entrectinib (Rx)

Brand and Other Names:Rozlytrek
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 100mg
  • 200mg

Non-small Cell Lung Cancer

Indicated for metastatic non-small cell lung cancer (NSCLC) in adults whose tumors are ROS1-positive

600 mg PO qDay

Continue until disease progression or unacceptable toxicity

Neurotrophic Tyrosine Receptor Kinase Gene Fusion Solid Tumors

Indicated for patients with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and progressed following treatment or have no satisfactory alternative therapy

600 mg PO qDay

Continue until disease progression or unacceptable toxicity

Dosage Modifications

Dosage modifications for adverse reactions

  • First dose reduction: 400 mg qDay
  • Second dose reduction: 200 mg qDay
  • Permanently discontinue if toxicities persist or recur following 2 dose reductions

Congestive heart failure

  • Grade 2 or 3: Withhold until recovered to Grade ≤1; resume at reduced dose
  • Grade 4: Permanently discontinue

Central nervous system effects

  • Intolerable Grade 2: Withhold until recovered to Grade ≤1; resume at reduced dose, as clinically appropriate
  • Grade 3: Withhold until recovered to Grade ≤1; resume at reduced dose
  • Grade 4: Permanently discontinue

Hepatoxicity

  • Grade 3
    • Withhold until recovered to Grade ≤1; resume at reduced dose;
    • If resolution occurs within 4 weeks, resume at same dose
    • If adverse reaction persists after 4 weeks, permanently discontinue
    • For recurrent Grade 3 events that resolve within 4 weeks, resume at a reduced dose
  • Grade 4
    • Withhold until recovered to Grade ≤1; resume at reduce dose;
    • If adverse reaction does not resolve within 4 weeks or Grade 4 events recurs, permanently discontinue
  • Elevated ALT or AST
    • ALT or AST >3x ULN with concurrent total bilirubin >1.5x ULN (in the absence of cholestasis or hemolysis): Permanently discontinue

Hyperuricemia

  • Symptomatic or Grade 4: Initiate urate-lowering therapy; withhold until improvement of signs or symptoms; resume at same or reduced dose

QTc prolongation

  • QTc >500 ms
    • Withhold until QTc interval recovers to baseline
    • Resume at same dose if causes of QT prolongation are identified and corrected
    • Resume at reduced dose if other causes of QT prolongation are not identified
  • Life-threatening arrhythmia
    • Torsade de pointes; polymorphic ventricular tachycardia; signs/symptoms of serious arrhythmia: Permanently discontinue

Vision disorders

  • Grade ≥2: Withhold until improvement or stabilization; resume at same dose or reduced dose, as clinically appropriate

Anemia or neutropenia

  • Grade 3 or 4: Withhold until recovery to Grade≤2; resume at same or reduced dose, as clinically appropriate

Other clinically relevant adverse reactions

  • Grade 3 or 4
    • Withhold until adverse reaction resolves to Grade 1 or baseline
    • Resume at same or reduced dose if resolved within 4 weeks
    • Permanently discontinue if adverse reaction does not resolve within 4 weeks or Grade 4 events recurs

Coadministration of moderate and strong CYP3A inhibitors

  • Avoid coadministration
  • If coadministration is unavoidable, reduce entrectinib dose as follows:
    • Moderate CYP3A Inhibitors: 200 mg PO qDay
    • Strong CYP3A Inhibitors: 100 mg PO qDay
    • After discontinuation of strong or moderate CYP3A inhibitor for 3-5 elimination half-lives, resume entrectinib dose taken prior to initiating the CYP3A inhibitor

Renal impairment

  • Mild-to-moderate (CrCl 30 to <90 mL/min): No dosage adjustment necessary
  • Severe (CrCl <30 mL/min): Not studied

Hepatic impairment

  • Mild (total bilirubin ≤1.5x ULN): No dosage adjustment necessary
  • Moderate-to-severe (total bilirubin >1.5x ULN): Not studied

