The following adverse reactions are discussed elsewhere in the labeling:
- Ocular Toxicity [see WARNINGS AND PRECAUTIONS]
- Hyperphosphatemia and Soft Tissue Mineralization [see WARNINGS 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 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 [see Clinical Studies]. 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 3 summarizes the adverse reactions in Study CBGJ398X2204. Table 4 summarizes select laboratory abnormalities in Study CBGJ398X2204.
Table 3: Adverse Reactions (≥15%) in Patients Receiving TRUSELTIQ in Study CBGJ398X2204
|All Grades (%)||Grade 3 or 4 a (%)|
|Skin and subcutaneous tissue disorders|
|Nail toxicity b||57||2*|
|Palmar-plantar erythrodysesthesia syndrome||33||7*|
|Abdominal pain d||26||5*|
|Eye disorders e|
|Dry eye f||44||0|
|Eyelash changes g||25||0|
|General disorders and administrative site conditions|
|Musculoskeletal and connective tissue disorders|
|Pain in extremity||17||2*|
|Nervous system disorders|
|Metabolism and nutrition disorders|
|Respiratory, thoracic and mediastinal disorders|
|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.
Clinically relevant adverse reactions occurring in ≤15% of patients included cataracts (12%) and fractures (1%).
Table 4: Select Laboratory Abnormalities (≥10%) Worsening from Baseline in Patients Receiving TRUSELTIQ in Study CBGJ398X2204
|All Grades (%)||Grade 3 or 4 (%)|
|Increased phosphate a||90||13|
|Increased alkaline phosphatase||54||8|
|Increased alanine aminotransferase||51||6|
|Increased aspartate aminotransferase||38||4|
|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).
Effects Of Other Drugs On TRUSELTIQ
Strong And Moderate CYP3A Inhibitors
Concomitant use of TRUSELTIQ with a strong or moderate CYP3A inhibitor may increase infigratinib plasma concentrations [see CLINICAL PHARMACOLOGY], which may increase the risk of adverse reactions. Avoid concomitant use of TRUSELTIQ with strong or moderate CYP3A inhibitors.
Strong And Moderate CYP3A Inducers
Concomitant use of TRUSELTIQ with a strong or moderate CYP3A inducer may decrease infigratinib plasma concentrations [see CLINICAL PHARMACOLOGY], which may reduce TRUSELTIQ anti-tumor activity. Avoid concomitant use of TRUSELTIQ with strong or moderate CYP3A inducers.
Gastric Acid Reducing Agents
The coadministration of TRUSELTIQ with a gastric acid reducing agent may decrease infigratinib plasma concentrations [see CLINICAL PHARMACOLOGY], which may reduce TRUSELTIQ anti-tumor activity.
Avoid concomitant use of TRUSELTIQ with proton pump inhibitors (PPIs), H2-antagonists, and locally-acting antacids. If coadministration of H2-antagonists or locally-acting antacids cannot be avoided, stagger administration of TRUSELTIQ [see DOSAGE AND ADMINISTRATION].
Read the entire FDA prescribing information for Truseltiq (Infigratinib Capsules)
© Truseltiq Patient Information is supplied by Cerner Multum, Inc. and Truseltiq Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.
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