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Home > Drugs > Entrectinib (systemic) (monograph)
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Entrectinib (systemic) (monograph)

https://themeditary.com/drug/entrectinib-systemic-monograph-18684.html
Medically Reviewed by Oluni Odunlami, MD TheMediTary.Com | Reviewed: Sep 26, 2023  Additional Content by TheMediTary.Com

Generic name: rozlytrek

Availability: Prescription only

Pregnancy & Lactation: Risk data available

Brand names: Rozlytrek, Entrectinib

Contents
Uses Warnings Before Taking Dosage Side effects Interactions

What is Entrectinib (systemic) (monograph)?

Introduction

Antineoplastic agent; potent inhibitor of multiple receptor tyrosine kinases including tropomyosin receptor kinases (Trk) A, TrkB, TrkC, c-ros oncogene-1 (ROS-1), and anaplastic lymphoma kinase (ALK).

Uses for Entrectinib (Systemic)

Non-small Cell Lung Cancer (NSCLC)

Treatment of ROS-1-positive metastatic NSCLC (based on an objective response rate of 78% in a cohort of patients with ROS-1-positive locally advanced or metastatic NSCLC).

Designated an orphan drug by FDA for treatment of TrkA-positive, TrkB-positive, TrkC-positive, ROS-1-positive, and ALK-positive NSCLC.

Confirmation of ROS-1 fusion by an FDA-approved test is necessary prior to initiation of therapy. In clinical studies, presence of ROS-1 fusion was determined by fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS).

Solid Tumors with Neurotrophic Receptor Tyrosine Kinase (NTRK) Gene Fusion

Treatment of solid tumors harboring an NTRK gene fusion (without a known acquired mutation for resistance) in patients who have metastatic disease or who may experience severe morbidity following surgical resection and whose disease progressed following prior therapy or those who are not candidates for other treatment options.

Accelerated approval based on objective response rate and duration of response. Continued approval may be contingent on verification and description of clinical benefit in confirmatory studies.

Designated an orphan drug by FDA for treatment of solid tumors harboring NTRK gene fusion.

Confirmation of NTRK fusion with an FDA-approved test is necessary prior to initiation of therapy. In clinical studies, presence of NTRK fusion status was determined by NGS or other nucleic acid-based tests.

Entrectinib (Systemic) Dosage and Administration

General

Pretreatment Screening

  • Confirm presence of ROS-1 fusion with an FDA-approved test in patients with metastatic NSCLC prior to initiation of therapy.

  • Confirm presence of NTRK fusion with an FDA-approved test prior to initiation of therapy for the treatment of locally advanced or metastatic solid tumors.

  • LVEF in patients with symptoms or known risk factors for heart failure.

  • Serum uric acid levels.

  • QT interval and serum electrolyte concentrations.

  • Verify pregnancy status in females of reproductive potential.

Patient Monitoring

  • Monitor for signs and symptoms of heart failure (e.g., dyspnea, edema).

  • Monitor liver function tests (e.g., ALT, AST) every 2 weeks during the first month of therapy, monthly thereafter, and as clinically indicated.

  • Assess serum uric acid levels periodically during therapy.

  • Monitor for signs and symptoms of hyperuricemia.

  • Monitor QT interval and serum electrolyte concentrations periodically during therapy. More frequent monitoring may be necessary in patients with preexisting QTc-interval prolongation or risk factors for developing QTc-interval prolongation (e.g., long QT syndrome, clinically important bradyarrhythmia, severe or uncontrolled heart failure, electrolyte abnormalities, concomitant use of drugs known to prolong QT interval).

Dispensing and Administration Precautions

  • Based on the Institute for Safe Medication Practices (ISMP), entrectinib is a high-alert medication that has a heightened risk of causing significant patient harm when used in error.

Administration

Oral Administration

Administer orally once daily without regard to food.

Swallow capsules whole; do not open, crush, chew, or dissolve.

Dosage

Pediatric Patients

Solid Tumors with NTRK Fusion
Oral

Adolescents ≥12 years of age with body surface area (BSA) >1.5 m2: 600 mg once daily. If concomitant use with moderate or potent CYP3A inhibitors cannot be avoided, adjust dosage of entrectinib.

Adolescents ≥12 years of age with BSA of 1.11–1.5 m2: 500 mg once daily.

Adolescents ≥12 years of age with BSA of 0.91–1.1 m2: 400 mg once daily.

Continue therapy until disease progression or unacceptable toxicity occurs.

