CONTRAINDICATIONS / PRECAUTIONS
Angina, cardiac disease, coronary artery bypass graft surgery (CABG), heart failure, myocardial infarction, myocarditis, ventricular dysfunction
Use entrectinib with caution in patients with a history of heart failure or cardiac disease. Congestive heart failure (CHF) has been reported in patients treated with entrectinib across clinical trials. In these trials, baseline cardiac function and routine cardiac monitoring other than ECGs were not conducted and eligibility criteria excluded patients with symptomatic CHF, myocardial infarction, unstable angina, and coronary artery bypass graft surgery (CABG) within 3 months of study entry. Assess left ventricular ejection fraction (LVEF) prior to initiation of therapy in patients with symptoms or known risk factors for CHF; monitor for signs and symptoms of ventricular dysfunction or CHF including shortness of breath and edema. Treatment interruption, dose reduction, or discontinuation may be necessary for patients who develop heart failure. Myocarditis in the absence of CHF has also been reported. For patients with myocarditis, with or without a decreased ejection fraction, MRI or cardiac biopsy may be required to make the diagnosis. Use entrectinib with caution in patients with heart failure or myocardial infarction due to an increased risk of prolonging the QT interval.
Anxiety, behavioral changes, depression, driving or operating machinery
Use entrectinib with caution in patients with a history of anxiety, depression, or cognitive or mental status changes. A broad spectrum of central nervous system (CNS) adverse reactions occurred in patients treated with entrectinib across clinical trials, including cognitive impairment, behavioral changes / mood disorders, dizziness, and insomnia or other sleep disturbances. The incidence of CNS adverse reactions, in general, was similar in patients with and without CNS metastases, although the incidence of dizziness, headache, paresthesias, balance disorders, and confusion appeared to be increased in patients with CNS metastases who had received prior CNS irradiation; the median time to onset was 1 month. Advise patient against driving or operating machinery if they are experiencing CNS adverse reactions. An interruption of therapy followed by dose reduction or discontinuation of therapy may be necessary for patients who develop CNS adverse reactions, depending on the severity.[64567]
Bone fractures
The risk of skeletal bone fractures is increased with entrectinib therapy. In adults, some fractures occurred after a fall or other trauma to the affected area; in pediatric patients, all fractures occurred in patients with minimal or no trauma. In general, there was an inadequate assessment for tumor involvement at the site of the fracture; however, radiologic abnormalities possibly indicative of tumor involvement were reported in some patients. Promptly evaluate patients with signs or symptoms of fractures (e.g., pain, changes in mobility, deformity). There are no data on the healing of known fractures and the risk of future fractures.[64567]
Hepatic disease, hepatotoxicity
Hepatotoxicity has also been reported in patients treated with entrectinib across clinical trials with a median time to onset of 2 weeks. Monitor liver function tests including ALT and AST every 2 weeks for the first month of treatment, then monthly thereafter and as clinically indicated. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary. Use entrectinib with caution in patients with known hepatic disease. No dosage adjustment is recommended for patients with mild hepatic impairment, but entrectinib has not been studied in patients with moderate [total bilirubin more than 1.5 to 3 times the upper level of normal (ULN)] and severe (total bilirubin more than 3 times ULN) hepatic impairment.
Hyperuricemia, tumor lysis syndrome (TLS)
Hyperuricemia has been reported in patients treated with entrectinib across clinical trials (n = 355), including one patient who died due to tumor lysis syndrome (TLS). Assess serum uric acid levels prior to initiating entrectinib therapy and periodically during treatment; monitor for signs and symptoms of hyperuricemia. If hyperuricemia occurs, interrupt entrectinib therapy and begin treatment with urate-lowering medications as clinically indicated; a dose reduction may be necessary.
Apheresis, AV block, bradycardia, cardiomyopathy, celiac disease, electrolyte imbalance, females, fever, geriatric, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE)
Use entrectinib with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause an electrolyte imbalance. Females, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation. In clinical trials, 3.1% of patients with at least one post-baseline ECG assessment experienced QTcF interval prolongation of more than 60 ms after starting entrectinib and 0.6% had a QTcF interval more than 500 milliseconds.[28432] [28457] [56592] [64567]
Visual impairment
Use with caution in patients with visual impairment; a variety of vision disorders and changes were reported in patients treated with entrectinib across pre-approval clinical trials. For patients with new visual changes or changes that interfere with activities of daily living, withhold entrectinib until improvement or stabilization and conduct an ophthalmological evaluation as clinically appropriate. Upon improvement or stabilization, resume the drug at same or reduced dose.
Pregnancy
Based on literature reports in humans with congenital mutations leading to changes in TRK signaling, animal studies, and its mechanism of action, entrectinib can cause fetal harm or death when administered during pregnancy. Pregnancy should be avoided by females of reproductive potential during entrectinib treatment and for at least 5 weeks after the final dose. Women who are pregnant or who become pregnant while receiving entrectinib should be apprised of the potential hazard to the fetus. There are no available data on the use of entrectinib in pregnant women. Published reports of individuals with congenital mutations in TRK pathway proteins suggest that decreases in TRK-mediated signaling are correlated with obesity, developmental delays, cognitive impairment, insensitivity to pain, and anhidrosis. Administration of entrectinib to pregnant rats during organogenesis resulted in body closure defects (e.g., omphalocele and gastroschisis) and malformations of the vertebrae, ribs, and limbs (micromelia and adactyly) at maternal exposures approximately 2.7 times the human exposure at the recommended dose (600 mg); embryolethality did not occur. Lower fetal weight and reduced skeletal ossification occurred at approximately 0.2 and 0.9 times the human exposure at the recommended dose, respectively.
