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Ensartinib (Monograph)

Brand name: Ensacove
Drug class: Antineoplastic Agents

Introduction

Ensartinib hydrochloride, a kinase inhibitor of anaplastic lymphoma kinase (ALK), is an antineoplastic agent.

Uses for Ensartinib

Ensartinib has the following uses:

Ensartinib hydrochloride is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) who have not previously received an ALK-inhibitor.

Ensartinib Dosage and Administration

General

Ensartinib hydrochloride is available in the following dosage form(s) and strength(s):

Capsules: 25 mg and 100 mg of ensartinib.

Dosage

Adults

Dosage and Administration

Cautions for Ensartinib

Contraindications

Hypersensitivity reaction to ensartinib hydrochloride, FD&C Yellow No. 5 (tartrazine), or to any of its components.

Warnings/Precautions

Warnings

Interstitial Lung Disease/Pneumonitis

Ensartinib can cause severe interstitial lung disease (ILD)/pneumonitis. In the pooled safety population, ILD/pneumonitis occurred in 5% of patients treated with ensartinib, including Grade 3 in 1.3% and Grade 4 in 0.4%. ILD/pneumonitis leading to dose interruption occurred in 0.4% and permanent discontinuation of ensartinib in 1.5% of patients.

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, and fever) during treatment with ensartinib. Immediately withhold therapy in patients with suspected ILD/pneumonitis. Permanently discontinue ensartinib if ILD/pneumonitis is confirmed.

Hepatotoxicity

Ensartinib can cause hepatotoxicity including drug-induced liver injury. In the pooled safety population, 59% of patients treated with ensartinib had increased alanine aminotransferase (ALT), including 5% Grade 3. Increased aspartate aminotransferase (AST) occurred in 58% of patients treated with ensartinib, including 1.8% Grade 3. Increased bilirubin occurred in 12% of patients treated with ensartinib, including 2.3% Grade 3 and 0.2% Grade 4. There was one case of drug-induced liver injury in ensartinib hydrochloride-treated patients.

The median time to first onset of increased ALT or AST was 5.3 weeks (range: 0.4 to 152 weeks). The dose of ensartinib was interrupted in 4.6% of patients for increased ALT or AST. Increased ALT or AST leading to dose reduction occurred in 2.6% and permanent discontinuation of ensartinib in 1.1% of patients. The dose of ensartinib was interrupted in 1.3% of patients for increased bilirubin. Increased bilirubin leading to dose reduction occurred in 0.7% and permanent discontinuation of ensartinib in 1.3% of patients.

Monitor liver function tests including ALT, AST, and total bilirubin at baseline and every 2 weeks during the first cycle of treatment with ensartinib, and then monthly and as clinically indicated. Withhold, reduce the dose, or permanently discontinue therapy based on the severity of the adverse reaction.

Dermatologic Adverse Reactions

Ensartinib can cause dermatologic adverse reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), rash, pruritus, and photosensitivity. In the pooled safety population, dermatologic adverse reactions occurred in 80% of patients receiving ensartinib, including Grade 3 in 14% of patients. Rash occurred in 72% of patients receiving ensartinib, including Grade 3 in 12% of patients. The median time to onset of rash was 9 days (range: 1 day to 17.3 months). Pruritus occurred in 32% of patients receiving ensartinib, with Grade 3 in 2.4%. There was one Grade 3 case (0.2%) of drug reaction with eosinophilia and systemic symptoms (DRESS). The dose of ensartinib was interrupted in 12% of patients for dermatologic adverse reactions. Dermatologic adverse reactions leading to dose reduction occurred in 11% and permanent discontinuation of ensartinib in 1.5% of patients. In the pooled safety population, photosensitivity occurred in 0.9% of patients receiving ensartinib; all were Grade 1.

Monitor patients for dermatologic adverse reactions during treatment with ensartinib. If dermatologic adverse reactions occur, treat with antihistamine, topical or systemic steroids based on the severity. Advise patients to limit direct sun exposure while taking ensartinib and for at least 1 week after discontinuation. Withhold, reduce the dose, or permanently discontinue therapy based on the severity of the adverse reaction.

Bradycardia

Ensartinib can cause symptomatic bradycardia.

In the pooled safety population, bradycardia (heart rate less than 60 beats per minute) occurred in 6% of patients treated with ensartinib. All bradycardia events were Grade 1 or 2. Bradycardia requiring dose reduction occurred in 0.2% and led to dose interruption in 0.4% of ensartinib-treated patients.

Monitor heart rate regularly during treatment with ensartinib. Withhold, reduce the dose, or permanently discontinue therapy based on severity.

Hyperglycemia

Ensartinib can cause hyperglycemia.

In the pooled safety population, based on laboratory data, 44% of patients receiving ensartinib experienced increased blood glucose, including Grade 3 in 2.5%. The median time to onset of increased blood glucose was 5.9 weeks (0.4 weeks to 3.4 years).

Assess fasting serum glucose at baseline and monitor serum glucose periodically during treatment with ensartinib. Withhold, reduce the dose, or permanently discontinue therapy based on severity.

Visual Disturbances

Ensartinib can cause visual disturbances including blurred vision, diplopia, photopsia, vitreous floaters, visual impairment, visual field defect, and reduced visual acuity.