Dosing Considerations

Patient selection

  • Select patients for treatment based on the following:
    • NSCLC: Presence of ROS1 rearrangement
    • Locally advanced or metastatic solid tumors: Presence of a NTRK gene fusion
    • FDA-approved tests for detecting ROS1 rearrangement for NSCLC and NTRK gene fusion in solid tumors are not available

Dosage Forms & Strengths

capsule

  • 100mg
  • 200mg

Neurotrophic Tyrosine Receptor Kinase Gene Fusion Solid Tumors

Indicated for adult and pediatric patients (≥12 years) with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and progressed following treatment or have no satisfactory alternative therapy

<12 years: Safety and efficacy not established

≥12 years

  • Recommended dosage is based on body surface area (BSA)
    • 0.91-1.1 m2: 400 mg PO qDay
    • 1.11-1.5 m2: 500 mg PO qDay
    • >1.5 m2: 600 mg PO qDay

Continue until disease progression or unacceptable toxicity

Dosage Modifications

Dosage modifications of adverse reactions

  • BSA 0.91-1.1 m2
    • First dose reduction: 300 mg qDay
    • Second dose reduction: 200 mg qDay
  • BSA >1.11 m2
    • First dose reduction: 400 mg qDay
    • Second dose reduction: 200 mg qDay
  • If toxicities persist or recur following 2 dose reductions, permanently discontinue

Congestive heart failure

  • Grade 2 or 3: Withhold until recovered to Grade ≤1; resume at reduced dose
  • Grade 4: Permanently discontinue

Central nervous system effects

  • Intolerable Grade 2: Withhold until recovered to Grade ≤1; resume at reduced dose, as clinically appropriate
  • Grade 3: Withhold until recovered to Grade ≤1; resume at reduced dose
  • Grade 4: Permanently discontinue

Hepatoxicity

  • Grade 3
    • Withhold until recovered to Grade ≤1
    • If resolution occurs within 4 weeks, resume at same dose
    • If adverse reaction persists after 4 weeks, permanently discontinue
    • For recurrent Grade 3 events that resolve within 4 weeks, resume at reduced dose
  • Grade 4
    • Withhold until recovered to Grade ≤1If resolution occurs within 4 weeks, resume at reduced dose
    • If adverse reaction does not resolve within 4 weeks or Grade 4 events recurs, permanently discontinue
  • Elevated ALT or AST
    • ALT or AST >3x ULN with concurrent total bilirubin >1.5x ULN (in the absence of cholestasis or hemolysis): Permanently discontinue

Hyperuricemia

  • Symptomatic or Grade 4: Initiate urate-lowering therapy; withhold until improvement of signs or symptoms; resume at same or reduced dose

QTc prolongation

  • QTc >500 ms
    • Withhold until QTc interval recovers to baseline
    • Resume at same dose if causes of QT prolongation are identified and corrected
    • Resume at reduced dose if other causes of QT prolongation are not identified
  • Life-threatening arrhythmia
    • Torsade de pointes; polymorphic ventricular tachycardia; signs/symptoms of serious arrhythmia: Permanently discontinue

Vision disorders

  • Grade ≥2: Withhold until improvement or stabilization; resume at same dose or reduced dose, as clinically appropriate

Anemia or neutropenia

  • Grade 3 or 4: Withhold until recovery to Grade ≤2; resume at same or reduced dose, as clinically appropriate

Other clinically relevant adverse reactions

  • Grade 3 or 4
    • Withhold until adverse reaction resolves to Grade 1 or baseline
    • Resume at same or reduced dose if resolved within 4 weeks
    • Permanently discontinue if adverse reaction does not resolve within 4 weeks or Grade 4 events recurs