Dosage Modification for Toxicity
Oral

Temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of drug may be necessary (see Table 2). When dosage modification is required in pediatric patients, reduce dosage of entrectinib as described .

Table 1: Dosage Reduction for Entrectinib Toxicity in Pediatric Patients

Dose Reduction Level

Recommended Dosage in Pediatric Patients ≥12 Years of Age with BSA >1.5 m2

Recommended Dosage in Pediatric Patients ≥12 Years of Age with BSA 1.11 to 1.5 m2

Recommended Dosage in Pediatric Patients ≥12 Years of Age with BSA 0.91 to 1.1 m2

First dose reduction

400 mg once daily

400 mg once daily

300 mg once daily

Second dose reduction

200 mg once daily

200 mg once daily

200 mg once daily

Subsequent modifications

Permanently discontinue therapy

Permanently discontinue therapy

Permanently discontinue therapy

If an adverse reaction occurs, modify treatment accordingly (see Table 2).

Table 2. Dosage Modification for Entrectinib Toxicity

Adverse Reaction and Severity

Modification

Heart Failure

Grade 2 or 3

Withhold therapy; when toxicity resolves to grade 1 or less, resume at reduced dosage

Grade 4

Permanently discontinue therapy

CNS Effects

Grade 2 (intolerable)

Withhold therapy; when toxicity resolves to baseline or grade 1 or less, resume at same or reduced dosage

Grade 3

Withhold therapy; when toxicity resolves to baseline or grade 1 or less, resume at reduced dosage

Grade 4

Permanently discontinue therapy

Hepatotoxicity

Grade 3

Withhold therapy. If toxicity resolves to baseline or grade 1 or less within 4 weeks, resume at same dosage; if toxicity does not resolve within 4 weeks, permanently discontinue therapy

Resume at a reduced dose for recurrent grade 3 events that resolve within 4 weeks

Grade 4

Withhold therapy. If toxicity resolves to baseline or grade 1 or less within 4 weeks, resume at reduced dosage; if toxicity does not resolve within 4 weeks, permanently discontinue therapy

Permanently discontinue therapy for recurrent grade 4 events

Elevated ALT or AST concentrations >3 times the ULN with concomitant total bilirubin concentrations >1.5 times the ULN in absence of cholestasis or hemolysis

Permanently discontinue therapy

Hyperuricemia

Symptomatic

Withhold therapy and initiate urate-lowering therapy; when toxicity improves, resume at same or reduced dosage

Grade 4

Withhold therapy and initiate urate-lowering therapy; when toxicity improves, resume at same or reduced dosage

Prolongation of QT Interval

QTc interval >500 msec

If other etiology of QT-interval prolongation is present: Withhold therapy and correct other causes of QT-interval prolongation; resume at same dosage when toxicity resolves to baseline

If no other etiology of QT-interval prolongation is present: Withhold therapy; resume at reduced dosage when toxicity resolves to baseline

Torsades de pointes, polymorphic ventricular tachycardia, or signs and/or symptoms of serious arrhythmia

Permanently discontinue therapy

Visual Disturbances

New visual symptoms, including changes that interfere with activities of daily living

Withhold therapy; when toxicity improves or stabilizes, resume at same or reduced dosage

Grade 2 or greater

Withhold therapy; when toxicity improves or stabilizes, resume at same or reduced dosage

Hematologic Toxicity

Grade 3 or 4 anemia or neutropenia

Withhold therapy; when toxicity improves to grade 2 or less, resume at same or reduced dosage

Other Toxicity

Grade 3 or 4 (clinically significant)

Withhold therapy; if toxicity resolves to baseline or grade 1 within 4 weeks, resume at same or reduced dosage; if toxicity does not resolve within 4 weeks, permanently discontinue therapy

Permanently discontinue for recurrent grade 4 events

Adults

NSCLC
Oral

600 mg once daily. Continue therapy until disease progression or unacceptable toxicity occurs.

If concomitant use with moderate or potent CYP3A inhibitors cannot be avoided, adjust dosage of entrectinib.

Solid Tumors with NTRK Fusion
Oral

600 mg once daily. Continue therapy until disease progression or unacceptable toxicity occurs.

If concomitant use with moderate or potent CYP3A inhibitors cannot be avoided, adjust dosage of entrectinib.

Dosage Modification for Toxicity
Oral

Temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of drug may be necessary. Recommendations for dosage modification for toxicity in pediatric patients also apply to adults (see Table 2). When dosage modification is required in adults, reduce dosage of entrectinib as described in Table 3.

