• Metastatic non-small cell lung cancer (NSCLC) in patients whose tumors are ROS1-positive.
• Solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic, or are likely to result in severe morbidity with surgical resection, and have either progressed following treatment or have no satisfactory alternative therapy.

Contraindicated in:

• Severe renal impairment
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• History of HF, MI, unstable angina, or coronary artery bypass graft surgery (↑ risk of HF)
• Long QT syndrome, bradyarrhythmias, uncontrolled HF, electrolyte abnormalities, or concurrent use of QT interval prolonging medications (↑ risk of QT interval prolongation)
• Moderate or severe hepatic impairment
• Women of reproductive potential and men with female partners of reproductive potential
• Pedi: ↑risk of bone fractures in children
• Pedi: Safety and effectiveness not established in children <18 yr (ROS-1 positive NSCLC); or 1 mo (solid tumors with a NTRK gene fusion).

CV: edema, hypotension, HF, myocarditis, QT interval prolongation, syncope.

Derm: rash.

EENT: blurred vision, cataracts, diplopia, eye floaters/flashes, photophobia, visual impairment.

Endo: hyperuricemia.

F and E: hyperkalemia, hypernatremia, hypocalcemia, hypophosphatemia.

GI: abdominal pain, constipation, diarrhea, dysphagia, hypoalbuminemia, ↑amylase, ↑lipase, ↑liver enzymes, nausea, vomiting, HEPATOTOXICITY.

GU: dehydration, ↑serum creatinine.

Hemat: anemia, lymphopenia, neutropenia.

Metab: ↓appetite, ↑weight.

MS: arthralgia, bone fractures, muscle weakness, myalgia.

Neuro: ataxia, balance disorder, confusion, dizziness, dysgeusia, fatigue, headache, paresthesia, peripheral neuropathy, agitation, amnesia, anxiety, aphasia, attention disturbances, cognitive disorders, depression, delirium, hallucinations, insomnia, memory impairment, mental status changes, sedation.

Resp: cough, dyspnea, pleural effusion, PULMONARY EMBOLISM.
Misc: fever.

Drug-Drug:

• Moderate or strong CYP3A4 inhibitors, including itraconazole, may ↑ levels and risk of toxicity; avoid concurrent use. If must use moderate or strong CYP3A4 inhibitor, ↓ entrectinib dose.
• Moderate or strong CYP3A4 inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use.
• QT interval prolonging medications may ↑ risk of QT interval prolongation; avoid concurrent use.

Drug-Food:

• Grapefruit juice may ↑ levels and risk of toxicity; avoid concurrent use.

• Capsules: 100 mg; 200 mg;
• Oral pellets: 50 mg/pkt;

ROS1-Positive Non-Small Cell Lung Cancer

• PO (Adults): 600 mg once daily until disease progression or unacceptable toxicity. Concurrent use of moderate CYP3A4 inhibitor — 200 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor — 100 mg once daily until disease progression or unacceptable toxicity.

NTRK Gene Fusion-Positive Solid Tumors

• PO (Adults): 600 mg once daily until disease progression or unacceptable toxicity. Concurrent use of moderate CYP3A4 inhibitor — 200 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor — 100 mg once daily until disease progression or unacceptable toxicity.
• PO (Children 2 yr and body surface area [BSA] >1.5 m²): 600 mg once daily until disease progression or unacceptable toxicity. Concurrent use of moderate CYP3A4 inhibitor — 200 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor — 100 mg once daily until disease progression or unacceptable toxicity.
• PO (Children 2 yr and BSA 1.11–1.5 m²): 400 mg once daily until disease progression or unacceptable toxicity. Concurrent use of moderate CYP3A4 inhibitor — 200 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor — 50 mg once daily until disease progression or unacceptable toxicity.
• PO (Children 2 yr and BSA 0.81–1.1 m²): 300 mg once daily until disease progression or unacceptable toxicity. Concurrent use of moderate CYP3A4 inhibitor — 100 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor — 50 mg once daily until disease progression or unacceptable toxicity.
• PO (Children 2 yr and BSA 0.51–0.8 m²): 200 mg once daily until disease progression or unacceptable toxicity. Concurrent use of moderate CYP3A4 inhibitor — 50 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor — 50 mg every other day until disease progression or unacceptable toxicity.
• PO (Children >2 yr and BSA 0.5 m²): 300 mg/m² once daily until disease progression or unacceptable toxicity.
• PO (Children >6 mo–<2 yr and BSA >1.5 m²): 600 mg once daily until disease progression or unacceptable toxicity.
• PO (Children >6 mo–<2 yr and BSA 1.11–1.5 m²): 400 mg once daily until disease progression or unacceptable toxicity.
• PO (Children >6 yr–<2 yr and BSA 0.81–1.1 m²): 300 mg once daily until disease progression or unacceptable toxicity.
• PO (Children >6 mo–<2 yr and BSA 0.51–0.8 m²): 200 mg once daily until disease progression or unacceptable toxicity.
• PO (Children >6 mo–<2 yr and BSA 0.5 m²): 300 mg/m² once daily until disease progression or unacceptable toxicity.
• PO (Children >1 mo–6 mo): 250 mg/m² once daily until disease progression or unacceptable toxicity.

Rozlytrek

• Acts as an inhibitor of the tropomyosin receptor tyrosine kinases (encoded by the NTRK genes), proto-oncogene tyrosine-protein kinase ROS1, and anaplastic lymphoma kinase, which ultimately inhibits grown of cancer cell lines.

• Decreased spread of NSCLC and certain solid tumors.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Absorption: Well absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Protein Binding: >99%.

Metabolism/Excretion: Primarily metabolized in the liver by the CYP3A4 isoenzyme to an active metabolite (M5). Primarily excreted in feces (36% as unchanged drug, 22% as M5), with minimal excretion in urine (3%).

Half-life: Entrectinib: 20 hr; M5: 40 hr.

(plasma concentrations)

• Instruct patient to take entrectinib as directed. Take missed dose as soon as remembered unless within 12 hr of next dose. If patient vomits immediately after taking, instruct patient to repeat dose. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
• May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to entrectinib is known.
• Advise patient to notify health care professional promptly if signs and symptoms if HF (persistent coughing or wheezing, increasing shortness of breath, trouble breathing when lying down, tiredness, weakness, fatigue, sudden weight gain, swelling in ankles, feet, or legs), central nervous system effects (dizziness, changes in mood, confusion, hallucinations, problems with concentration, attention, memory, and sleep), liver problems (loss of appetite, nausea or vomiting, pain on upper right side of stomach area) changes in electrical activity of the heart (feeling faint, light-headed, or dizzy or feeling heart beating irregularly or fast) or vision problems (double vision, seeing flashes of light, blurry vision, light hurting your eyes, new or increased floaters) occur.
• Inform patient that entrectinib may increase risk of bone fractures. Advise patient to notify health care professional if fractures occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for at least 5 wk after final dose of entrectinib. Advise males with female partners of reproductive potential to use effective contraception during and for 3 mo after final dose. Advise patient to avoid breastfeeding during and for 7 days after final dose.

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