Entrectinib (Monograph)

Brand name: Rozlytrek
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Jul 10, 2024. Written by ASHP.

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

Non-small Cell Lung Cancer (NSCLC)

Treatment of ROS-1-positive 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 rearrangement in tumor or plasma specimens by an FDA-approved test is necessary prior to initiation of therapy. Testing using plasma specimens is only appropriate when tumor tissue is not available for testing.

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

Treatment of solid tumors in adults and pediatric patients >1 month of age harboring an NTRK gene fusion (without a known acquired mutation for resistance), who have metastatic disease or who are likely to experience severe morbidity following surgical resection, and whose disease has no satisfactory alternative treatment or progressed following prior therapy.

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 in tumor or plasma specimens with an FDA-approved test is necessary prior to initiation of therapy. Testing using plasma specimens is only appropriate when tumor tissue is not available for testing.

Entrectinib Dosage and Administration

General

Pretreatment Screening

Confirm presence of ROS-1 rearrangement 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.
Evaluate LVEF.
Assess serum uric acid levels.
Assess 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 QT_c-interval prolongation or risk factors for developing QT_c-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).

Administration

Administer orally without regard to food.

Available as oral capsules and pellets; clinicians should prescribe the most appropriate dosage form based on dose required and patient needs.

If a dose is missed, take missed dose as soon as it is remembered unless next dose is due within 12 hours. If a dose is vomited immediately after administration, administer an additional dose to make up for the vomited dose.

Capsules

Swallow capsules whole or use capsules to prepare an oral suspension (for oral or enteral tube administration). Do not crush or chew capsules if swallowing whole.

Whole capsules are intended for administration in patients who can swallow a whole capsule and whose doses are in multiples of 100 mg.

Capsules prepared as an oral suspension are intended for use in patients who have difficulty or inability to swallow capsules or patients who require enteral (e.g., gastric or nasogastric tube) administration. Should also use capsules prepared as a suspension for patients who require dose increments of 10 mg. Compound the oral suspension by carefully opening the appropriate number of capsules and pouring the contents into room temperature drinking water or milk. Let the suspension sit for 15 minutes and then administer immediately. Patients should drink water after taking the oral suspension to ensure that the drug has been completely swallowed. Discard any unused suspension if not used within 2 hours.

If enteral administration is necessary, administer the oral suspension via a gastric or nasogastric tube. For dosing volumes ≥3 mL, use an enteral tube that is 8 FR or higher. Divide dosing volumes ≥3 mL into at least 2 aliquots and a dosing volume of 30 mL into at least 3 (10 mL) aliquots. Flush the tube with an equivalent volume of water or milk after administration of each aliquot.

Refer to the entrectinib prescribing information for more specific information on the preparation of entrectinib capsules as a suspension for oral or enteral tube administration.

Pellets

Pellet formulation is intended for patients who have difficulty or inability to swallow whole capsules, but can swallow soft foods, and whose doses are in multiples of 50 mg.

Sprinkle pellets on 1 or more spoonfuls of soft food (e.g., applesauce, yogurt, pudding). Take pellets within 20 minutes of preparation and drink water after administration to ensure the drug has been completely swallowed.

Do not use pellets to prepare an oral suspension. Do not use partial quantities of pellets from a packet to prepare a dose. Do not use pellet formulation for enteral administration as pellets may clog the tube.

Dosage

Pediatric Patients

Solid Tumors with NTRK Fusion

Oral

Pediatric patients with BSA ≥1.51 m ²: 600 mg once daily.

Pediatric patients >1 month to ≤6 months of age: 250 mg/m² once daily.

Table 1 presents the recommended dosage for pediatric patients >6 months of age, based on BSA.

Continue therapy until disease progression or unacceptable toxicity occurs.

BSA categories and recommended dosage are based on closely matching exposures to a target dose of 300 mg/m².

Table 1. Recommended Dosage of Entrectinib in Pediatric Patients >6 Months of Age.1
Body Surface Area (BSA)	Recommended Dosage
≤0.50 m²	300 mg/m² once daily
0.51 to 0.80 m²	200 mg once daily
0.81 to 1.10 m²	300 mg once daily
1.11 to 1.50 m²	400 mg once daily

Adults

NSCLC

Oral

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

Solid Tumors with NTRK Fusion

Oral

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

Dosage Modification for Toxicity

Temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of drug may be necessary in patients experiencing certain adverse effects. When necessary, reduce dosage as described in Table 2. Permanently discontinue entrectinib in patients who are unable to tolerate therapy after 2 dose reductions.

Table 2: Dosage Reduction for Entrectinib Toxicity.1
Starting Dose (once daily)	First Dose Reduction	Second Dose Reduction
250 mg/m² or 300 mg/m²	Reduce dose to two-thirds of the starting dose	Reduce dose to one-third of the starting dose
200 mg	150 mg once daily	100 mg once daily
300 mg	200 mg once daily	100 mg once daily
400 mg	300 mg once daily	200 mg once daily
600 mg	400 mg once daily	200 mg once daily

Table 3 indicates the recommended dosage modification (i.e., temporary interruption of therapy, dosage reduction, discontinuance of therapy) for certain adverse effects according to severity.

