperm during therapy and
for 3 months following the last dose of Erleada
[see Use in Specific Populations (8.3)].
Manufactured by:
Janssen Ortho LLC
Gurabo, PR 00778
Manufactured for:
Janssen Products, LP
Horsham, PA 19044
© 2019 Janssen
Pharmaceutical Companies
|
This Patient
Information has been approved by the U.S. Food and Drug Administration.
|
Revised: 09/2019
|
|
PATIENT INFORMATION
Erleada® (er lee'dah)
(apalutamide)
Tablets
|
|
What is Erleada?
Erleada is a prescription medicine used for the treatment of prostate cancer:
that
has spread to other parts of the body and still responds to a medical or
surgical treatment that lowers testosterone, ORthat
has not spread to other parts of the body and no longer responds to a
medical or surgical treatment that lowers testosterone.
It is not known
if Erleada is safe and effective in females.
It is not known if Erleada is safe and effective in children.
|
|
Before taking Erleada, tell your healthcare provider about all your
medical conditions, including if you:
have a
history of heart diseasehave
high blood pressurehave
diabeteshave
abnormal amounts of fat or cholesterol in your blood (dyslipidemia)have a
history of seizures, brain injury, stroke, or brain tumorsare
pregnant or plan to become pregnant. Erleada can cause harm to your unborn
baby and loss of pregnancy (miscarriage).have a
partner who is pregnant or may become pregnant.Males
who have female partners who are able to become pregnant should use
effective birth control (contraception) during treatment and for 3
months after the last dose of Erleada.Males
should use a condom during sex with a pregnant female.
Talk with your
healthcare provider if you have questions about birth control.
are
breastfeeding or plan to breastfeed. It is not known if Erleada passes
into breast milk.
Tell your healthcare provider about all the medicines you take, including prescription and
over-the-counter medicines, vitamins, and herbal supplements. Erleada can
interact with many other medicines.
You should not start or stop any medicine before you talk with the healthcare
provider that prescribed Erleada.
Know the medicines you take. Keep a list of them with you to show to your
healthcare provider and pharmacist when you get a new medicine.
|
|
How should I take Erleada?
Take
Erleada exactly as your healthcare provider tells you.Your
healthcare provider may change your dose if needed.Do not
stop taking your prescribed dose of Erleada without talking with your
healthcare provider first.Take
your prescribed dose of Erleada 1 time a day, at the same time each day.Take
Erleada with or without food.Swallow
Erleada tablets whole.If you
miss a dose of Erleada, take your normal dose as soon as possible on the
same day. Return to your normal schedule on the following day. You
should not take extra tablets to make up the missed dose.You
should start or continue a gonadotropin-releasing hormone (GnRH) analog
therapy during your treatment with Erleada unless you have had a surgery
to lower the amount of testosterone in your body (surgical castration).If you take too much Erleada, call your
healthcare provider or go to the nearest hospital emergency room.
|
|
What are the possible side effects of Erleada?
Erleada may cause serious side effects including:
Heart Disease. Blockage of the arteries in
the heart that can lead to death has happened in some people during
treatment with Erleada. Your healthcare provider will monitor you for
signs and symptoms of heart problems during your treatment with Erleada.
Call your healthcare provider or go to the nearest emergency room right
away if you get chest pain or discomfort at rest or with activity, or
shortness of breath during your treatment with Erleada.Fractures and falls. Erleada treatment can cause
bones and muscles to weaken and may increase your risk for falls and fractures.
Falls and fractures have happened in people during treatment with
Erleada. Your healthcare provider will monitor your risks for falls and
fractures during treatment with Erleada.Seizure. Treatment with Erleada may increase your
risk of having a seizure. You should avoid activities where a sudden
loss of consciousness could cause serious harm to yourself or others.
Tell your healthcare provider right away if you have a loss of
consciousness or seizure. Your healthcare provider will stop Erleada if
you have a seizure during treatment.
The most common side effects of Erleada include:
|
|
· feeling
very tired
· joint
pain
· rash.
Tell your healthcare provider if you get a rash.
· decreased
appetite
· fall
|
· weight
loss
· hypertension
· hot
flash
· diarrhea
· fracture
|
|
Erleada may
cause fertility problems in males, which may affect the ability to father
children. Talk to your healthcare provider if you have concerns about
fertility. Do not donate sperm
during treatment with Erleada and for 3 months after the last dose of Erleada.
Tell 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 Erleada.
