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Ceritinib(LDK378)

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Ceritinib is used to treat patients with metastatic non-small cell lung cancer (NSCLC) who are positive for anaplastic lymphoma kinase (ALK) and whose tumors are progressing or cannot tolerate Crotinib (crizotinib).

Product Description

Basic Characteristics

Product Name Ceritinib(LDK378)
CAS Number 1032900-25-6
Molecular Formula C28H36CIN5O3S
Formula Weight 558.135
Synonyms LDK-378;

NVP-LDK378;

NVP-LDK378-NX;

5-Chloro-N2-[5-methyl-4-(piperidin-4-yl)-2-(propan-2-yloxy)phenyl]-N4-[2-(propan-2-ylsulfonyl)phenyl]pyrimidine-2,4-diamine.

Appearance White to off-white powder
Storage and Handling Store it at room temperature and away from excess heat and moisture.

 

Ceritinib(LDK378)Description

Ceritinib is used for the treatment of patients with anaplastic lymphoma tumor-positive (ALK +) metastatic non-small cell lung cancer (NSCLC) who have worsened or are intolerant to crizotinib after treatment with crizotinib .

The chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) as an oncogenic driver has thoroughly changed the treatment of non-small-cell lung cancer. In the past decade, targeted drugs have emerged as an efficient personalized strategy for ALK-rearranged non-small-cell lung cancer. The accelerated approval of potent ALK inhibitors, such as crizotinib and more recently ceritinib (LDK378), based on the well designed phase I/II trials has been a landmark success in clinical cancer research and contributes a new era of oncogenic targeted therapy characterized by elegant clinical trial design. ceritinib to be a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer are also presented.

 

Ceritinib(LDK378)Mechanism of Action

Ceritinib is used to treat patients with metastatic non-small cell lung cancer (NSCLC) who are positive for anaplastic lymphoma kinase (ALK) and whose tumors are progressing or cannot tolerate Crotinib (crizotinib).

Ceritinib is a selective and potent inhibitor of anaplastic lymphoma kinase (ALK). In normal physiology, ALK functions as a key step in the development and function of nervous system tissue. However, chromosomal translocation and fusion give rise to an oncogenic form of ALK that has been implicated in progression of NSCLC. Ceritinib thus acts to inhibit this mutated enzyme and stop cell proliferation, ultimately halting cancer progression. Because ceritinib is considered a targeted cancer therapy, an FDA-approved test is required to determine which patients are candidates for ceritinib. This test, developed by Roche, is the VENTANA ALK (D5F3) CDx Assay and is used to identify ALK-positive NSCLC patients who would benefit from ceritinib treatment.

 

Ceritinib(LDK378)Application

Ceritinib is an anaplastic lymphoma kinase (ALK)-positive inhibitor primarily used for the treatment of metastatic NSCLC.Previously, it was only indicated for patients who had developed resistant to crizotinib, another ALK-positive inhibitor, but has since had its usage expanded to serve as a primary option for metastatic NSCLC.

 

Ceritinib(LDK378)Side Effects & Warning

Serious adverse effects include gastrointestinal toxicity, hepatotoxicity, interstitial lung disease, prolonged QT syndrome, hyperglycemia, bradycardia, and pancreatitis.

The most commonly reported side effects were diarrhea, nausea, elevated liver enzymes, vomiting, abdominal pain, fatigue, decreased appetite, and constipation. Due to the risk of elevated liver enzymes, liver function tests should be performed every two weeks for the first 9 weeks of treatment.

Finally, ceritinib is both a substrate and potent inhibitor of the enzyme CYP3A4, so medications should be monitored carefully that may interact with ceritinib.

 

Also call your doctor at once if you have:

▪ severe diarrhea;

▪ headache, confusion, change in mental status, vision loss, seizure (convulsions);

▪ little or no urination;

▪ unusual bleeding (nosebleeds, heavy menstrual bleeding), or any other bleeding that will not stop;

▪ signs of stomach bleeding–bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;

▪ heart problems–chest pain, pain in your jaw or shoulder, swelling, rapid weight gain, feeling short of breath;

▪ signs of a blood clot–sudden numbness or weakness, problems with vision or speech;

▪ liver problems–dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

▪ low calcium level–muscle spasms or contractions, numbness or tingly feeling (around your mouth, or in your fingers and toes);

▪ increased blood pressure–severe headache, blurred vision, pounding in your neck or ears, anxiety, nosebleed.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

 

Reference

[1] “Zykadia (ceritinib) Capsules, for Oral Use. Full Prescribing Information” (PDF). Novartis Pharmaceuticals Corporation. Retrieved 14 February 2017.

[2] “International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 71” (PDF). World Health Organization. 2014. p. 79. Retrieved 14 February 2017

[3] “FDA Approves Ceritinib for ALK-Positive Lung Cancer”. Medscape. April 29, 2014.

[4] “Prescribing data” (PDF). www.pharma.us.novartis.com. Retrieved 2019-06-12.

[5] “FDA Expands Ceritinib Approval for Lung Cancer”. National Cancer Institute. 27 June 2017.