Common Adverse Reactions and Clinical Manifestations of Lorlatinib

The common adverse reactions of Lorlatinib include metabolic abnormalities, central nervous system (CNS) symptoms, edema, weight gain, and peripheral neuropathy. Most of these reactions are mild to moderate, but monitoring and management should be tailored to individual patient conditions.

Common Adverse Reactions and Clinical Manifestations of Lorlatinib

Metabolic Abnormalities

Hypercholesterolemia/Hypertriglyceridemia:Occurring in approximately 80% of patients, this condition requires intervention via dietary control or medications (e.g., statins).

Elevated Blood Glucose:Some patients may develop insulin resistance or have an increased risk of diabetes, necessitating regular blood glucose monitoring.

Central Nervous System Effects

Headache, dizziness, and memory impairment:These symptoms are associated with the drug’s ability to cross the blood-brain barrier and are usually transient.

Mood or behavioral changes:Such as anxiety, depression, and hallucinations (with an incidence rate of approximately 2–7%). Discontinuation of the drug is required in severe cases.

Edema and Weight Gain

Edema of the extremities or face occurs in around 30% of patients, which is linked to fluid and sodium retention induced by the drug.

Weight gain is mostly associated with metabolic abnormalities or changes in appetite, requiring dietary control and body fat monitoring.

Peripheral Neuropathy

Manifested as numbness, tingling, or hypoesthesia in the hands and feet, this condition can be alleviated by dose adjustment or administration of neurotrophic drugs.

Gastrointestinal Reactions

Symptoms such as diarrhea, nausea, and vomiting are generally mild and can be improved by adjusting medication administration time or implementing symptomatic treatment.

Severe Adverse Reactions Requiring Vigilant Monitoring

Interstitial Lung Disease/Pneumonitis (incidence < 1%)

Clinical manifestations include cough, dyspnea, and low-grade fever. Immediate drug discontinuation and glucocorticoid therapy are required.

Cardiotoxicity

QT interval prolongation: May trigger arrhythmias, necessitating regular monitoring of electrocardiograms (ECG) and electrolytes.

Bradycardia: Rarely occurs; it is necessary to assess whether the patient has comorbid cardiac diseases.

Hepatic Dysfunction

Elevated transaminase levels occur in approximately 15% of patients. In severe cases, temporary drug suspension and hepatoprotective treatment are indicated.

Principles for Managing Adverse Reactions

Graded Management

Mild (Grade 1–2): Generally, no drug discontinuation is required; symptomatic treatment alone suffices (e.g., antiemetics, lipid-lowering agents).

Moderate to severe (Grade 3–4): Temporary drug suspension or dose reduction is needed until symptoms resolve.

Regular Monitoring

Laboratory tests: Include lipid profiles, blood glucose, liver function, and electrolytes (conducted every 2–4 weeks).

Imaging and functional assessments: Such as chest computed tomography (CT) to screen for pulmonary toxicity, and ECG to monitor QT interval.

Patient Education

Patients should seek immediate medical attention if they experience dyspnea, chest pain, severe headache, or behavioral abnormalities.

Patients should avoid self-administering medications that may exacerbate metabolic abnormalities (e.g., hormonal agents).

The adverse reactions of lorlatinib vary significantly among individuals. Clinically, personalized management plans should be formulated based on the patient’s underlying diseases and concomitant medications. Timely communication of symptom changes and standardized follow-up are crucial to ensuring the safe use of the drug.