Ceritinib
Overview
Ceritinib is an oral tyrosine kinase inhibitor specifically targeting anaplastic lymphoma kinase (ALK) gene rearrangements. It is primarily used to treat metastatic non-small cell lung cancer (NSCLC) in patients whose tumors harbor ALK-positive mutations, particularly after progression or intolerance to crizotinib therapy. By inhibiting ALK, ceritinib disrupts cancer cell proliferation and survival, offering a targeted therapeutic approach.
Background and Date of Approval
Ceritinib, marketed under the brand name Zykadia, was approved by the U.S. Food and Drug Administration (FDA) in 2014 for the treatment of ALK-positive metastatic NSCLC. Its approval was based on clinical trials demonstrating its efficacy in patients who had previously been treated with crizotinib. The drug’s development represents a significant advancement in personalized cancer therapy, focusing on specific genetic mutations to guide treatment.
Uses
Ceritinib is indicated for the treatment of adult patients with metastatic NSCLC whose tumors are ALK-positive, as detected by an FDA-approved test. It is recommended for patients who have experienced disease progression or are intolerant to crizotinib. The use of ceritinib is contingent upon the presence of ALK-positive mutations, underscoring the importance of genetic testing in the management of lung cancer.
Administration
Ceritinib is administered orally in capsule form. The recommended dosage is 450 mg once daily with food. It is crucial to take ceritinib consistently at the same time each day to maintain even drug levels in the body. If a dose is missed, it should be taken as soon as possible unless the next dose is due within 12 hours. In case of vomiting, the patient should not take an additional dose and should continue with the next scheduled dose.
Side Effects
Common side effects of ceritinib include gastrointestinal symptoms such as nausea, diarrhea, and abdominal pain. Other reported side effects encompass fatigue, loss of appetite, and elevated liver enzymes. These side effects are generally manageable and may subside with continued therapy. Patients should be monitored regularly to assess and manage any adverse reactions.
Warnings
Serious adverse events associated with ceritinib include hepatotoxicity, interstitial lung disease, bradycardia, and pancreatitis. Liver function tests should be conducted before initiating treatment and periodically thereafter. Any signs of liver dysfunction, such as jaundice or dark urine, should prompt immediate medical attention. Additionally, ceritinib may cause QT interval prolongation; thus, patients should be monitored for cardiac abnormalities.
Precautions
Before initiating ceritinib therapy, a thorough assessment of the patient’s medical history is essential, particularly concerning liver function and cardiac health. Concomitant use of strong CYP3A inhibitors or inducers should be avoided, as they can significantly affect ceritinib plasma concentrations. Patients should be advised to inform their healthcare provider of all medications they are taking, including over-the-counter drugs and supplements, to prevent potential drug interactions.
Expert Tips
Prescribers should ensure that patients are adequately informed about the potential side effects of ceritinib and the importance of adhering to the prescribed dosing schedule. Pharmacists should counsel patients on proper administration techniques and the significance of regular follow-up appointments to monitor treatment efficacy and safety. Collaboration among healthcare providers is essential to optimize patient outcomes.