TRUSELTIQ SIDE EFFECTS
- Generic Name: infigratinib capsules
- Brand Name: Truseltiq
SIDE EFFECTS
The following adverse reactions are discussed elsewhere in the labeling:
- Ocular Toxicity
- Hyperphosphatemia and Soft Tissue Mineralization
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 pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to TRUSELTIQ as a single agent at 125 mg orally once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles in 351 patients in Study CBGJ398X2204 and in patients with other advanced solid tumors or hematological malignancies. Among 351 patients who received TRUSELTIQ, 27% were exposed for 6 months or longer and 10% were exposed for greater than one year.
Previously Treated, Unresectable Locally Advanced Or Metastatic Cholangiocarcinoma
The safety of TRUSELTIQ was evaluated in Study CBGJ398X2204, which included 108 patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement. Patients were treated orally with TRUSELTIQ 125 mg once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles, until disease progression or unacceptable toxicity. The median duration of treatment was 5.5 months (range: 0.03 to 28.3 months).
The median age of TRUSELTIQ treated patients was 53 years (range 23-81), 62% were females, and 72% were White.
Serious adverse reactions occurred in 32% of patients receiving TRUSELTIQ. Serious adverse reactions in ≥2% of patients who received TRUSELTIQ included infections, anemia, pyrexia, abdominal pain, hypercalcemia, and sepsis. Fatal adverse reactions occurred in 1 (0.9%) patient who received TRUSELTIQ and was due to sepsis.
Permanent discontinuation due to an adverse reaction occurred in 15% of patients who received TRUSELTIQ. Adverse reactions requiring permanent discontinuation in ≥1% of patients were blood creatinine increased, fatigue, subretinal fluid, and calcinosis.
Dosage interruptions due to an adverse reaction occurred in 64% of patients who received TRUSELTIQ. Adverse reactions requiring dosage interruption in ≥5% of patients included hyperphosphatemia, hypercalcemia, palmar-plantar erythrodysesthesia syndrome, stomatitis, diarrhea, and blood creatinine increased.
Dosage reductions due to an adverse reaction occurred in 60% of patients who received TRUSELTIQ. Adverse reactions requiring dosage reductions in ≥2% of patients who received TRUSELTIQ included hyperphosphatemia, stomatitis, palmar-plantar erythrodysesthesia syndrome, increased blood creatinine, increased lipase, hypercalcemia, and onycholysis.
The most common (≥20%) adverse reactions were nail toxicity, stomatitis, dry eye, fatigue, alopecia, palmarplantar erythrodysesthesia syndrome, arthralgia, dysgeusia, constipation, abdominal pain, dry mouth, eyelash changes, diarrhea, dry skin, decreased appetite, vision blurred and vomiting. The most common laboratory abnormalities (≥20%) were increased creatinine, increased phosphate, decreased phosphate, increased alkaline phosphatase, decreased hemoglobin, increased alanine aminotransferase, increased lipase, increased calcium, decreased lymphocytes, decreased sodium, increased triglycerides, increased aspartate aminotransferase, increased urate, decreased platelets, decreased leukocytes, decreased albumin, increased bilirubin and decreased potassium.
Table 1 summarizes the adverse reactions in Study CBGJ398X2204. Table 4 summarizes select laboratory abnormalities in Study CBGJ398X2204.
