Cabometyx

Cabometyx is used to treat kidney cancer (renal cell carcinoma, RCC), liver cancer (hepatocellular carcinoma), differentiated thyroid cancer (DTC), and pancreatic neuroendocrine tumors (pNET) or extra-pancreatic neuroendocrine tumors (epNET). It is an oral tablet taken once daily.

Cabometyx blocks multiple enzymes that drive tumor growth, spread, and blood vessel formation, slowing cancer progression. It belongs to the multikinase inhibitor drug class.

Cabometyx (cabozantinib) gained FDA approval on November 29, 2012. There is no generic.

Cabometyx is FDA-approved to treat the following cancers:

• Renal cell carcinoma (RCC, the most common type of kidney cancer) that has spread (advanced RCC): As monotherapy (alone) In combination with nivolumab, in people who have not already had treatment for advanced RCC
• Hepatocellular carcinoma (HCC, primary liver cancer) in patients previously treated with sorafenib
• Differentiated thyroid cancer (DTC) in adults and children 12 years and older 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.
• Previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET) or extra-pancreatic neuroendocrine tumors (epNET) in adults and children 12 years and older

It is not known if Cabometyx is safe and effective in children younger than 12 years of age.

• Take Cabometyx exactly as your healthcare provider tells you to take it.
• Do not take Cabometyx with food. Take Cabometyx on an empty stomach at least 1 hour before or at least 2 hours after eating.
• Swallow Cabometyx tablets whole.
• Do not crush, chew, or split Cabometyx tablets.

Before you take Cabometyx, tell your healthcare provider about all of your medical conditions, including if you:

• Have had a liver problem other than liver cancer
• Have a recent history of bleeding, including coughing up or vomiting blood, or black tarry stools.
• Have an open or healing wound
• Have high blood pressure
• Have heart problems
• Have a low calcium level in your blood (hypocalcemia)
• Plan to have any surgery, dental procedure, or have had a recent surgery. You should stop taking Cabometyx at least 3 weeks before planned surgery
• Are pregnant, or plan to become pregnant
• Are breastfeeding or plan to breastfeed.

Pregnancy

Cabometyx can harm your unborn baby.

• If you can become pregnant, your healthcare provider will check your pregnancy status before you start treatment with Cabometyx.
• Females who can become pregnant should use effective birth control (contraception) during treatment and for 4 months after their last dose of Cabometyx.
• Talk to your healthcare provider about birth control methods that may be right for you.
• If you become pregnant or think you are pregnant, tell your healthcare provider right away.

Breastfeeding

It is not known if Cabometyx passes into your breast milk. Do not breastfeed during treatment and for 4 months after your last dose of Cabometyx.

Common Side Effects

The most common side effects of Cabometyx are:

• Tiredness
• Nausea and vomiting
• Constipation
• Decreased appetite
• Weight decreased.

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

• 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. Talk to your healthcare provider if you have concerns about fertility.

Serious side effects and warnings

Cabometyx may cause the following serious side effects.

Bleeding (hemorrhage)

Cabometyx can cause severe bleeding that may lead to death. Tell your healthcare provider right away if you get any signs of bleeding during treatment with Cabometyx, including:

• Coughing up blood or blood clots
• Vomiting blood, or if your vomit looks like coffee grounds
• Red or black (looks like tar) stools
• Menstrual bleeding that is heavier than normal
• Any unusual or heavy bleeding

Perforations and fistulas

Cabometyx can cause a tear in your stomach or intestinal wall (perforation) or an abnormal connection between 2 parts of your body (fistula). Tell your healthcare provider right away if you get tenderness or pain in your stomacharea (abdomen) that is severe, or that does not go away.

Blood clots, stroke, heart attack, and chest pain

Cabometyx may affect the way your blood clots and increase the risk of blood clots, a stroke, heart attack, or chest pain. Get emergency help right away if you get:

• Swelling or pain in your arms or legs
• Shortness of breath
• Feel lightheaded or faint
• Sweating more than usual
• Numbness or weakness of your face, arm or leg, especially on one side of your body
• Sudden confusion, trouble speaking, or understanding
• Sudden trouble seeing in one or both eyes
• Sudden trouble walking
• Dizziness, loss of balance, or coordination
• A sudden severe headache.

High blood pressure (hypertension)

Hypertension is common with Cabometyx and sometimes can be severe. Your healthcare provider will check your blood pressure before starting Cabometyx and regularly during treatment. If needed, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you develop severe headaches, nose bleeds, tiredness or confusion, vision changes, chest pain, trouble breathing, irregular heartbeat, or blood in your urine.

Heart problems

Cabometyx can cause heart failure that may lead to death. Your healthcare provider may check your heart function before and during treatment with Cabometyx. Tell your healthcare provider right away if you get any of the following signs and symptoms:

• Feeling like your heart is pounding, racing, or beating irregularly
• Swelling of your ankles or feet
• Feeling lightheaded
• Shortness of breath
• Tiredness

Diarrhea

Diarrhea is common with Cabometyx and can be severe. If needed, your healthcare provider may prescribe medicine to treat your diarrhea. Tell your healthcare provider right away if you have frequent loose, watery bowel movements.

