Cabozantinib (Side Effects)

In this article, we will discuss Cabozantinib (Side Effects). So, let’s get started.

Side Effects

Hemorrhage

Severe hemorrhage occurred with Cabozantinib. The incidence of Grade ≥ 3 hemorrhagic events was 2.1% in Cabozantinib-treated patients and 1.6% in everolimus-treated patients. Fatal hemorrhages also occurred in the cabozantinib clinical program. Do not administer Cabozantinib to patients that have or are at risk for severe hemorrhage.

GI Perforations and Fistulas

In a randomized study in renal cell carcinoma, fistulas were reported in 1.2% (including 0.6% anal fistula) of CABOMETYX-treated patients and 0% of everolimus-treated patients. Gastrointestinal (GI) perforations were reported in 0.9% of Cabozantinib-treated patients and 0.6% of everolimus-treated patients. Fatal perforations occurred in the cabozantinib clinical program. Monitor patients for symptoms of fistulas and perforations. Discontinue Cabozantinib in patients who experience a fistula which cannot be appropriately managed or a GI perforation.

Thrombotic Events

Cabozantinib treatment results in an increased incidence of thrombotic events. Venous thromboembolism was reported in 7.3% of cabozantinib-treated patients and 2.5% of everolimus-treated patients. Pulmonary embolism occurred in 3.9% of cabozantinib-treated patients and 0.3% of everolimus-treated patients. Events of arterial thromboembolism were reported in 0.9% of Cabozantinib-treated patients and 0.3% of everolimus-treated patients. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue Cabozantinib in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.

Hypertension and Hypertensive Crisis

Cabozantinib treatment results in an increased incidence of treatment-emergent hypertension. Hypertension was reported in 37% (15% Grade ≥ 3) of Cabozantinib-treated patients and 7.1% (3.1% Grade ≥ 3) of everolimus-treated patients. Monitor blood pressure prior to initiation and 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. Discontinue Cabozantinib if there is evidence of hypertensive crisis or severe hypertension despite optimal medical management.

Diarrhea

Diarrhea occurred in 74% of patients treated with Cabozantinib and in 28% of patients treated with everolimus. Grade 3 diarrhea occurred in 11% of Cabozantinib-treated patients and in 2% of everolimus-treated patients. Withhold Cabozantinib in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume Cabozantinib at a reduced dose. Dose modification due to diarrhea occurred in 26% of patients.

Palmar-Plantar Erythrodysesthesia Syndrome

Palmar-plantar erythrodysesthesia syndrome (PPES) occurred in 42% of patients treated with Cabozantinib and in 6% of patients treated with everolimus. Grade 3 PPES occurred in 8.2% of Cabozantinib-treated patients and in <1% of everolimus-treated patients. Withhold Cabozantinib in patients who develop intolerable Grade 2 PPES or Grade 3 PPES until improvement to Grade 1; resume Cabozantinib at a reduced dose. Dose modification due to PPES occurred in 16% of patients.

Reversible Posterior Leukoencephalopathy Syndrome

Reversible Posterior Leukoencephalopathy Syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. 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. Cabozantinib administration to pregnant animals during organogenesis resulted in embryolethality at exposures below those occurring clinically at the recommended dose, and in increased incidences of skeletal variations in rats and visceral variations and malformations in rabbits. 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.

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