Cabometyx

What is Cabometyx?

• Cabometyx (Cabozantinib) is a kinase inhibitor used to treat differentiated thyroid cancer, hepatocellular carcinoma, renal cell carcinoma.

Cabozantinib

What are the uses of this medicine?

Cabometyx (Cabozantinib) is a medicine used to treat: people with advanced kidney cancer (renal cell carcinoma). Cabometyx may be used:

• alone to treat people with renal cell carcinoma (RCC) that has spread (advanced RCC).
• in combination with nivolumab when your cancer has spread (advanced RCC), and you have not already had treatment for your advanced RCC.

• people with liver cancer (hepatocellular carcinoma) who have been previously treated with the medicine sorafenib.

• adults and children 12 years of age and older who have a type of thyroid cancer called differentiated thyroid cancer (DTC), that has spread (locally advanced or metastatic), and,
• has progressed after treatment with a VEGFR-targeted treatment, and
• your DTC can no longer be treated with radioactive iodine, or you are not able to receive radioactive iodine treatment

How does this medicine work?

• Cabozantinib (ka" boe zan' ti nib) is an orally available, small molecule, multi-kinase inhibitor with activity against hepatocyte growth factor receptor (MET), vascular endothelial growth factor receptor 2 (VEGFR-2), and rearranged during transfection (RET), cell surface tyrosine kinase receptors which are overexpressed in several forms of cancer.
• Cabozantinib has been evaluated as therapy of several forms of advanced and metastatic carcinomas and has shown efficacy in medullary thyroid and renal cell carcinoma.

Who Should Not Use this medicine ?

• This medicine have no usage limitations.

What drug interactions can this medicine cause?

• Avoid coadministration of Cabometyx with strong CYP3A4 inhibitors. Reduce the dosage of Cabometyx if coadministration with strong CYP3A4 inhibitors cannot be avoided. Avoid grapefruit or grapefruit juice which may also increase exposure of cabozantinib.
• Avoid coadministration of Cabometyx with strong CYP3A4 inducers. Increase the dosage of Cabometyx if coadministration with strong CYP3A4 inducers cannot be avoided. Avoid St. John’s wort which may also decrease exposure of cabozantinib.

Is this medicine FDA approved?

• In April 2016, the FDA granted approval for marketing the tablet formulation (Cabometyx) as a second line treatment for kidney cancer and the same was approved in the European Union in September of that year.

How should this medicine be used?

• Stop treatment with Cabometyx at least 3 weeks prior to scheduled surgery, including dental surgery.
• Do NOT substitute Cabometyx tablets with cabozantinib capsules.

Recommended dosage: Recommended Dosage for Renal Cell Carcinoma:

• The recommended dosage of Cabometyx as a single agent is 60 mg once daily until disease progression or unacceptable toxicity administered as recommended.

Recommended Dosage for Hepatocellular Carcinoma:

• The recommended dosage of Cabometyx as a single agent is 60 mg once daily until disease progression or unacceptable toxicity administered as recommended.

Recommended Dosage for Differentiated Thyroid Cancer:

• The recommended dosage of Cabometyx as a single agent for adult and pediatric patients 12 years of age and older with BSA greater than or equal to 1.2 m2 is 60 mg once daily until disease progression or unacceptable toxicity administered as recommended.
• The recommended dosage of Cabometyx as a single agent in pediatric patients 12 years of age and older with BSA less than 1.2 m2 is 40 mg once daily.

Administration:

• Take Cabometyx exactly as your healthcare provider tells you to take it.
• Do not take Cabometyx with food. Take Cabometyx at least 1 hour before or at least 2 hours after eating.
• Swallow Cabometyx tablets whole.
• Do not crush Cabometyx tablets.
• If you miss a dose and your next scheduled dose is in:
• less than 12 hours, take your next dose at the normal time. Do not make up the missed dose.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: 20 mg, 40 mg, and 60 mg.

This medicine is available in fallowing brand namesː

• Cabometyx

What side effects can this medication cause?

The most common side effects of Cabometyx include:

• tiredness
• decreased appetite
• nausea and vomiting
• weight loss
• constipation

The most common side effects of Cabometyx when used in combination with nivolumab include:

• tiredness
• mouth sores
• rash
• low thyroid hormone levels (hypothyroidism)
• pain in muscles, bones, and joints
• decreased appetite
• nausea
• changes in the way things taste
• stomach-area (abdominal) pain
• cough
• upper respiratory tract infection

Cabometyx may cause fertility problems in females and males, which may affect your ability to have children.