Contraception requirements, male-mediated teratogenicity, pregnancy testing, reproductive risk
Counsel patients about the reproductive risk and contraception requirements during entrectinib treatment. Entrectinib can be teratogenic if taken by the mother during pregnancy. Females of reproductive potential should avoid pregnancy and use effective contraception during and for at least 5 weeks after the final dose of entrectinib. Females of reproductive potential should undergo pregnancy testing prior to initiation of entrectinib. Women who become pregnant while receiving entrectinib should be apprised of the potential hazard to the fetus. Due to the risk of male-mediated teratogenicity, males with female partners of reproductive potential should use effective contraception during and for at least 3 months after treatment with entrectinib.
Breast-feeding
Due to the potential for serious adverse reactions in a nursing infant from entrectinib, advise women to discontinue breast-feeding during treatment and for 7 days after the final dose. It is not known whether entrectinib is present in human milk, although many drugs are excreted in human milk.[64567]
Children, infants
There is limited clinical experience with entrectinib in children and infants. The safety and efficacy of entrectinib in pediatric patients less than 12 years of age with solid tumors who have an NTRK gene fusion have not been established. The safety and efficacy of entrectinib in pediatric patients with ROS1-positive NSCLC have also not been established. The safety of entrectinib in pediatric patients 12 years and older was established based on extrapolation of data in adults and 30 pediatric patients (younger than 2 years, n = 2; 2 to 11 years, n = 23; 12 to 17 years, n = 5). Of the studied pediatric patients, 57% had metastatic disease and 44% had locally advanced disease. The most common cancers were neuroblastoma (47%), primary CNS tumors (30%), and sarcoma (10%). In an expanded safety database including 338 adult patients and 30 pediatric patients, neutropenia, bone fractures, weight gain, thrombocytopenia, lymphopenia, increased GGT, and device-related infections were more common in pediatric patients. However, due to the small number of patients, single-arm trial design, and other confounding factors, it is not possible to determine whether the difference in the incidence of adverse reactions to entrectinib is related to patient age or other factors. The efficacy of entrectinib in adolescents is based on extrapolation of data from 3 open-label, single-arm clinical trials in adult patients with solid tumors having an NTRK gene fusion. Also, pharmacokinetic data in adolescents (age 12 and older) based on BSA resulted in similar systemic exposure compared to adults receiving the recommended dose of 600 mg.[64567]
DRUG INTERACTIONS
Adagrasib: (Major) Avoid coadministration of entrectinib with adagrasib due to increased entrectinib exposure and additive risk for QT/QTc interval prolongation and torsade de pointes (TdP). If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. Additionally, consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. If adagrasib is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of adagrasib. Entrectinib is a CYP3A substrate, adagrasib is a strong CYP3A inhibitor, and both medications may prolong the QT interval. Coadministration of another strong CYP3A inhibitor increased the overall exposure of entrectinib by 6-fold.
Alfuzosin: (Major) Avoid coadministration of entrectinib with alfuzosin due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Alfuzosin may prolong the QT interval in a dose-dependent manner.
Amiodarone: (Major) Avoid coadministration of entrectinib with amiodarone due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
Amisulpride: (Major) Avoid coadministration of entrectinib with amisulpride due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs. Entrectinib has been associated with QT prolongation. Amisulpride causes dose- and concentration -dependent QT prolongation.
Amobarbital: (Major) Avoid coadministration of entrectinib with amobarbital due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; amobarbital is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of entrectinib with clarithromycin due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If clarithromycin is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of clarithromycin. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; clarithromycin is a strong CYP3A4 inhibitor that is associated with an established risk for QT prolongation and torsade de pointes (TdP). Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Anagrelide: (Major) Avoid coadministration of entrectinib with anagrelide due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Torsade de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects.
Apalutamide: (Major) Avoid coadministration of entrectinib with apalutamide due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; apalutamide is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the entrectinib AUC by 77% in a drug interaction study.
Apomorphine: (Major) Avoid coadministration of entrectinib with apomorphine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Aprepitant, Fosaprepitant: (Major) Avoid coadministration of entrectinib with aprepitant, fosaprepitant due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If aprepitant, fosaprepitant is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of aprepitant, fosaprepitant. Entrectinib is a CYP3A4 substrate; when administered as a 3 day oral regimen, aprepitant is a moderate inhibitor of CYP3A4. Single oral and IV doses have not been shown to alter concentrations of CYP3A4 substrates. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Aripiprazole: (Major) Concomitant use of entrectinib and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Arsenic Trioxide: (Major) Avoid coadministration of entrectinib with arsenic trioxide due to the risk of QT prolongation. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Entrectinib has been associated with QT prolongation.
Artemether; Lumefantrine: (Major) Avoid coadministration of entrectinib with artemether; lumefantrine due to the risk of QT prolongation. Consider ECG monitoring if entrectinib must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine is associated with prolongation of the QT interval. Entrectinib has been associated with QT prolongation.
Asenapine: (Major) Avoid coadministration of entrectinib with asenapine due to the risk of QT prolongation. Both entrectinib and asenapine have been associated with QT prolongation.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid coadministration of entrectinib with butalbital due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; butalbital is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Avoid coadministration of entrectinib with butalbital due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; butalbital is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Atazanavir: (Major) Avoid coadministration of entrectinib with atazanavir due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If atazanavir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of atazanavir. Entrectinib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Atazanavir; Cobicistat: (Major) Avoid coadministration of entrectinib with atazanavir due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If atazanavir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of atazanavir. Entrectinib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study. (Major) Avoid coadministration of entrectinib with cobicistat due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If cobicistat is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of cobicistat. Entrectinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Atomoxetine: (Major) Concomitant use of entrectinib with atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Azithromycin: (Major) Avoid coadministration of azithromycin with entrectinib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Entrectinib has been associated with QT prolongation.
