• Hemorrhage
• Perforations and Fistulas
• Thrombotic Events
• Hypertension and Hypertensive Crisis
• Diarrhea
• Palmar-plantar Erythrodysesthesia
• Proteinuria
• Osteonecrosis of the Jaw
• Wound Complications
• Reversible Posterior Leukoencephalopathy Syndrome

 

Pregnancy: Cabozantinib can cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk.

Lactation: 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, women should be advised not to breastfeed during treatment with Cabozantinib and for 4 months after the final dose.

Contraception: Cabozantinib can cause fetal harm when administered to a pregnant woman.

Females: Females of reproductive potential should be advised to use effective contraception during treatment with Cabozantinib and for 4 months after the final dose.

Infertility: Females and Males: Based on findings in animals, Cabozantinib may impair fertility in females and males of reproductive potential.

 

Hemorrhage: Severe and fatal hemorrhages occurred with Cabozantinib. Discontinue Cabozantinib for Grade 3 or 4 hemorrhage. Do not administer Cabozantinib to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of Cabozantinib-treated patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of Cabozantinib-treated patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue Cabozantinib in patients who experience a fistula that cannot be appropriately managed or a GI perforation.

Thrombotic Events: Cabozantinib increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism occurred in 2% of Cabozantinib treated patients. Fatal thrombotic events occurred in Cabozantinib-treated patients. Discontinue Cabozantinib in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention.

Hypertension and Hypertensive Crisis: Cabozantinib can cause hypertension, including hypertensive crisis. Do not initiate Cabozantinib in patients with uncontrolled hypertension. Monitor blood pressure regularly during Cabozantinib treatment. Withhold Cabozantinib for hypertension that is not adequately controlled with medical management; when controlled, resume Cabozantinib at a reduced dose. Discontinue Cabozantinib for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Diarrhea: Diarrhea occurred in 63% of patients treated with Cabozantinib. Withhold Cabozantinib until improvement to Grade 1 and resume Cabozantinib at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

Palmar-Plantar Erythrodysesthesia: Palmar-plantar erythrodysesthesia (PPE) occurred in 44% of patients treated with Cabozantinib. Withhold Cabozantinib until improvement to Grade 1 and resume Cabozantinib at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Proteinuria: Proteinuria was observed in 7% of patients receiving Cabozantinib. Monitor urine protein regularly during Cabozantinib treatment. Discontinue Cabozantinib in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw: Osteonecrosis of the jaw (ONJ) occurred in <1% of patients treated with Cabozantinib. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to initiation of Cabozantinib and periodically during Cabozantinib. Advise patients regarding good oral hygiene practices. Withhold Cabozantinib for at least 28 days prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold Cabozantinib for development of ONJ until complete resolution.

Wound Complications: Wound complications have been reported with Cabozantinib. Stop Cabozantinib at least 28 days prior to scheduled surgery. Resume Cabozantinib after surgery based on clinical judgment of adequate wound healing. Withhold Cabozantinib in patients with dehiscence or wound healing complications requiring medical intervention.

Reversible Posterior Leukoencephalopathy Syndrome: Reversible Posterior Leukoencephalopathy Syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, can occur with Cabozantinib. Perform an evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function. Discontinue Cabozantinib in patients who develop RPLS.

Embryo-Fetal Toxicity: Based on data from animal studies and its mechanism of action, Cabozantinib can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Cabozantinib 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.