Entrectinib
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omid Afkhami-Ardakani
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Overview
Entrectinib is a Tyrosine Kinase Inhibitor that is FDA approved for the treatment of Adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are ROS1-positive. And also adult and pediatric patients 12 years of age and older with solid tumors.. Common adverse reactions include Fatigue, Constipation, Dysgeusia (altered taste), Edema, Dizziness, Diarrhea, Nausea, Dysesthesia (abnormal sensation), Dyspnea (shortness of breath), Myalgia (muscle pain), Cognitive impairment, Increased weight, Cough, Vomiting, Pyrexia (fever), Arthralgia (joint pain), Vision disorders..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Metastatic ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): 600 mg orally once daily. NTRK Gene Fusion-Positive Solid Tumors: 600 mg orally once daily.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Entrectinib in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Entrectinib in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
NTRK Gene Fusion-Positive Solid Tumors (Ages 12 and older): 600 mg orally once daily.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Entrectinib in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Entrectinib in pediatric patients.
Contraindications
Severe hepatic impairment. Known hypersensitivity to Entrectinib or any component of the formulation.
Warnings
Congestive Heart Failure Central Nervous System Effects Skeletal Fractures Hepatotoxicity Hyperuricemia QT Interval Prolongation Vision Disorders
Adverse Reactions
Clinical Trials Experience
Fatigue, Constipation, Dysgeusia (altered taste), Edema, Dizziness, Diarrhea, Nausea, Dysesthesia (abnormal sensation), Dyspnea (shortness of breath), Myalgia (muscle pain), Cognitive impairment, Increased weight, Cough, Vomiting, Pyrexia (fever), Arthralgia (joint pain), Vision disorders.
Postmarketing Experience
There is limited information regarding Entrectinib Postmarketing Experience in the drug label.
Drug Interactions
Strong CYP3A inhibitors can increase Entrectinib exposure, potentially leading to toxicity. Dose adjustment may be necessary. Strong CYP3A inducers can decrease Entrectinib exposure, potentially reducing efficacy. Avoid concomitant use if possible. Avoid concomitant use of Entrectinib with other QT-prolonging drugs to minimize the risk of additive QT prolongation.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Entrectinib in women who are pregnant.
Pregnancy Category (AUS):
Females are Advised to use effective contraception during treatment and for 5 weeks after the last dose.
Labor and Delivery
There is no information regarding the presence of Entrectinib in human milk. Advise women not to breastfeed during treatment and for 7 days after the last dose.
Nursing Mothers
There is no FDA guidance on the use of Entrectinib in women who are nursing.
Pediatric Use
Entrectinib is approved for use in pediatric patients 12 years and older with NTRK fusion-positive solid tumors.
Geriatic Use
No overall differences in safety or effectiveness were observed between elderly and younger patients, but some older patients may experience greater susceptibility to certain adverse effects, such as cognitive impairment.
Gender
There is no FDA guidance on the use of Entrectinib with respect to specific gender populations.
Race
There is no FDA guidance on the use of Entrectinib with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Entrectinib in patients with renal impairment.
Hepatic Impairment
Avoid use of Entrectinib in patients with severe hepatic impairment. Dose adjustments may be required for moderate hepatic impairment based on liver function monitoring.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Entrectinib in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Entrectinib in patients who are immunocompromised.
Administration and Monitoring
Administration
Administer 600 mg orally once daily. Entrectinib can be taken with or without food.
Monitoring
Monitor ECG and electrolytes periodically to detect QT prolongation. Perform liver function tests every 2 weeks during the first month of treatment, then monthly thereafter. Monitor for central nervous system (CNS) symptoms such as cognitive impairment and dizziness.
IV Compatibility
Not applicable.
Overdosage
Symptoms of overdose may include aggravated adverse reactions, such as dizziness, cognitive impairment, or cardiac effects. There is no specific antidote for Entrectinib. In the event of overdose, provide supportive care and monitor vital signs and ECG.
Pharmacology
There is limited information regarding Entrectinib Pharmacology in the drug label.
Mechanism of Action
Entrectinib is a tyrosine kinase inhibitor that targets NTRK1/2/3, ROS1, and ALK. It works by inhibiting these kinases, which are involved in the growth of certain cancer cells.
Structure
There is limited information regarding Entrectinib Structure in the drug label.
Pharmacodynamics
Entrectinib reduces tumor growth in cancers driven by NTRK, ROS1, or ALK gene fusions.
Pharmacokinetics
Absorption: Peak plasma concentrations occur approximately 4–6 hours after oral administration. Metabolism: Metabolized primarily by CYP3A4. Elimination: Approximately 83% excreted in feces and 3% in urine. Half-life: The terminal half-life is approximately 20 hours.
Nonclinical Toxicology
There is limited information regarding Entrectinib Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Entrectinib Clinical Studies in the drug label.
How Supplied
Entrectinib is supplied as 100 mg and 200 mg film-coated tablets, available in bottles of 30 tablets each.
Storage
Store Entrectinib at 20°C to 25°C (68°F to 77°F). Excursions are permitted to 15°C to 30°C (59°F to 86°F). Keep in a tightly sealed container, away from moisture and heat.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
Patients should be informed to: Take Entrectinib once daily at the same time. Report any symptoms of dizziness, confusion, or shortness of breath. Avoid using other QT-prolonging medications without consulting their healthcare provider. Use effective contraception during treatment and for 5 weeks after the last dose.
Precautions with Alcohol
Alcohol may exacerbate CNS symptoms, such as dizziness or confusion. Patients are advised to avoid or limit alcohol consumption during treatment with Entrectinib.
Brand Names
Rozlytrek is the primary brand name for Entrectinib.
Look-Alike Drug Names
There is limited information regarding Entrectinib 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.