Bedaquiline: (Major) Avoid coadministration of entrectinib with bedaquiline due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs. Discontinue bedaquiline if evidence of serious ventricular arrhythmia or QTcF interval greater than 500 milliseconds. Bedaquiline prolongs the QT interval. Entrectinib has been associated with QT prolongation.
Berotralstat: (Major) Avoid coadministration of entrectinib with berotralstat due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If berotralstat is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of berotralstat. Entrectinib is a CYP3A4 substrate; berotralstat is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Bexarotene: (Major) Avoid coadministration of entrectinib with bexarotene due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; bexarotene is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bosentan: (Major) Avoid coadministration of entrectinib with bosentan due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; bosentan is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Buprenorphine: (Major) Concomitant use of buprenorphine and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Buprenorphine; Naloxone: (Major) Concomitant use of buprenorphine and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Butalbital; Acetaminophen: (Major) Avoid coadministration of entrectinib with butalbital due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; butalbital is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid coadministration of entrectinib with butalbital due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; butalbital is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid coadministration of entrectinib with butalbital due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; butalbital is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Cabotegravir; Rilpivirine: (Major) Avoid coadministration of entrectinib with rilpivirine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Carbamazepine: (Major) Avoid coadministration of entrectinib with carbamazepine due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the entrectinib AUC by 77% in a drug interaction study.
Cenobamate: (Major) Avoid coadministration of entrectinib with cenobamate due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; cenobamate is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Ceritinib: (Major) Avoid coadministration of entrectinib with ceritinib due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If ceritinib is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of ceritinib. Additionally, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for ceritinib if QT prolongation occurs. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; ceritinib is a strong CYP3A4 inhibitor that is associated with concentration-dependent QT prolongation. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Chloramphenicol: (Major) Avoid coadministration of entrectinib with chloramphenicol due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If chloramphenicol is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of chloramphenicol. Entrectinib is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Chloroquine: (Major) Avoid coadministration of chloroquine with entrectinib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Entrectinib has been associated with QT prolongation.
Chlorpromazine: (Major) Avoid coadministration of entrectinib with chlorpromazine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP).
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciprofloxacin: (Major) Avoid coadministration of entrectinib with ciprofloxacin due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If ciprofloxacin is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of ciprofloxacin. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; ciprofloxacin is a moderate CYP3A4 inhibitor that has been associated with rare cases of QT prolongation and torsade de pointes (TdP) during postmarketing surveillance. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Cisapride: (Contraindicated) Coadministration of cisapride with entrectinib is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias, including TdP and death, have been reported with cisapride. Entrectinib has been associated with QT prolongation.
Citalopram: (Major) Concomitant use of citalopram and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary
Clarithromycin: (Major) Avoid coadministration of entrectinib with clarithromycin due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If clarithromycin is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of clarithromycin. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; clarithromycin is a strong CYP3A4 inhibitor that is associated with an established risk for QT prolongation and torsade de pointes (TdP). Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Clofazimine: (Major) Concomitant use of clofazimine and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clozapine: (Major) Avoid coadministration of entrectinib with clozapine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death.
Cobicistat: (Major) Avoid coadministration of entrectinib with cobicistat due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If cobicistat is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of cobicistat. Entrectinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of promethazine and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Codeine; Promethazine: (Major) Concomitant use of promethazine and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Conivaptan: (Major) Avoid coadministration of entrectinib with conivaptan due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If conivaptan is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of conivaptan. Entrectinib is a CYP3A substrate; conivaptan is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Crizotinib: (Major) Avoid coadministration of entrectinib with crizotinib due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If crizotinib is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of crizotinib. Additionally, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; crizotinib is a moderate CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Cyclosporine: (Major) Avoid coadministration of entrectinib with cyclosporine due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If cyclosporine is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of cyclosporine. Entrectinib is a CYP3A4 substrate; cyclosporine is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Dabrafenib: (Major) Avoid coadministration of entrectinib with dabrafenib due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; dabrafenib is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Danazol: (Major) Avoid coadministration of entrectinib with danazol due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If danazol is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of danazol. Entrectinib is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Darunavir: (Major) Avoid coadministration of entrectinib with darunavir due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If darunavir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of darunavir. Entrectinib is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Darunavir; Cobicistat: (Major) Avoid coadministration of entrectinib with cobicistat due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If cobicistat is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of cobicistat. Entrectinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study. (Major) Avoid coadministration of entrectinib with darunavir due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If darunavir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of darunavir. Entrectinib is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of entrectinib with cobicistat due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If cobicistat is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of cobicistat. Entrectinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study. (Major) Avoid coadministration of entrectinib with darunavir due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If darunavir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of darunavir. Entrectinib is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of entrectinib with ritonavir due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If ritonavir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of ritonavir. Entrectinib is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Dasatinib: (Major) Avoid coadministration of entrectinib with dasatinib due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
Degarelix: (Major) Avoid coadministration of entrectinib with degarelix due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval.
Delavirdine: (Major) Avoid coadministration of entrectinib with delavirdine due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If delavirdine is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of delavirdine. Entrectinib is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Desflurane: (Major) Avoid coadministration of entrectinib with halogenated anesthetics due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Halogenated anesthetics can prolong the QT interval.
