What is Brigatinib used for?

**Introduction to Brigatinib**

Brigatinib, marketed under the trade name Alunbrig, is a targeted cancer therapy drug developed by ARIAD Pharmaceuticals, which is now a subsidiary of Takeda Oncology. This medication specifically targets anaplastic lymphoma kinase (ALK) and is classified as a tyrosine kinase inhibitor (TKI). ALK is a gene that can mutate and form abnormal proteins that drive the growth of cancer cells. Brigatinib is primarily indicated for the treatment of non-small cell lung cancer (NSCLC) in patients who have the ALK-positive gene mutation. Initially approved by the U.S. Food and Drug Administration (FDA) in April 2017, Brigatinib has since been used in clinical settings to improve the lives of patients suffering from this specific type of lung cancer, especially those who have not responded well to other treatments such as crizotinib.

**Brigatinib Mechanism of Action**

Brigatinib works by inhibiting the activity of the ALK protein kinase, which plays a pivotal role in the proliferation and survival of cancer cells. The ALK gene can fuse with other genes to create abnormal proteins that promote cancer cell growth. When Brigatinib is administered, it binds to the ATP-binding pocket of the ALK protein, thereby blocking its kinase activity. This halts the downstream signaling pathways responsible for cell proliferation, ultimately inducing apoptosis in the cancer cells.

One of the distinguishing features of Brigatinib is its ability to overcome various ALK mutations that confer resistance to first-generation ALK inhibitors like crizotinib. Because of this, Brigatinib is often used in patients who have developed resistance to other ALK inhibitors. Additionally, Brigatinib shows efficacy in crossing the blood-brain barrier, making it a valuable option for treating brain metastases associated with ALK-positive NSCLC.

**How to Use Brigatinib**

Brigatinib is administered orally in the form of tablets. The treatment regimen generally begins with a lower dose to assess the patient's tolerance to the drug. The initial recommended dosage is 90 mg once daily for the first seven days. If the patient tolerates this initial dose without severe side effects, the dosage is then increased to 180 mg once daily.

The absorption of Brigatinib is not significantly affected by food, so it can be taken with or without meals. However, it is crucial to take the medication at the same time each day to maintain consistent levels in the bloodstream. Patients are advised to swallow the tablets whole, without crushing, chewing, or splitting them.

The onset of action for Brigatinib varies among individuals. Some patients may start to see improvements within a few weeks, while for others, it may take longer. Periodic monitoring through imaging studies and clinical assessments is essential to evaluate the drug's efficacy and adjust the treatment plan accordingly.

**What is Brigatinib Side Effects**

Like all medications, Brigatinib comes with a range of potential side effects. The most common side effects include nausea, diarrhea, fatigue, cough, headache, and elevated levels of liver enzymes. These side effects are usually manageable and can often be mitigated with supportive care measures.

However, Brigatinib also has some serious side effects that necessitate close monitoring and, in some cases, discontinuation of treatment. One of the most concerning side effects is severe interstitial lung disease (ILD) or pneumonitis, which can occur particularly within the first week of treatment. Symptoms of ILD include difficulty breathing, cough, and fever, and patients should be instructed to report these symptoms immediately to their healthcare provider.

Another significant side effect is hypertension or elevated blood pressure, which may require the initiation of antihypertensive therapy. In rare cases, Brigatinib can cause bradycardia (slow heart rate), visual disturbances, and hyperglycemia (elevated blood sugar levels). Regular monitoring of blood pressure, heart rate, and blood glucose levels is recommended during treatment.

Brigatinib is contraindicated in patients with known hypersensitivity to the drug or any of its components. Additionally, caution is advised for patients with a history of severe ILD or significant cardiovascular issues.

**What Other Drugs Will Affect Brigatinib**

Brigatinib is metabolized primarily by the CYP3A4 enzyme in the liver. As a result, the efficacy and safety profile of Brigatinib can be affected by other drugs that inhibit or induce this enzyme. For instance, strong CYP3A4 inhibitors such as ketoconazole, itraconazole, and ritonavir can increase the plasma concentration of Brigatinib, leading to an elevated risk of adverse effects. Conversely, strong CYP3A4 inducers such as rifampin, carbamazepine, and phenytoin can decrease the plasma concentration of Brigatinib, potentially reducing its effectiveness.

Patients should inform their healthcare providers of all the medications they are currently taking, including prescription drugs, over-the-counter medications, and herbal supplements. Grapefruit and grapefruit juice are also known to inhibit CYP3A4 and should be avoided during Brigatinib treatment to minimize the risk of increased drug levels.

In conclusion, Brigatinib represents a significant advancement in the treatment of ALK-positive NSCLC, offering hope to patients who have exhausted other treatment options. Its targeted mechanism of action, ability to overcome resistance mutations, and efficacy in treating brain metastases make it a valuable tool in the oncology arsenal. However, careful monitoring and management of side effects are essential to ensure the best possible outcome for patients receiving Brigatinib therapy.