Balversa
Generic Name: erdafitinib
Dosage Form: tablet, film coated
Medically reviewed by
Drugs.com. Last updated on Apr 1, 2019.
Indications
and Usage for Balversa
Balversa™ is indicated for
the treatment of adult patients with locally advanced or metastatic urothelial
carcinoma that has:
susceptible FGFR3 or FGFR2
genetic alterations, andprogressed during or following
at least one line of prior platinum-containing chemotherapy, including
within 12 months of neoadjuvant or adjuvant platinum-containing
chemotherapy.
Select patients for therapy
based on an FDA-approved companion diagnostic for Balversa [see Dosage and Administration (2.1) and Clinical Studies (14)].
This indication is approved
under accelerated approval based on tumor response rate. Continued approval for
this indication may be contingent upon verification and description of clinical
benefit in confirmatory trials [see Clinical Studies (14)].
Balversa
Dosage and AdministrationPatient Selection
Select patients for the
treatment of locally advanced or metastatic urothelial carcinoma with Balversa
based on the presence of susceptible FGFR genetic alterations in tumor
specimens as detected by an FDA-approved companion diagnostic.
[see Clinical Studies (14.1)].
Information on FDA-approved
tests for the detection of FGFR genetic alterations in urothelial cancer is
available at: http://www.fda.gov/CompanionDiagnostics.
Recommended Dosage and Schedule
The recommended starting
dose of Balversa is 8 mg (two 4 mg tablets) orally once daily, with a dose
increase to 9 mg (three 3 mg tablets) once daily based on serum phosphate (PO4) levels and tolerability at
14 to 21 days [see Dosage and Administration (2.3)].
Swallow tablets whole with
or without food. If vomiting occurs any time after taking Balversa, the next
dose should be taken the next day. Treatment should continue until disease
progression or unacceptable toxicity occurs.
If a dose of Balversa is
missed, it can be taken as soon as possible on the same day. Resume the regular
daily dose schedule for Balversa the next day. Extra tablets should not be
taken to make up for the missed dose.
Dose
Increase based on Serum Phosphate Levels
Assess serum phosphate
levels 14 to 21 days after initiating treatment. Increase the dose of Balversa
to 9 mg once daily if serum phosphate level is < 5.5 mg/dL and there are no
ocular disorders or Grade 2 or greater adverse reactions. Monitor phosphate
levels monthly for hyperphosphatemia [see Pharmacodynamics (12.2)].
Dose Modifications for Adverse Reactions
The recommended dose
modifications for adverse reactions are listed in Table 1.
Table 1: Balversa Dose Reduction
Schedule
|
|
Dose
|
1st dose reduction
|
2nd dose reduction
|
3rd dose reduction
|
4th dose reduction
|
5th dose reduction
|
|
9 mg ⭢
(three 3 mg tablets)
|
8 mg
(two 4 mg tablets)
|
6 mg
(two 3 mg tablets)
|
5 mg
(one 5 mg tablet)
|
4 mg
(one 4 mg tablet)
|
Stop
|
|
|
|
8 mg ⭢
(two 4 mg tablets)
|
6 mg
(two 3 mg tablets)
|
5 mg
(one 5 mg tablet)
|
4 mg
(one 4 mg tablet)
|
Stop
|
|
Table 2 summarizes
recommendations for dose interruption, reduction, or discontinuation of Balversa
in the management of specific adverse reactions.
Table 2: Dose Modifications for Adverse
Reactions
|
|
Adverse
Reaction
|
Balversa
Dose Modification
|
|
*
Dose adjustment graded using the National Cancer
Institute Common Terminology Criteria for Adverse Events (NCI CTCAEv4.03).
|
|
Hyperphosphatemia
|
|
In all patients,
restrict phosphate intake to 600–800 mg daily. If serum phosphate is above
7.0 mg/dL, consider adding an oral phosphate binder until serum phosphate
level returns to < 5.5 mg/dL.
|
|
5.6–6.9 mg/dL
(1.8–2.3 mmol/L)
|
Continue
Balversa at current dose.
|
|
7.0–9.0 mg/dL
(2.3–2.9 mmol/L)
|
Withhold
Balversa with weekly reassessments until level returns to < 5.5 mg/dL (or
baseline). Then restart Balversa at the same dose level. A dose reduction may
be implemented for hyperphosphatemia lasting > 1 week.
|
|
> 9.0 mg/dL
(> 2.9 mmol/L)
|
Withhold
Balversa with weekly reassessments until level returns to < 5.5 mg/dL (or
baseline). Then may restart Balversa at 1 dose level lower.
|
|
> 10.0 mg/dL
(> 3.2 mmol/L) or significant alteration in baseline renal function or
Grade 3 hypercalcemia
|
Withhold
Balversa with weekly reassessments until level returns to < 5.5 mg/dL (or
baseline). Then may restart Balversa at 2 dose levels lower.
|
|
Central Serous Retinopathy/Retinal Pigment Epithelial Detachment
(CSR/RPED)
|
|
Grade 1:
Asymptomatic; clinical or diagnostic observations only
|
Withhold until
resolution. If resolves within 4 weeks, resume at the next lower dose level.
Then, if no recurrence for a month, consider re-escalation. If stable for 2
consecutive eye exams but not resolved, resume at the next lower dose level.
|
|
Grade 2: Visual
acuity 20/40 or better or ≤ 3 lines of decreased vision from baseline
|
Withhold until
resolution. If resolves within 4 weeks, may resume at the next lower dose
level.
|
|
Grade 3: Visual
acuity worse than 20/40 or > 3 lines of decreased vision from baseline
|
Withhold until
resolution. If resolves within 4 weeks, may resume two dose levels lower. If
recurs, consider permanent discontinuation.
|
|
Grade 4: Visual
acuity 20/200 or worse in affected eye
|
Permanently
discontinue.
|
|
Other Adverse Reactions *
|
|
Grade 3
|
Withhold
Balversa until resolves to Grade 1 or baseline, then may resume dose level
lower.
|
|
Grade 4
|
Permanently
discontinue.
|
Dosage
Forms and Strengths
Tablets:
3 mg: Yellow, round biconvex,
film-coated, debossed with "3" on one side; and "EF"
on the other side.4 mg:Orange,
round biconvex, film-coated, debossed with "4" on one side; and
"EF" on the other side.5 mg: Brown, round biconvex,
film-coated, debossed with "5" on one side; and "EF"
on the other side.Contraindications
None.