Table 3. Dosage Reduction for Entrectinib Toxicity in Adults.1

Dose Reduction Level

Recommended Dosage

First dose reduction

400 mg once daily

Second dose reduction

200 mg once daily

Subsequent modification

Permanently discontinue entrectinib

Special Populations

Hepatic Impairment

Mild hepatic impairment (total bilirubin concentration ≤1.5 times the ULN): No dosage adjustment required.

Renal Impairment

Mild or moderate renal impairment (Clcr 30 to <90 mL/minute): No dosage adjustment required.

Geriatric Patients

No specific dosage recommendations.

Detailed Entrectinib dosage information

Warnings

Contraindications

  • Manufacturer states none known.

Warnings/Precautions

Heart Failure

Heart failure reported; median time to onset is 2 months. Resolves in 75% of patients following initiation of appropriate treatment for heart failure and interruption or discontinuance of drug.

Assess LVEF prior to initiation of therapy in patients with symptoms or known risk factors for heart failure. Monitor for signs and symptoms of heart failure (e.g., dyspnea, edema). For patients with myocarditis with or without a decreased ejection fraction, diagnosis may require magnetic resonance imaging (MRI) or cardiac biopsy. If new onset or worsening heart failure occurs, interrupt therapy, initiate appropriate therapy for heart failure, and reassess LVEF; dosage reduction or permanent discontinuance of therapy may be necessary. and

CNS Effects

Entrectinib can cause a variety of adverse CNS effects including cognitive impairment, mood disorder, dizziness, and sleep disturbance.

Inform patients and their caregivers of the risk of adverse CNS effects. Advise patients not to drive or operate hazardous machinery if they are experiencing adverse CNS effects. If adverse CNS effects occur, interruption of therapy, dosage reduction, or permanent discontinuance of therapy may be necessary.

Fractures

Fractures, mostly involving the lower extremity (e.g., hip, femoral or tibial shaft) reported. Sometimes associated with trauma (e.g., fall) in adults and with minimal or no trauma in pediatric patients. Radiographic abnormalities potentially indicating bone metastases reported in some patients.

Promptly evaluate patients with signs or symptoms of fracture (e.g., pain, changes in mobility, deformity). Effect on healing of known fractures or long-term fracture risk is unknown.

Hepatotoxicity

Hepatotoxicity reported; median time to onset of elevated AST or ALT concentrations is 2 weeks.

Monitor liver function tests (e.g., ALT, AST), every 2 weeks during the first month of therapy, monthly thereafter, and as clinically indicated. If hepatotoxicity occurs, interruption of therapy, dosage reduction, or permanent discontinuance of therapy may be necessary.

Hyperuricemia

Hyperuricemia, sometimes symptomatic, reported. Grade 4 hyperuricemia (associated with tumor lysis syndrome) resulted in death in one patient.

Assess serum uric acid levels prior to initiating entrectinib and then periodically during therapy. Monitor patients for signs and symptoms of hyperuricemia. In patients experiencing signs or symptoms of hyperuricemia, initiate urate-lowering therapy as clinically indicated and interrupt entrectinib therapy; dosage reduction may be necessary.

Prolongation of the QT Interval

Prolongation of QTc interval reported.

Monitor QT interval and electrolyte concentrations at baseline and periodically during therapy. More frequent monitoring may be necessary in patients with preexisting QTc-interval prolongation or risk factors for developing QTc-interval prolongation (e.g., long QT syndrome, clinically important bradyarrhythmia, severe or uncontrolled heart failure, electrolyte abnormalities, concomitant use of drugs known to prolong QT interval). If QTc-interval prolongation occurs, temporary interruption of entrectinib therapy, dosage reduction, or permanent discontinuance of therapy may be necessary.

Visual Disturbances

Visual disturbances (i.e., blurred vision, photophobia, diplopia, visual impairment, photopsia, cataract, vitreous floaters) reported.

In patients who report new visual symptoms, including changes that interfere with activities of daily living, temporarily interrupt entrectinib therapy and perform an ophthalmologic evaluation as clinically appropriate; dosage reduction may be necessary.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm. Teratogenicity and embryofetal toxicity (i.e., reduced fetal weight, reduced skeletal ossification) demonstrated in animals.

Literature reports in individuals with congenital mutations in the tropomyosin receptor kinase (Trk) pathway suggest decreased Trk-mediated signaling may be associated with obesity, developmental delays, cognitive impairment, insensitivity to pain, and anhidrosis.

