Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
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)
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%)
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
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.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%)
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)
Images
Formulary
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.