Coadministration of moderate and strong CYP3A inhibitors

  • Avoid coadministration
  • If coadministration is unavoidable, reduce entrectinib dose as follows:
    • Moderate CYP3A Inhibitors: 200 mg PO qDay
    • Strong CYP3A Inhibitors: 100 mg PO qDay
    • After discontinuation of strong or moderate CYP3A inhibitor for 3-5 elimination half-lives, resume entrectinib dose taken prior to initiating the CYP3A inhibitor

Renal impairment

  • Mild-to-moderate (CrCl 30 to <90 mL/min): No dosage adjustment necessary
  • Severe (CrCl <30 mL/min): Not studied

Hepatic impairment

  • Mild (total bilirubin ≤1.5x ULN): No dosage adjustment necessary
  • Moderate-to-severe (total bilirubin >1.5x ULN): Not studied

Dosing Considerations

Patient selection

  • Select patients for treatment based on the following:
    • NSCLC: Presence of ROS1 rearrangement
    • Locally advanced or metastatic solid tumors: Presence of a NTRK gene fusion
    • FDA-approved tests for detecting ROS1 rearrangement for NSCLC and NTRK gene fusion in solid tumors are not available
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Interactions

Interaction Checker

and entrectinib

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    Interactions Found

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      Serious - Use Alternative

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            Contraindicated (1)

            • lefamulin

              lefamulin will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lefamulin is contraindicated with CYP3A substrates know to prolong the QT interval.

            Serious - Use Alternative (166)

            • abametapir

              abametapir will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • alfuzosin

              alfuzosin and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • amiodarone

              amiodarone and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              amiodarone will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • anagrelide

              anagrelide and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • apalutamide

              apalutamide will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • apomorphine

              apomorphine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • aprepitant

              aprepitant will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • aripiprazole

              aripiprazole and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • armodafinil

              armodafinil will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • arsenic trioxide

              arsenic trioxide and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • artemether

              artemether and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • asenapine

              asenapine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • atazanavir

              atazanavir will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • atomoxetine

              atomoxetine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • bexarotene

              bexarotene will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • bicalutamide

              bicalutamide will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • bosentan

              bosentan will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • brigatinib

              brigatinib will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • carbamazepine

              carbamazepine will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ceritinib

              ceritinib will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

              ceritinib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • chloramphenicol

              chloramphenicol will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • chloroquine

              chloroquine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • chlorpromazine

              chlorpromazine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • ciprofloxacin

              ciprofloxacin and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • citalopram

              citalopram and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • clarithromycin

              clarithromycin and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              clarithromycin will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • clobazam

              clobazam will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • clofazimine

              clofazimine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • clotrimazole

              clotrimazole will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • clozapine

              clozapine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              clozapine will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • cobicistat

              cobicistat will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • conivaptan

              conivaptan will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • crizotinib

              crizotinib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              crizotinib will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • cyclosporine

              cyclosporine will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • dabrafenib

              dabrafenib will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • darunavir

              darunavir will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • dasatinib

              dasatinib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • degarelix

              degarelix and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • desflurane

              desflurane and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • desipramine

              desipramine will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • diltiazem

              diltiazem will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • disopyramide

              disopyramide and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • dofetilide

              dofetilide and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • dolasetron

              dolasetron and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • doxycycline

              doxycycline will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • dronedarone

              dronedarone and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              dronedarone will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • droperidol

              droperidol and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • efavirenz

              efavirenz and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              efavirenz will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • eliglustat

              eliglustat and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • encorafenib

              encorafenib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              encorafenib will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • enzalutamide

              enzalutamide will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • eribulin

              eribulin and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin base

              erythromycin base and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              erythromycin base will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              erythromycin ethylsuccinate will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • erythromycin lactobionate

              erythromycin lactobionate and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              erythromycin lactobionate will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • erythromycin stearate

              erythromycin stearate and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              erythromycin stearate will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • escitalopram

              escitalopram and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • etravirine

              etravirine will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ezogabine

              ezogabine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • fexinidazole

              fexinidazole and entrectinib both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.

              fexinidazole will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • fingolimod

              fingolimod and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • flecainide

              flecainide and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • fluconazole

              fluconazole and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              fluconazole will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • fluoxetine

              fluoxetine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • fluvoxamine

              fluvoxamine will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidabole, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.5m2. Resume previous entrectinib dose after discontinuing moderate CYP3A4 inhibitor for 3-5 elimination half-lives.