Avoid pregnancy during therapy. Perform pregnancy test prior to initiation of entrectinib in women of reproductive potential. Women of reproductive potential should use effective contraceptive methods while receiving the drug and for ≥5 weeks after the last dose. Men who are partners of such women should use effective methods of contraception while receiving the drug and for 3 months after the last dose. If used during pregnancy or if patient becomes pregnant, apprise patient of potential fetal hazard.

Specific Populations

Pregnancy

May cause fetal harm.

Lactation

Not known whether entrectinib or its metabolites distribute into human milk or affect milk production or nursing infants.

Discontinue nursing during therapy and for 1 week after the last dose.

Pediatric Use

Safety and efficacy not established in pediatric patients with NSCLC.

Safety and efficacy in pediatric patients ≥12 years of age with solid tumors harboring NTRK gene fusion are supported by extrapolation of data from 3 noncomparative studies in adults and limited safety data in 30 pediatric patients. Grade 3 or 4 neutropenia, fractures, weight gain, thrombocytopenia, lymphopenia, elevations in γ-glutamyltransferase (GGT, γ-glutamyltranspeptidase, GGTP) concentrations, and device-related infection occurred more frequently in pediatric patients compared with adults.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether efficacy and safety are similar to those in younger adults.

Hepatic Impairment

Mild hepatic impairment (total bilirubin concentration ≤1.5 times the ULN): No clinically important effect on pharmacokinetics.

Effect of moderate hepatic impairment (total bilirubin > 1.5 – 3 times ULN with any aspartateaminotransferase) or severe hepatic impairment (total bilirubin >3 times ULN with any aspartate aminotransferase) on pharmacokinetics not established.

Consider the risk/benefit profile in patients with moderate to severe hepatic impairment. Monitor more frequenty for adverse reactions in these patients as they may be at increased risk for adverse reactions.

Renal Impairment

Mild to moderate renal impairment (Clcr 30 to <90 mL/minute): No clinically important effect on pharmacokinetics.

Effect of severe renal impairment (Clcr <30 mL/minute) on pharmacokinetics not established.

Common Adverse Effects

Adverse effects (≥20%): fatigue, constipation, dysgeusia, edema, dizziness, diarrhea, nausea, dysesthesia, dyspnea, myalgia, cognitive impairment, increased weight, cough, vomiting, pyrexia, arthralgia, and vision disorders.

How should I use Entrectinib (systemic) (monograph)

General

Pretreatment Screening

  • Confirm presence of ROS-1 fusion with an FDA-approved test in patients with metastatic NSCLC prior to initiation of therapy.

  • Confirm presence of NTRK fusion with an FDA-approved test prior to initiation of therapy for the treatment of locally advanced or metastatic solid tumors.

  • LVEF in patients with symptoms or known risk factors for heart failure.

  • Serum uric acid levels.

  • QT interval and serum electrolyte concentrations.

  • Verify pregnancy status in females of reproductive potential.

Patient Monitoring

  • Monitor for signs and symptoms of heart failure (e.g., dyspnea, edema).

  • Monitor liver function tests (e.g., ALT, AST) every 2 weeks during the first month of therapy, monthly thereafter, and as clinically indicated.

  • Assess serum uric acid levels periodically during therapy.

  • Monitor for signs and symptoms of hyperuricemia.

  • Monitor QT interval and serum electrolyte concentrations periodically during therapy. More frequent monitoring may be necessary in patients with preexisting QTc-interval prolongation or risk factors for developing QTc-interval prolongation (e.g., long QT syndrome, clinically important bradyarrhythmia, severe or uncontrolled heart failure, electrolyte abnormalities, concomitant use of drugs known to prolong QT interval).

Dispensing and Administration Precautions

  • Based on the Institute for Safe Medication Practices (ISMP), entrectinib is a high-alert medication that has a heightened risk of causing significant patient harm when used in error.

Administration

Oral Administration

Administer orally once daily without regard to food.

Swallow capsules whole; do not open, crush, chew, or dissolve.

Dosage

Pediatric Patients

Solid Tumors with NTRK Fusion
Oral

Adolescents ≥12 years of age with body surface area (BSA) >1.5 m2: 600 mg once daily. If concomitant use with moderate or potent CYP3A inhibitors cannot be avoided, adjust dosage of entrectinib.

Adolescents ≥12 years of age with BSA of 1.11–1.5 m2: 500 mg once daily.