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 Erleada?
Store
Erleada at room temperature between 68°F to 77°F (20°C to 25°C).Store
Erleada in the original package.The
bottle of Erleada contains a desiccant packet to help keep your medicine
dry (protect it from moisture). Do not throw away (discard) the
desiccant.Protect
Erleada from light and moisture.
Keep Erleada and all medicines out of the reach of children.
|
|
General information about the safe and effective use of Erleada.
Medicines are sometimes prescribed for purposes other than those listed in a
Patient Information leaflet. Do not use Erleada for a condition for which it
was not prescribed. Do not give Erleada to other people, even if they have
the same symptoms that you have. It may harm them. If you would like more
information, talk with your healthcare provider. You can ask your healthcare
provider or pharmacist for information about Erleada that is written for
health professionals.
|
|
What are the ingredients in Erleada?
Active ingredient: apalutamide
Inactive ingredients: colloidal anhydrous
silica, croscarmellose sodium, hydroxypropyl methylcellulose-acetate
succinate, magnesium stearate, microcrystalline cellulose, and silicified
microcrystalline cellulose. The film-coating contains iron oxide black, iron
oxide yellow, polyethylene glycol, polyvinyl alcohol, talc, and titanium
dioxide.
Manufactured by: Janssen Ortho LLC,
Gurabo, PR 00778
Manufactured for: Janssen Products, LP,
Horsham, PA 19044
© 2019 Janssen Pharmaceutical Companies
For more information, call Janssen Products, LP at 1-800-526-7736
(1-800-JANSSEN) or go to www.Erleada.com.
|
PRINCIPAL
DISPLAY PANEL - 60 mg Tablet Bottle Label
NDC 59676-600-12
Erleada™
(apalutamide) tablets
60
mg
Each tablet contains 60 mg
of
apalutamide.
Rx
only
120
Tablets
janssen
|
Erleada
apalutamide tablet, film coated
|
|
Product
Information
|
|
Product
Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:59676-600
|
|
Route of
Administration
|
ORAL
|
DEA
Schedule
|
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
Apalutamide (Apalutamide)
|
Apalutamide
|
60 mg
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
SILICON
DIOXIDE
|
|
|
Croscarmellose
sodium
|
|
|
HYPROMELLOSE
ACETATE SUCCINATE 16070722 (3 MM2/S)
|
|
|
Magnesium
stearate
|
|
|
Microcrystalline
cellulose
|
|
|
FERROSOFERRIC
OXIDE
|
|
|
FERRIC
OXIDE YELLOW
|
|
|
POLYETHYLENE
GLYCOL, UNSPECIFIED
|
|
|
POLYVINYL
ALCOHOL, UNSPECIFIED
|
|
|
Talc
|
|
|
Titanium
dioxide
|
|
|
|
Product
Characteristics
|
|
Color
|
GREEN
(slightly yellowish to greyish green)
|
Score
|
no score
|
|
Shape
|
OVAL (Oblong)
|
Size
|
17mm
|
|
Flavor
|
|
Imprint
Code
|
AR;60
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:59676-600-12
|
120 TABLET,
FILM COATED in 1 BOTTLE
|
|
|
2
|
NDC:59676-600-99
|
120 TABLET,
FILM COATED in 1 BOTTLE
|
|
|
3
|
NDC:59676-600-56
|
2 BLISTER PACK
in 1 CARTON
|
|
|
3
|
|
28 TABLET,
FILM COATED in 1 BLISTER PACK
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA210951
|
02/14/2018
|
|
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Labeler - Janssen Products, LP (804684207)
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Establishment
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Name
|
Address
|
ID/FEI
|
Operations
|
|
Janssen
Pharmaceuticals, Inc.
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080236951
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API
MANUFACTURE(59676-600)
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|
Establishment
|
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Name
|
Address
|
ID/FEI
|
Operations
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Johnson &
Johnson Private Limited
|
|
677603030
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ANALYSIS(59676-600)
|
|
Establishment
|
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Name
|
Address
|
ID/FEI
|
Operations
|
|
Janssen
Pharmaceutica NV
|
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374747970
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API
MANUFACTURE(59676-600)
|
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Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Janssen Ortho
LLC
|
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805887986
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MANUFACTURE(59676-600)
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Establishment
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Name
|
Address
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ID/FEI
|
Operations
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Janssen Cilag
SpA
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542797928
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PACK(59676-600)
|
Janssen Products, LP
