Comarit Capsul

Cabozantinib is a kinase inhibitor indicated for the treatment of-

• Patients with advanced renal cell carcinoma (RCC)
• Patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib

In vitro biochemical and/or cellular assays have shown that cabozantinib inhibits the tyrosine kinase activity of MET, VEGFR-1, -2 and -3, AXL, RET, ROS1, TYRO3, MER, KIT, TRKB, FLT-3, and TIE-2. These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, drug resistance, and maintenance of the tumor microenvironment.

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.

Administration

• Stop treatment with Cabozantinib at least 28 days prior to scheduled surgery, including dental surgery
• Do not substitute Cabozantinib tablets with cabozantinib capsules.
• Do not administer Cabozantinib with food. Administer at least 1 hour before or at least 2 hours after eating
• Swallow Cabozantinib tablets whole. Do not crush Cabozantinib tablets.
• Do not take a missed dose within 12 hours of the next dose.
• Modify the dose for certain patients with hepatic impairment and for patients taking drugs known to strongly induce or inhibit CYP450

• Strong CYP3A4 inhibitors: Reduce the Cabozantinib dosage if coadministration cannot be avoided.
• Strong CYP3A4 inducers: Increase the Cabozantinib dosage if coadministration cannot be avoided.

Cabozantinib may cause serious side effects, including:

• bleeding (hemorrhage)
• a tear in your stomach or intestinal wall (perforation) or an abnormal connection between 2
• parts of your body (fistula)
• blood clots, stroke, heart attack, and chest pain
• high blood pressure (hypertension)
• diarrhea
• a skin problem called hand-foot skin reaction
• protein in your urine and possible kidney problems

Based on findings from animal studies and its mechanism of action, Cabozantinib can cause fetal harm when administered to a pregnant woman. There is no information regarding the presence of Cabozantinib or its metabolites in human milk, or their effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Cabozantinib and for 4 months after the final dose.

• Hemorrhage: Do not administer Cabozantinib if recent history of hemorrhage.
• Perforations and Fistulas: Monitor for symptoms. Discontinue Cabozantinib for unmanageable fistula or GI perforation.
• Thrombotic Events: Discontinue Cabozantinib for myocardial infarction, cerebral infarction, or other serious thromboembolic events.
• Hypertension and Hypertensive Crisis: Monitor blood pressure regularly. Interrupt for hypertension that is not adequately controlled with anti-hypertensive therapy. Discontinue Cabozantinib for hypertensive crisis or severe hypertension that cannot be controlled with
• anti-hypertensive therapy.
• Diarrhea: May be severe. Interrupt Cabozantinib immediately until diarrhea resolves or decreases to Grade 1. Recommend standard antidiarrheal treatments.
• Palmar-plantar erythrodysesthesia (PPE): Interrupt Cabozantinib treatment until PPE resolves or decreases to Grade 1.
• Proteinuria: Monitor urine protein. Discontinue for nephrotic syndrome.
• Osteonecrosis of the jaw: Withhold Cabozantinib for at least 28 days prior to invasive dental procedures and for development of ONJ.
• Wound complications: Withhold Cabozantinib for dehiscence or complications requiring medical intervention. 
• Reversible posterior leukoencephalopathy syndrome (RPLS): Discontinue Cabozantinib.
• Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 4 months after the last dose.

One case of overdosage was reported following administration of another formulation of cabozantinib; a patient inadvertently took twice the intended dose for 9 days. The patient suffered Grade 3 memory impairment, Grade 3 mental status changes, Grade 3 cognitive disturbance, Grade 2 weight loss, and Grade 1 increase in BUN. The extent of recovery was not documented.

Cytotoxic Chemotherapy

• Pediatric Use: The safety and effectiveness of Cabozantinib in pediatric patients have not been established.
• Geriatric Use: No overall differences in safety or effectiveness were observed between these patients and younger patients.
• Renal Impairment: No dosage adjustment is recommended in patients with mild or moderate renal impairment.

Store Cabozantinib at room temperature 20°C to 25°C