This site is intended for US healthcare professionals only

Dosing for CABOMETYX® (cabozantinib) aRCC monotherapy

On This Page:

CABOMETYX aRCC monotherapy dosing1

RECOMMENDED
STARTING DOSE*		 FIRST
REDUCTION		 SECOND
REDUCTION

60 mg
once daily
40 mg
once daily
20 mg
once daily*
RECOMMENDED STARTING DOSE* 60 mg once daily
FIRST REDUCTION 40 mg once daily
SECOND REDUCTION 20 mg once daily*

Tablets shown are not actual size.

*

If previously received 20 mg once daily, resume at same dose. If not tolerated, discontinue CABOMETYX.

Pharmacokinetics

The predicted terminal half-life of CABOMETYX is approximately 99 hours.1

In the CABOSUN and METEOR trials, the mean average daily doses were 49 mg and 45 mg, respectively2

Dose modifications1

You may need to adjust the CABOMETYX dose based on individual patient safety and tolerability.

For intolerable Grade 2 ARs, Grade 3-4 ARs, and ONJ

Withhold CABOMETYX

Wait until improvement or resolution (return to baseline or resolution to Grade 1)

Restart CABOMETYX at a dose reduced by 20 mg
For patients who previously received CABOMETYX at 20 mg once daily:
RESTART CABOMETYX at 20 mg once daily if tolerated; otherwise, DISCONTINUE

  • ONJ occurred in <1% of patients treated with CABOMETYX. Withhold CABOMETYX for development of ONJ until complete resolution
  • Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed
  • Permanently discontinue CABOMETYX for Grade 3 or 4 hemorrhage, development of a GI perforation or Grade 4 fistula, acute myocardial infarction or Grade 2 or higher cerebral infarction, Grade 3 or 4 arterial thromboembolic events or Grade 4 venous thromboembolic events, Grade 4 hypertension/hypertensive crisis or Grade 3 hypertension/hypertensive crisis that cannot be controlled, nephrotic syndrome, or reversible posterior leukoencephalopathy syndrome
  • Modify dose for certain patients with hepatic impairment and patients taking drugs known to strongly induce or inhibit CYP3A4

Recommended administration of CABOMETYX1

Administer on an empty stomach

Administer CABOMETYX at least 1 hour before or at least 2 hours after eating

Swallow CABOMETYX tablet whole

Do not crush, chew, or split CABOMETYX tablets

  • Do not substitute CABOMETYX tablets with cabozantinib capsules

Guidance for your patients if they miss a dose1

If the next scheduled dose is:

IN LESS THAN 12 HOURS

  • Do not make up the missed dose
  • Take the next dose at the usual time

IN 12 HOURS OR MORE

  • Talk to your doctor or nurse if you miss a dose

Recommended dose of CABOMETYX for patients with hepatic impairment1

Child-Pugh B: Reduce the starting dose of CABOMETYX to 40 mg once daily in patients with moderate hepatic impairment.

  • Avoid CABOMETYX in patients with severe hepatic impairment (Child-Pugh C)

When strong CYP3A4 inhibitors cannot be avoided1

When strong CYP3A4 inhibitors cannot be avoided by patients on CABOMETYX + OPDIVO, reduce dose by 20 mg

Reduce the daily dose of CABOMETYX if concomitant use with strong CYP3A4 inhibitors cannot be avoided.

Resume CABOMETYX at the dose used prior to initiating the strong CYP3A4 inhibitor 2-3 days after discontinuation of the strong inhibitor.

Examples of strong CYP3A4 inhibitors†:

  • Boceprevir
  • Clarithromycin
  • Conivaptan
  • Grapefruit juice
  • Indinavir/ritonavir
  • Itraconazole
  • Ketoconazole
  • Lopinavir/ritonavir 
  • Nefazodone
  • Nelfinavir
  • Posaconazole
  • Ritonavir
  • Saquinavir/ritonavir
  • Voriconazole

 

When strong or moderate CYP3A4 inducers cannot be avoided1

When strong CYP3A4 inducers cannot be avoided by patients on CABOMETYX + OPDIVO, increase dose by 20 mg

Increase the daily dose of CABOMETYX if concomitant use with strong or moderate CYP3A4 inducers cannot be avoided.

Resume CABOMETYX at the dose used prior to initiating the strong or moderate CYP3A4 inducer 2-3 days after discontinuation of the strong or moderate inducer.

  • Do not exceed a daily dose of 80 mg
Examples of strong CYP3A4 inducers†:
  • Rifampin
  • Phenytoin
  • Carbamazepine
  • St. John’s wort
Examples of moderate CYP3A4 inducers†:
  • Bosentan 
  • Phenobarbital 
  • Etravirine 
  • Dabrafenib

†Examples listed may not be comprehensive.

Download the CABOMETYX Dosing and Administration Guide

Download

Download the CABOMETYX Treatment Management Guide

Download
Back to Top

AR=adverse reaction; aRCC=advanced renal cell carcinoma; CYP3A4=cytochrome P450 family 3 subfamily A member 4; ONJ=osteonecrosis of the jaw.