Deutetrabenazine: (Major) Avoid coadministration of entrectinib with deutetrabenazine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
Dexamethasone: (Major) Avoid coadministration of entrectinib with dexamethasone due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; dexamethasone is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Dextromethorphan; Quinidine: (Major) Avoid coadministration of entrectinib with quinidine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP).
Diltiazem: (Major) Avoid coadministration of entrectinib with diltiazem due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If diltiazem is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of diltiazem. Entrectinib is a CYP3A4 substrate; diltiazem is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Disopyramide: (Major) Avoid coadministration of entrectinib with disopyramide due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP).
Dofetilide: (Major) Avoid coadministration of entrectinib with dofetilide due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
Dolasetron: (Major) Avoid coadministration of entrectinib with dolasetron due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolutegravir; Rilpivirine: (Major) Avoid coadministration of entrectinib with rilpivirine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Donepezil: (Major) Avoid coadministration of entrectinib with donepezil due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy.
Donepezil; Memantine: (Major) Avoid coadministration of entrectinib with donepezil due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy.
Dronedarone: (Contraindicated) Coadministration of dronedarone with entrectinib is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Entrectinib has been associated with QT prolongation. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1,600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
Droperidol: (Major) Avoid coadministration of entrectinib with droperidol due to the risk of QT prolongation. If coadministration cannot be avoided, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Entrectinib has been associated with QT prolongation. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal.
Duvelisib: (Major) Avoid coadministration of entrectinib with duvelisib due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If duvelisib is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of duvelisib. Entrectinib is a CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Efavirenz: (Major) Avoid coadministration of entrectinib with efavirenz due to additive risk of QT prolongation and decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; efavirenz is a moderate CYP3A4 inducer that has been associated with QTc prolongation. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of entrectinib with efavirenz due to additive risk of QT prolongation and decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; efavirenz is a moderate CYP3A4 inducer that has been associated with QTc prolongation. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of entrectinib with efavirenz due to additive risk of QT prolongation and decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; efavirenz is a moderate CYP3A4 inducer that has been associated with QTc prolongation. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Elagolix: (Major) Avoid coadministration of entrectinib with elagolix due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; elagolix is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid coadministration of entrectinib with elagolix due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; elagolix is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Eliglustat: (Major) Avoid coadministration of entrectinib with eliglustat due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of entrectinib with cobicistat due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If cobicistat is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of cobicistat. Entrectinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of entrectinib with cobicistat due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If cobicistat is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of cobicistat. Entrectinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Avoid coadministration of entrectinib with rilpivirine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of entrectinib with rilpivirine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Encorafenib: (Major) Avoid coadministration of encorafenib and entrectinib due to QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib has been associated with dose-dependent QT prolongation. Entrectinib has also been associated with QT prolongation.
Enzalutamide: (Major) Avoid coadministration of entrectinib with enzalutamide due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; enzalutamide is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the entrectinib AUC by 77% in a drug interaction study.
Eribulin: (Major) Avoid coadministration of entrectinib with eribulin due to the risk of QT prolongation. If coadministration cannot be avoided, ECG monitoring is recommended. Both entrectinib and eribulin have been associated with QT prolongation.
Erythromycin: (Major) Avoid coadministration of entrectinib with erythromycin due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If erythromycin is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of erythromycin. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; erythromycin is a moderate CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Escitalopram: (Major) Concomitant use of entrectinib and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Eslicarbazepine: (Major) Avoid coadministration of entrectinib with eslicarbazepine due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; eslicarbazepine is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Etravirine: (Major) Avoid coadministration of entrectinib with etravirine due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; etravirine is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Fedratinib: (Major) Avoid coadministration of entrectinib with fedratinib due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If fedratinib is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of fedratinib. Entrectinib is a CYP3A4 substrate; fedratinib is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Fingolimod: (Major) Avoid coadministration of entrectinib with fingolimod due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
Flecainide: (Major) Avoid coadministration of entrectinib with flecainide due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Fluconazole: (Major) Avoid coadministration of entrectinib with fluconazole due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If fluconazole is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of fluconazole. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; fluconazole is a moderate CYP3A4 inhibitor that has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Fluoxetine: (Major) Concomitant use of entrectinib and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluphenazine: (Minor) Fluphenazine is associated with a possible risk for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation, such as entrectinib.
Fluvoxamine: (Major) Avoid coadministration of entrectinib with fluvoxamine due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If fluvoxamine is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of fluvoxamine. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; fluvoxamine is a moderate CYP3A4 inhibitor that has been associated with QT prolongation and torsade de pointes (TdP) in postmarketing use. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Fosamprenavir: (Major) Avoid coadministration of entrectinib with fosamprenavir due to increased entrectinib exposure which may increase the risk for entrectinib-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If fosamprenavir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of fosamprenavir. Entrectinib is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor is predicted to increase the overall exposure of entrectinib by 3-fold.
Foscarnet: (Major) Avoid coadministration of entrectinib with foscarnet due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Both QT prolongation and torsade de pointes (TdP) have been reported during postmarketing use of foscarnet.
Fosphenytoin: (Major) Avoid coadministration of entrectinib with fosphenytoin due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; fosphenytoin is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the entrectinib AUC by 77% in a drug interaction study.
Fostemsavir: (Major) Avoid coadministration of entrectinib with fostemsavir due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, 4 times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Gemifloxacin: (Major) Avoid coadministration of entrectinib with gemifloxacin due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Major) Avoid coadministration of entrectinib with gemtuzumab due to the risk of QT prolongation. If coadministration is necessary, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Entrectinib has been associated with QT prolongation. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Gilteritinib: (Major) Avoid coadministration of entrectinib with gilteritinib due to the risk of QT prolongation. If coadministration is necessary, monitor for evidence of QT prolongation during treatment. Both entrectinib and gilteritinib have been associated with QT prolongation.
