General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Genetic Implications:

Pronunciation:
en-sar-ti-nib

Trade Name(s)

• Ensacove

Ther. Class.

antineoplastics

Pharm. Class.

kinase inhibitors

Indications

 Anaplastic lymphoma kinase (ALK)-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) in patients who have not previously received an ALK inhibitor.

Action

Inhibits ALK as well as MET and ROS1, resulting in antitumor activity.

Therapeutic Effect(s):

Improved progression-free survival.

Pharmacokinetics

Absorption: Extent of absorption following oral administration unknown.

Distribution: Extensively distributed to tissues.

Protein Binding: 91.6%.

Metabolism and Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme; 91% excreted in feces (38% as unchanged drug); 10% excreted in urine (4% as unchanged drug).

Half-life: 30 hr.

TIME/ACTION PROFILE (plasma concentrations)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity (contains tartrazine);
• Severe hepatic impairment (total bilirubin >3 times upper limit of normal [ULN]);
• OB:   Pregnancy;
• Lactation:  Lactation.

Use Cautiously in:

• Aspirin hypersensitivity;
• Moderate hepatic impairment (total bilirubin >1.5–≥3 times ULN);
• Rep:   Women of reproductive potential and men with female partners of reproductive potential;
• Pedi:   Safety and effectiveness not established in children;
• Geri:   Older adults may have ↑ risk of adverse reactions.

Adverse Reactions/Side Effects

CV: edema, bradycardia

Derm: alopecia, dry skin, pruritus, rash, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), photosensitivity

EENT: blurred vision, diplopia, photopsia, visual impairment, vitreous floaters

Endo: hyperglycemia

F and E: hypocalcemia, hyponatremia, hypophosphatemia, hypermagnesemia, hypokalemia

GI: ↑ liver enzymes, constipation, hypoalbuminemia, nausea, vomiting, ↑ amylase, HEPATOTOXICITY

GU: ↑ serum creatinine

Hemat: anemia, bleeding, lymphopenia

Metabolic: ↓ appetite, hyperuricemia

MS: ↑ CK, pain

Neuro: dizziness, dysgeusia, fatigue

Resp: cough, respiratory tract infection, INTERSTITIAL LUNG DISEASE (ILD)/PNEUMONITIS

Misc: fever

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

•  Strong CYP3A4 inhibitors  and  moderate CYP3A4 inhibitors  may ↑ levels and risk of toxicity; avoid concurrent use.
•  Strong CYP3A4 inducers  and  moderate CYP3A4 inducers  may ↓ levels and effectiveness; avoid concurrent use.
•  P-glycoprotein inhibitors  may ↑ levels and risk of toxicity; avoid concurrent use.

Route/Dosage

PO (Adults): 225 mg once daily; continue until disease progression or unacceptable toxicity.

Availability

Capsules: 25 mg, 100 mg

Assessment

• Assess for ILD/pneumonitis (dyspnea, cough, fever).  If any Grade ILD/pneumonitis occurs,  permanently discontinue ensartinib.
• Assess for dermatologic adverse reactions (DRESS, rash, pruritus, photosensitivity).  If Grade 1 dermatologic reactions occur,  consider topical corticosteroids.  If Grade 2 dermatologic reactions occur, administer topical corticosteroids. If no improvement in ≤7 days after starting topical corticosteroids, administer PO corticosteroids. If no improvement in ≤7 days after starting PO corticosteroids, hold ensartinib until Grade ≤1. Resume at ↓ dose.  If Grade 3 dermatologic reactions occur,  hold ensartinib. Administer topical corticosteroids. If no improvement after 7 days of starting topical corticosteroids, administer PO corticosteroids. Resume at ↓ dose upon improvement to Grade ≤1.  If Grade 4 dermatologic reactions occur,  permanently discontinue ensartinib. Administer systemic corticosteroids and consider antibiotic use.
• Assess and monitor for bradycardia (HR <60 bpm) during treatment.  If symptomatic bradycardia occurs,  hold ensartinib until asymptomatic or resting HR >60 bpm. If a concurrent medication known to cause bradycardia is identified and discontinued or dose adjusted, resume ensartinib at same dose when asymptomatic bradycardia or resting HR >60 bpm. If no concurrent medication known to cause bradycardia is identified or if contributing concurrent medications are not discontinued or dose adjusted, resume ensartinib at ↓ dose when asymptomatic or resting HR >60 bpm.  If bradycardia with life-threatening consequences occurs or if urgent intervention indicated,  permanently discontinue ensartinib if no contributing concurrent medication is identified. If contributing concurrent medication is identified and discontinued or dose adjusted, resume ensartinib at ↓ dose when asymptomatic bradycardia or a resting HR of >60 bpm, with frequent monitoring as clinically indicated.  For recurrence, permanently discontinue ensartinib.
• Assess for visual disturbances (blurred vision, diplopia, photopsia, vitreous floaters, visual impairment, visual field defect, ↓ visual acuity).  If Grade 2 or 3 visual disturbances occur,  hold ensartinib until Grade ≤1; then resume at ↓ dose.  If Grade 4 visual disturbances occur,  permanently discontinue ensartinib. Obtain an ophthalmologic evaluation for patients with new or worsening visual symptoms.
• Assess for other adverse reactions.  If Grade 3 or 4 adverse reactions occur, hold ensartinib until Grade ≤1. Resume at ↓ dose.  If recurrent Grade 4 adverse reactions occur,  permanently discontinue ensartinib.

