BALVERSA SIDE EFFECTS

Last updated on MDtodate: 10/03/2022

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 .