Glasdegib: (Major) Avoid coadministration of glasdegib with entrectinib due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Entrectinib has been associated with QT prolongation.
Goserelin: (Major) Avoid coadministration of entrectinib with goserelin due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Androgen deprivation therapy (i.e., goserelin) may prolong the QT/QTc interval.
Granisetron: (Major) Avoid coadministration of entrectinib with granisetron due to the risk of QT prolongation. Both entrectinib and granisetron have been associated with QT prolongation.
Grapefruit juice: (Major) Advise patients to avoid grapefruit juice or grapefruit-containing foods while taking entrectinib due to increased entrectinib exposure. Entrectinib is a CYP3A4 substrate; grapefruit juice is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Halogenated Anesthetics: (Major) Avoid coadministration of entrectinib with halogenated anesthetics due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Halogenated anesthetics can prolong the QT interval.
Haloperidol: (Major) Avoid coadministration of entrectinib with haloperidol due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Histrelin: (Major) Avoid coadministration of entrectinib with histrelin due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval.
Hydroxychloroquine: (Major) Concomitant use of hydroxychloroquine and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Major) Concomitant use of hydroxyzine and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ibutilide: (Major) Avoid coadministration of entrectinib with ibutilide due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Idelalisib: (Major) Avoid coadministration of entrectinib with idelalisib due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If idelalisib is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of idelalisib. Entrectinib is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Iloperidone: (Major) Avoid coadministration of entrectinib with iloperidone due to the risk of QT prolongation. Both entrectinib and iloperidone have been associated with QT prolongation.
Imatinib: (Major) Avoid coadministration of entrectinib with imatinib due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If imatinib is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of imatinib. Entrectinib is a CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Indinavir: (Major) Avoid coadministration of entrectinib with indinavir due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If indinavir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of indinavir. Entrectinib is a CYP3A4 substrate; indinavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab with entrectinib due to the potential for additive QT prolongation and torsade de pointes. If coadministration is unavoidable, obtain ECGs and electrolytes prior to the start of treatment and periodically during treatment. Both entrectinib and inotuzumab have been associated with QT prolongation.
Isavuconazonium: (Major) Avoid coadministration of entrectinib with isavuconazonium due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If isavuconazonium is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of isavuconazonium. Entrectinib is a CYP3A4 substrate; isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Isoflurane: (Major) Avoid coadministration of entrectinib with halogenated anesthetics due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Halogenated anesthetics can prolong the QT interval.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of entrectinib with rifampin due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of rifampin decreased the entrectinib AUC by 77% in a drug interaction study.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of entrectinib with rifampin due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of rifampin decreased the entrectinib AUC by 77% in a drug interaction study.
Itraconazole: (Major) Avoid coadministration of entrectinib with itraconazole due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If itraconazole is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of itraconazole. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; itraconazole is a strong CYP3A4 inhibitor that has been associated with prolongation of the QT interval. Coadministration of itraconazole increased the AUC of entrectinib by 6-fold in a drug interaction study.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with entrectinib due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Entrectinib has been associated with QT prolongation.
Ketoconazole: (Major) Avoid coadministration of entrectinib with ketoconazole due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If ketoconazole is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of ketoconazole. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; ketoconazole is a strong CYP3A4 inhibitor that has been associated with prolongation of the QT interval. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of entrectinib with clarithromycin due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If clarithromycin is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of clarithromycin. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; clarithromycin is a strong CYP3A4 inhibitor that is associated with an established risk for QT prolongation and torsade de pointes (TdP). Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Lapatinib: (Major) Avoid coadministration of entrectinib with lapatinib due to the risk of QT prolongation. If coadministration is necessary, monitor for evidence of QT prolongation during treatment. Entrectinib has been associated with QT prolongation. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib.
Lefamulin: (Major) Coadministration of lefamulin tablets is contraindicated with entrectinib due to increased entrectinib exposure which may result in QT prolongation and torsade de pointes (TdP). Avoid use of lefamulin injection with entrectinib. If coadministration of lefamulin injection cannot be avoided, ECG monitoring is recommended during treatment. Entrectinib is a sensitive CYP3A4 substrate that has been associated with QT prolongation. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown.
Lenacapavir: (Major) Avoid coadministration of entrectinib with lenacapavir due to increased entrectinib exposure which may increase the risk for entrectinib-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If lenacapavir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of lenacapavir. Entrectinib is a CYP3A substrate; lenacapavir is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor is predicted to increase the overall exposure of entrectinib by 3-fold.
Lenvatinib: (Major) Avoid coadministration of entrectinib with lenvatinib due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Prolongation of the QT interval has also been reported with lenvatinib therapy.
Letermovir: (Major) Avoid coadministration of entrectinib with letermovir due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If letermovir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of letermovir. Entrectinib is a CYP3A4 substrate; letermovir is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Leuprolide: (Major) Avoid coadministration of entrectinib with leuprolide due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Major) Avoid coadministration of entrectinib with leuprolide due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Levofloxacin: (Major) Concomitant use of levofloxacin and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Levoketoconazole: (Major) Avoid coadministration of entrectinib with ketoconazole due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If ketoconazole is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of ketoconazole. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; ketoconazole is a strong CYP3A4 inhibitor that has been associated with prolongation of the QT interval. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Lithium: (Major) Concomitant use of lithium and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lofexidine: (Major) Avoid coadministration of entrectinib with lofexidine due to the risk of QT prolongation. If coadministration cannot be avoided, ECG monitoring is recommended. Entrectinib has been associated with QT prolongation. Lofexidine also prolongs the QT interval.