Warnings
and PrecautionsOcular Disorders
Balversa can cause ocular
disorders, including central serous retinopathy/retinal pigment epithelial
detachment (CSR/RPED) resulting in visual field defect.
CSR/RPED was reported in 25%
of patients treated with Balversa, with a median time to first onset of 50
days. Grade 3 CSR/RPED, involving central field of vision, was reported in 3%
of patients. CSR/RPED resolved in 13% of patients and was ongoing in 13% of
patients at the study cutoff. CSR/RPED led to dose interruptions and reductions
in 9% and 14% of patients, respectively and 3% of patients discontinued
Balversa.
Dry eye symptoms occurred in
28% of patients during treatment with Balversa and were Grade 3 in 6% of
patients. All patients should receive dry eye prophylaxis with ocular demulcents
as needed.
Perform monthly
ophthalmological examinations during the first 4 months of treatment and every
3 months afterwards, and urgently at any time for visual symptoms.
Ophthalmological examination should include assessment of visual acuity, slit lamp
examination, fundoscopy, and optical coherence tomography.
Withhold Balversa when CSR
occurs and permanently discontinue if it does not resolve within 4 weeks or if
Grade 4 in severity. For ocular adverse reactions, follow the dose modification
guidelines [see Dosage and Administration (2.3)].
Hyperphosphatemia
Increases in phosphate
levels are a pharmacodynamic effect of Balversa [see Pharmacodynamics (12.2)]. Hyperphosphatemia
was reported as adverse reaction in 76% of patients treated with Balversa. The
median onset time for any grade event of hyperphosphatemia was 20 days (range:
8 –116) after initiating Balversa. Thirty-two percent of patients received
phosphate binders during treatment with Balversa.
Monitor for
hyperphosphatemia and follow the dose modification guidelines when
required [see Dosage and Administration 2.2, 2.3].
Embryo-Fetal Toxicity
Based on the mechanism of
action and findings in animal reproduction studies, Balversa can cause fetal
harm when administered to a pregnant woman. In an embryo-fetal toxicity study,
oral administration of erdafitinib to pregnant rats during the period of
organogenesis caused malformations and embryo-fetal death at maternal exposures
that were less than the human exposures at the maximum human recommended dose
based on area under the curve (AUC). Advise pregnant women of the potential
risk to the fetus. Advise female patients of reproductive potential to use
effective contraception during treatment with Balversa and for one month after
the last dose. Advise male patients with female partners of reproductive
potential to use effective contraception during treatment with Balversa and for
one month after the last dose [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1)].
Adverse
Reactions
The following serious
adverse reactions are also described elsewhere in the labeling:
Ocular Disorders
[see Warning and Precautions (5.1)].Hyperphosphatemia
[see Warning 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
practice.
The safety of Balversa was
evaluated in the BLC2001 study that included 87 patients with locally advanced
or metastatic urothelial carcinoma which had susceptible FGFR3 or FGFR2 genetic
alterations, and which progressed during or following at least one line of
prior chemotherapy including within 12 months of neoadjuvant or adjuvant
chemotherapy [see Clinical Studies (14.1)]. Patients were
treated with Balversa at 8 mg orally once daily; with a dose increase to 9 mg
in patients with phosphate levels <5.5 mg/dL on Day 14 of Cycle 1. Median
duration of treatment was 5.3 months (range: 0 to 17 months).
The most common adverse
reactions (ARs) including laboratory abnormalities (≥20%) were phosphate
increased, stomatitis, fatigue, creatinine increased, diarrhea, dry mouth,
onycholysis, alanine aminotransferase increased, alkaline phosphatase
increased, sodium decreased, decreased appetite, albumin decreased, dysgeusia,
hemoglobin decreased, dry skin, aspartate aminotransferase increased, magnesium
decreased, dry eye, alopecia, palmar-plantar erythrodysesthesia syndrome,
constipation, phosphate decreased, abdominal pain, calcium increased, nausea,
and musculoskeletal pain. The most common Grade 3 or greater ARs (>1%) were
stomatitis, nail dystrophy, palmar-plantar erythrodysesthesia syndrome,
paronychia, nail disorder, keratitis, onycholysis, and hyperphosphatemia.
An adverse reaction with a
fatal outcome in 1% of patients was acute myocardial infarction.
Serious adverse reactions
occurred in 41% of patients including eye disorders (10%).
Permanent discontinuation
due to an adverse reaction occurred in 13% of patients. The most frequent reasons
for permanent discontinuation included eye disorders (6%).
Dosage interruptions
occurred in 68% of patients. The most frequent adverse reactions requiring
dosage interruption included hyperphosphatemia (24%), stomatitis (17%), eye
disorders (17%), and palmar-plantar erythro-dysaesthesia syndrome (8%).
Dose reductions occurred in
53% of patients. The most frequent adverse reactions for dose reductions
included eye disorders (23%), stomatitis (15%), hyperphosphatemia (7%),
palmar-plantar erythro-dysaesthesia syndrome (7%), paronychia (7%), and nail
dystrophy (6%).
Table 3 presents ARs
reported in ≥10% of patients treated with Balversa at 8 mg once daily.