Lab Test Considerations:

• Verify negative pregnancy status before starting treatment.
• Monitor fasting serum glucose at baseline and periodically during therapy. May cause hyperglycemia.  If Grade 3 hyperglycemia (>250 mg/dL) despite antihyperglycemic therapy or Grade 4 hyperglycemia occurs, hold ensartinib until hyperglycemia controlled; then resume at ↓ dose. If hyperglycemic control cannot be achieved with medical management, permanently discontinue ensartinib.
• Monitor ALT, AST, and total bilirubin at baseline, then every 2 wk during 1st cycle, and then monthly and as clinically indicated. May cause hepatotoxicity.  If Grade 3 or 4 ↑ (>5 times ULN) of either ALT or AST with concurrent total bilirubin ↑ ≤ 2 times ULN occurs,  hold ensartinib until Grade ≤1 (≤3 times ULN). Resume at ↓ dose.  If Grade 2–4 ↑ (>3 times ULN) of either ALT or AST with concurrent total bilirubin ↑ >2 times ULN in the absence of cholestasis or hemolysis occurs, permanently discontinue ensartinib.
• Monitor CK levels.  If CK ↑ >5 times ULN,  temporarily hold ensartinib until recovery to baseline or ≤2.5 times ULN; then resume at same dose.  If CK ↑ >10 times ULN or 2nd occurrence of CK ↑ >5 times ULN,  temporarily hold ensartinib until recovery to baseline or ≤2.5 times ULN; then resume at ↓ dose.
• Monitor uric acid level at baseline and periodically during therapy. May cause hyperuricemia.  If symptomatic or Grade 4 hyperuricemia occurs, start urate-lowering medication. Hold ensartinib until improvement of signs/symptoms. Resume at same or ↓ dose.
• May ↓ albumin, phosphate, calcium, sodium, potassium, lymphocytes, and hemoglobin. May ↑ serum creatinine, magnesium, amylase, and gamma glutamyl transferase.

Implementation

• PO  Administer daily with or without food.  DNC: Swallow capsules whole; do not crush or chew.  Do not open or dissolve the contents of the capsule.
•  Recommended Dose Reductions for Adverse Reactions:  1st dose reduction: 200 mg once daily.  2nd dose reduction:  150 mg once daily. Permanently discontinue ensartinib if unable to tolerate 150 mg once daily. Once the dose has been ↓, do not subsequently ↑ the dose.

Patient/Family Teaching

• Explain purpose and side effects of medication. Advise patient to read  Patient Information  before starting therapy. If a dose is missed, take the missed dose as soon as possible unless the next dose is due within 12 hr. Do not take two doses on same day. If vomiting occurs after taking a dose, do not take an additional dose and take the next dose at its scheduled time.
• Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
• Advise patient of the signs/symptoms of severe adverse reactions such as hepatotoxicity and ILD/pneumonitis. If symptoms occur, notify health care provider immediately.
• Inform patient of dermatologic adverse reactions. Advise to limit direct sun exposure during treatment and for >1 wk after discontinuation.
• Advise patient to report any unexplained muscle pain, tenderness, or weakness.
• Inform patient of the risks of new or worsening hyperglycemia during treatment and the need to periodically monitor glucose levels. Advise patients with diabetes mellitus or glucose intolerance that antihyperglycemic medications may need to be adjusted during treatment.
• Advise patient that this product contains FD&C Yellow No. 5 (tartrazine), which may cause allergic-type or asthma-type reactions in certain susceptible persons (e.g., patients who also have aspirin hypersensitivity). Advise patient to seek immediate medical attention if symptoms of an allergic reaction occur.
• Rep:  May cause fetal harm. Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected. Advise women not to breastfeed during treatment and for 1 wk after last dose. Advise women of reproductive potential and men with female partners of reproductive potential to use effective contraception during treatment and for 1 wk after last dose.

Evaluation/Desired Outcomes

Improved progression-free survival.