Ceritinib Noxalk 150mg

[Ceritinib | Introduction]

Ceritinib is an anticancer medication supplied as hard gelatin capsules; the contents of the capsules consist of a white to off-white powder.

[Basic Information]

Ceritinib Chinese Synonyms: 5-Chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine

Ceritinib English Synonyms:

5-Chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine

[Physicochemical Properties]

[Description] This product consists of hard gelatin capsules containing a white to off-white powder. It is a novel medication for the treatment of lung cancer.

[Boiling Point] 1184.5 ℃

[Log P] 5.62

[MR] 155.59 [cm³/mol]

[Henry's Law] 13.95

[CLogP] 6.7134

[CMR] 15.3001

[Indications] Indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on or who are intolerant to crizotinib.

[Mechanism of Action] Ceritinib is an ALK inhibitor. It exerts an inhibitory effect on cells expressing EML4-ALK and NPM-ALK fusion proteins, and it is capable of overcoming crizotinib resistance. [Adverse Reactions] The most common adverse reactions (incidence rate of at least 25%) are diarrhea, nausea, elevated transaminases, vomiting, abdominal pain, fatigue, decreased appetite, and constipation.

[Therapeutic Area] The therapeutic area is anticancer medication.

[Storage] Store at 25°C; the permissible range for Ceritinib is 15°C to 30°C.

[Target]

Target: As a tyrosine kinase, ALK influences the growth of tumor cells; therefore, Ceritinib acts on ALK-positive NSCLC patients, particularly those exhibiting fusions between the EML4 gene and the ALK gene (EML4-ALK), as well as NPM-ALK fusions.

Mechanism of Action: Ceritinib targets ALK, exerting an inhibitory effect on cells expressing EML4-ALK and NPM-ALK fusion proteins, thereby inhibiting the proliferation of tumor cells.

This product is indicated for the treatment of the following patients: Ceritinib is indicated for the treatment of ALK-positive metastatic NSCLC patients, and is of particular utility in patients whose disease has progressed following treatment with Crizotinib, or who are intolerant to Crizotinib.

[Dosage and Administration]

It is recommended that this product be administered in a medical facility with relevant experience, under the guidance of specialized medical personnel. Furthermore, it is recommended that ALK gene assessment be performed to obtain a fully validated ALK-positive status result.

Capsule formulation; strength: 150 mg.

The recommended dose is 750 mg (equivalent to 5 capsules), taken once daily. Administer orally on an empty stomach (at least 2 hours before or after a meal); however, note that the medication should not be taken concurrently with grape juice, grapefruit juice, or similar beverages. Treatment should continue until disease progression occurs or until the patient is unable to tolerate the toxicity; dosage reduction may be considered as appropriate, based on the patient's clinical status and the nature of any adverse reactions. [Adverse Reactions]

(1) Decreased Appetite, Abdominal Pain, Diarrhea, Nausea, Vomiting: Nearly half of patients experience persistent gastrointestinal reactions while taking Ceritinib. To mitigate the severity of these symptoms, patients should maintain good dietary habits in their daily lives, prioritize food hygiene, and consume nutrient-rich foods. If symptoms occur, antiemetics or antidiarrheals may be administered; in severe cases, the dosage of Ceritinib may need to be reduced.

(2) Hyperglycemia: The drug may induce elevated blood glucose levels. Blood glucose concentrations should be monitored regularly throughout the course of treatment. If hyperglycemia occurs that cannot be controlled through diet, exercise, or medication, the dosage should be reduced, or Ceritinib treatment should be permanently discontinued.

(3) Hepatic Impairment: The drug may cause hepatotoxicity, elevated transaminase levels, jaundice, and other hepatic abnormalities. Patients should undergo regular monitoring of liver function; if abnormalities are detected, prompt medical intervention is required. In cases of severe hepatic impairment, the dosage must be reduced or the drug discontinued.

(4) Cardiotoxicity: The drug may cause bradycardia, congestive heart failure, and other cardiac complications. Patients should monitor their heart rate, blood pressure, and ECG while taking the medication. If these conditions cannot be controlled, the dosage must be reduced, or the use of Ceritinib must be permanently discontinued.

(5) Interstitial Lung Disease (ILD): Approximately 4% of patients are at risk of developing ILD, particularly those with pre-existing pulmonary conditions. Should ILD occur, the administration of Ceritinib must be discontinued.

(6) Embryo-Fetal Toxicity: The drug may pose risks to fetal growth and development; therefore, women of childbearing potential must utilize effective contraception while taking this medication.

(7) Studies conducted during the clinical trial phase of Ceritinib have identified cases of neuropathy. Patients should remain vigilant regarding this risk and seek immediate medical attention if any symptoms of neuropathy are observed. [Combination Therapy and Drug Resistance]

Combination Therapy: Ceritinib is primarily indicated for patients who have developed resistance to or experienced disease progression following treatment with crizotinib. Furthermore, experimental studies suggest that combining ceritinib with other medications may increase toxic side effects; consequently, the development and clinical application of combination regimens involving ceritinib remain limited. Patients may, however, attempt to continue taking crizotinib concurrently with ceritinib, provided that careful attention is paid to potential overlapping toxicities.

Drug Resistance: The mechanisms underlying the development of drug resistance may include secondary mutations in the *ALK* gene, amplification of the *ALK* fusion gene copy number, among other factors.

Once resistance to ceritinib has also developed, the use of targeted therapies is generally no longer considered. Instead, patients may explore alternative treatment modalities, such as biological response modifiers, immunotherapies, or Traditional Chinese Medicine (TCM). Alternatively, patients willing to undergo further testing may opt for repeat genomic profiling to identify other actionable genetic alterations, thereby enabling the use of targeted therapies specifically tailored to their unique molecular profile—a "precision medicine" approach.

[Product Specifications]

Product Name: Ceritinib / Noxalk 150mg

Common Name: Ceritinib

Composition: Ceritinib (Noxalk) 150mg

Dosage Form: Capsules

Specification: 90 capsules per pack

Manufacturer: Natco Pharma Ltd

Indications: Ceritinib is indicated for the treatment of patients with *ALK*-positive metastatic non-small cell lung cancer (NSCLC), and plays a pivotal role in the management of patients who have experienced disease progression or demonstrated intolerance following treatment with crizotinib.

Dosage and Administration: The recommended dosage of ceritinib is 450 mg (3 capsules) taken orally once daily. Ceritinib should be taken on an empty stomach.