Renal Cell Carcinoma: Cabozantinib is indicated for the management of patients with advanced renal cell carcinoma (RCC).
Hepatocellular Carcinoma: Cabozantinib is also indicated for patients with hepatocellular carcinoma (HCC) who have previously been treated with sorafenib.
Cabozantinib inhibits a wide range of receptor tyrosine kinases including MET, VEGFR-1, VEGFR-2, VEGFR-3, AXL, RET, ROS1, TYRO3, MER, KIT, TRKB, FLT-3, and TIE-2. These kinases are involved in normal cellular functions as well as cancer-related processes such as tumor growth, metastasis, angiogenesis, drug resistance, and maintenance of the tumor microenvironment.
Absorption: The median time to reach peak plasma concentration (Tmax) is approximately 3 to 4 hours after administration. Following a single 140 mg dose, Cmax is about 19% higher compared to capsule formulation, while the difference in AUC is less than 10%.
Distribution: The apparent volume of distribution (Vd/F) is approximately 319 L. Cabozantinib is highly bound to plasma proteins (≥99.7%).
Elimination: The terminal half-life is around 99 hours, and the clearance at steady state (CL/F) is about 2.2 L/hour.
Metabolism: Cabozantinib is metabolized mainly via the CYP3A4 enzyme.
Excretion: Approximately 81% of the administered radioactive dose is recovered within 48 days. About 54% is excreted in feces and 27% in urine. Around 43% of the dose is excreted unchanged in feces and is not detectable in urine after 72 hours.
Recommended Dosage for Renal Cell Carcinoma: The recommended dosage of Cabozantinib is 60 mg once daily without food until the patient no longer experiences clinical benefit or experiences unacceptable toxicity.
Recommended Dosage for Hepatocellular Carcinoma: The recommended dosage of Cabozantinib is 60 mg once daily without food until disease progression or unacceptable toxicity. Or, as directed by the registered physicians.
Pediatric Use: The safety and effectiveness of Cabozantinib in pediatric patients have not been established.
Cabozantinib exposure may be significantly affected by drugs that influence CYP3A4 enzyme activity. Strong CYP3A4 inhibitors can increase cabozantinib levels, thereby raising the risk of adverse effects. Concomitant use should be avoided; if unavoidable, dose reduction is recommended. Grapefruit or grapefruit juice should also be avoided as it may increase drug exposure.
On the other hand, strong CYP3A4 inducers may decrease cabozantinib levels and reduce its effectiveness. Co-administration should be avoided; if necessary, an increased dose may be considered. Herbal products like St. John’s Wort should also be avoided as they can lower cabozantinib exposure.
Cabozantinib is contraindicated in patients with known hypersensitivity to cabozantinib or any of the components of the formulation.
Common and serious adverse effects associated with cabozantinib include hemorrhage, gastrointestinal perforation and fistula formation, thrombotic events, hypertension including hypertensive crisis, diarrhea, palmar-plantar erythrodysesthesia (hand-foot syndrome), proteinuria, osteonecrosis of the jaw, wound healing complications, and reversible posterior leukoencephalopathy syndrome.
Pregnancy: Cabozantinib may cause harm to the fetus when administered during pregnancy. There is insufficient data in pregnant women to fully assess the drug-related risk.
Lactation: It is unknown whether cabozantinib or its metabolites are present in human milk or affect milk production. Due to the risk of serious adverse effects in the breastfed infant, women should avoid breastfeeding during treatment and for at least 4 months after the last dose.
Contraception: Cabozantinib may cause fetal harm; therefore, effective contraception should be used during treatment.
Females: Women of childbearing potential should use effective contraception during therapy and continue for at least 4 months after the final dose.
Infertility: Based on animal studies, cabozantinib may impair fertility in both males and females.
Hemorrhage: Severe and potentially fatal bleeding events have been reported. Cabozantinib should be discontinued in cases of Grade 3 or 4 hemorrhage and avoided in patients with recent bleeding history such as hemoptysis, hematemesis, or melena.
Perforations and Fistulas: Gastrointestinal perforations and fistulas, including fatal cases, have been reported. Patients should be monitored for symptoms such as abscess or sepsis. Discontinue treatment if serious complications occur.
Thrombotic Events: Cabozantinib increases the risk of thromboembolic events, including pulmonary embolism and arterial thrombosis. Fatal events have been reported. Discontinue in cases of serious thrombotic complications.
Hypertension and Hypertensive Crisis: Cabozantinib may cause high blood pressure, including severe cases. Do not initiate treatment in uncontrolled hypertension. Monitor blood pressure regularly and adjust dose as needed. Discontinue in severe or uncontrolled cases.
Proteinuria: Proteinuria has been observed. Regular monitoring is recommended. Discontinue if nephrotic syndrome develops.
Osteonecrosis of the Jaw: Cases of jaw bone damage have been reported. Conduct dental examination before and during treatment. Maintain good oral hygiene and avoid invasive dental procedures when possible.
Wound Complications: Impaired wound healing may occur. Stop treatment at least 28 days before surgery and resume based on healing status.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS): This rare neurological condition may occur. Monitor for symptoms like seizures, headache, vision changes, or confusion. Discontinue if diagnosed.
Embryo-Fetal Toxicity: Cabozantinib can cause fetal harm. Women should use effective contraception during treatment and for at least 4 months afterward.
A case of overdose has been reported where a patient accidentally took double the intended dose for several days, resulting in memory impairment, mental changes, cognitive disturbance, weight loss, and increased blood urea nitrogen. Recovery outcome was not clearly documented.
Tyrosine Kinase Inhibitor
Store below 30°C in a cool, dry place, protected from sunlight. Keep out of reach of children.
What is Cabozantinib for?
What does Cabozantinib do?
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Can Cabozantinib be taken during pregnancy?
