Overview
11 DESCRIPTION ENSACOVE capsules contain ensartinib, a kinase inhibitor, present as ensartinib hydrochloride with the chemical name 6-amino-5-[(1 R )-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-N-{4-[(3 R ,5 S )- 3,5-dimethylpiperazine-1-carbonyl]phenyl}pyridazine-3-carboxamide, dihydrochloride. The molecular formula is C26H27Cl2FN6O3·2HCl and its molecular weight is 634.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 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. 12.2 Pharmacodynamics Exposure-response relationship Ensartinib exposure-response relationships and the time course of the pharmacodynamic response have not been fully characterized.
Indications
- 1 INDICATIONS AND USAGE ENSACOVE is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC)as detected by an FDA-approved test [see Dosage and Administration ( 2.1 )] who have not previously received an ALK-inhibitor. ENSACOVE is a kinase inhibitor indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test who have not previously received an ALK-inhibitor.
Common Doses
- 225 mg
- 200 mg
- 150 mg
- 250 mg
Dosage
2 DOSAGE AND ADMINISTRATION Select patients with ALK-positive locally advanced or metastatic NSCLC for treatment with ENSACOVE. ( 2.1 ) Prior to initiating ENSACOVE, evaluate liver function tests and fasting blood glucose. ( 2.2 ) Recommended dosage: 225 mg orally once daily with or without food until disease progression or unacceptable toxicity. ( 2.3 ) 2.1 Patient Selection Select patients for the treatment of locally advanced or metastatic NSCLC with ENSACOVE based on the presence of ALK rearrangement(s) in tumor specimens [see Clinical Studies ( 14.1 )] .
Contraindications
- 4 CONTRAINDICATIONS ENSACOVE is contraindicated in patients who have experienced a severe hypersensitivity reaction to ENSACOVE, FD&C Yellow No. 5 (tartrazine), or to any of its components [see Warnings and Precautions ( 5.10 )] . Hypersensitivity reaction to ENSACOVE, FD&C Yellow No. 5 (tartrazine), or to any of its components. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions ( 5.1 )] Hepatoxicity [see Warnings and Precautions ( 5.2 )] Dermatologic Adverse Reactions [see Warnings and Precautions ( 5.3 )] Bradycardia [see Warnings and Precautions ( 5.4 )] Hyperglycemia [see Warnings and Precautions ( 5.5 )] Visual Disturbances [see Warnings and Precautions ( 5.6 )] Increased Creatine Phosphokinase [see Warnings and Precautions ( 5.7 )] Hyperuricemia [see Warnings and Precautions ( 5.
Interactions
- 7 DRUG INTERACTIONS Moderate or Strong CYP3A Inhibitors : Avoid concomitant use with ENSACOVE. ( 7.1 ) Moderate or Strong CYP3A Inducers : Avoid concomitant use with ENSACOVE. ( 7.1 ) P-gp Inhibitor : Avoid concomitant use with ENSACOVE. ( 7.1 ) 7.1 Effect of Other Drugs on ENSACOVE Table 5 describes drug interactions where concomitant use of another drug affects ENSACOVE. Table 5: Effect of Other Drugs on ENSACOVE Strong or Moderate CYP3A Inhibitors Prevention or Management Avoid concomitant use of strong or moderate CYP3A inhibitors with ENSACOVE.