BALVERSA SIDE EFFECTS
- Generic Name: erdafitinib tablets
- Brand Name: Balversa
- Drug Class: FGFR Inhibitors
SIDE EFFECTS
The following serious adverse reactions are also described elsewhere in the labeling:
- Ocular Disorders [see WARNING AND PRECAUTIONS].
- Hyperphosphatemia [see WARNING AND PRECAUTIONS].
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]. 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 1: Adverse Reactions Reported in ≥ 10% (Any Grade) or ≥5% (Grade 3-4) of Patients
| Adverse Reaction | BALVERSA 8 mg daily (N=87) |
|
| All Grades (%) | Grade 3-4 (%) | |
| 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 decreasedβ | 16 | 0 |
| *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 ÞIncludes back pain, musculoskeletal discomfort, musculoskeletal pain, musculoskeletal chest pain, neck pain, pain in extremity &bate; Includes weight decreased and cachexia |
||
Table 2: Laboratory Abnormalities Reported in ≥ 10% (All Grade) or ≥ 5% (Grade 3-4) of Patients
| Laboratory Abnormality | BALVERSA 8 mg daily (N=86*) |
|
| All Grades (%) | Grade 3-4 (%) | |
| 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 |
| * One of the 87 patients had no laboratory tests. | ||
SRC: NLM .