Side Effects and Adverse Reactions of Lorlatinib

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

Side Effects of Lorlatinib Requiring Immediate Medical Attention

Seek immediate medical attention if any of the following side effects occur while taking lorlatinib:

Very Common Side Effects

(1) Uncontrolled behavior, aggression, agitation, anxiety, black, tarry stools, bleeding gums, blood in urine or stools, blurred vision or other visual changes, body aches or pain, burning, crawling, itching, numbness, prickling, “pins and needles”, stabbing or tingling pain;

(2) Changes in behavior, chills, cough, deficits in intelligence, short-term memory, learning ability, and attention, difficult or labored breathing, discouragement, dizziness, dry mouth, ear congestion, false or unusual sense of well-being, feeling sad or empty, fever;

(3) Red, dry skin, fruity breath odor, headache, hoarseness, increased appetite, increased thirst, increased urination, irritability, loss of appetite, loss of interest or pleasure, loss of voice, 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, rash, slow or fast heartbeat, sneezing, sore throat, stomach pain, sweating, swelling;

(5) Excited talk, mood, and behavior, suicidal thoughts, tightness in the chest, trouble concentrating, trouble sleeping, troubled breathing, unexplained weight loss, unsteady gait or clumsiness, unusual bleeding or bruising, unusual tiredness or weakness, vomiting, weakness in the arms, hands, legs, or feet.

Mild Side Effects of Lorlatinib

Consult a healthcare professional if any of the following side effects persist, are bothersome, or if you have any questions about them:

Very Common Side Effects

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

Side Effects of Lorlatinib for Healthcare Professional Reference

1. Very Common Adverse Reactions (incidence ≥ 10%)

(1) Musculoskeletal

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

(2) Ocular

Visual disturbances (e.g., diplopia, photophobia, photopsia, blurred vision, visual acuity reduced, visual impairment, vitreous floaters).

(3) Metabolic

Hypercholesterolemia, hypertriglyceridemia, edema (peripheral edema, eyelid edema, facial 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 increased total cholesterol, Grade 3 or 4 increased triglycerides.

(4) Psychiatric

Cognitive effects (e.g., amnesia, cognitive disorder, dementia, attention deficit disorder, memory impairment, mental impairment, attention-deficit/hyperactivity disorder, confusional state, delirium, disorientation, dyslexia), mood changes, sleep changes (e.g., abnormal dreams, insomnia, nightmares, sleep disorder, somniloquy, somnambulism).

(5) Hepatic

Grade 4 increased ALT/AST when co-administered with strong CYP450 3A inducer;

Grade 3 increased ALT/AST when co-administered with strong CYP450 3A inducer.

(6) Respiratory

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

(7) Hematologic

Anemia, thrombocytopenia, lymphopenia.

(8) Nervous System

Peripheral neuropathy (e.g., burning sensation, carpal tunnel syndrome, paresthesia, formication, gait disturbance, hypoesthesia, muscle weakness, neuralgia, peripheral neuropathy, neurotoxicity, dysesthesia, peripheral sensory neuropathy, sensory disturbance), speech disorders (e.g., aphasia, dysarthria, slurred speech).

(9) Skin

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

(10) Others

Asthenia/fatigue, pyrexia.

2. Common Adverse Reactions (incidence 1%–10%)

(1) Psychiatric

Hallucination, altered mental status.

(2) Hepatic

Grade 2 increased ALT/AST when co-administered with strong CYP450 3A inducer.

(3) Respiratory

Interstitial lung disease (ILD), pneumonitis.

(4) Nervous System

Seizure.

(5) Cardiovascular

Atrioventricular block, hypertension.