Table 3: Adverse Reactions Reported in ≥
10% (Any Grade) or ≥5% (Grade 3–4) of Patients
|
|
|
Balversa 8 mg daily (N=87)
|
|
Adverse
Reaction
|
All Grades (%)
|
Grade 3–4 (%)
|
|
*
Includes abdominal pain, abdominal discomfort,
abdominal pain upper, and abdominal pain lower
†
Includes asthenia, fatigue, lethargy, and malaise
‡
Includes onycholysis, onychoclasis, nail disorder,
nail dystrophy, and nail ridging
§
Includes dry skin and xerostomia
¶
Includes dry eye, xerophthalmia, keratitis, foreign
body sensation, and corneal erosion
#
Includes dyspnea and dyspnea exertional
Þ
Includes back pain, musculoskeletal discomfort, musculoskeletal
pain, musculoskeletal chest pain, neck pain, pain in extremity
ß
Includes weight decreased and cachexia
|
|
Any
|
100
|
67
|
|
Gastrointestinal disorders
|
92
|
24
|
|
Stomatitis
|
56
|
9
|
|
Diarrhea
|
47
|
2
|
|
Dry
mouth
|
45
|
0
|
|
Constipation
|
28
|
1
|
|
Abdominal
pain*
|
23
|
2
|
|
Nausea
|
21
|
1
|
|
Vomiting
|
13
|
2
|
|
Metabolism and nutrition disorders
|
90
|
16
|
|
Decreased
appetite
|
38
|
0
|
|
General disorders and admin. site conditions
|
69
|
13
|
|
Fatigue†
|
54
|
10
|
|
Pyrexia
|
14
|
1
|
|
Skin and subcutaneous disorders
|
75
|
16
|
|
Onycholysis‡
|
41
|
10
|
|
Dry
skin§
|
34
|
0
|
|
Palmar-plantar
erythrodysaesthesia
|
26
|
6
|
|
Alopecia
|
26
|
0
|
|
Nail
discoloration
|
11
|
0
|
|
Eye disorders
|
62
|
11
|
|
Dry
eye¶
|
28
|
6
|
|
Vision
blurred
|
17
|
0
|
|
Lacrimation
increased
|
10
|
0
|
|
Nervous system disorders
|
57
|
5
|
|
Dysgeusia
|
37
|
1
|
|
Infections and infestations
|
56
|
20
|
|
Paronychia
|
17
|
3
|
|
Urinary
tract infection
|
17
|
6
|
|
Conjunctivitis
|
11
|
0
|
|
Respiratory, thoracic and mediastinal disorders
|
40
|
7
|
|
Oropharyngeal
pain
|
11
|
1
|
|
Dyspnea#
|
10
|
2
|
|
Renal and urinary tract disorders
|
38
|
10
|
|
Hematuria
|
11
|
2
|
|
Musculoskeletal and connective tissue disorders
|
31
|
0
|
|
Musculoskeletal
painÞ
|
20
|
0
|
|
Arthralgia
|
11
|
0
|
|
Investigations
|
44
|
5
|
|
Weight
decreasedß
|
16
|
0
|
Table 4: Laboratory Abnormalities
Reported in ≥ 10% (All Grade) or ≥ 5% (Grade 3–4) of Patients
|
|
|
Balversa 8 mg daily (N=86*)
|
|
Laboratory
Abnormality
|
All Grades (%)
|
Grade 3–4 (%)
|
|
*
One of the 87 patients had no laboratory tests.
|
|
Hematology
|
|
Hemoglobin
decreased
|
35
|
3
|
|
Platelets
decreased
|
19
|
1
|
|
Leukocytes
decreased
|
17
|
0
|
|
Neutrophils
decreased
|
10
|
2
|
|
Chemistry
|
|
Phosphate
increased
|
76
|
1
|
|
Creatinine
increased
|
52
|
5
|
|
Sodium
decreased
|
40
|
16
|
|
Alanine
aminotransferase increased
|
41
|
1
|
|
Alkaline
phosphatase increased
|
41
|
1
|
|
Albumin
decreased
|
37
|
0
|
|
Aspartate
aminotransferase increased
|
30
|
0
|
|
Magnesium
decreased
|
30
|
1
|
|
Phosphate
decreased
|
24
|
9
|
|
Calcium
increased
|
22
|
3
|
|
Potassium
increased
|
16
|
0
|
|
Fasting
glucose increased
|
10
|
0
|
Drug
InteractionsEffect of Other Drugs on Balversa
Table 5 summarizes drug
interactions that affect the exposure of Balversa or serum phosphate level and
their clinical management.
Table 5: Drug Interactions that Affect
Balversa
|
|
Strong CYP2C9 or CYP3A4 Inhibitors
|
|
Clinical Impact
|
· Co-administration
of Balversa with strong inhibitors of CYP2C9 or CYP3A4 increased erdafitinib
plasma concentrations [see Clinical Pharmacology (12.3)].
· Increased
erdafitinib plasma concentrations may lead to increased drug-related
toxicity [see Warnings and Precautions (5)].
|
|
Clinical
Management
|
· Consider
alternative therapies that are not strong inhibitors of CYP2C9 or CYP3A4
during treatment with Balversa.
· If
co-administration of a strong inhibitor of CYP2C9 or CYP3A4 is unavoidable,
monitor closely for adverse reactions and consider dose modifications
accordingly [see Dosage and Administration (2.3)]. If
the strong inhibitor is discontinued, the Balversa dose may be increased in
the absence of drug-related toxicity.
|
|
Strong CYP2C9 or CYP3A4 Inducers
|
|
Clinical Impact
|
· Co-administration
of Balversa with strong inducers of CYP2C9 or CYP3A4 may decrease erdafitinib
plasma concentrations significantly [see Clinical Pharmacology (12.3)].
· Decreased
erdafitinib plasma concentrations may lead to decreased activity.
|
|
Clinical
Management
|
· Avoid
co-administration of strong inducers of CYP2C9 or CYP3A4 with Balversa.
|
|
Moderate CYP2C9 or CYP3A4 Inducers
|
|
Clinical Impact
|
· Co-administration
of Balversa with moderate inducers of CYP2C9 or CYP3A4 may decrease
erdafitinib plasma concentrations [see Clinical Pharmacology (12.3)].
· Decreased
erdafitinib plasma concentrations may lead to decreased activity.
|
|
Clinical
Management
|
· If a
moderate CYP2C9 or CYP3A4 inducer must be co-administered at the start of
Balversa treatment, administer Balversa dose as recommended (8 mg once daily
with potential to increase to 9 mg once daily based on serum phosphate levels
on Days 14 to 21 and tolerability).
· If a
moderate CYP2C9 or CYP3A4 inducer must be co-administered after the initial
dose increase period based on serum phosphate levels and tolerability,
increase Balversa dose up to 9 mg.
· When
a moderate inducer of CYP2C9 or CYP3A4 is discontinued, continue Balversa at
the same dose, in the absence of drug-related toxicity.
|
|
Serum Phosphate Level-Altering Agents
|
|
Clinical Impact
|
· Co-administration
of Balversa with other serum phosphate level-altering agents may increase or
decrease serum phosphate levels [see Pharmacodynamics (12.2)].
· Changes
in serum phosphate levels due to serum phosphate level-altering agents (other
than erdafitinib) may interfere with serum phosphate levels needed for the
determination of initial dose increased based on serum phosphate levels [see Dosage and Administration (2.3)].
|
|
Clinical
Management
|
· Avoid
co-administration of serum phosphate level-altering agents with Balversa
before initial dose increase period based on serum phosphate levels (Days 14
to 21) [see Dosage and Administration (2.3)].
|
Effect of Balversa on Other Drugs
Table 6 summarizes the
effect of Balversa on other drugs and their clinical management.
Table 6: Balversa Drug Interactions that
Affect Other Drugs
|
|
CYP3A4 Substrates
|
|
Clinical Impact
|
· Co-administration
of Balversa with CYP3A4 substrates may alter the plasma concentrations of
CYP3A4 substrates [see Clinical Pharmacology (12.3)].
