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Monotherapy Dosing

Available in 3 strengths to help you find the right dose for your patients when needed1

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

 

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)

Pharmacokinetics

The predicted terminal half-life of CABOMETYX is approximately 99 hours1


Recommended administration of CABOMETYX1

  • 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


  • Take the missed dose as soon as possible
  • Take the next dose at the usual time

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 20mg

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 severe hemorrhage, development of a GI perforation or Grade 4 fistula, acute myocardial infarction or arterial/venous thromboembolic events that require medical intervention, severe hypertension that cannot be controlled with anti-hypertensive therapy or hypertensive crisis, nephrotic syndrome or RPLS.
  • Modify dose for certain patients with hepatic impairment and patients taking drugs known to strongly induce or inhibit CYP3A4

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

*Examples listed may not be comprehensive.

 

When strong CYP3A4 inducers cannot be avoided1

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

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

  • Do not exceed a daily dose of 80 mg

Examples of strong CYP3A4 inducers:*

  • Rifampin
  • Phenytoin
  • Carbamazepine
  • St. John’s wort

*Examples listed may not be comprehensive.

Download the CABOMETYX Dosing and Administration Guide

Download the CABOMETYX Treatment Management Guide


*

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

AR=adverse reaction; GI=gastrointestinal; ONJ=osteonecrosis of the jaw; RCC=renal cell carcinoma; RPLS=reversible posterior leukoencephalopathy syndrome.

References:

  1. CABOMETYX® (cabozantinib) Prescribing Information. Exelixis, Inc, 2021.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

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

Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 36% (17% Grade 3 and <1% Grade 4) 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 with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Proteinuria: Proteinuria was observed in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. 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, if possible. Withhold CABOMETYX for development of ONJ until complete resolution.

Impaired Wound Healing: Wound complications occurred with CABOMETYX. 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. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

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

ADVERSE REACTIONS

The most commonly reported (≥20%) adverse reactions are: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, vomiting, weight decreased, constipation, and dysphonia.

DRUG INTERACTIONS

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

Strong CYP3A4 Inducers: If coadministration with strong 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.

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

INDICATIONS

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