Possible side effects of brigatinib and how to deal with them

Brigatinib (also known as Brigatinib, English name: Brigatinib) is a second-generation ALK (anaplastic lymphoma kinase) inhibitor, mainly used to treat patients with ALKPatients with non-small cell lung cancer (NSCLC) with fusion gene mutations have shown significant efficacy in second-line treatment, especially after failure of the first-generation drug crizotinib (Crizotinib). Brigatinib has advantages in prolonging progression-free survival and improving central nervous system control rate, but it may also cause a variety of side effects during use. This article will systematically introduce the common side effects of brigatinib and how to deal with them, to help patients and doctors better manage the medication process.

1. Common side effects of brigatinib

1. Pulmonary adverse reactions (early pulmonary toxicity)

The most vigilant adverse reaction of brigatinib is "early pulmonary toxicity", also known as pneumonia-like reactions, which often appear within a few days after taking the drug. Symptoms include coughing, shortness of breath, shortness of breath, low oxygen and even fever. Although the incidence is relatively low, if not detected and intervened in time, it can be life-threatening.

Handling suggestions:

It is recommended that patients start with a lower dose (such as 90mg/days), observe 7 days without adverse reactions, and then increase to the standard dose of 180mg/days;

Once suspected pulmonary symptoms occur, discontinue medication immediately and conduct imaging examinations and blood oxygen monitoring;

For mild pulmonary toxicity, glucocorticoids can be used for anti-inflammatory treatment, and re-challenge can be considered after symptoms are relieved;

In patients with severe pulmonary toxicity, brigatinib should be permanently discontinued and switched to an alternative regimen.

2. Elevated creatinine and effects on renal function

Brigatinib may cause an increase in serum creatinine and affect renal function, which is particularly concerning in patients with existing renal function impairment.

Handling suggestions:

Check serum creatinine levels regularly before treatment and during medication;

If the increase is large or accompanied by changes in urine output, it should be evaluated whether it is caused by drugs, and the dose should be adjusted or medication suspended if necessary;

At the same time, be careful not to combine it with other drugs that are toxic to the kidneys.

3. Hypertension

Brigatinib can cause an increase in blood pressure, especially early in treatment or in patients with other cardiovascular diseases.

Handling suggestions:

Blood pressure should be assessed and controlled before starting treatment;

Blood pressure changes should be monitored regularly during treatment;

Patients with elevated blood pressure can be managed with conventional antihypertensive drugs, such asACEI, ARB or calcium channel blockers;

If blood pressure control is difficult, dose reduction or suspension of brigatinib should be considered.

4. Gastrointestinal reactions (nausea, diarrhea)

Brigatinib may also cause mild to moderate gastrointestinal reactions, such as nausea, diarrhea, loss of appetite, etc. Such side effects have a greater impact on quality of life.

Handling suggestions:

You can choose to take the medication with food to reduce stomach irritation;

Antiemetics (such as ondansetron) can be used for those with severe nausea;

For those with more severe diarrhea, it is recommended to use antidiarrheal drugs such as loperamide;

At the same time, fluids, electrolytes and nutritional maintenance are required.

5. Elevated muscle enzymes (CK increased)

During brigatinib treatment, some patients may experience an increase in creatine kinase (CK), indicating a possible risk of myotoxicity.

Handling suggestions:

Check your CK levels regularlyespecially if you have muscle soreness or fatigue;

IfCK rises to 3-5 times more than the normal value, it is recommended to reduce the dose or discontinue the drug for observation;

SevereCK When elevated levels are accompanied by myalgia or muscle damage, medication should be suspended and supportive treatment should be provided.

6. Visual and nervous system abnormalities

Brigatinib may cause neurological symptoms such as blurred vision, diplopia, headache, balance disorders, etc., which are generally reversible.

Handling suggestions:

Typically these reactions occur early in treatment;

If symptoms are mild and tolerable, observation can continue;

If it affects normal life or continues to worsen, it is recommended to reduce the dosage or discontinue the drug, and conduct further neurological evaluation.

7. Elevated pancreatic enzymes (amylase, lipase)

Some patients may experience elevated pancreatic enzymes, but this is not necessarily accompanied by clinical symptoms of pancreatitis.

Handling suggestions:

Test pancreatic enzymes regularly;

If there are no symptoms and the increase is not significant, treatment can be continued;

If accompanied by abdominal pain, nausea, or elevated altitude, discontinuation of the drug should be considered and pancreatitis should be ruled out.

2. Precautions for medication use in special groups

Elderly people: may have poorer tolerance to drugs and should be more closely monitored for side effects;

Patients with hepatic and renal insufficiency: Brigatinib is metabolized by the liver, so patients with hepatic insufficiency should use it with caution or adjust the dose;

Patients taking concomitant medications: Brigatinib is a CYP3A enzyme substrate, avoid co-administration with strong CYP3A inhibitors or inducers;

Pregnant and lactating women: Brigatinib has potential teratogenic risks to the fetus and is contraindicated during pregnancy; it is unclear whether it is secreted into breast milk during lactation. The pros and cons should be weighed before deciding whether to discontinue the drug or breastfeeding.

3. Summary and suggestions

Brigatinib, as a highly targeted second-generation ALK inhibitor, can significantly prolong the progression-free survival of ALK-positive NSCLC patients and improve the control rate of central metastasis. However, there are many types of side effects with varying degrees of severity, which require strict monitoring and individualized management during clinical use. Attention should be paid to pulmonary toxicity in the early stages of treatment, and hypertension, elevated creatinine, and muscle enzyme changes should be prevented during long-term use.

It is recommended that patients undergo regular imaging examinations, blood biochemistry and symptom assessment during treatment, and maintain close communication with their attending physician. Once symptoms of discomfort occur, timely feedback should be provided to facilitate early intervention to ensure maximum drug efficacy and reduce the interference of adverse reactions on life. Scientific management of side effects is the key to ensuring successful brigatinib treatment and improving quality of life.

Reference materials:https://www.drugs.com