Lorlatinib Long-Term Side Effects: What Patients Should Know About Fatigue and Swelling

Release date: 2026-03-05 17:16:17     Recommended: 76

Lorlatinib is a novel, third-generation, small-molecule dual ALK/ROS1 tyrosine kinase inhibitor developed by Pfizer Inc., USA.

Lorlatinib Side Effects Requiring Immediate Medical Attention

When taking Lorlatinib, seek medical attention immediately if you experience any of the following side effects:

More Common Side Effects

(1) Loss of control of behavior, aggression, agitation, anxiety, black, tarry stools, bleeding gums, blood in the urine or stools, blurred vision or other vision changes, body aches or pain, burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings;

(2) Changes in behavior, chills, cough, deficits in intelligence, short-term memory, learning ability, and concentration, difficulty or trouble breathing, discouragement, dizziness, dry mouth, feeling of fullness in the ears, false or unusual sense of well-being, feelings of sadness or emptiness, fever;

(3) Flushing, dryness of the skin, fruity breath odor, headache, hoarseness or loss of voice, increased appetite, increased thirst, increased urine output, irritability, loss of appetite, loss of interest or pleasure, lower back or side pain, nausea, nervousness;

(4) Painful or difficult urination, pale skin, pinpoint red spots on the skin, ringing in the ears, runny or stuffy nose, seeing, hearing, or feeling things that are not there, skin rash, slow or fast heartbeat, sneezing, sore throat, stomach pain, sweating, swelling;

(5) Talkativeness, mood, and behavior that are overly excited, thoughts of suicide or self-harm, tightness in the chest, trouble concentrating, trouble sleeping, trouble breathing, unexplained weight loss, unsteadiness or clumsiness, unusual bleeding or bruising, unusual tiredness or weakness, vomiting, weakness in the arms, hands, legs, or feet.

Less Severe Side Effects of Lorlatinib

When taking Lorlatinib, consult your healthcare professional if any of the following side effects persist, are bothersome, or if you have any questions about them:

More Common Side Effects

Abnormal dreams, back pain, constipation, difficulty with moving, difficulty speaking, drowsiness, joint pain, muscle aches, cramps, pain, or stiffness, pain in the arms or legs, talking in your sleep, swelling of the joints.

Lucius Pharmaceuticals Lorlatinib Side Effects Reference for Healthcare Professionals

Very Common Adverse Reactions (Incidence 10% or greater)

(1) Musculoskeletal

Arthralgia, myalgia/musculoskeletal pain, back pain, pain in extremity.

(2) Ocular

Visual disturbance (e.g., diplopia, photophobia, flashes of light, blurred vision, reduced visual acuity, visual impairment, vitreous floaters).

(3) Metabolic

Hypercholesterolemia, hypertriglyceridemia, edema (peripheral edema, eyelid edema, face edema, generalized edema, localized edema, periorbital edema, peripheral swelling, swelling), hyperglycemia, hypoalbuminemia, weight increased, lipase increased, alkaline phosphatase increased, amylase increased, hypophosphatemia, hyperkalemia, hypomagnesemia, Grade 3 or 4 total cholesterol increased, Grade 3 or 4 triglycerides increased.

(4) Psychiatric

Cognitive effects (e.g., amnesia, cognitive disorder, dementia, disturbance in attention, memory impairment, mental impairment, attention deficit/hyperactivity disorder, confusional state, delirium, disorientation, dyslexia), mood effects, sleep effects (e.g., abnormal dreams, insomnia, nightmare, sleep disorder, sleep talking, somnambulism).

(5) Hepatic

Grade 4 ALT/AST increased (when used with strong CYP3A inducers), Grade 3 ALT/AST increased (when used with strong CYP3A inducers).

(6) Respiratory

Dyspnea, cough, upper respiratory tract infection (e.g., fungal upper respiratory infection, viral upper respiratory infection).

(7) Hematologic

Anemia, thrombocytopenia, lymphopenia.

(8) Nervous System

Peripheral neuropathy (e.g., burning sensation, carpal tunnel syndrome, formication, gait disturbance, hypoesthesia, muscular weakness, neuralgia, neuropathy peripheral, neurotoxicity, paresthesia, peripheral sensory neuropathy, sensory disturbance), speech disorder (e.g., aphasia, dysarthria, slow speech).

(9) Skin

Rash (e.g., acneiform dermatitis, maculopapular rash, pruritic rash, rash).

(10) Other

Asthenia/fatigue, pyrexia.

Common Adverse Reactions (Incidence 1%-10%)

(1) Psychiatric

Hallucination, mental status changes.

(2) Hepatic

Grade 2 ALT/AST increased (when used with strong CYP3A inducers).

(3) Respiratory

Interstitial lung disease (ILD), pneumonitis.

(4) Nervous System

Seizure.

(5) Cardiovascular

Atrioventricular block, hypertension.