Lonafarnib: (Major) Avoid coadministration of entrectinib with lonafarnib due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If lonafarnib is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of lonafarnib. Entrectinib is a CYP3A4 substrate; lonafarnib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Loperamide: (Major) Avoid coadministration of entrectinib with loperamide due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest.
Loperamide; Simethicone: (Major) Avoid coadministration of entrectinib with loperamide due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest.
Lopinavir; Ritonavir: (Major) Avoid coadministration of entrectinib with ritonavir due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If ritonavir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of ritonavir. Entrectinib is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study. (Major) Avoid coadministration of lopinavir with entrectinib due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Both drugs have been associated with QT prolongation.
Lorlatinib: (Major) Avoid coadministration of entrectinib with lorlatinib due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; lorlatinib is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of entrectinib with lumacaftor; ivacaftor due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; lumacaftor; ivacaftor is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the entrectinib AUC by 77% in a drug interaction study.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of entrectinib with lumacaftor; ivacaftor due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; lumacaftor; ivacaftor is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the entrectinib AUC by 77% in a drug interaction study.
Macimorelin: (Major) Avoid coadministration of macimorelin with entrectinib as concurrent use may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Entrectinib has been associated with QT prolongation.
Maprotiline: (Major) Avoid coadministration of entrectinib with maprotiline due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Mavacamten: (Major) Avoid coadministration of entrectinib with mavacamten due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A substrate; mavacamten is a moderate CYP3A inducer. Coadministration of a moderate CYP3A inducer is predicted to reduce the entrectinib overall exposure by 56%.
Mefloquine: (Major) Avoid coadministration of entrectinib with mefloquine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Meperidine; Promethazine: (Major) Concomitant use of promethazine and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Methadone: (Major) Avoid coadministration of entrectinib with methadone due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Methadone is considered to be associated with an increased risk for QT prolongation and torsade de pointes (TdP), especially at higher doses (more than 200 mg/day but averaging approximately 400 mg/day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
Methohexital: (Major) Avoid coadministration of entrectinib with methohexital due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; methohexital is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Metronidazole: (Major) Concomitant use of metronidazole and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Midostaurin: (Major) Avoid coadministration of entrectinib with midostaurin due to the risk of QT prolongation. If coadministration cannot be avoided, consider interval assessments of QT by EKG. Entrectinib has been associated with QT prolongation. QT prolongation was reported in patients who received midostaurin in clinical trials.
Mifepristone: (Major) Avoid coadministration of entrectinib with mifepristone due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If mifepristone is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of mifepristone. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; mifepristone is a strong CYP3A4 inhibitor that is associated with dose-related prolongation of the QT interval. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Mirtazapine: (Major) Concomitant use of entrectinib and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mitotane: (Major) Avoid coadministration of entrectinib with mitotane due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; mitotane is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the entrectinib AUC by 77% in a drug interaction study.
Mobocertinib: (Major) Concomitant use of mobocertinib and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Modafinil: (Major) Avoid coadministration of entrectinib with modafinil due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; modafinil is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Moxifloxacin: (Major) Avoid coadministration of entrectinib with moxifloxacin due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Quinolones have been associated with a risk of QT prolongation. Although extremely rare, TdP has been reported during postmarketing surveillance of moxifloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
Nafcillin: (Major) Avoid coadministration of entrectinib with nafcillin due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; nafcillin is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Nefazodone: (Major) Avoid coadministration of entrectinib with nefazodone due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If nefazodone is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of nefazodone. Entrectinib is a CYP3A4 substrate; nefazodone is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Nelfinavir: (Major) Avoid coadministration of entrectinib with nelfinavir due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If nelfinavir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of nelfinavir. Entrectinib is a CYP3A4 substrate; nelfinavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Netupitant, Fosnetupitant; Palonosetron: (Major) Avoid coadministration of entrectinib with netupitant due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If netupitant is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of netupitant. Entrectinib is a CYP3A4 substrate; netupitant is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Nilotinib: (Major) Avoid coadministration of entrectinib with nilotinib due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If nilotinib is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of nilotinib. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; nilotinib is a moderate CYP3A4 inhibitor that has been associated with sudden death and QT interval prolongation. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Nirmatrelvir; Ritonavir: (Major) Avoid coadministration of entrectinib with ritonavir due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If ritonavir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of ritonavir. Entrectinib is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Octreotide: (Major) Avoid coadministration of entrectinib with octreotide due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If octreotide is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of octreotide. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; octreotide is a moderate CYP3A4 inhibitor that has been associated with arrhythmias, sinus bradycardia, and conduction disturbances during therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Ofloxacin: (Major) Concomitant use of ofloxacin and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine: (Major) Avoid coadministration of entrectinib with olanzapine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Olanzapine; Fluoxetine: (Major) Avoid coadministration of entrectinib with olanzapine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. (Major) Concomitant use of entrectinib and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine; Samidorphan: (Major) Avoid coadministration of entrectinib with olanzapine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of entrectinib with ritonavir due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If ritonavir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of ritonavir. Entrectinib is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid coadministration of entrectinib with rifabutin due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; rifabutin is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Ondansetron: (Major) Concomitant use of ondansetron and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
Osilodrostat: (Major) Avoid coadministration of entrectinib with osilodrostat due to the risk of QT prolongation. If coadministration is necessary, monitor ECGs during treatment. Entrectinib has been associated with QT prolongation. Osilodrostat is associated with dose-dependent QT prolongation.