Hand-foot skin reaction

Hand-foot skin reactions are common with Cabometyx and can be severe. Tell your healthcare provider right away if you have rashes, redness, pain, swelling, or blisters on the palms of your hands or soles of your feet.

Liver problems

Liver problems may happen during treatment with Cabometyx. When Cabometyx is taken in combination with nivolumab, severe changes in liver function tests may happen more often than if you take Cabometyx alone. Your healthcare provider will do blood tests to check your liver function before and during treatment with Cabometyx. Tell your healthcare provider right away if you develop symptoms of liver problems, including yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach-area (abdomen), dark urine, bleeding, or bruising more easily than normal.

Adrenal gland problems

Your healthcare provider will monitor you for this problem. Your healthcare provider may prescribe hormone replacement therapy or corticosteroid medicines if needed. Tell your healthcare provider right away if you develop any of the following signs or symptoms: extreme tiredness, dizziness or fainting, weakness, nausea, or vomiting.

Protein in your urine and possible kidney problems

Symptoms may include swelling in your hands, arms, legs, or feet. Your healthcare provider will check you for this problem during treatment with Cabometyx.

Severe jawbone problems (osteonecrosis)

Your healthcare provider should examine your mouth before you start and during treatment with Cabometyx. Tell your dentist that you are taking Cabometyx. It is important for you to practice good mouth care during treatment with Cabometyx. Tell your healthcare provider right away if you develop any symptoms of jaw problems, including: jaw pain, toothache, or sores on your gums.

Wound healing problems

Wound healing problems have happened in people who take Cabometyx. Tell your healthcare provider if you plan to have any surgery before or during treatment with Cabometyx.

• You should stop taking Cabometyx at least 3 weeks before planned surgery.
• Your healthcare provider should tell you when you may start taking Cabometyx again after surgery.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS)

A condition called reversible posterior leukoencephalopathy syndrome can happen during treatment with Cabometyx. Tell your healthcare provider right away if you have headaches, seizures, confusion, changes in vision, or problems thinking.

Change in thyroid function

Cabometyx can cause changes in your thyroid function, including changes to thyroid hormone levels in your blood. Your healthcare provider will do blood tests to check your thyroid function before and during treatment with Cabometyx.

Decreased calcium level in your blood (hypocalcemia)

Cabometyx can cause you to have a decreased amount of calcium in your blood. Your healthcare provider will do blood tests to check you for this problem and give you calcium if needed. Tell your healthcare provider right away if you get any of the following signs or symptoms:

• Muscle stiffness or muscle spasms
• Sudden weight gain
• Numbness or tingling in your fingers, toes, or around your mouth
• Swelling of your arms, hands, legs, and ankles
• Seizures.

Notes:

Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with Cabometyx if you have certain side effects.

These are not all of the possible side effects of Cabometyx. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Cabometyx (cabozantinib) works by blocking multiple tyrosine kinase enzymes, including MET, VEGFR, AXL, RET, and others. These enzymes regulate normal cell functions but also drive cancer-related processes like tumor growth, spread, blood vessel formation, drug resistance, and tumor microenvironment maintenance.

Cabometyx (cabozantinib) belongs to the drug class called multikinase inhibitors. It may also be called a VEGF/VEGFR inhibitor.

• Administer on an empty stomach at least 1 hour before or at least 2 hours after eating.
• Stop treatment with Cabometyx at least 3 weeks before scheduled surgery, including dental surgery.

Adult Dose of Cabometyx for RCC

• Monotherapy: 60 mg orally once daily
• Combination therapy: 40 mg orally once daily with: nivolumab 240 mg by intravenous infusion every 2 weeks

OR

• nivolumab 480 mg by intravenous infusion every 4 weeks

OR

• nivolumab 600 mg and hyaluronidase 10,000 units subcutaneously every 2 weeks

OR

• nivolumab 1,200 mg and hyaluronidase 20,000 units subcutaneously every 4 weeks

Adult Dose of Cabometyx for HCC

• 60 mg orally once daily

Adult and Pediatric 12+ Dose of Cabometyx for DTC, pNET, epNET

• ≥40 kg: 60 mg orally once daily
• <40 kg: 40 mg orally once daily.

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.

Avoid drinking grapefruit juice, eating grapefruit, or taking supplements that contain grapefruit or St. John’s wort during treatment with Cabometyx.

Tell your healthcare provider about all the medicines you take, including prescription or over-the-counter medicines, vitamins, and herbal supplements. Cabometyx and certain other medicines may affect each other, causing side effects.

Do NOT substitute Cabometyx tablets with cabozantinib capsules.

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

Keep out of the reach of children.

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.

Available as 20 mg, 40 mg, 60 mg, oral tablets.

Cabometyx is manufactured for Exelixis, Inc. Alameda, CA 94502.