· Altered
plasma concentrations of CYP3A4 substrates may lead to loss of activity or
increased toxicity of the CYP3A4 substrates.
|
|
Clinical
Management
|
· Avoid
co-administration of Balversa with sensitive substrates of CYP3A4 with narrow
therapeutic indices.
|
|
OCT2 Substrates
|
|
Clinical Impact
|
· Co-administration
of Balversa with OCT2 substrates may increase the plasma concentrations of
OCT2 substrates [see Clinical Pharmacology (12.3)].
· Increased
plasma concentrations of OCT2 substrates may lead to increased toxicity of
the OCT2 substrates.
|
|
Clinical
Management
|
· Consider
alternative therapies that are not OCT2 substrates or consider reducing the
dose of OCT2 substrates (e.g., metformin) based on tolerability.
|
|
P-glycoprotein (P-gp) Substrates
|
|
Clinical Impact
|
· Co-administration
of Balversa with P-gp substrates may increase the plasma concentrations of
P-gp substrates [see Clinical Pharmacology (12.3)].
· Increased
plasma concentrations of P-gp substrates may lead to increased toxicity of
the P-gp substrates.
|
|
Clinical
Management
|
· If
co-administration of Balversa with P-gp substrates is unavoidable, separate
Balversa administration by at least 6 hours before or after administration of
P-gp substrates with narrow therapeutic index.
|
USE IN
SPECIFIC POPULATIONSPregnancy
Risk
Summary
Based on the mechanism of
action and findings in animal reproduction studies, Balversa can cause fetal
harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There
are no available data on Balversa use in pregnant women to inform a
drug-associated risk. Oral administration of erdafitinib to pregnant rats
during organogenesis caused malformations and embryo-fetal death at maternal
exposures that were less than the human exposures at the maximum recommended
human dose based on AUC (see Data). Advise pregnant women and
females of reproductive potential of the potential risk to the fetus.
The estimated background
risk of major birth defects and miscarriage for the indicated population is
unknown. All pregnancies have a background risk of birth defect, loss, or other
adverse outcomes. In theU.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 toxicity
study, erdafitinib was orally administered to pregnant rats during the period
of organogenesis. Doses ≥4mg/kg/day (at total maternal exposures <0.1% of
total human exposures at the maximum recommended human dose based on AUC)
produced embryo-fetal death, major blood vessel malformations and other
vascular anomalies, limb malformations (ectrodactyly, absent or misshapen long
bones), an increased incidence of skeletal anomalies in multiple bones
(vertebrae, sternebrae, ribs), and decreased fetal weight.
Lactation
Risk
Summary
There are no data on the
presence of erdafitinib in human milk, or the effects of erdafitinib on the
breastfed child, or on milk production. Because of the potential for serious
adverse reactions from erdafitinib in a breastfed child, advise lactating women
not to breastfeed during treatment with Balversa and for one month following
the last dose.
Females and Males of Reproductive Potential
Pregnancy
Testing
Pregnancy testing is
recommended for females of reproductive potential prior to initiating treatment
with Balversa.
Contraception
Females
Balversa can cause fetal
harm when administered to a pregnant woman. Advise females of reproductive
potential to use effective contraception during treatment with Balversa and for
one month after the last dose [see Use in Specific Population (8.1)].
Males
Advise male patients with
female partners of reproductive potential to use effective contraception during
treatment with Balversa and for one month after the last dose [see Use in Specific Populations (8.1)].
Infertility
Females
Based on findings from
animal studies, Balversa may impair fertility in females of reproductive
potential [see Nonclinical Toxicology (13.1)].
Pediatric Use
Safety and effectiveness of
Balversa in pediatric patients have not been established.
In 4 and 13-week repeat-dose
toxicology studies in rats and dogs, toxicities in bone and teeth were observed
at an exposure less than the human exposure (AUC) at the maximum recommended
human dose. Chondroid dysplasia/metaplasia were reported in multiple bones in
both species, and tooth abnormalities included abnormal/irregular denting in
rats and dogs and discoloration and degeneration of odontoblasts in rats.
Geriatric Use
Of the 416 patients treated
with Balversa in clinical studies, 45% were 65 years of age or older, and 12%
were 75 years of age or older. No overall differences in safety or
effectiveness were observed between these patients and younger patients [see Clinical Studies (14)].
CYP2C9 Poor Metabolizers
CYP2C9*3/*3
Genotype: Erdafitinib plasma concentrations
were predicted to be higher in patients with the CYP2C9*3/*3 genotype. Monitor
for increased adverse reactions in patients who are known or suspected to have
CYP2C9*3/*3 genotype [see Pharmacogenomics (12.5)].
Balversa
Description
Erdafitinib, the active
ingredient in Balversa, is a kinase inhibitor. The chemical name is
N-(3,5-dimethoxyphenyl)-N'-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2-diamine.
Erdafitinib is a yellow powder. It is practically insoluble, or insoluble to
freely soluble in organic solvents, and slightly soluble to practically
insoluble, or insoluble in aqueous media over a wide range of pH values. The
molecular formula is C25H30N6O2 and molecular weight is 446.56.
Chemical structure of
erdafitinib is as follows:
Balversa (erdafitinib) is
supplied as 3 mg, 4 mg or 5 mg film-coated tablets for oral administration and
contains the following inactive ingredients:
Tablet Core: Croscarmellose
sodium, Magnesium stearate (from vegetable source), Mannitol, Meglumine, and
Microcrystalline Cellulose.
Film Coating: (Opadry amb
II): Glycerol monocaprylocaprate Type I,
Polyvinyl alcohol-partially hydrolyzed, Sodium lauryl sulfate, Talc, Titanium
dioxide, Iron oxide yellow, Iron oxide red (for the orange and brown tablets
only), Ferrosoferric oxide/iron oxide black (for the brown tablets only).
Balversa -
Clinical PharmacologyMechanism of Action
Erdafitinib is a kinase
inhibitor that binds to and inhibits enzymatic activity of FGFR1, FGFR2, FGFR3
and FGFR4 based on in vitro data.
Erdafitinib also binds to RET, CSF1R, PDGFRA, PDGFRB, FLT4, KIT, and VEGFR2.
Erdafitinib inhibited FGFR phosphorylation and signaling and decreased cell
viability in cell lines expressing FGFR genetic alterations, including point
mutations, amplifications, and fusions. Erdafitinib demonstrated antitumor
activity in FGFR-expressing cell lines and xenograft models derived from tumor
types, including bladder cancer.