            • formoterol

              formoterol and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • fosamprenavir

              fosamprenavir will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • fostamatinib

              fostamatinib will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • gemifloxacin

              gemifloxacin and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • gemtuzumab

              gemtuzumab and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • glasdegib

              glasdegib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • goserelin

              goserelin and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • granisetron

              granisetron and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • grapefruit

              grapefruit will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid grapefruit products with entrectinib, a CYP3A4 substrate.

            • haloperidol

              haloperidol and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              haloperidol will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • histrelin

              histrelin and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • hydroxychloroquine sulfate

              hydroxychloroquine sulfate and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • ibutilide

              ibutilide and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • idelalisib

              idelalisib will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • iloperidone

              iloperidone and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              iloperidone will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • imatinib

              imatinib will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • indacaterol, inhaled

              indacaterol, inhaled and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • indinavir

              indinavir will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • inotuzumab

              inotuzumab and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • isoniazid

              isoniazid will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • itraconazole

              itraconazole will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • ketoconazole

              ketoconazole will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • lapatinib

              lapatinib will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

              lapatinib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • larotrectinib

              larotrectinib will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • lenvatinib

              lenvatinib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • letermovir

              letermovir will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • leuprolide

              leuprolide and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • levofloxacin

              levofloxacin and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • lofexidine

              lofexidine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • lopinavir

              lopinavir and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              lopinavir will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • lorlatinib

              lorlatinib will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lumefantrine

              lumefantrine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • methadone

              methadone and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • metronidazole

              metronidazole will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • mifepristone

              mifepristone and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              mifepristone will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • mitotane

              mitotane will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • mobocertinib

              mobocertinib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.

            • modafinil

              modafinil will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • moxifloxacin

              moxifloxacin and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • nafcillin

              nafcillin will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • nefazodone

              nefazodone will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • nelfinavir

              nelfinavir will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • netupitant/palonosetron

              netupitant/palonosetron will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • nilotinib

              nilotinib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • ofloxacin

              ofloxacin and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • olanzapine

              olanzapine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • osimertinib

              osimertinib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • paliperidone

              paliperidone and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • panobinostat

              panobinostat and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • pasireotide

              pasireotide and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • pazopanib

              pazopanib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • pentamidine

              pentamidine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • phenobarbital

              phenobarbital will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • phenytoin

              phenytoin will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • pimavanserin

              pimavanserin and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • pimozide

              pimozide and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • pitolisant

              pitolisant and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • posaconazole

              posaconazole will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • primaquine

              primaquine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • primidone

              primidone will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • procainamide

              procainamide and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • propafenone

              propafenone and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • quetiapine

              quetiapine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • quinidine

              quinidine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • quinine

              quinine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • ranolazine

              ranolazine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • ribociclib

              ribociclib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              ribociclib will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • rifabutin

              rifabutin will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • rifampin

              rifampin will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • rifapentine

              rifapentine will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • risperidone

              risperidone and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • ritonavir

              ritonavir will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • romidepsin

              romidepsin and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • saquinavir

              saquinavir and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              saquinavir will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • schisandra

              schisandra will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • secobarbital

              secobarbital will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • sertraline

              sertraline will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • sorafenib

              sorafenib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • sotalol

              sotalol and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • stiripentol

              stiripentol will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • sunitinib

              sunitinib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • telavancin

              telavancin and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • telotristat ethyl

              telotristat ethyl will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tetrabenazine

              tetrabenazine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • tetracycline

              tetracycline will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • thioridazine

              thioridazine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • tipranavir

              tipranavir will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • toremifene

              toremifene and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • trazodone

              trazodone and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • triclabendazole

              triclabendazole and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • triptorelin

              triptorelin and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • tucatinib

              tucatinib will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • vandetanib

              vandetanib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • vemurafenib

              vemurafenib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • verapamil

              verapamil will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • voriconazole

              voriconazole and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              voriconazole will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

            • voxelotor

              voxelotor will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            • ziprasidone

              ziprasidone and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            Monitor Closely (19)

            • albuterol

              albuterol and entrectinib both increase QTc interval. Use Caution/Monitor.