Adolescents ≥12 years of age with BSA of 0.91–1.1 m2: 400 mg once daily.

Continue therapy until disease progression or unacceptable toxicity occurs.

Dosage Modification for Toxicity
Oral

Temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of drug may be necessary (see Table 2). When dosage modification is required in pediatric patients, reduce dosage of entrectinib as described .

Table 1: Dosage Reduction for Entrectinib Toxicity in Pediatric Patients

Dose Reduction Level

Recommended Dosage in Pediatric Patients ≥12 Years of Age with BSA >1.5 m2

Recommended Dosage in Pediatric Patients ≥12 Years of Age with BSA 1.11 to 1.5 m2

Recommended Dosage in Pediatric Patients ≥12 Years of Age with BSA 0.91 to 1.1 m2

First dose reduction

400 mg once daily

400 mg once daily

300 mg once daily

Second dose reduction

200 mg once daily

200 mg once daily

200 mg once daily

Subsequent modifications

Permanently discontinue therapy

Permanently discontinue therapy

Permanently discontinue therapy

If an adverse reaction occurs, modify treatment accordingly (see Table 2).

Table 2. Dosage Modification for Entrectinib Toxicity

Adverse Reaction and Severity

Modification

Heart Failure

Grade 2 or 3

Withhold therapy; when toxicity resolves to grade 1 or less, resume at reduced dosage

Grade 4

Permanently discontinue therapy

CNS Effects

Grade 2 (intolerable)

Withhold therapy; when toxicity resolves to baseline or grade 1 or less, resume at same or reduced dosage

Grade 3

Withhold therapy; when toxicity resolves to baseline or grade 1 or less, resume at reduced dosage

Grade 4

Permanently discontinue therapy

Hepatotoxicity

Grade 3

Withhold therapy. If toxicity resolves to baseline or grade 1 or less within 4 weeks, resume at same dosage; if toxicity does not resolve within 4 weeks, permanently discontinue therapy

Resume at a reduced dose for recurrent grade 3 events that resolve within 4 weeks

Grade 4

Withhold therapy. If toxicity resolves to baseline or grade 1 or less within 4 weeks, resume at reduced dosage; if toxicity does not resolve within 4 weeks, permanently discontinue therapy

Permanently discontinue therapy for recurrent grade 4 events

Elevated ALT or AST concentrations >3 times the ULN with concomitant total bilirubin concentrations >1.5 times the ULN in absence of cholestasis or hemolysis

Permanently discontinue therapy

Hyperuricemia

Symptomatic

Withhold therapy and initiate urate-lowering therapy; when toxicity improves, resume at same or reduced dosage

Grade 4

Withhold therapy and initiate urate-lowering therapy; when toxicity improves, resume at same or reduced dosage

Prolongation of QT Interval

QTc interval >500 msec

If other etiology of QT-interval prolongation is present: Withhold therapy and correct other causes of QT-interval prolongation; resume at same dosage when toxicity resolves to baseline

If no other etiology of QT-interval prolongation is present: Withhold therapy; resume at reduced dosage when toxicity resolves to baseline

Torsades de pointes, polymorphic ventricular tachycardia, or signs and/or symptoms of serious arrhythmia

Permanently discontinue therapy

Visual Disturbances

New visual symptoms, including changes that interfere with activities of daily living

Withhold therapy; when toxicity improves or stabilizes, resume at same or reduced dosage

Grade 2 or greater

Withhold therapy; when toxicity improves or stabilizes, resume at same or reduced dosage

Hematologic Toxicity

Grade 3 or 4 anemia or neutropenia

Withhold therapy; when toxicity improves to grade 2 or less, resume at same or reduced dosage

Other Toxicity

Grade 3 or 4 (clinically significant)

Withhold therapy; if toxicity resolves to baseline or grade 1 within 4 weeks, resume at same or reduced dosage; if toxicity does not resolve within 4 weeks, permanently discontinue therapy

Permanently discontinue for recurrent grade 4 events

Adults

NSCLC
Oral

600 mg once daily. Continue therapy until disease progression or unacceptable toxicity occurs.

If concomitant use with moderate or potent CYP3A inhibitors cannot be avoided, adjust dosage of entrectinib.

Solid Tumors with NTRK Fusion
Oral

600 mg once daily. Continue therapy until disease progression or unacceptable toxicity occurs.

If concomitant use with moderate or potent CYP3A inhibitors cannot be avoided, adjust dosage of entrectinib.