Pharmacodynamics
Cardiac
Electrophysiology
Based on evaluation of QTc
interval in an open-label, dose escalation and dose expansion study in 187
patients with cancer, erdafitinib had no large effect (i.e., > 20 ms) on the
QTc interval.
Serum
Phosphate
Erdafitinib increased serum
phosphate level as a consequence of FGFR inhibition. Balversa should be
increased to the maximum recommended dose to achieve target serum phosphate
levels of 5.5–7.0 mg/dL in early cycles with continuous daily dosing [see Dosage and Administration (2.3)].
In erdafitinib clinical
trials, the use of drugs which can increase serum phosphate levels, such as
potassium phosphate supplements, vitamin D supplements, antacids,
phosphate-containing enemas or laxatives, and medications known to have
phosphate as an excipient were prohibited unless no alternatives exist. To
manage phosphate elevation, phosphate binders were permitted. Avoid concomitant
use with agents that can alter serum phosphate levels before the initial dose
increase period based on serum phosphate levels [see Drug Interactions (7.1)].
Pharmacokinetics
Following administration of
8 mg once daily, the mean (coefficient of variation [CV%]) erdafitinib
steady-state maximum observed plasma concentration (Cmax), area under the curve (AUCtau), and minimum observed
plasma concentration (Cmin) were 1,399 ng/mL (51%), 29,268 ng∙h/mL (60%), and 936 ng/mL
(65%), respectively.
Following single and repeat
once daily dosing, erdafitinib exposure (maximum observed plasma concentration
[Cmax]
and area under the plasma concentration time curve [AUC]) increased
proportionally across the dose range of 0.5 to 12 mg (0.06 to 1.3 times the
maximum approved recommended dose). Steady state was achieved after 2 weeks
with once daily dosing and the mean accumulation ratio was 4-fold.
Absorption
Median time to achieve peak
plasma concentration (tmax) was 2.5 hours (range: 2 to 6 hours).
Effect
of Food
No clinically meaningful
differences with erdafitinib pharmacokinetics were observed following
administration of a high-fat and high-calorie meal (800 calories to 1,000
calories with approximately 50% of total caloric content of the meal from fat)
in healthy subjects.
Distribution
The mean apparent volume of
distribution of erdafitinib was 29 L in patients.
Erdafitinib protein binding
was 99.8% in patients, primarily to alpha-1-acid glycoprotein.
Elimination
The mean total apparent
clearance (CL/F) of erdafitinib was 0.362 L/h in patients.
The mean effective half-life
of erdafitinib was 59 hours in patients.
Metabolism
Erdafitinib is primarily
metabolized by CYP2C9 and CYP3A4. The contribution of CYP2C9 and CYP3A4 in the
total clearance of erdafitinib is estimated to be 39% and 20% respectively.
Unchanged erdafitinib was the major drug-related moiety in plasma, there were
no circulating metabolites.
Excretion
Following a single oral dose
of radiolabeled erdafitinib, approximately 69% of the dose was recovered in
feces (19% as unchanged) and 19% in urine (13% as unchanged).
Specific
Populations
No clinically meaningful
trends in the pharmacokinetics of erdafitinib were observed based on age (21–88
years), sex, race, body weight (36–132 kg), mild (eGFR [estimated glomerular
filtration rate, using modification of diet in renal disease equation] 60 to 89
mL/min/1.73 m2) or moderate (eGFR 30–59 mL/min/1.73 m2) renal impairment or mild
hepatic impairment (total bilirubin ≤ ULN and AST > ULN, or total bilirubin
> 1.0–1.5 × ULN and any AST).
The pharmacokinetics of
erdafitinib in patients with severe renal impairment, renal impairment
requiring dialysis, moderate or severe hepatic impairment is unknown.
Drug
Interaction Studies
Clinical Studies and
Model-Based Approaches Strong CYP2C9 Inhibitors:
Erdafitinib mean ratios (90%
CI) for Cmax and AUCinf were 121% (99.9, 147) and 148% (120, 182), respectively,
when co-administered with fluconazole, a strong CYP2C9 inhibitor and moderate
CYP3A4 inhibitor, relative to erdafitinib alone.
Strong
CYP3A4 Inhibitors:
Erdafitinib mean ratios (90%
CI) for Cmax and AUCinf were 105% (86.7, 127) and 134% (109, 164), respectively,
when co-administered with itraconazole (a strong CYP3A4 inhibitor and P-gp
inhibitor) relative to erdafitinib alone.
Strong
CYP3A4/2C9 Inducers:
Simulations suggested that
rifampicin (a strong CYP3A4/2C9 inducer) may significantly decrease erdafitinib
Cmax and
AUC.
In
Vitro Studies
CYP
Substrates:
Erdafitinib is a time
dependent inhibitor and inducer of CYP3A4. The effect of erdafitinib on a
sensitive CYP3A4 substrate is unknown. Erdafitinib is not an inhibitor of other
major CYP isozymes at clinically relevant concentrations.
Transporters:
Erdafitinib is a substrate
and inhibitor of P-gp. P-gp inhibitors are not expected to affect erdafitinib
exposure to a clinically relevant extent. Erdafitinib is an inhibitor of OCT2.
Erdafitinib does not inhibit
BCRP, OATP1B, OATP1B3, OAT1, OAT3, OCT1, MATE-1, or MATE-2K at clinically
relevant concentrations.
Acid-Lowering
Agents:
Erdafitinib has adequate
solubility across the pH range of 1 to 7.4. Acid-lowering agents (e.g.,
antacids, H2-antagonists, proton pump inhibitors) are not expected to affect
the bioavailability of erdafitinib.
Pharmacogenomics
CYP2C9 activity is reduced
in individuals with genetic variants, such as the CYP2C9*2 and CYP2C9*3
polymorphisms. Erdafitinib exposure was similar in subjects with CYP2C9*1/*2
and *1/*3 genotypes relative to subjects with CYP2C9*1/*1 genotype (wild type).
No data are available in subjects characterized by other genotypes (e.g.,
*2/*2, *2/*3, *3/*3). Simulation suggested no clinically meaningful differences
in erdafitinib exposure in subjects with CYP2C9*2/*2 and *2/*3 genotypes. The
exposure of erdafitinib is predicted to be 50% higher in subjects with the
CYP2C9*3/*3 genotype, estimated to be present in 0.4% to 3% of the population
among various ethnic groups.
