Infigratinib

Infigratinib
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Parth Vikram Singh, MBBS[2]

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Overview

Infigratinib is a kinase inhibitor that is FDA approved for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.. Common adverse reactions include {{{adverseReactions}}}.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

• Confirm t*Confirm the presence of an FGFR2 fusion or rearrangement prior to initiation of treatment with TRUSELTIQ.
• Recommended dosage: 125 mg orally once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles.
• Take on an empty stomach at least 1 hour before or 2 hours after food, at approximately the same time each day.
• Swallow capsules whole with a glass of water. Do not crush, chew or dissolve.
• Mild and Moderate Renal Impairment: The recommended dosage is 100 mg orally once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles.
• Mild Hepatic Impairment: The recommended dosage is 100 mg orally once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles.
• Moderate Hepatic Impairment: The recommended dosage is 75 mg orally once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles. he presence of an FGFR2 fusion or rearrangement prior to initiation of treatment with TRUSELTIQ.
• Recommended dosage: 125 mg orally once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles.
• Take on an empty stomach at least 1 hour before or 2 hours after food, at approximately the same time each day.
• Swallow capsules whole with a glass of water. Do not crush, chew or dissolve.
• Mild and Moderate Renal Impairment: The recommended dosage is 100 mg orally once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles.
• Mild Hepatic Impairment: The recommended dosage is 100 mg orally once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles.
• Moderate Hepatic Impairment: The recommended dosage is 75 mg orally once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Infigratinib in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Infigratinib in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Infigratinib FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Infigratinib in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Infigratinib in pediatric patients.

Contraindications

None.

Warnings

Ocular Toxicity

Retinal Pigment Epithelial Detachment (RPED)

• TRUSELTIQ can cause RPED, which may cause symptoms such as blurred vision.
• Among 351 patients who received TRUSELTIQ across clinical trials.

where ophthalmologic monitoring did not routinely include optical coherence tomography (OCT), RPED occurred in 11% of patients, including patients with asymptomatic RPED. The median time to first onset of RPED was 26 days. RPED led to dose interruption/reduction of TRUSELTIQ in 3.4% of patients, and permanent discontinuation in 0.6% of patients.

• Perform a comprehensive ophthalmic examination including OCT prior to initiation of TRUSELTIQ, at 1 month, at 3 months, and then every 3 months thereafter during treatment. Refer patients for ophthalmic evaluation urgently for onset of visual symptoms, and follow-up every 3 weeks until resolution or discontinuation of TRUSELTIQ.

Withhold TRUSELTIQ as recommended.

Dry Eye

Among 351 patients who received TRUSELTIQ across clinical trials,dry eye occurred in 29% of patients. Treat patients with ocular demulcents as needed.

====Hyperphosphatemia and Soft Tissue Mineralization====

• TRUSELTIQ can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcinosis, non-uremic calciphylaxis, vascular calcification, and myocardial calcification. Increases in phosphate levels are a pharmacodynamic effect of TRUSELTIQ .

Among 351 patients who received TRUSELTIQ across clinical trials], hyperphosphatemia was reported in 82% of patients based on laboratory values above the upper limit of normal. The median time to onset of hyperphosphatemia was 8 days (range 1-349). Phosphate binders were received by 83% of patients who received TRUSELTIQ. Monitor for hyperphosphatemia throughout treatment. Initiate phosphate lowering therapy when serum phosphate level is >5.5 mg/dL. For serum phosphate level >7.5 mg/dL, withhold TRUSELTIQ and initiate phosphate lowering therapy. Withhold, dose reduce, or permanently discontinue TRUSELTIQ based on duration and severity of hyperphosphatemia.

Embryo-Fetal Toxicity

• Based on findings in animal studies and its mechanism of action, TRUSELTIQ can cause fetal harm when administered to a pregnant woman. Oral administration of infigratinib to pregnant animals during the period of organogenesis caused malformations, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure based on area under the curve (AUC) at the clinical dose of 125 mg.
• Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TRUSELTIQ and for 1 month after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with TRUSELTIQ and for 1 month after the final dose.

Adverse Reactions

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, palmar-plantar 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.

Adverse Reactions (≥15%) in Patients Receiving TRUSELTIQ in Study CBGJ398X2204

Adverse Reactions (≥15%) in Patients Receiving TRUSELTIQ in Study CBGJ398X2204

Select Laboratory Abnormalities (≥10%) Worsening from Baseline in Patients Receiving TRUSELTIQ in Study CBGJ398X2204

Select Laboratory Abnormalities (≥10%) Worsening from Baseline in Patients Receiving TRUSELTIQ in Study CBGJ398X2204

Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 4.03). 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).

Postmarketing Experience

There is limited information regarding Infigratinib Postmarketing Experience in the drug label.

Drug Interactions

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, 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, 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, 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.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Infigratinib in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Infigratinib in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Infigratinib during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Infigratinib in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Infigratinib in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Infigratinib in geriatric settings.

Gender

There is no FDA guidance on the use of Infigratinib with respect to specific gender populations.

Race

There is no FDA guidance on the use of Infigratinib with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Infigratinib in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Infigratinib in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Infigratinib in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Infigratinib in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Infigratinib Administration in the drug label.

Monitoring

There is limited information regarding Infigratinib Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Infigratinib and IV administrations.

Overdosage

There is limited information regarding Infigratinib overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Infigratinib Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Infigratinib Mechanism of Action in the drug label.

Structure

There is limited information regarding Infigratinib Structure in the drug label.

Pharmacodynamics

There is limited information regarding Infigratinib Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Infigratinib Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Infigratinib Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Infigratinib Clinical Studies in the drug label.

How Supplied

There is limited information regarding Infigratinib How Supplied in the drug label.

Storage

There is limited information regarding Infigratinib Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Infigratinib Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Infigratinib interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

TRUSELTIQ

Look-Alike Drug Names

There is limited information regarding Infigratinib Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.