            • arformoterol

              arformoterol and entrectinib both increase QTc interval. Use Caution/Monitor.

            • azithromycin

              azithromycin increases toxicity of entrectinib by QTc interval. Use Caution/Monitor.

            • belzutifan

              belzutifan will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

            • cenobamate

              cenobamate will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • deutetrabenazine

              deutetrabenazine and entrectinib both increase QTc interval. Modify Therapy/Monitor Closely. For patients requiring deutetrabenazine doses >24 mg/day and are taking other drugs known to prolong QTc, assess the QTc interval before and after increasing the dose of deutetrabenazine or other medications known to prolong QTc.

            • elagolix

              elagolix will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • fedratinib

              fedratinib will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fostemsavir

              entrectinib and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

            • istradefylline

              istradefylline will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • ivacaftor

              ivacaftor will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • osilodrostat

              osilodrostat and entrectinib both increase QTc interval. Use Caution/Monitor.

            • ozanimod

              ozanimod and entrectinib both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.

            • ponesimod

              ponesimod and entrectinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • rucaparib

              rucaparib will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • selpercatinib

              selpercatinib increases toxicity of entrectinib by QTc interval. Use Caution/Monitor.

            • siponimod

              siponimod and entrectinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • tazemetostat

              tazemetostat will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • voclosporin

              voclosporin, entrectinib. Either increases effects of the other by QTc interval. Use Caution/Monitor.

            Minor (0)

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              Adverse Effects

              >10%

              All grades

              • Increased creatinine (73%)
              • Anemia (67%)
              • Hyperuricemia (52%)
              • Fatigue (48%)
              • Constipation (46%)
              • Dysgeusia (44%)
              • Increased AST (44%)
              • Edema (40%)
              • Lymphopenia (40%)
              • Increased ALT (38%)
              • Hyponatremia (35%)
              • Diarrhea (35%)
              • Dysesthesia (34%)
              • Nausea (34%)
              • Hypocalcemia (34%)
              • Hypophosphatemia (30%)
              • Dyspnea (30%)
              • Increased lipase (28%)
              • Hypoalbuminemia (28%)
              • Dizziness (28%)
              • Neutropenia (28%)
              • Myalgia (28%)
              • Cognitive impairment (27%)
              • Increased amylase (26%)
              • Hyperkalemia (25%)
              • Increased weight (25%)
              • Increased alkaline phosphatase (25%)
              • Cough (24%)
              • Vomiting (24%)
              • Pyrexia (21%)
              • Arthralgia (21%)
              • Vision disorders (21%)
              • Peripheral sensory neuropathy (18%)
              • Headache (18%)
              • Hypotension (18%)
              • Ataxia (17%)
              • Abdominal pain (16%)
              • Sleep (14%)
              • Urinary tract infection (13%)
              • Decreased appetite (13%)
              • Muscular weakness (12%)
              • Back pain (12%)
              • Extremity pain (11%)
              • Rash (11%)

              Grade 3 or 4

              • Lymphopenia (12%)

              1-10%

              All grades

              • Mood disorders (10%)
              • Dehydration (10%)
              • Lung infection (10%)
              • Anemia (9%)
              • Neutropenia (7%)
              • Pneumonia (3.9%)
              • Dyspnea (3.7%)
              • Pleural effusion (3.4%)
              • Sepsis (2.5%)
              • Pulmonary embolism (2.3%)
              • Respiratory failure (2%)
              • Pyrexia (2%)