Dosage Modification for Toxicity
Oral

Temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of drug may be necessary. Recommendations for dosage modification for toxicity in pediatric patients also apply to adults (see Table 2). When dosage modification is required in adults, reduce dosage of entrectinib as described in Table 3.

Table 3. Dosage Reduction for Entrectinib Toxicity in Adults.1

Dose Reduction Level

Recommended Dosage

First dose reduction

400 mg once daily

Second dose reduction

200 mg once daily

Subsequent modification

Permanently discontinue entrectinib

Special Populations

Hepatic Impairment

Mild hepatic impairment (total bilirubin concentration ≤1.5 times the ULN): No dosage adjustment required.

Renal Impairment

Mild or moderate renal impairment (Clcr 30 to <90 mL/minute): No dosage adjustment required.

Geriatric Patients

No specific dosage recommendations.

Detailed Entrectinib dosage information
Entrectinib (systemic) (monograph) Dosage information (more detail)

What other drugs will affect Entrectinib (systemic) (monograph)?

Metabolized principally by CYP3A4 to form M5 (major active metabolite), and to a lesser extent by CYP isoenzymes 2C9 and 1C19.

Entrectinib is not a substrate of P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP), but M5 is a substrate of both P-gp and BCRP.

Neither entrectinib nor M5 is a substrate of organic anion transport protein (OATP) 1B1 or 1B3.

Drugs and Foods Affecting Hepatic Microsomal Enzymes

Potent inhibitors of CYP3A: Possible increased systemic exposure to, and increased toxicity of, entrectinib. Avoid concomitant use. If concomitant use cannot be avoided in adults and pediatric patients ≥12 years of age with BSA >1.5 m2, reduce entrectinib dosage to 100 mg once daily. When concomitant use of the potent CYP3A inhibitor is discontinued, return entrectinib dosage (after 3–5 elimination half-lives of the CYP3A inhibitor) to dosage used prior to initiation of the potent CYP3A inhibitor.

Moderate inhibitors of CYP3A: Possible increased systemic exposure to, and increased toxicity of, entrectinib. Avoid concomitant use. If concomitant use cannot be avoided in adults and pediatric patients ≥12 years of age with BSA >1.5 m2, reduce entrectinib dosage to 200 mg once daily. When concomitant use of the moderate CYP3A inhibitor is discontinued, return entrectinib dosage (after 3–5 elimination half-lives of the CYP3A inhibitor) to dosage used prior to initiation of the moderate CYP3A inhibitor.

Inducers of CYP3A: Possible decreased systemic exposure to, and decreased therapeutic efficacy of, entrectinib. Avoid concomitant use.

Drugs that Prolong the QT Interval

Because entrectinib has been associated with QT-interval prolongation, avoid concomitant use with other drugs with known potential to prolong the QT interval.

Specific Drugs and Foods

Drug or Food

Interaction

Comments

Digoxin

Digoxin peak concentrations and AUC increased by 28 and 18%, respectively

Efavirenz

Decreased systemic exposure of entrectinib expected

Avoid concomitant use

Erythromycin

Increased systemic exposure of entrectinib expected

Avoid concomitant use; if concomitant use cannot be avoided in adults and pediatric patients ≥12 years of age with BSA >1.5 m2, reduce entrectinib dosage to 200 mg once daily

When erythromycin is discontinued, return entrectinib dosage (after 3–5 elimination half-lives of erythromycin) to prior dosage

Grapefruit juice

Possible increased systemic exposure of entrectinib

Avoid concomitant use

Itraconazole

Increased peak plasma concentration and AUC of entrectinib 1.7- and 6-fold, respectively

Avoid concomitant use; if concomitant use cannot be avoided in adults and pediatric patients ≥12 years of age with BSA >1.5 m2, reduce entrectinib dosage to 100 mg once daily

When itraconazole is discontinued, return entrectinib dosage (after 3–5 elimination half-lives of itraconazole) to prior dosage

Lansoprazole

Entrectinib peak concentrations and AUC decreased by 23 and 25%, respectively

Midazolam

Midazolam peak concentrations decreased by 21% and AUC increased by 50%

Rifampin

Entrectinib peak concentrations and AUC decreased by 56 and 77%, respectively

Avoid concomitant use

More about Entrectinib (systemic) (monograph) (Rozlytrek)

Dosage information
Entrectinib (systemic) (monograph) Side Effects
During pregnancy
Drug images
Side effects
Drug class: Drugs

Related treatment guides

Solid Tumors
Non-Small Cell Lung Cancer
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