In the pooled safety population, 8% of patients receiving ensartinib experienced visual disturbance, including 0.2% Grade 3. Visual disturbances led to dose interruption in 0.4% of patients.

Obtain an ophthalmologic evaluation in patients with new or worsening visual symptoms during treatment with ensartinib. Withhold, reduce the dose, or permanently discontinue therapy based on severity.

Increased Creatine Phosphokinase

In the pooled safety population, of the 203 patients with creatine phosphokinase (CPK) laboratory data available, increased CPK occurred in 43% of patients who received ensartinib. The incidence of Grade 3 increased CPK was 1.5% and 0.5% were Grade 4. The median time to onset of increased CPK was 123 days (range: 13 days to 22 months). Increased CPK leading to dose interruption occurred in 0.2% and dose reduction in 0.4%.

Advise patients to report any unexplained muscle pain, tenderness, or weakness. Monitor CPK levels during treatment with ensartinib. Withhold, reduce the dose, or permanently discontinue therapy based on severity.

Hyperuricemia

Ensartinib can cause hyperuricemia.

In the pooled safety population, based on adverse reactions, 6% of patients experienced hyperuricemia, with 0.4% Grade 3 and 0.7% Grade 4. Nine patients (1.9%) required hydration and two patients (0.4%) required urate-lowering medication.

Monitor serum uric acid levels prior to initiating ensartinib and periodically during treatment. Initiate treatment with urate-lowering medications as clinically indicated. Withhold, reduce the dose, or permanently discontinue therapy based on severity.

Embryo-Fetal Toxicity

Based on findings from animal studies and its mechanism of action, ensartinib can cause fetal harm when administered to a pregnant woman. In embryo-fetal developmental studies, oral administration of ensartinib to pregnant rats during the period of organogenesis caused adverse developmental outcomes, including embryo-fetal mortality, alterations to growth, and structural abnormalities. Adverse embryo-fetal findings were seen at maternal exposures approximately equivalent to the human exposure at the recommended dose of 225 mg/day based on area under the curve (AUC). Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ensartinib and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with ensartinib and for 1 week after the last dose.

FD&C Yellow No. 5 (Tartrazine)

This product contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

Specific Populations

Pregnancy

Based on findings from animal studies and its mechanism of action, ensartinib can cause fetal harm when administered to a pregnant woman. There are no available data on the use of ensartinib in pregnant women to inform a drug-associated risk. Oral administration of ensartinib to pregnant rats during the period of organogenesis caused adverse developmental outcomes, including embryo-fetal mortality, alterations to growth, and structural abnormalities. Adverse embryo-fetal findings were seen at maternal exposures approximately equivalent to the human exposure at the recommended dose of 225 mg/day based on AUC. Advise pregnant women of the potential risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Lactation

There are no data on the presence of ensartinib or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with ensartinib and for 1 week after the last dose.

Females and Males of Reproductive Potential

Ensartinib can cause fetal harm when administered to a pregnant woman.

Pediatric Use

The safety and effectiveness of ensartinib in pediatric patients have not been established.

Geriatric Use

Of the 458 patients enrolled in clinical studies and received ensartinib 225 mg once daily, 16% of the participants were 65 years of age or older. Clinical studies of ensartinib did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger patients. Exploratory analysis suggests a higher incidence of serious adverse events (43% vs 27%), more frequent adverse events leading to treatment discontinuations (18% vs 10%), and dose modifications (34% vs 16%) in patients 65 years of age or older as compared to those younger than 65 years.

Hepatic Impairment

Ensartinib is primarily metabolized by the liver and patients with hepatic impairment may have increased exposures. Avoid use of ensartinib for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST) since it has not been studied in this population. Monitor patients with moderate hepatic impairment (total bilirubin >1.5 to ≤ 3 ULN and any AST) for increased adverse reactions and adjust ensartinib dosage as clinically indicated. No dosage modification is recommended for patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal (ULN) and AST > ULN or total bilirubin 1 to 1.5 x ULN and any AST).

Common Adverse Effects

Most common adverse reactions (incidence ≥20%) were rash, musculoskeletal pain, constipation, pruritus, cough, nausea, edema, vomiting, fatigue, and pyrexia.

Most common Grade 3-4 laboratory abnormality (incidence ≥2%) were increased uric acid, decreased lymphocytes, increased alanine aminotransferase, decreased phosphate, increased gamma glutamyl transferase, increased magnesium, increased amylase, decreased sodium, increased glucose, decreased hemoglobin, increased bilirubin, decreased potassium, and increased creatine phosphokinase.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Actions

Mechanism of Action

Ensartinib is a kinase inhibitor of anaplastic lymphoma kinase (ALK) and inhibits other kinases including MET and ROS1. In vitro, ensartinib inhibited phosphorylation of ALK and its downstream signaling proteins AKT, ERK, and S6, thereby blocking ALK-mediated signaling pathways and inhibiting proliferation in cell lines harboring ALK fusions and mutations. In vivo, ensartinib showed anti-tumor activity in a mouse xenograft model of human NSCLC harboring an ALK fusion.

Advice to Patients

Additional Information

AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Ensartinib Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

25 mg (of ensartinib)

Ensacove™

Xcovery Holdings

100 mg (of ensartinib)

Ensacove™

Xcovery Holdings

AHFS DI Essentials™. © Copyright 2025, Selected Revisions March 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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