Table 1: Adverse Reactions (≥15%) in Patients Receiving TRUSELTIQ in Study CBGJ398X2204
| Adverse Reaction | TRUSELTIQ N=108 |
|
| All Grades (%) | Grade 3 or 4 a (%) | |
| Skin and subcutaneous tissue disorders | ||
| Nail toxicity b | 57 | 2* |
| Alopecia | 38 | 0 |
| Palmar-plantar erythrodysesthesia syndrome | 33 | 7* |
| Dry skin | 23 | 0 |
| Gastrointestinal disorders | ||
| Stomatitis c | 56 | 15* |
| Constipation | 30 | 1* |
| Abdominal pain d | 26 | 5* |
| Dry mouth | 25 | 0 |
| Diarrhea | 24 | 3* |
| Vomiting | 21 | 1* |
| Nausea | 19 | 1* |
| Dyspepsia | 17 | 0 |
| Eye disorders e | ||
| Dry eye f | 44 | 0 |
| Eyelash changes g | 25 | 0 |
| Vision blurred | 21 | 0 |
| General disorders and administrative site conditions | ||
| Fatigue h | 44 | 4* |
| Edema i | 17 | 1* |
| Pyrexia | 15 | 1* |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 32 | 0 |
| Pain in extremity | 17 | 2* |
| Nervous system disorders | ||
| Dysgeusia | 32 | 0 |
| Headache | 17 | 1* |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 22 | 1* |
| Respiratory, thoracic and mediastinal disorders | ||
| Epistaxis | 18 | 0 |
| Investigations | ||
| Weight decreased | 15 | 2* |
| Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 4.03). a Events of Grade 3 only (no Grade 4 occurred) are marked with an asterisk. b Includes ingrown nail, nail bed bleeding, nail bed disorder, nail bed inflammation, nail bed tenderness, nail discoloration, nail isorder, nail dystrophy, nail hypertrophy, nail infection, nail ridging, onychalgia, onychoclasis, onycholysis, onychomadesis, onychomycosis, and paronychia. c Includes mouth ulceration and stomatitis. d Includes abdominal pain, abdominal pain upper, abdominal discomfort, and abdominal pain lower. e Severity of eye disorders is not represented by CTCAE Grading f Includes dry eye, keratitis, lacrimation increased, pinguecula, and punctate keratitis. g Includes blepharitis, eyelash changes, eyelash discoloration, growth of eyelashes, trichiasis, and trichomegaly. h Includes asthenia and fatigue. i Includes edema peripheral and edema. |
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Clinically relevant adverse reactions occurring in ≤15% of patients included cataracts (12%) and fractures (1%).
Table 2: Select Laboratory Abnormalities (≥10%) Worsening from Baseline in Patients Receiving TRUSELTIQ in Study CBGJ398X2204
| Laboratory Abnormality | TRUSELTIQ N=108 |
|
| All Grades (%) | Grade 3 or 4 (%) | |
| Hematology | ||
| Decreased hemoglobin | 53 | 5 |
| Decreased lymphocytes | 43 | 9 |
| Decreased platelets | 37 | 4 |
| Decreased leukocytes | 26 | 3 |
| Decreased neutrophils | 14 | 2 |
| Chemistry | ||
| Increased creatinine | 93 | 7 |
| Increased phosphate a | 90 | 13 |
| Decreased phosphate | 64 | 31 |
| Increased alkaline phosphatase | 54 | 8 |
| Increased alanine aminotransferase | 51 | 6 |
| Increased lipase | 44 | 7 |
| Increased calcium | 43 | 7 |
| Decreased sodium | 41 | 20 |
| Increased triglycerides | 38 | 3 |
| Increased aspartate aminotransferase | 38 | 4 |
| Increased urate | 37 | 37 |
| Decreased albumin | 24 | 1 |
| Increased bilirubin | 24 | 6 |
| Decreased potassium | 21 | 3 |
| Increased cholesterol | 18 | 1 |
| Increased potassium | 17 | 3 |
| Decreased calcium | 10 | 2 |
| The denominator used to calculate the rate varied from 104 to 107 based on the number of patients with a baseline value and at least one post-treatment value. These laboratory abnormalities are values that reflect worsening from baseline. Graded per NCI CTCAE 4.03. a NCI CTCAE 4.03 does not define grades for increased phosphate. Laboratory value shift table categories were used to assess increased phosphorus levels (Grades ≥3 defined as ≥9mg/dL). |
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SRC: NLM .