Nonclinical
ToxicologyCarcinogenesis, Mutagenesis, and Impairment of Fertility
Carcinogenicity studies have
not been conducted with erdafitinib.
Erdafitinib was not
mutagenic in a bacterial reverse mutation (Ames) assay and was not clastogenic in
an in vitro micronucleus or an in vivo rat bone marrow micronucleus assay.
Fertility studies in animals
have not been conducted with erdafitinib. In the 3-month repeat-dose toxicity
study, erdafitinib showed effects on female reproductive organs (necrosis of
the ovarian corpora lutea) in rats at an exposure less than the human exposure
(AUC) at maximum recommended human dose.
Clinical
StudiesUrothelial Carcinoma with Susceptible FGFR Genetic Alterations
Study BLC2001 (NCT02365597)
was a multicenter, open-label, single-arm study to evaluate the efficacy and
safety of Balversa in patients with locally advanced or metastatic urothelial
carcinoma(mUC). Fibroblast growth factor receptor (FGFR) mutation status for
screening and enrollment of patients was determined by a clinical trial assay
(CTA). The efficacy population consists of a cohort of eighty-seven patients
who were enrolled in this study with disease that had progressed on or after at
least one prior chemotherapy and that had at least 1 of the following genetic
alterations: FGFR3 gene mutations (R248C, S249C, G370C, Y373C) or FGFR gene
fusions (FGFR3-TACC3, FGFR3-BAIAP2L1, FGFR2-BICC1, FGFR2-CASP7), as determined
by the CTA performed at a central laboratory. Tumor samples from 69 patients
were tested retrospectively by the QIAGEN therascreen® FGFR RGQ RT-PCR Kit,
which is the FDA-approved test for selection of patients with mUC for Balversa.
Patients received a starting
dose of Balversa at 8 mg once daily with a dose increase to 9 mg once daily in
patients whose serum phosphate levels were below the target of 5.5 mg/dL
between days 14 and 17; a dose increase occurred in 41% of patients. Balversa
was administered until disease progression or unacceptable toxicity. The major
efficacy outcome measures were objective response rate (ORR) and duration of
response (DoR), as determined by blinded independent review committee (BIRC)
according to RECIST v1.1.
The median age was 67 years
(range: 36 to 87 years), 79% were male, and 74% were Caucasian. Most patients
(92%) had a baseline Eastern Cooperative Oncology Group (ECOG) performance
status of 0 or 1. Sixty-six percent of patients had visceral metastases.
Eighty-four (97%) patients received at least one of cisplatin or carboplatin
previously. Fifty-six percent of patients only received prior cisplatin-based
regimens, 29% received only prior carboplatin-based regimens, and 10% received
both cisplatin and carboplatin-based regimens. Three (3%) patients had disease
progression following prior platinum-containing neoadjuvant or adjuvant therapy
only. Twenty-four percent of patients had been treated with prior anti
PD-L1/PD-1 therapy.
Efficacy results are
summarized in Table 7 and Table 8. Overall response rate was 32.2%. Responders
included patients who had previously not responded to anti PD-L1/PD-1 therapy.
Table 7: Efficacy Results for Study
BLC2001
|
|
|
BIRC* assessment
|
|
Endpoint
|
N=87
|
|
ORR = CR + PR
CI = Confidence Interval
|
|
*
BIRC: Blinded Independent Review Committee
|
|
ORR (95% CI)
|
32.2% (22.4, 42.0)
|
|
Complete
response (CR)
|
2.3%
|
|
Partial
response (PR)
|
29.9%
|
|
Median DoR in
months (95% CI)
|
5.4 (4.2, 6.9)
|
Table 8: Efficacy Results by FGFR Genetic
Alteration
|
|
|
BIRC* assessment
|
|
ORR = CR + PR
CI = Confidence Interval
|
|
*
BIRC: Blinded Independent Review Committee
†
Both responders had FGFR3-TACC3_V1 fusion
‡
One patient with a FGFR2-CASP7/FGFR3-TACC3_V3 fusion
is reported in both FGFR2 fusion and FGFR3 fusion above
|
|
FGFR3 Point
Mutation
|
N=64
|
|
ORR
(95% CI)
|
40.6% (28.6, 52.7)
|
|
FGFR3
Fusion †, ‡
|
N=18
|
|
ORR
(95% CI)
|
11.1% (0, 25.6)
|
|
FGFR2
Fusion ‡
|
N=6
|
|
ORR
|
0
|
How
Supplied/Storage and Handling
Balversa™ (erdafitinib)
tablets are available in the strengths and packages listed below:
3 mg tablets: Yellow, round
biconvex, film-coated, debossed with "3" on one side and
"EF" on the other side.
–
Bottle of 56-tablets with child resistant closure (NDC
59676-030-56).
–
Bottle of 84-tablets with child resistant closure (NDC
59676-030-84).
4 mg tablets:Orange, round biconvex, film-coated, debossed with
"4" on one side and "EF" on the other side.
–
Bottle of 28-tablets with child resistant closure (NDC
59676-040-28).
–
Bottle of 56-tablets with child resistant closure (NDC
59676-040-56).
5 mg tablets: Brown, round
biconvex, film-coated, debossed with "5" on one side and
"EF" on the other side.
–
Bottle of 28-tablets with child resistant closure (NDC
59676-050-28).
Store at 20°C–25°C
(68°F–77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].
Patient
Counseling Information
Advise the patient to read
the FDA-approved patient labeling (Patient Information).
FGFR
genetic alterations: Advise patients that
evidence of a susceptible FGFR3 or FGFR2 mutation or gene fusion within the
tumor specimen is necessary to identify patients for whom treatment is
indicated [see Dosage and Administration (2.1)].
Ocular
disorders: Advise patients to contact their
healthcare provider if they experience any visual changes [see Warnings and Precautions (5.1)]. In
order to prevent or treat dry eyes, advise patients to use artificial tear
substitutes, hydrating or lubricating eye gels or ointments frequently, at
least every 2 hours during waking hours [see Dosage and Administration (2.3)].
Skin,
mucous or nail disorders: Advise patients to contact
their healthcare provider if they experience progressive or intolerable skin,
mucous or nail disorders [see Adverse Reactions (6.1)].
Hyperphosphatemia: Advise patients that their healthcare provider will assess
their serum phosphate level between 14 and 21 days of initiating treatment and
will adjust the dose if needed [see Warnings and Precautions (5.2)]. During
this initial phosphate-assessment period, advise patients to avoid concomitant
use with agents that can alter serum phosphate levels. Advise patients that,
after the initial phosphate assessment period, monthly phosphate level
monitoring for hyperphosphatemia should be performed during treatment with
Balversa [see Drug Interactions (7.1)].
