Several things patients must know when taking the drug: What are the warnings and precautions for cabozantinib?

In clinical studies of cabozantinib (Cabozantinib), warnings and precautions such as bleeding, perforation and fistula, thrombotic events, hypertension and hypertensive crisis, diarrhea, palmar-plantar red blood cell paresthesia, hepatotoxicity, adrenal insufficiency, proteinuria, osteonecrosis of the jaw, impaired wound healing, reversible posterior leukoencephalopathy syndrome, thyroid dysfunction, hypocalcemia, etc. have occurred. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Bleeding: Severe and fatal bleeding has occurred with cabozantinib. According to recommendations, cabozantinib should be discontinued in case of grade 3 or 4 bleeding and before surgery; do not use cabozantinib in patients with a recent history of bleeding (including hemoptysis, hematemesis, or melena).

2. Perforation and fistula: may include gastrointestinal perforation, including fatal cases. Monitor patients for signs and symptoms of fistulas and perforations, including abscesses and sepsis. Cabozantinib should be discontinued in patients who develop Grade 4 fistulas or gastrointestinal perforations.

3. Thrombotic events: Cabozantinib increases the risk of thrombotic events, which may include venous thromboembolism (pulmonary embolism), arterial thromboembolism, etc. Cabozantinib should be discontinued in patients who experience an acute myocardial infarction or a serious arterial or venous thromboembolic event requiring medical intervention.

4. Hypertension and hypertensive crisis: Do not use cabozantinib in patients with uncontrolled hypertension. Monitor blood pressure regularly during treatment. Cabozantinib should be discontinued in patients with hypertension not adequately controlled by medical therapy and resumed at a reduced dose when the condition is controlled. Cabozantinib should be permanently discontinued in severe hypertension or hypertensive crisis that is not controlled by antihypertensive therapy.

5. Diarrhea: Monitor and manage patients taking antidiarrheal medications as directed. Discontinue cabozantinib before improvement to grade ≤ 1 and continue cabozantinib after reducing the dose.

6. Palm-Plantar red blood cell paresthesia (PPE): For intolerable Level 2 PPE or Level 3 PPE, suspend cabozantinib until improvement to Level 1 and resume use at a reduced dose.

7. Hepatotoxicity: Combination of cabozantinib and nivolumab can lead to hepatotoxicity, with grade 3 and 4 ALT and AST elevations occurring more frequently than cabozantinib alone. Monitor liver enzymes before starting treatment and periodically during treatment. Consider monitoring hepatic enzymes more frequently than with single dose administration. For elevated liver enzymes, interrupt cabozantinib and nivolumab and consider administration of corticosteroids.

8. Adrenal insufficiency: Combination of cabozantinib andnivolumab can cause primary or secondary adrenal insufficiency. For grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement, including systemic corticosteroids, as clinically indicated.

9. Proteinuria: Monitor urine protein regularly during cabozantinib treatment. For grade 2 or 3 proteinuria, discontinue cabozantinib until improvement to grade ≤ 1 proteinuria, then reduce the dose. Cabozantinib should be discontinued in patients who develop nephrotic syndrome.

10. Osteonecrosis of the jaw (ONJ): can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gum ulcers or erosions, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Have an oral examination before starting cabozantinib and periodically during treatment. Patients are advised to maintain good oral hygiene habits. If possible, stop using cabozantinib at least 3 weeks before scheduled dental surgery or invasive dental procedures.

11. Impaired wound healing: Wound complications occurred with cabozantinib. Discontinue cabozantinib at least 3 weeks before elective surgery. Do not use cabozantinib for at least 2 weeks after major surgery and until the wound has completely healed.

12. Reversible posterior leukoencephalopathy syndrome (RPLS): It is a subcortical vasogenic edema syndrome diagnosed through characteristic MRI findings, which can occur in the chin. Perform an RPLS evaluation on any patient who experiences seizures, headaches, visual disturbances, confusion, or changes in mental function. Cabozantinib should be discontinued in patients who develop RPLS.

13. Thyroid dysfunction: Mainly hypothyroidism. Before starting cabozantinib treatment, patients should be evaluated for signs of thyroid dysfunction and monitored for signs and symptoms of thyroid dysfunction during treatment. Thyroid function testing and dysfunction management should be performed as clinically indicated.

14. Hypocalcemia: Monitor blood calcium levels during treatment and replace calcium supplements as needed.

15. Embryo-Fetal toxicity: Based on animal study data and its mechanism of action, cabozantinib taken by pregnant women may cause harm to the fetus. Administration of cabozantinib to pregnant animals during organogenesis resulted in embryonic lethality at lower than clinically recommended doses and increased incidence of skeletal variants in rats and visceral variants and malformations in rabbits. Inform pregnant women of potential risks to the fetus. Advise females of childbearing potential to use effective contraception during treatment and for 4 months after the last dose.