Side Effects and Adverse Reactions of Cabozantinib

Cabozantinib is a broad‑spectrum multi‑targeted anticancer drug that inhibits at least 9 targets, including MET, VEGFR1/2/3, ROS1, RET, AXL, NTRK, and KIT.

Side Effects Requiring Immediate Medical Attention

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

1. Common side effects

(1) Blurred vision, burning, numbness, tingling, or pain; confusion; constipation; dark urine; skin discoloration; decreased urine output; diarrhea; difficulty breathing or swallowing; headache; dry mouth; dry skin and hair; fainting; feeling cold;

(2) Hair loss; headache; hoarseness; rapid heart rate; lightheadedness; loss of appetite; mood depression; muscle spasms, twitching, and stiffness; nausea or vomiting; nervousness; pain in the chest, groin, or legs (especially calves); ringing in the ears; shortness of breath;

(3) Red, swollen, or painful skin; peeling skin on palms and soles; severe, sudden headache; rash or sores; slow or fast heartbeat; slurred speech; stomach pain; sudden loss of coordination; sudden severe weakness or numbness in the arm or leg; sunken eyes;

(4) Thirst; unsteady walk or clumsiness; unusual tiredness or weakness; vision changes; weakness in the arms, hands, legs, or feet; weight gain; wrinkled skin; yellowing of the eyes or skin.

2. Uncommon side effects

(1) Bleeding gums; bloody, black, or tarry stools; coughing up blood; heartburn; heavy feeling in the jaw; increased menstrual flow or vaginal bleeding; indigestion; loose teeth; mood or mental changes; muscle spasms in the hands, arms, feet, legs, or face;

(2) Nosebleeds; numbness and tingling around the mouth, fingertips, or feet; pain, swelling, or numbness in the mouth or jaw; paralysis; prolonged bleeding from wounds; red or dark brown urine;

(3) Seizures; severe stomach pain, cramps, or burning; tremors; trouble breathing; severe and persistent vomiting that resembles coffee grounds.

3. Rare side effects

Abnormal color vision; double vision; halos around lights; night blindness; sensitivity to light; tunnel vision.

Mild Side Effects of Cabozantinib

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

Common mild side effects

(1) Belching; bleeding after bowel movements; altered taste; changes in hair color; decreased appetite; weight loss; difficulty having a bowel movement; difficulty moving; fear; tiredness or loss of strength;

(2) Loss of taste; muscle pain; joint pain; rash; sore throat; stomach discomfort, upset, or pain; swelling or inflammation of the mouth; uncomfortable swelling around the anus; voice changes.

Side Effects of Cabozantinib for Healthcare Professional Reference

1. Hepatobiliary Disorders

Very common: Elevated alanine aminotransferase (ALT), elevated aspartate aminotransferase (AST), increased alkaline phosphatase, hyperbilirubinemia.

Common: Cholelithiasis.

Uncommon: Hepatic encephalopathy.

2. Gastrointestinal Disorders

Very common: Diarrhea, stomatitis, nausea, oral pain, constipation, abdominal pain, vomiting, dysphagia, dyspepsia, glossalgia.

Common: Hemorrhoids, gastrointestinal perforation, gastrointestinal fistula, gastrointestinal hemorrhage, pancreatitis, anal fissure, anal inflammation, cheilitis.

Uncommon: Esophagitis.

3. Endocrine Disorders

Very common: Increased blood thyroid-stimulating hormone.

Common: Hypothyroidism, adrenal insufficiency.

Uncommon: Amenorrhea.

4. Hematologic Disorders

Very common: Lymphopenia, neutropenia, thrombocytopenia.

Uncommon: Increased eosinophil count, increased platelet count.

Post-marketing reports: Aneurysms (including aorta), arterial dissection, and arterial rupture.

5. Skin and Subcutaneous Tissue Disorders

Very common: Palmar‑plantar erythrodysesthesia syndrome, hair color changes/depigmentation/graying, dry skin, alopecia, erythema.

Common: Hyperkeratosis, folliculitis, acne, blisters, abnormal hair growth, skin desquamation, skin hypopigmentation.

Uncommon: Skin ulcer, telangiectasia.

6. Metabolism and Nutrition Disorders

Very common: Weight loss, decreased appetite, hypocalcemia, hypophosphatemia, hypomagnesemia, hypokalemia, hyponatremia, increased blood lactate dehydrogenase, increased blood creatine phosphokinase.

Common: Dehydration, hypoalbuminemia.

7. Nervous System Disorders

Very common: Dysgeusia, headache, dizziness.

Common: Paresthesia, peripheral sensory neuropathy, peripheral neuropathy, ageusia, tremor.

Uncommon: Posterior reversible encephalopathy syndrome, ataxia, disturbance in attention, loss of consciousness, speech disorder, transient ischemic attack.

8. Musculoskeletal and Connective Tissue Disorders

Very common: Arthralgia, muscle spasms.

Common: Musculoskeletal chest pain, osteonecrosis of the jaw (ONJ).

Uncommon: Rhabdomyolysis.

9. Cardiovascular Disorders

Very common: Increased blood pressure, hypertension.

Common: Hypotension, venous thromboembolism, arterial thromboembolism, atrial fibrillation.

Uncommon: Angina pectoris, supraventricular tachycardia, shortened activated partial thromboplastin time.

Frequency not known: QT prolongation.

10. Genitourinary Disorders

Common: Proteinuria, dysuria, hematuria.

Uncommon: Vaginal bleeding.

11. Eye Disorders

Common: Blurred vision.

Uncommon: Cataract, conjunctivitis.

12. Psychiatric Disorders

Common: Anxiety, depression, confusional state.

Uncommon: Abnormal dreams, delirium.

13. Respiratory, Thoracic and Mediastinal Disorders

Very common: Dysphonia (up to 20%), oropharyngeal pain.

Common: Non-gastrointestinal fistula (including tracheal fistula, mediastinal emphysema, tracheoesophageal fistula), pulmonary embolism, respiratory tract hemorrhage (including lung, bronchus, trachea), pneumonia, aspiration pneumonia.

Uncommon: Atelectasis, pharyngeal edema, pneumonitis.

14. General Disorders and Administration Site Conditions

Very common: Fatigue, asthenia, mucosal inflammation.

Common: Abscess (including visceral, intra-abdominal, skin, dental), fungal infection (including skin, oral, genital), ear pain, tinnitus, pallor, cold extremities, impaired wound healing/wound complications, chills, facial edema.

Uncommon: Aspergilloma, hearing impairment, cyst, facial pain, localized edema.

Frequency not known: Hemorrhage.

Note:

Very common: ≥ 10%

Common: 1% – 10%

Uncommon: 0.1% – 1%