              Grade 3 or 4

              • Increased lipase (10%)
              • Hyperuricemia (10%)
              • Hypophosphatemia (7%)
              • Increased weight (7%)
              • Dyspnea (6%)
              • Lung infection (5-6%)
              • Increased amylase (5.4%)
              • Fatigue/asthenia (5%)
              • Cognitive disorders (4.5%)
              • Hyperglycemia (3.8%)
              • Pulmonary embolism (3.4%)
              • Hypoxia (3.4%)
              • Pleural effusion (3.1%)
              • Hypoalbuminemia (2.9%)
              • Increased ALT (2.9%)
              • Hypotension (2.8%)
              • Increased AST (2.7%)
              • Syncope (2.5%)
              • Urinary tract infection (2.3-2.5%)
              • Increased creatinine (2.1%)
              • Diarrhea (2%)
              • Hypocalcemia (1.8%)
              • Dehydration (1.1%)
              • Myalgia (1.1%)
              • Back pain (1%)

              <1%

              Grade 3 or 4

              • Increased alkaline phosphatase (0.9%)
              • Hyponatremia (0.9%)
              • Rash (0.8%)
              • Vision disorders (0.8%)
              • Muscular weakness (0.8%)
              • Ataxia (0.8%)
              • Arthralgia (0.6%)
              • Mood disorders (0.6%)
              • Sleep disorders (0.6%)
              • Decreased appetite (0.3%)
              • Pain in extremity (0.3%)
              • Cough (0.3%)
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              Warnings

              Contraindications

              None

              Cautions

              Increase of fractures reported; promptly evaluate patients with signs or symptoms (eg, pain, changes in mobility, deformity) of fractures

              Increased liver transaminase reported; monitor liver tests every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated

              Hyperuricemia reported, as well as elevated uric acid levels; assess serum uric acid levels prior to initiation and periodically during treatment

              Vision disorders have occurred, including blurred vision, photophobia, diplopia, visual impairment, photopsia, cataract, and vitreous floaters

              Based on literature reports in humans with congenital mutations leading to changes in TRK signaling, findings from animal studies, and its mechanism of action, fetal harm may occur when administered to a pregnant woman

              QT prolongation

              • QT prolongation reported; patients with at least 1 post-baseline ECG assessment experienced prolonged QT interval of >60 ms after starting treatment
              • Assess QT interval and electrolytes at baseline and periodically during treatment
              • Adjust monitoring frequency based on risk factors such as congestive heart failure (CHF), electrolyte abnormalities, or concomitant medications known to prolong the QTc interval

              CNS adverse reactions

              • CNS adverse reactions reported, including cognitive impairment, mood disorders, dizziness, and sleep disturbances
              • Advise patients and caregivers of these risks
              • Instruct patients not to drive or operate hazardous machinery if experiencing CNS adverse reactions

              Congestive heart failure

              • CHF occurred in clinical trials
              • Among patients with CHF, median time to onset was 2 months
              • Myocarditis in the absence of CHF was also documented
              • Assess left ventricular ejection fraction before initiation in patients with symptoms or known risk factors for CHF
              • Monitor for clinical signs and symptoms of CHF, including shortness of breath and edema
              • For patients with myocarditis, with or without a decreased ejection fraction, MRI or cardiac biopsy may be required to make the diagnosis

              Drug interaction overview

              Entrectinib is a CYP3A4 substrate

              • Moderate and strong CYP3A inhibitors
                • Coadministration with a strong or moderate CYP3A inhibitor increases entrectinib plasma concentrations, which could increase frequency or severity of adverse reactions
                • Avoid coadministration
                • If coadministration is unavoidable, reduce dose
                • Grapefruit products are CYP3A4 inhibitors; avoid these products during treatment
              • Moderate and strong CYP3A inducers
                • Coadministration with a strong or moderate CYP3A inducer decreases entrectinib plasma concentrations, which may reduce entrectinib efficacy
                • Avoid coadministration
              • Drugs that prolong QT interval
                • QTc interval prolongation can occur
                • Avoid coadministration with other products with a known potential to prolong QT interval
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              Pregnancy & Lactation