Table 3. Dosage Modification for Entrectinib Toxicity.1
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
QT_c 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 therapy for recurrent grade 4 events

Concomitant Use with CYP3A Inhibitors

Avoid concomitant use of entrectinib with moderate and strong inhibitors of CYP3A. If concomitant use cannot be avoided in adults and pediatric patients ≥2 years of age, reduce dosage of entrectinib as noted in Table 4 and limit coadministration to 14 days or less. After discontinuation of a moderate or strong CYP3A inhibitor for 3-5 elimination half-lives, resume entrectinib dose that was taken prior to initiating the CYP3A inhibitor.

For pediatric patients with a starting dose <200 mg, avoid coadministration with a strong or moderate CYP3A inhibitor.

Table 4. Recommended Dose Modifications of Entrectinib for Concomitant Use with Moderate or Strong CYP3A Inhibitors.1
Starting Dose	Moderate CYP3A Inhibitor	Strong CYP3A Inhibitor
200 mg	50 mg once daily	50 mg on alternate days
300 mg	100 mg once daily	50 mg once daily
400 mg	200 mg once daily	50 mg once daily
600 mg	200 mg once daily	100 mg once daily

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 (Cl_cr 30 to <90 mL/minute): No dosage adjustment required.

Geriatric Patients

No specific dosage recommendations.

Cautions for Entrectinib

Contraindications

None.

Warnings/Precautions

Heart Failure

Heart failure reported; median time to onset is 2 months. In clinical trials, heart failure resolved in 50% of patients (6 of 12) 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.

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 hip or lower extremity reported.

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 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 QT_c interval reported.

Monitor QT interval and electrolyte concentrations at baseline and periodically during therapy. More frequent monitoring may be necessary in patients with preexisting QT_c-interval prolongation or risk factors for developing QT_c-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 QT_c-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.

Embryo-Fetal Toxicity

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 females of reproductive potential. Such females should use effective contraceptive methods while receiving the drug and for ≥5 weeks after the last dose. Male patients with female partners of reproductice potential should use effective methods of contraception while receiving the drug and for 3 months after the last dose.

Specific Populations

Pregnancy

May cause fetal harm. (See Embryo-Fetal Toxicity under Cautions.)

If used during pregnancy or if patient becomes pregnant, apprise patient of potential fetal hazard.

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.

Females and Males of Reproductive Potential

Verify pregnancy status in females of reproductive potential prior to starting therapy. Advise such females to use effective contraception during treatment andfor at least 5 weeks following last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 months following last dose.

Pediatric Use

Safety and efficacy not established in pediatric patients with NSCLC.

Safety and efficacy of entrectinib established in pediatric patients >1 month of age with solid tumors harboring NTRK gene fusion.

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 aspartate aminotransferase) or severe hepatic impairment (total bilirubin >3 times ULN with any aspartate aminotransferase) on pharmacokinetics not established.

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

Renal Impairment

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

Effect of severe renal impairment (Cl_cr <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, vision disorders.

Drug Interactions

Metabolized principally by CYP3A4 to form M5 (major active metabolite).

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

Moderate and strong 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 ≥2 years of age, reduce dosage of entrectinib as noted in Table 4 and limit coadministration to 14 days or less. When concomitant use of the strong 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 strong CYP3A inhibitor.

In pediatric patients <2 years of age: avoid concomitant use of moderate or strong CYP3A inhibitors.

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 known 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 ≥2 years of age, reduce entrectinib dosage as noted in Table 4 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 ≥2 years of age, reduce entrectinib dosage as noted in Table 4 When itraconazole is discontinued, return entrectinib dosage (after 3–5 elimination half-lives of itraconazole) to prior dosage
Lansoprazole	Entrectinib capsule: peak concentrations and AUC decreased by 23 and 25%, respectively Entrectinib capsule as oral suspension: peak concentrations and AUC increased by 17 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

Entrectinib Pharmacokinetics

Absorption

Bioavailability

Pharmacokinetics of entrectinib and its active metabolite are linear and time-independent over a dosage range of 100–400 mg/m² when coadministered with food.

Peak plasma concentrations achieved in 4–6 hours following oral administration.

Steady-state concentrations of entrectinib and its active metabolite achieved within 1–2 weeks; systemic accumulation is approximately 2-fold.

Food

Administration with a high-fat, high-calorie meal has no clinically important effect on systemic exposure of capsules.

Distribution

Extent

Not known whether entrectinib or its metabolites are distributed into human milk.

Crosses blood-brain barrier in animals.

Plasma Protein Binding

Entrectinib and M5: >99% bound to plasma proteins.

