Alectinib is a tyrosine kinase inhibitor (TKI) indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. It works by selectively inhibiting the activity of ALK fusion proteins, which are oncogenic drivers in a subset of NSCLC tumors. Alectinib has demonstrated efficacy in controlling tumor growth and improving progression-free survival in patients with ALK-positive NSCLC.
Recommended Dose and Dosage Regimen
The recommended dose of alectinib for patients with ALK-positive metastatic NSCLC is 600 milligrams (mg) orally twice daily with food. Treatment should continue until disease progression or unacceptable toxicity occurs. Dose modifications may be necessary to manage adverse reactions, and dose interruptions or discontinuations may be required based on individual patient tolerability.
Frequency of Administration
Alectinib is administered orally twice daily, approximately 12 hours apart, with food. Patients should adhere to the prescribed dosing schedule and take alectinib consistently at the same times each day to maintain therapeutic drug levels in the bloodstream. If a dose is missed, patients should take it as soon as remembered, unless it is within 12 hours of the next scheduled dose.
Route of Administration
Alectinib is available as oral capsules for administration. The capsules should be swallowed whole with a glass of water and should not be opened, crushed, or chewed. Alectinib can be taken with or without food, but it should be taken consistently with the same meal each day to ensure optimal absorption and efficacy.
Mechanism of Action (MOA)
Alectinib is a potent and selective inhibitor of ALK tyrosine kinase activity. It binds to the adenosine triphosphate (ATP)-binding site of ALK fusion proteins, preventing phosphorylation and activation of downstream signaling pathways involved in cell proliferation and survival. By inhibiting ALK signaling, alectinib suppresses tumor growth and induces apoptosis in ALK-positive NSCLC cells, leading to tumor regression and improved clinical outcomes.
Pharmacokinetics (PK)
Following oral administration, alectinib is rapidly absorbed into the bloodstream, with peak plasma concentrations reached within 2 to 6 hours. It undergoes extensive metabolism in the liver via cytochrome P450 enzymes, primarily CYP3A4, to form pharmacologically inactive metabolites. The elimination half-life of alectinib is approximately 33 hours, allowing for twice-daily dosing. Alectinib and its metabolites are predominantly eliminated in the feces.
Pharmacodynamics (PD)
The pharmacodynamic effects of alectinib are mediated by its inhibition of ALK tyrosine kinase activity. By blocking ALK signaling, alectinib disrupts aberrant signaling pathways that drive tumor growth and metastasis in ALK-positive NSCLC. Preclinical studies have shown that alectinib exhibits potent antitumor activity against ALK-driven tumors, leading to tumor regression and prolonged survival in animal models.
Primary Indications
Alectinib is indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. It is approved as a second-line or subsequent-line therapy for ALK-positive NSCLC following disease progression on crizotinib or as initial therapy for patients who are intolerant to crizotinib.
Contraindications
Alectinib is contraindicated in patients with known hypersensitivity to alectinib or any component of the formulation. It should not be used concomitantly with strong cytochrome P450 3A inhibitors, as this may increase systemic exposure to alectinib and the risk of adverse effects. Alectinib should also be avoided in patients with severe hepatic impairment or moderate-to-severe renal impairment.
Purpose of Taking Medication
The purpose of taking alectinib is to inhibit tumor growth and prolong survival in patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC). Alectinib targets the underlying molecular driver of NSCLC by selectively inhibiting ALK tyrosine kinase activity, leading to tumor regression and improved clinical outcomes. Regular use of alectinib as prescribed by the healthcare provider is essential for achieving and maintaining therapeutic efficacy.
Usage Instructions
Patients should take alectinib orally twice daily with food, approximately 12 hours apart. The capsules should be swallowed whole and should not be opened, crushed, or chewed. Patients should continue treatment until disease progression or unacceptable toxicity occurs, as directed by their healthcare provider. Dose modifications or interruptions may be necessary based on individual patient tolerability.
Precautions and Care
Patients receiving alectinib should be monitored for signs of hepatotoxicity, interstitial lung disease, cardiac toxicity, and QT interval prolongation, which are potential adverse effects associated with alectinib therapy. Regular liver function tests, pulmonary function tests, and electrocardiograms may be recommended during treatment to assess for potential toxicity. Patients should be educated about the signs and symptoms of adverse reactions and instructed to seek medical attention if they occur.
Dietary Considerations
There are no specific dietary restrictions associated with alectinib therapy. Patients should maintain a balanced diet and adequate hydration to support overall health and well-being during treatment. However, patients should avoid consuming grapefruit or grapefruit juice while taking alectinib, as it may increase systemic exposure to the drug and the risk of adverse effects.
Possible Side Effects
Common side effects of alectinib may include fatigue, constipation, peripheral edema, myalgia, anemia, and elevated liver enzymes. Serious adverse reactions, including hepatotoxicity, interstitial lung disease, bradycardia, and QT interval prolongation, may occur rarely. Patients should be advised to report any new or worsening symptoms to their healthcare provider promptly for proper evaluation and management.
Storage and Disposal
Alectinib capsules should be stored at room temperature (20°C to 25°C; 68°F to 77°F) in their original packaging to protect them from light and moisture. Unused capsules should be kept in the original blister pack and discarded according to local regulations for pharmaceutical waste disposal. Patients should not dispose of alectinib capsules in household trash or wastewater.
Conclusion
Alectinib is a tyrosine kinase inhibitor (TKI) indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. By selectively inhibiting ALK tyrosine kinase activity, alectinib suppresses tumor growth and improves progression-free survival in patients with ALK-positive NSCLC. Close monitoring and regular follow-up are essential for optimizing therapeutic outcomes and minimizing the risk of adverse effects during alectinib therapy. Patients should adhere to the prescribed dosing schedule and report any adverse reactions to their healthcare provider for proper evaluation and management.
Important Note: Always consult with a healthcare professional for personalized medical advice and guidance regarding the use of given drug, especially regarding dosing, administration, and potential side effects. Your healthcare provider can provide tailored recommendations based on your individual medical history, current medications, and specific treatment needs. Never self-adjust your given drug regimen or discontinue treatment without first consulting your healthcare provider. If you have any questions or concerns about given drug or its use, talk to your doctor or pharmacist for further information and assistance.