              Pregnancy

              Based on literature reports in humans with congenital mutations leading to changes in TRK signaling, findings from animal studies, and its mechanism of action, fetal harm may occur when administered to a pregnant woman

              No data available on use in pregnant women

              Verify pregnancy status of females of reproductive potential before initiating treatment

              Animal data

              • Administration of entrectinib to pregnant rats during organogenesis resulted in malformations at maternal exposures ~2.7 times the human exposure at the 600-mg dose
              • Advise pregnant women of the potential risk to a fetus

              Contraception

              • Females of reproductive potential: Use effective contraception during treatment and for at least 5 weeks following the final dose
              • Males with female partners of reproductive potential: Use effective contraception during treatment and for 3 months following the final dose

              Lactation

              There are no data on the presence of entrectinib or its metabolites in human milk or their effects on either the breastfed child or on milk production

              Owing to the potential adverse reactions in breastfed children from entrectinib, advise a lactating woman to discontinue breastfeeding during treatment and for 7 days after the final dose

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              An inhibitor of tropomyosin receptor tyrosine kinases (TRKs) TRKA, TRKB, and TRKC (encoded by the neurotrophic tyrosine receptor kinase [NTRK] genes NTRK1, NTRK2, and NTRK3, respectively), proto-oncogene tyrosine-protein kinase ROS1 (ROS1), and anaplastic lymphoma kinase (ALK); also, inhibits JAK2 and TNK2

              Major active metabolite of entrectinib, M5, showed similar in vitro activity against TRK, ROS1, and ALK

              Fusion proteins that include TRK, ROS1, or ALK kinase domains can drive tumorigenic potential through hyperactivation of downstream signaling pathways, leading to unconstrained cell proliferation

              Absorption

              Steady-state achieved within 1 week for entrectinib and 2 weeks for M5

              Peak plasma time: 4-6 hr (entrectinib plasma level; 600-mg dose)

              Peak plasma concentration

              • Single dose: 2250 nM (entrectinib); 622 nM (M5)
              • Steady-state: 3130 nM (entrectinib); 1,250 nM (M5

              AUC

              • Single dose: 31,800 nM·hr (entrectinib); 10,200 nM·hr (M5)
              • Steady-state: 48,000 nM·hr (entrectinib); 24,000 nM·hr (M5)

              Distribution

              Protein bound: >99% (entrectinib and M5)

              Vd: 551 L (entrectinib); 81.1 L (M5)

              Metabolism

              Metabolized primarily by CYP3A4 (~76%); forms active metabolite M5 (formed by CYP3A4); the only major active circulating metabolite identified

              M5 has similar pharmacological potency to entrectinib in vitro and circulating M5 exposures at steady-state in patients were 40% of the corresponding entrectinib exposure

              Elimination

              Clearance: 19.6 L/hr (entrectinib); 52.4 L/hr (M5)

              Half-life: 20 hr (entrectinib); 40 hr (M5)

              Excretion: Feces (83% [36% as unchanged entrectinib; 22% as M5]) urine (3%)

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              Administration

              Oral Administration

              Take orally with or without food

              Swallow capsules whole; do not open, crush, chew, or dissolve contents of capsule

              Missed dose

              • If dose is missed, take missed dose unless the next dose is due within 12 hr
              • If patient vomits immediately after taking a dose, repeat that dose

              Storage

              Store <30ºC (86ºF)

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              Images

              No images available for this drug.
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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

              Adding plans allows you to compare formulary status to other drugs in the same class.

              To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

              Adding plans allows you to:

              • View the formulary and any restrictions for each plan.
              • Manage and view all your plans together – even plans in different states.
              • Compare formulary status to other drugs in the same class.
              • Access your plan list on any device – mobile or desktop.

              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.