Elimination

Metabolism

Principally metabolized by CYP3A4 to form M5.

Elimination Route

Eliminated in the feces (83% [36% as unchanged drug, 22% as M5]) and urine (3%).

Half-life

Entrectinib: 20 hours.

M5: 40 hours.

Stability

Storage

Oral

Capsules

20-25°C; excursions permitted between 15-30°C.

Store in original container, tightly closed to protect from moisture.

If prepared as an oral suspension, store at <30°C for no more than 2 hours.

Pellets

20-25°C; excursions permitted between 15-30°C.

Store in original container; protect from moisture.

Actions

Potent inhibitor of TrkA, TrkB, TrkC, ROS-1, and ALK.
TrkA, TrkB, and TrkC are encoded by NTRK1, NTRK2, and NTRK3 and are involved in the initiation of various cascades of intracellular signaling events (i.e., Ras/MAPK/ERK, PI3K/Akt, and PLCγ1/Pkc signal transduction pathways) that lead to cell proliferation, differentiation, apoptosis, and regulation of processes critical to neuron survival in the central and peripheral nervous systems.
Chromosomal rearrangements of NTRK1, NTRK2, and NTRK3 genes result in formation of a constitutively active chimeric Trk oncogenic fusion protein and dysregulation of Trk signaling and subsequent tumorigenesis.
Fusion proteins including ROS-1 or ALK kinase domains also activate tumorigenesis through hyperactivation of downstream signaling pathways.
Inhibits cancer cell lines derived from multiple tumor types harboring NTRK, ROS-1, and ALK fusion genes.
Major metabolite, M5, has similar inhibitory activity for TrkA, TrkB, TrkC, ROS-1, and ALK to that of entrectinib.
In vitro, 10- to 100-fold more potent than crizotinib in activity against ROS-1, and 7- to 8-fold more potent than crizotinib in activity against ALK.
Inhibits Janus kinase 2 (JAK2) and tyrosine kinase nonreceptor 2 (TNK2).
Clinical resistance attributed to secondary point mutations of NTRK kinase domain (e.g., G595R and G667C point mutations in the TrkA kinase domain; G623R point mutation in the TrkC kinase domain) reported.

Advice to Patients

Advise patients to read the FDA-approved patient information.
Advise patients to swallow entrectinib capsules whole and to not chew or crush the capsules.
Patients and caregivers should use a provided measuring device (e.g., oral syringe, measuring cup) to prepare and measure the prescribed dose if taking entrectinib capsules as an oral suspension. Instruct patients and/or caregivers on how to use the measuring device and inform patients that they may need to measure out a portion of the prepared oral suspension to receive the prescribed dosage. Instruct patients and/or caregivers that the oral suspension should be taken immediately after preparation or stored at room temperature (<30°C) for no more than 2 hours.
Instruct patients and caregivers that entrectinib oral pellets should be sprinkled on one or more sponfuls of a soft food (e.g., applesauce, yogurt, or pudding) and must be taken within 20 minutes of preparation.
If a dose is missed, advise patients to take missed dose as soon as it is remembered unless the next dose is due within 12 hours. If a dose is vomited immediately after administration, an additional dose should be administered to make up for the vomited dose.
Risk of heart failure. Stress importance of informing clinician promptly if new or worsening signs or symptoms of heart failure (e.g., dyspnea, edema) occur.
Risk of CNS effects. Stress importance of informing clinician if new or worsening CNS effects (i.e., cognitive impairment, mood disorders, dizziness, sleep disturbance) occur. Advise patients to avoid driving or operating hazardous machinery if they experience CNS effects.
Risk of hepatotoxicity and importance of monitoring liver function. Stress importance of informing clinician promptly if symptoms of hepatotoxicity (e.g., loss of appetite, nausea, vomiting, upper right abdominal pain) occur.
Risk of fractures. Stress importance of informing clinician if symptoms such as pain, changes in mobility, or deformity occur.
Risk of hyperuricemia. Stress importance of informing clinician if signs or symptoms associated with hyperuricemia occur.
Risk of QT-interval prolongation. Stress importance of informing clinician promptly if abnormal heartbeat or feelings of faintness, lightheadedness, or dizziness occur.
Risk of visual disturbances. Stress importance of informing clinician if visual disturbances (e.g., blurring, photophobia, diplopia, photopsia, light sensitivity, new or increased floaters) occur.
Risk of fetal harm. Advise females of reproductive potential to use effective methods of contraception while receiving entrectinib and for ≥5 weeks after the last dose. Advise males with female partners of reproductive potential to use effective methods of contraception while receiving the drug and for 3 months after the last dose. Advise females to inform their clinicians if they are or plan to be pregnant. If pregnancy occurs, advise pregnant women of potential risk to the fetus.
Advise females to avoid breastfeeding while receiving the drug and for 1 week after the last dose.
Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Obtain entrectinib through designated specialty pharmacies and distributors.