Cabozantinib

Cabozantinib is a prescription medication used for the treatment of medullary thyroid cancer, renal cell carcinoma, hepatocellular carcinoma and differentiated thyroid cancer.

• Cabozantinib is available under various brand names: Cometriq, Cabometyx.

Common side effects of Cabozantinib include:

• stomach pain,
• nausea,
• vomiting,
• loss of appetite,
• diarrhea,
• constipation,
• pain, redness, swelling, or sores in the mouth or troat,
• trouble speaking,
• changes in taste,
• stuffy nose,
• sneezing,
• sore throat,
• cough,
• rash,
• pain in the muscles, bones, and joints,
• abnormal liver function tests or other blood tests,
• tiredness,
• weight loss, and
• hair color turning lighter.

Serious side effects of Cabozantinib include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• severe stomach pain,
• choking or gagging when you eat or drink,
• severe headache,
• blurred vision,
• pounding in the necks or ears,
• vomiting,
• diarrhea,
• constipation that are severe and ongoing,
• swelling in the hands, arms, legs, or feet,
• easy bruising,
• unusual bleeding (nosebleeds, bleeding gums, heavy menstrual bleeding, any bleeding that will not stop),
• bloody or tarry stools,
• cough with bloody mucus,
• vomit that looks like coffee grounds,
• yellowing of the skin or eyes (jaundice),
• pain, blisters, bleeding, or severe rash in the palms of the hands or the soles of the feet,
• confusion,
• thinking problems,
• weakness,
• vision changes,
• seizures,
• lightheadedness,
• jaw pain or numbness,
• red or swollen gums,
• loose teeth,
• slow healing after dental work,
• fever,
• mouth sores,
• skin sores,
• sore throat,
• cough,
• trouble breathing,
• nausea,
• vomiting,
• extreme tiredness,
• dizziness,
• weakness,
• fainting,
• sudden numbness or weakness on one side of the body,
• problems with vision or balance,
• trouble speaking or understanding sentences,
• chest pain,
• trouble breathing, and
• swelling or pain in an arm or leg

Rare side effects of Cabozantinib include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Capsule (Cometriq)

• 20 mg
• 80 mg

Tablet (Cabometyx)

• 20 mg
• 40 mg
• 60 mg

Medullary Thyroid Cancer

Adult dosage

• 140 mg orally every day

Renal cell carcinoma

Adult dosage

Combination with nivolumab

• Cabozantinib 40 mg orally every day PLUS nivolumab 240 mg IV every 2 weeks or 480 mg IV every 4 weeks
• Continue until disease progression or unacceptable toxicity

Nivolumab only: Continue for up to 2 years

Single agent

• 60 mg orally every day
• Continue until disease progression or unacceptable toxicity occurs

Hepatocellular Carcinoma

Adult dosage

• 60 mg orally every day

Differentiated Thyroid Cancer

Adult dosage

• BSA above 1.2 m2: 60 mg orally every day

Pediatric dosage

• BSA less than 1.2 m2: 40 mg orally every day
• BSA above 1.2 m2: 60 mg orally every day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first

• Cabozantinib has severe interactions with no other drugs.
• Cabozantinib  has serious interactions with at least 57 other drugs.
• Cabozantinib has moderate interactions with at least 53  drugs.
• Cabozantinib has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Cabozantinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Cabozantinib?”

Cautions

• GI perforations and fistulas reported; monitor patients for symptoms of perforations and fistulas, including abscess and discontinue therapy in patients who experience a Grade 4 fistula or a GI perforation
• Serious and fatal hemorrhage reported; do not administer Cabometyx to patients with risk for severe hemorrhage
• Incidence of Grade 3 to 5 hemorrhagic events was 5% in treated patients in RCC and HCC studies
• Thromboembolic events reported; discontinue if acute MI or any other arterial thromboembolic event develops
• May impair wound healing; stop treatment at least 28 days prior to schedules surgery; withhold with dehiscence or wound healing complications requiring medical intervention
• Osteonecrosis of the jaw reported (rare); discontinue at least 28 days prior to invasive dental procedures
• Increases risk of treatment-emergent hypertension; discontinue for severe hypertension that cannot be controlled with antihypertensive therapy
• Palmar-plantar erythrodysesthesia syndrome reported; withhold treatment if needed (see Dosage Modifications)
• Proteinuria may occur
• Fetal harm may occur when administered to a pregnant woman (see Pregnancy)
• Reversible posterior leukoencephalopathy syndrome (RPLS) reported (rare)
• In combination with nivolumab, may cause primary or secondary adrenal insufficiency; initiate symptomatic treatment, including hormone replacement, as clinically indicated; withhold drug and/or nivolumab depending on severity
• Withhold therapy for at least 3 weeks prior to elective surgery; do not administer therapy for at least 2 weeks after major surgery and until adequate wound healing; the safety of resumption of therapy after resolution of wound healing complications not established
• Hypocalcemia may occur; monitor blood calcium levels and replace calcium as necessary during treatment; withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity
• Thyroid dysfunction
  • Thyroid dysfunction, primarily hypothyroidism, observed
  • Assess for signs of thyroid dysfunction before initiating and monitor for signs and symptoms of thyroid dysfunction during treatment
  • Perform thyroid function testing and manage dysfunction as clinically indicated
  • Hepatotoxicity
  • In combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to drug alone
  • Monitor liver enzymes before initiation of and periodically throughout treatment; consider more frequent monitoring of liver enzymes as compared to when drugs are administered as single agents
  • For elevated liver enzymes, interrupt combination with nivolumab and consider administering corticosteroids
• Diarrhea
  • Cabometyx only
    • Diarrhea occurred in 74% of patients treated with Cabometyx and in 28% of patients treated with everolimus
    • Grade 3 diarrhea occurred in 11% of Cabometyx-treated patients and in 2% of everolimus-treated patients (see Dosage Modifications)
• Drug interactions overview
  • CYP3A4 inhibitors
    • Cometriq: Administration of a strong CYP3A4 inhibitor, ketoconazole to healthy subjects increased single-dose plasma cabozantinib exposure by 38%
    • Cabometyx: Coadministration with a strong CYP3A4 inhibitor increased the exposure of cabozantinib, which may increase the risk of exposure-related adverse reactions
  • CYP3A4 inducers
    • Cometriq: Administration of a strong CYP3A4 inducer, rifampin to healthy subjects decreased single-dose plasma cabozantinib exposure by 77%
    • Cabometyx: Coadministration with a strong CYP3A4 inducer decreased the exposure of cabozantinib, which may reduce efficacy

Pregnancy & Lactation

• Based on its mechanism of action, can cause fetal harm when administered to pregnant women
• Verify pregnancy status of females of reproductive potential before initiation
• Advise females of reproductive potential to use effective contraception during treatment and for 4 months after the final dose
• May impair male and female fertility
• Lactation
  • Unknown whether distributed in breast milk
  • Because of potential for serious adverse reactions in a breastfed infant from cabozantinib, advise females of reproductive potential to not breastfeed during treatment and for 4 months after the final dose