References:

  1. CABOMETYX® (cabozantinib) Prescribing Information. Exelixis, Inc.
  2. Data on file. Exelixis, Inc.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: CABOMETYX can cause severe and fatal hemorrhages. The incidence of Grade 3-5 hemorrhagic events was 5% in CABOMETYX patients in RCC, HCC, and DTC studies. Discontinue CABOMETYX for Grade 3-4 hemorrhage and before surgery. Do not administer to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Fistulas, including fatal cases, and gastrointestinal (GI) perforations, including fatal cases, each occurred in 1% of CABOMETYX patients. Monitor for signs and symptoms, and discontinue CABOMETYX in patients with Grade 4 fistulas or GI perforation.

Thrombotic Events: CABOMETYX can cause arterial or venous thromboembolic event. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events have occurred. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 37% (16% Grade 3 and <1% Grade 4) of CABOMETYX patients. In CABINET (n=195), hypertension occurred in 65% (26% Grade 3) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled; when controlled, resume at a reduced dose. Permanently discontinue CABOMETYX for severe hypertension that cannot be controlled with antihypertensive therapy or for hypertensive crisis.

Diarrhea: CABOMETYX can cause diarrhea and it occurred in 62% (10% Grade 3) of treated patients. Monitor and manage patients using antidiarrheals as indicated. Withhold CABOMETYX until improvement to ≤ Grade 1; resume at a reduced dose.

Palmar-Plantar Erythrodysesthesia (PPE): CABOMETYX can cause PPE and it occurred in 45% of treated patients (13% Grade 3). Withhold CABOMETYX until PPE resolves or decreases to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Hepatotoxicity: CABOMETYX in combination with nivolumab in RCC can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone. With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. Monitor liver enzymes before initiation of treatment and periodically. Consider more frequent monitoring as compared to when the drugs are administered as single agents. Consider withholding CABOMETYX and/or nivolumab, initiating corticosteroid therapy, and/or permanently discontinuing the combination for severe or life-threatening hepatotoxicity.

Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Withhold CABOMETYX and/or nivolumab and resume CABOMETYX at a reduced dose depending on severity.

Proteinuria: Proteinuria was observed in 8% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. For Grade 2 or 3 proteinuria, withhold CABOMETYX until improvement to ≤ Grade 1 proteinuria; resume CABOMETYX at a reduced dose. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): CABOMETYX can cause ONJ and it occurred in <1% of treated patients. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures. Withhold CABOMETYX for development of ONJ until complete resolution; resume at a reduced dose.

Impaired Wound Healing: CABOMETYX can cause impaired wound healing. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): CABOMETYX can cause RPLS. Perform evaluation for RPLS and diagnose by characteristic finding on MRI any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Thyroid Dysfunction: CABOMETYX can cause thyroid dysfunction, primarily hypothyroidism, and it occurred in 19% of treated patients (0.4% Grade 3). Assess for signs of thyroid dysfunction prior to the initiation of CABOMETYX and monitor for signs and symptoms during treatment.

Hypocalcemia: CABOMETYX can cause hypocalcemia, with the highest incidence in DTC patients. Based on the safety population, hypocalcemia occurred in 13% of CABOMETYX patients (2% Grade 3 and 1% Grade 4).

Monitor blood calcium levels and replace calcium as necessary during treatment. Withhold and resume CABOMETYX at a reduced dose upon recovery or permanently discontinue CABOMETYX depending on severity.

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women of the potential risk to a fetus and advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the last dose.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions are:

CABOMETYX as a single agent: diarrhea, fatigue, PPE, decreased appetite, hypertension, nausea, vomiting, weight decreased, and constipation.

CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

DRUG INTERACTIONS

Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

Strong or Moderate CYP3A4 Inducers: If coadministration with strong or moderate CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

Pediatric Use: Physeal widening has been observed in children with open growth plates when treated with CABOMETYX. Physeal and longitudinal growth monitoring is recommended in children (12 years and older) with open growth plates. Consider interrupting or discontinuing CABOMETYX if abnormalities occur. The safety and effectiveness of CABOMETYX in pediatric patients less than 12 years of age have not been established.

Please see full Prescribing Information.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

Indications

CABOMETYX® (cabozantinib) is indicated for the treatment of adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET). 

CABOMETYX is indicated for the treatment of adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated extrapancreatic neuroendocrine tumors (epNET)​. 

CABOMETYX, in combination with nivolumab, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC). 

CABOMETYX is indicated for the treatment of patients with advanced renal cell carcinoma (RCC). 

CABOMETYX is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. 

CABOMETYX is indicated for the treatment of adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible.

CABOMETYX® (cabozantinib) is indicated for the treatment of adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET). 

CABOMETYX is indicated for the treatment of adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated extrapancreatic neuroendocrine tumors (epNET)​. 

CABOMETYX, in combination with nivolumab, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC). 

CABOMETYX is indicated for the treatment of patients with advanced renal cell carcinoma (RCC). 

CABOMETYX is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. 

CABOMETYX is indicated for the treatment of adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible.

OPDIVO® and the related logo are registered trademarks of Bristol-Myers Squibb Company.

visual type treatment for Exelixis logo

© 2025 Exelixis, Inc.  04/25 CA-3660