BALVERSA (Page 2 of 6)

3 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.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Ocular 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)].

5.2 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].

5.3 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)].

6 ADVERSE REACTIONS

The following serious adverse reactions are also described elsewhere in the labeling:

6.1 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 pain Þ 20 0
Arthralgia 11 0
Investigations 44 5
Weight decreased ß 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

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