Drug
Interactions: Advise patients to inform their
healthcare providers of all concomitant medications, including prescription
medicines, over-the-counter drugs, and herbal products [see Drug Interactions (7.1, 7.2)].
Dosing
Instructions: Instruct patients to swallow the
tablets whole once daily with or without food. If vomiting occurs any time
after taking Balversa, advise patients to take the next dose the next
day. [see Dosage and Administration (2.1)].
Missed
dose: If a dose is missed, advise patients to take the missed as
soon as possible. Resume the regular daily dose schedule for Balversa the next
day. Extra tablets should not be taken to make up for the missed dose [see Dosage and Administration (2.3)].
Embryo-Fetal
Toxicity: Advise pregnant women and females of
reproductive potential of the potential risk to the fetus. Advise females to
inform their healthcare providers of a known or suspected pregnancy [see Warning and Precautions (5.3) and Use in Specific Population (8.1)].
Advise female patients of reproductive potential to use effective contraception
during treatment and for one month after the last dose of Balversa. Advise male
patients with female partners of reproductive potential to use effective
contraception during treatment and for one month after the last dose of
Balversa [see Use in Specific Populations (8.3)].
Lactation: Advise females not to breastfeed during treatment with
Balversa and for one month after the last dose [see Use in Specific Populations (8.2)].
Product ofSwitzerland
Manufactured for:
Janssen Products, LP
Horsham,PA19044
Under license from Astex
Therapeutics Limited.
©2019 Janssen Pharmaceutical
Companies
|
This Patient
Information has been approved by the U.S. Food and Drug Administration.
|
Issued: April
2019
|
|
PATIENT INFORMATION
Balversa™ (bal-VER-sah)
(erdafitinib) tablets
|
|
What is Balversa?
Balversa is a prescription medicine used to treat adults with bladder cancer
(urothelial cancer) that has spread or cannot be removed by surgery:
which
has a certain type of abnormal "FGFR" gene, andwho
have tried at least one other chemotherapy medicine that contains
platinum, and it did not work or is no longer working.
Your healthcare
provider will test your cancer for certain types of abnormal FGFR genes and
make sure that Balversa is right for you.
It is not known if Balversa is safe and effective in children.
|
|
Before taking Balversa tell your healthcare provider about all of
your medical conditions, including if you:
have
vision or eye problems.are
pregnant or plan to become pregnant. Balversa can harm your unborn baby.
You should not become pregnant during treatment with Balversa.
Females who can become pregnant:Your
healthcare provider may do a pregnancy test before you start treatment
with Balversa.You
should use effective birth control during treatment and for 1 month
after the last dose of Balversa. Talk to your healthcare provider about
birth control methods that may be right for you.Tell
your healthcare provider right away if you become pregnant or think you
may be pregnant.
Males with female partners who can become pregnant:
You
should use effective birth control when sexually active during
treatment with Balversa and for 1 month after the last dose.are
breastfeeding or plan to breastfeed. Do not breastfeed during treatment
and for 1 month after the last dose of Balversa.
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 Balversa?
Take
Balversa exactly as your healthcare provider tells you.Take
Balversa 1 time each day.Swallow
Balversa tablets whole with or without food.Your
healthcare provider may change your dose of Balversa, temporarily stop
or completely stop treatment if you get certain side effects.If you
miss a dose of Balversa, take the missed dose as soon as possible on the
same day. Take your regular dose of Balversa the next day. Do not take
more Balversa than prescribed to make up for the missed dose.If you vomit after taking Balversa, do not take
another Balversa tablet. Take your regular dose of Balversa the next
day.
|
|
What are the possible side effects of Balversa?
Balversa may cause serious side effects, including:
Eye problems. Eye problems are common with
Balversa but can also be serious. Eye problems include dry or inflamed
eyes, inflamed cornea (front part of the eye) and disorders of the
retina, an internal part of the eye. Tell your healthcare provider right
away if you develop blurred vision, loss of vision or other visual
changes. You should use artificial tear substitutes, hydrating or
lubricating eye gels or ointments at least every 2 hours during waking
hours to help prevent dry eyes. During treatment with Balversa, your
healthcare provider will send you to see an eye specialist.High phosphate levels in the blood
(hyperphosphatemia). Hyperphosphatemia is common with Balversa but can also be
serious. Your healthcare provider will check your blood phosphate level
between 14 and 21 days after starting treatment with Balversa, and then
monthly, and may change your dose if needed.
The most common side effects of Balversa include:
|
|
· mouth
sores
· feeling
tired
· change
in kidney function
· diarrhea
· dry
mouth
· nails
separate from the bed or poor formation of the nail
· change
in liver function
· low
salt (sodium) levels
· decreased
appetite
· change
in sense of taste
|
· low
red blood cells (anemia)
· dry
skin
· dry
eyes
· hair
loss
· redness,
swelling, peeling or tenderness, mainly on the hands or feet ('hand-foot
syndrome')
· constipation
· stomach
(abdominal) pain
· nausea
· muscle
pain
|
|
Tell your
healthcare provider right away if you develop any nail or skin problems
including nails separating from the nail bed, nail pain, nail bleeding,
breaking of the nails, color or texture changes in your nails, infected skin
around the nail, an itchy skin rash, dry skin, or cracks in the skin.
Balversa may affect fertility in females who are able to become pregnant.
Talk to your healthcare provider if this is a concern for you.
These are not all possible side effects of Balversa. For more information,
ask your healthcare provider or pharmacist.
Call your healthcare provider for medical advice about side effects. You may
report side effects to FDA at 1-800-FDA-1088.
|
|
How should I store Balversa?
Store
Balversa tablets at room temperature between 68°F to 77°F (20°C to
25°C).
Keep Balversa and all medicines out of the reach of children.
|
|
General information about the safe and effective use of Balversa.
Medicines are sometimes prescribed for purposes other than those listed in
Patient Information leaflets. Do not use Balversa for a condition for which
it was not prescribed. Do not give Balversa 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 for information about Balversa that is written for
healthcare professionals.
|
|
What are the ingredients in Balversa?
Active ingredient: erdafitinib
Inactive ingredients:
Tablet Core: Croscarmellose sodium, Magnesium stearate (from vegetable
source), Mannitol, Meglumine, and Microcrystalline Cellulose.