Cabometyx 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
• hypertension
• diarrhea
• a skin problem called hand-foot skin reaction
• liver problems
• adrenal gland problems
• protein in your urine and possible kidney problems
• osteonecrosis
• wound healing problems
• Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
• change in thyroid function
• hypocalcemia

What special precautions should I follow?

• Severe and fatal hemorrhages occurred with Cabometyx. Do not administer Cabometyx if recent history of hemorrhage.
• Fistulas, including fatal cases, occurred in 1% of Cabometyx-treated patients. Monitor for symptoms. Discontinue Cabometyx for Grade 4 fistula or perforation.
• Cabometyx increased the risk of thrombotic events. Discontinue Cabometyx for myocardial infarction or serious venous or arterial thromboembolic events.
• Cabometyx can cause hypertension, including hypertensive crisis. Monitor blood pressure regularly. Interrupt for hypertension that is not adequately controlled with anti-hypertensive therapy. Discontinue Cabometyx for hypertensive crisis or severe hypertension that cannot be controlled with anti-hypertensive therapy.
• Diarrhea occurred in patients treated with Cabometyx. Interrupt Cabometyx until diarrhea resolves or decreases to ≤Grade 1, resume at reduced dose. Recommend standard antidiarrheal treatments.
• Palmar-plantar erythrodysesthesia (PPE) occurred in patients treated with Cabometyx. Interrupt Cabometyx treatment until PPE resolves or decreases to Grade 1.
• Cabometyx in combination with nivolumab can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider withholding Cabometyx and/or nivolumab, initiating corticosteroid therapy, and/or permanently discontinuing the combination for severe or life- threatening hepatotoxicity.
• Cabometyx in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold Cabometyx and/or nivolumab depending on severity.
• Proteinuria was observed in patients receiving Cabometyx. Monitor urine protein. Interrupt Cabometyx until proteinuria resolves to ≤ Grade 1, resume Cabometyx at a reduced dose. Discontinue for nephrotic syndrome.
• Osteonecrosis of the jaw (ONJ) occurred. Withhold Cabometyx for at least 3 weeks prior to invasive dental procedures and for development of ONJ.
• Wound complications occurred with Cabometyx. Withhold Cabometyx for at least 3 weeks before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of Cabometyx after resolution of wound healing complications has not been established.
• Reversible Posterior Leukoencephalopathy Syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, can occur with Cabometyx. Discontinue Cabometyx.
• Thyroid dysfunction, primarily hypothyroidism, has been observed with Cabometyx. Monitor thyroid function before and during treatment with Cabometyx.
• Cabometyx can cause hypocalcemia. Withhold Cabometyx and resume at reduced dose upon recovery or permanently discontinue Cabometyx depending on severity.
• Based on data from animal studies and its mechanism of action, Cabometyx can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• memory impairment
• mental status changes
• cognitive disturbance
• weight loss

Management of overdosage:

• In the event of an overdose, appropriate supportive treatment should be initiated.

Can this medicine be used in pregnancy?

• Based on findings from animal studies and its mechanism of action, Cabometyx can cause fetal harm when administered to a pregnant woman.
• There are no available data in pregnant women to inform the drug-associated risk.

Can this medicine be used in children?

• The safety and effectiveness of Cabometyx for the treatment of differentiated thyroid cancer (DTC) have been established in pediatric patients aged 12 years and older.
• The safety and effectiveness of Cabometyx in pediatric patients less than 12 years of age have not been established.

What are the active and inactive ingredients in this medicine?

• Active ingredient: cabozantinib
• Inactive ingredients: microcrystalline cellulose, lactose anhydrous, hydroxypropyl cellulose, croscarmellose sodium, colloidal silicon dioxide, and magnesium stearate. The film coating contains hypromellose, titanium dioxide, triacetin, and iron oxide yellow.

Who manufactures and distributes this medicine?

• Manufactured for Exelixis, Inc. Alameda, CA

What should I know about storage and disposal of this medication?

• Store Cabometyx at room temperature between 68°F to 77°F (20°C to 25°C).

• Dailymed label info on Cabometyx
• FDA Cabometyx

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