Osimertinib: (Major) Avoid coadministration of entrectinib with osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Entrectinib has been associated with QT prolongation.
Oxaliplatin: (Major) Avoid coadministration of entrectinib with oxaliplatin due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking entrectinib due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Entrectinib has been associated with QT prolongation.
Pacritinib: (Major) Concomitant use of pacritinib and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Avoid coadministration of paliperidone with entrectinib due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Paliperidone has been associated with QT prolongation; torsade de pointes and ventricular fibrillation have been reported in the setting of overdose. Entrectinib has been associated with QT prolongation.
Panobinostat: (Major) Avoid coadministration of entrectinib with panobinostat due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. QT prolongation has also been reported with panobinostat.
Pasireotide: (Major) Avoid coadministration of entrectinib with pasireotide due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Pazopanib: (Major) Avoid coadministration of entrectinib with pazopanib due to the risk of QT prolongation. If coadministration cannot be avoided, closely monitor the patient for QT interval prolongation. Entrectinib has been associated with QT prolongation. Pazopanib has also been reported to prolong the QT interval.
Pentamidine: (Major) Avoid coadministration of entrectinib with pentamidine due to the risk of QT prolongation. Both entrectinib and systemic pentamidine have been associated with QT prolongation.
Perphenazine: (Minor) Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation, such as entrectinib.
Perphenazine; Amitriptyline: (Minor) Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation, such as entrectinib.
Pexidartinib: (Major) Avoid coadministration of entrectinib with pexidartinib due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Phenobarbital: (Major) Avoid coadministration of entrectinib with phenobarbital due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the entrectinib AUC by 77% in a drug interaction study.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of entrectinib with phenobarbital due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the entrectinib AUC by 77% in a drug interaction study.
Phenytoin: (Major) Avoid coadministration of entrectinib with phenytoin due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; phenytoin is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the entrectinib AUC by 77% in a drug interaction study.
Pimavanserin: (Major) Avoid coadministration of entrectinib with pimavanserin due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Pimavanserin also prolongs the QT interval.
Pimozide: (Contraindicated) Coadministration of pimozide with entrectinib is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and TdP. Entrectinib has been associated with QT prolongation.
Pitolisant: (Major) Avoid coadministration of pitolisant with entrectinib as concurrent use may increase the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Pitolisant also prolongs the QT interval.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking entrectinib due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP); additive immunosuppression may also occur which may extend the duration or severity of immune suppression. If treatment initiation is considered, seek advice from a cardiologist and monitor for signs and symptoms of infection. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Entrectinib has been associated with QT prolongation.
Posaconazole: (Major) Avoid coadministration of entrectinib with posaconazole due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If posaconazole is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of posaconazole. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; posaconazole is a strong CYP3A4 inhibitor that has been associated with QT prolongation and torsade de pointes. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Primaquine: (Major) Avoid coadministration of entrectinib with primaquine due to the risk of QT prolongation. Both entrectinib and primaquine have been associated with QT prolongation.
Primidone: (Major) Avoid coadministration of entrectinib with primidone due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; primidone is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the entrectinib AUC by 77% in a drug interaction study.
Procainamide: (Major) Avoid coadministration of entrectinib with procainamide due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
Prochlorperazine: (Minor) Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation, such as entrectinib.
Promethazine: (Major) Concomitant use of promethazine and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Dextromethorphan: (Major) Concomitant use of promethazine and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Phenylephrine: (Major) Concomitant use of promethazine and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Propafenone: (Major) Concomitant use of propafenone and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quetiapine: (Major) Concomitant use of quetiapine and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinidine: (Major) Avoid coadministration of entrectinib with quinidine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP).
Quinine: (Major) Avoid coadministration of entrectinib with quinine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP).
Ranolazine: (Major) Avoid coadministration of entrectinib with ranolazine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval.
Relugolix: (Major) Avoid coadministration of entrectinib with relugolix due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid coadministration of entrectinib with relugolix due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Ribociclib: (Major) Avoid coadministration of entrectinib with ribociclib due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If ribociclib is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of ribociclib. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; ribociclib is a strong CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation. The ribociclib ECG changes occurred within the first four weeks of treatment and were reversible with dose interruption. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Ribociclib; Letrozole: (Major) Avoid coadministration of entrectinib with ribociclib due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If ribociclib is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of ribociclib. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; ribociclib is a strong CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation. The ribociclib ECG changes occurred within the first four weeks of treatment and were reversible with dose interruption. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Rifabutin: (Major) Avoid coadministration of entrectinib with rifabutin due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; rifabutin is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Rifampin: (Major) Avoid coadministration of entrectinib with rifampin due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Coadministration of rifampin decreased the entrectinib AUC by 77% in a drug interaction study.
Rifapentine: (Major) Avoid coadministration of entrectinib with rifapentine due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the entrectinib AUC by 77% in a drug interaction study.
Rilpivirine: (Major) Avoid coadministration of entrectinib with rilpivirine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Risperidone: (Major) Avoid coadministration of entrectinib with risperidone due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Ritonavir: (Major) Avoid coadministration of entrectinib with ritonavir due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If ritonavir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of ritonavir. Entrectinib is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Romidepsin: (Major) Avoid coadministration of entrectinib with romidepsin due to the risk of QT prolongation. If coadministration is necessary, consider monitoring electrolytes and ECGs at baseline and periodically during treatment. Entrectinib has been associated with QT prolongation. Romidepsin has been reported to prolong the QT interval.