Film Coating (Opadry amb II): Glycerol monocaprylocaprate Type I, Polyvinyl
alcohol-partially hydrolyzed, Sodium lauryl sulfate, Talc, Titanium dioxide,
Iron oxide yellow, Iron oxide red (for the orange and brown tablets only),
Ferrosoferric oxide/iron oxide black (for the brown tablets only).
Manufactured by: Janssen-Cilag SpA,Latina,Italy
Manufactured for: Janssen Products, LP,Horsham,PA19044
© 2019 Janssen Pharmaceutical Companies
For more information call Janssen Products, LP at 1-800-526-7736
(1-800-JANSSEN) or go to www.Balversa.com.
|
PRINCIPAL
DISPLAY PANEL - 3 mg Tablet Bottle Carton
NDC 59676-030-56
Balversa™
(erdafitinib) tablets
3 mg
Each film-coated tablet
contains 3 mg of erdafitinib.
Rx only
56 film-coated tablets
PRINCIPAL
DISPLAY PANEL - 4 mg Tablet Bottle Carton
NDC 59676-040-56
Balversa™
(erdafitinib) tablets
4 mg
Each film-coated tablet
contains 4 mg of erdafitinib.
Rx only
56 film-coated tablets
PRINCIPAL
DISPLAY PANEL - 5 mg Tablet Bottle Carton
NDC 59676-050-28
Balversa™
(erdafitinib) tablets
5 mg
Each film-coated tablet
contains 5 mg of erdafitinib.
Rx only
28 film-coated tablets
|
Balversa
erdafitinib tablet, film coated
|
|
Product
Information
|
|
Product
Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:59676-030
|
|
Route of
Administration
|
ORAL
|
DEA
Schedule
|
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
Erdafitinib (Erdafitinib)
|
Erdafitinib
|
3 mg
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
Croscarmellose
sodium
|
|
|
Magnesium
stearate
|
|
|
Mannitol
|
|
|
Meglumine
|
|
|
Microcrystalline
Cellulose
|
|
|
GLYCERYL
MONOCAPRYLOCAPRATE
|
|
|
POLYVINYL
ALCOHOL, UNSPECIFIED
|
|
|
SODIUM
LAURYL SULFATE
|
|
|
TALC
|
|
|
TITANIUM
DIOXIDE
|
|
|
FERRIC
OXIDE YELLOW
|
|
|
|
Product
Characteristics
|
|
Color
|
YELLOW
|
Score
|
no score
|
|
Shape
|
OVAL (biconvex
shaped)
|
Size
|
8mm
|
|
Flavor
|
|
Imprint Code
|
3;EF
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:59676-030-56
|
1 BOTTLE in 1
CARTON
|
|
|
1
|
|
56 TABLET,
FILM COATED in 1 BOTTLE
|
|
|
2
|
NDC:59676-030-84
|
1 BOTTLE in 1
CARTON
|
|
|
2
|
|
84 TABLET,
FILM COATED in 1 BOTTLE
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA212018
|
04/12/2019
|
|
|
|
Balversa
erdafitinib tablet, film coated
|
|
Product
Information
|
|
Product
Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:59676-040
|
|
Route of
Administration
|
ORAL
|
DEA
Schedule
|
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
Erdafitinib (Erdafitinib)
|
Erdafitinib
|
4 mg
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
Croscarmellose
sodium
|
|
|
Magnesium
stearate
|
|
|
Mannitol
|
|
|
Meglumine
|
|
|
Microcrystalline
Cellulose
|
|
|
GLYCERYL
MONOCAPRYLOCAPRATE
|
|
|
POLYVINYL
ALCOHOL, UNSPECIFIED
|
|
|
SODIUM
LAURYL SULFATE
|
|
|
TALC
|
|
|
TITANIUM
DIOXIDE
|
|
|
FERRIC
OXIDE YELLOW
|
|
|
FERRIC
OXIDE RED
|
|
|
|
Product
Characteristics
|
|
Color
|
ORANGE
|
Score
|
no score
|
|
Shape
|
OVAL (biconvex
shaped)
|
Size
|
8mm
|
|
Flavor
|
|
Imprint
Code
|
4;EF
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:59676-040-28
|
1 BOTTLE in 1
CARTON
|
|
|
1
|
|
28 TABLET,
FILM COATED in 1 BOTTLE
|
|
|
2
|
NDC:59676-040-56
|
1 BOTTLE in 1
CARTON
|
|
|
2
|
|
56 TABLET,
FILM COATED in 1 BOTTLE
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA212018
|
04/12/2019
|
|
|
|
Balversa
erdafitinib tablet, film coated
|
|
Product
Information
|
|
Product
Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:59676-050
|
|
Route of
Administration
|
ORAL
|
DEA
Schedule
|
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
Erdafitinib (Erdafitinib)
|
Erdafitinib
|
5 mg
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
Croscarmellose
sodium
|
|
|
Magnesium
stearate
|
|
|
Mannitol
|
|
|
Meglumine
|
|
|
Microcrystalline
Cellulose
|
|
|
GLYCERYL
MONOCAPRYLOCAPRATE
|
|
|
POLYVINYL
ALCOHOL, UNSPECIFIED
|
|
|
SODIUM
LAURYL SULFATE
|
|
|
TALC
|
|
|
TITANIUM
DIOXIDE
|
|
|
FERRIC
OXIDE YELLOW
|
|
|
FERRIC
OXIDE RED
|
|
|
FERROSOFERRIC
OXIDE
|
|
|
|
Product
Characteristics
|
|
Color
|
BROWN
|
Score
|
no score
|
|
Shape
|
OVAL (biconvex
shaped)
|
Size
|
9mm
|
|
Flavor
|
|
Imprint
Code
|
5;EF
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:59676-050-28
|
1 BOTTLE in 1
CARTON
|
|
|
1
|
|
28 TABLET,
FILM COATED in 1 BOTTLE
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing End
Date
|
|
NDA
|
NDA212018
|
04/12/2019
|
|
|
|
Labeler - Janssen Products LP (804684207)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Cilag AG
|
|
483237103
|
API
MANUFACTURE(59676-030, 59676-040, 59676-050)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Johnson & Johnson
Private Limited
|
|
677603030
|
ANALYSIS(59676-030,
59676-040, 59676-050)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Janssen Cilag
SpA
|
|
542797928
|
MANUFACTURE(59676-030,
59676-040, 59676-050), ANALYSIS(59676-030, 59676-040, 59676-050),
PACK(59676-030, 59676-040, 59676-050)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
AndersonBrecon
Inc.
|
|
053217022
|
PACK(59676-030,
59676-040, 59676-050)
|
Janssen Products LP
