Lorlatinib has a characteristic adverse-effect profile that differs from many conventional chemotherapy medicines. Some effects are laboratory abnormalities, while others affect neurological, cardiovascular, pulmonary or metabolic systems.
Common adverse reactions
Current U.S. labeling identifies adverse reactions occurring in at least 20% of treated patients including:
- Edema
- Peripheral neuropathy
- Weight gain
- Cognitive effects
- Fatigue
- Dyspnea
- Arthralgia
- Diarrhea
- Mood effects
- Cough
Common laboratory abnormalities include hypercholesterolemia and hypertriglyceridemia, as well as anemia, hyperglycemia and changes in liver enzymes among others.
Important serious risks
| Risk | Why it matters |
|---|---|
| CNS effects | Can involve cognition, mood, speech, sleep, mental status or seizures |
| Hyperlipidemia | Cholesterol and triglycerides can become substantially elevated |
| Atrioventricular block | Can affect cardiac electrical conduction |
| Pneumonitis/ILD | Can cause potentially serious lung inflammation |
| Hypertension | Blood pressure may become elevated |
| Hyperglycemia | Blood glucose can increase |
| Hepatotoxicity | Particularly important with strong CYP3A inducers |
| Peripheral neuropathy | Can cause sensory or motor symptoms |
Central nervous system effects
CNS effects are a particularly important part of lorlatinib’s safety profile. They can include cognitive changes, mood changes, speech abnormalities, sleep changes, psychotic effects and seizures.
Lipid abnormalities
Hypercholesterolemia and hypertriglyceridemia are among the characteristic laboratory effects of lorlatinib. Lipid-lowering therapy may be initiated or intensified by the healthcare professional when clinically appropriate.
Weight gain and edema
Weight gain and fluid retention can occur during treatment. Persistent or significant changes should be discussed with the treating team.
Lung toxicity
Interstitial lung disease or pneumonitis can be serious. New or worsening respiratory symptoms require prompt medical assessment.
When urgent medical attention may be needed
Urgent evaluation may be appropriate for:
- New seizures
- Severe confusion or major mental-status changes
- Severe mood or behavioral changes
- Significant breathing difficulty
- New or worsening cough with respiratory symptoms
- Fainting or symptoms suggesting abnormal heart rhythm
- Severe chest symptoms
- Signs of serious allergic or systemic reaction
Monitoring
Monitoring should be individualized and may include lipid testing, blood pressure, glucose, liver tests, neurological assessment and cardiac evaluation when clinically indicated.