Saquinavir: (Major) Avoid coadministration of entrectinib with saquinavir boosted with ritonavir due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If saquinavir/ritonavir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of saquinavir/ritonavir. Additionally, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; saquinavir/ritonavir is a strong CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation, which may increase the risk for serious arrhythmias such as torsade de pointes (TdP). Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Secobarbital: (Major) Avoid coadministration of entrectinib with secobarbital due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; secobarbital is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Selpercatinib: (Major) Avoid coadministration of entrectinib with selpercatinib due to the risk of QT prolongation. Monitor ECGs more frequently for QT prolongation if coadministration is necessary. Entrectinib has been associated with QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy.
Sertraline: (Major) Concomitant use of sertraline and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Avoid coadministration of entrectinib with halogenated anesthetics due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Halogenated anesthetics can prolong the QT interval.
Siponimod: (Major) Avoid coadministration of entrectinib with siponimod due to the risk of QT prolongation. If coadministration cannot be avoided, consult a cardiologist regarding appropriate monitoring. Entrectinib has been associated with QT prolongation. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study.
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Solifenacin: (Major) Avoid coadministration of entrectinib with solifenacin due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
Sorafenib: (Major) Avoid coadministration of sorafenib with entrectinib due to the risk of additive QT prolongation. Sorafenib is associated with QTc prolongation. Entrectinib has also been associated with QT prolongation.
Sotalol: (Major) Concomitant use of sotalol and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sotorasib: (Major) Avoid coadministration of entrectinib with sotorasib due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; sotorasib is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of entrectinib with St. John's Wort due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; St. John's Wort is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the entrectinib AUC by 77% in a drug interaction study.
Sunitinib: (Major) Avoid coadministration of entrectinib with sunitinib due to the risk of QT prolongation. If coadministration is necessary, monitor for evidence of QT prolongation. Both entrectinib and sunitinib have been associated with QT prolongation.
Tacrolimus: (Major) Avoid coadministration of entrectinib with tacrolimus due to the risk of QT prolongation. If coadministration is necessary, consider ECG and electrolyte monitoring periodically during treatment. Entrectinib has been associated with QT prolongation. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP).
Tamoxifen: (Major) Concomitant use of tamoxifen and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Telavancin: (Major) Avoid coadministration of entrectinib with telavancin due to the risk of QT prolongation. Both entrectinib and telavancin have been associated with QT prolongation.
Tetrabenazine: (Major) Avoid coadministration of entrectinib with tetrabenazine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
Thioridazine: (Contraindicated) Coadministration of thioridazine with entrectinib is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and TdP. Entrectinib has been associated with QT prolongation.
Tipranavir: (Major) Avoid coadministration of entrectinib with tipranavir due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If tipranavir is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of tipranavir. Entrectinib is a CYP3A4 substrate; tipranavir is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Tolterodine: (Major) Avoid coadministration of entrectinib with tolterodine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
Toremifene: (Major) Avoid coadministration of entrectinib with toremifene due to the risk of QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes. Entrectinib has been associated with QT prolongation. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner.
Trandolapril; Verapamil: (Major) Avoid coadministration of entrectinib with verapamil due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If verapamil is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of verapamil. Entrectinib is a CYP3A4 substrate; verapamil is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Trazodone: (Major) Concomitant use of trazodone and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triclabendazole: (Major) Concomitant use of triclabendazole and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Trifluoperazine: (Minor) Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation, such as entrectinib.
Triptorelin: (Major) Avoid coadministration of entrectinib with triptorelin due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
Tucatinib: (Major) Avoid coadministration of entrectinib with tucatinib due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If tucatinib is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of tucatinib. Entrectinib is a CYP3A4 substrate; tucatinib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Vandetanib: (Major) Avoid coadministration of vandetanib with entrectinib due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Entrectinib has been associated with QT prolongation.
Vardenafil: (Major) Concomitant use of vardenafil and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vemurafenib: (Major) Avoid coadministration of entrectinib with vemurafenib due to the risk of QT prolongation. If concomitant use is unavoidable, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Both entrectinib and vemurafenib have been associated with QT prolongation.
Venlafaxine: (Major) Concomitant use of venlafaxine and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Verapamil: (Major) Avoid coadministration of entrectinib with verapamil due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If verapamil is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of verapamil. Entrectinib is a CYP3A4 substrate; verapamil is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Voclosporin: (Major) Avoid concomitant use of entrectinib and voclosporin due to the risk of additive QT prolongation. Entrectinib has been associated with QT prolongation. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of entrectinib with clarithromycin due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If clarithromycin is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of clarithromycin. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; clarithromycin is a strong CYP3A4 inhibitor that is associated with an established risk for QT prolongation and torsade de pointes (TdP). Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Voriconazole: (Major) Avoid coadministration of entrectinib with voriconazole due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If voriconazole is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of voriconazole. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; voriconazole is a strong CYP3A4 inhibitor that is associated with QT prolongation and rare cases of torsade de pointes (TdP). Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Vorinostat: (Major) Avoid coadministration of entrectinib with vorinostat due to the risk of QT prolongation. Both entrectinib and vorinostat have been associated with QT prolongation.
Voxelotor: (Major) Avoid coadministration of entrectinib with voxelotor due to increased entrectinib exposure which may increase the risk for entrectinib-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If voxelotor is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of voxelotor. Entrectinib is a CYP3A substrate; voxelotor is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor is predicted to increase the overall exposure of entrectinib by 3-fold.
Ziprasidone: (Major) Avoid coadministration of entrectinib with ziprasidone due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors.