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

Recommended
starting dose

down
60mg

First reduction

down
40mg

Second reduction

20mg

Tablets shown are not actual size.

  • Do not substitute CABOMETYX tablets with cabozantinib capsules

Pharmacokinetics

  • The predicted terminal half-life is approximately 99 hours
Dosing

Support your patients who may require a dose reduction

Download the form
Dosing

Exelixis Access Services® (EASE) enrollment, including co-pay and Patient Assistance Program (PAP)

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You may need to adjust the CABOMETYX dose based on individual patient safety and tolerability1

If ARs occur, consider supportive care and/or adjust the dose

FOR GRADE 4 OR INTOLERABLE GRADE ≤3 ARs THAT REQUIRE A DOSE REDUCTION

withhold next
 

Withhold

CABOMETYX

next
withhold next
 

Wait

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

next
withhold
 

Restart

For patients who previously received 60 mg or 40 mg: RESTART CABOMETYX at a dose reduced by 20 mg

Resume

For patients who previously received 20 mg: RESUME CABOMETYX at 20 mg if tolerated; otherwise, DISCONTINUE

 

  • Permanently discontinue CABOMETYX for development of unmanageable fistula or GI perforation, severe hemorrhage, arterial thromboembolic event, hypertensive crisis or severe hypertension despite optimal medical management, nephrotic syndrome, or reversible posterior leukoencephalopathy syndrome

The overall efficacy results in the CABOMETYX trials were achieved in the context of dose adjustments and reductions1,2

GI=gastrointestinal.

Dosing

Additional details around dosing and administration

Download the guide
Dosing

Support your patients who may require a dose reduction

Download the form

Holding and reducing the dose can help to manage ARs with CABOMETYX1

  • In the first-line trial, discontinuation rates due to ARs were similar between CABOMETYX (21%) and sunitinib (22%)
  • In the second-line trial, discontinuation rates due to ARs were similar between CABOMETYX (10%) and everolimus (10%)

The overall efficacy results with CABOMETYX across both trials were achieved in the context of dose adjustments and reductions1,2

Recommended administration of CABOMETYX

How to take CABOMETYX

DO NOT EAT
for at least 2 hours before
Swallow whole
DO NOT CRUSH
8 oz of water
DO NOT EAT
for at least
1 hour after
  • Do not substitute CABOMETYX tablets with cabozantinib capsules

 

Guidance for your patients if they miss a dose

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
  • Do not ingest foods (eg, grapefruit or grapefruit juice) or nutritional supplements that are known to inhibit cytochrome P450 during CABOMETYX treatment
  • A high-fat meal increased Cmax and AUC values by 41% and 57%, respectively, relative to fasting conditions in healthy subjects administered a single 140-mg oral dose of cabozantinib capsules

AUC=area under the curve.

Drug Interactions

When strong CYP3A4 inhibitors cannot be avoided1

Reduce Dose by 20mg

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

 

  • Resume previous dose of CABOMETYX after discontinuing a strong CYP3A4 inhibitor for 2 to 3 days1

Examples of strong CYP3A4 inhibitors1

Boceprevir, clarithromycin, conivaptan, grapefruit juice,* indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, and voriconazole.

When strong CYP3A4 inducers cannot be avoided1

Reduce Dose by 20mg

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

 

  • Resume previous dose of CABOMETYX after discontinuing a strong CYP3A4 inducer for 2 to 3 days1
    • The daily dose of CABOMETYX should not exceed 80 mg

Examples of strong CYP3A4 inducers1

Rifampin, phenytoin, carbamazepine, phenobarbital, rifabutin, rifapentine, and St. John’s Wort.†

*The effect of grapefruit juice varies widely among brands and is concentration-, dose-, and preparation-dependent. Studies have shown that it can be classified as a “strong CYP3A inhibitor” when a certain preparation is used (eg, high dose, double strength) or as a “moderate CYP3A inhibitor” when another preparation is used (eg, low dose, single strength).
The effect of St. John’s Wort varies widely and is preparation-dependent.

 

 

INDICATION

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

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: Severe and fatal hemorrhages have occurred with CABOMETYX. In RCC trials, the incidence of Grade ≥3 hemorrhagic events was 3% in CABOMETYX patients. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.

Gastrointestinal (GI) Perforations and Fistulas: In RCC trials, GI perforations were reported in 1% of CABOMETYX patients. Fatal perforations occurred in patients treated with CABOMETYX. In RCC studies, fistulas were reported in 1% of CABOMETYX patients. Monitor patients for symptoms of perforations and fistulas, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a GI perforation or a fistula that cannot be appropriately managed.

Thrombotic Events: Thrombotic events increased with CABOMETYX. In RCC trials, venous thromboembolism occurred in 9% (including 5% pulmonary embolism) and arterial thromboembolism occurred in 1% of CABOMETYX patients. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.

Hypertension and Hypertensive Crisis: Treatment-emergent hypertension, including hypertensive crisis, increased with CABOMETYX. In RCC trials, hypertension was reported in 44% (18% Grade ≥3) of CABOMETYX patients. Monitor blood pressure prior to initiation and regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX if there is evidence of hypertensive crisis or for severe hypertension that cannot be controlled with antihypertensive therapy or medical management.

Diarrhea: In RCC trials, diarrhea occurred in 74% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume CABOMETYX at a reduced dose.

Palmar-Plantar Erythrodysesthesia (PPE): In RCC trials, PPE occurred in 42% of CABOMETYX patients. Grade 3 PPE occurred in 8% of CABOMETYX patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPE or Grade 3 PPE until improvement to Grade 1; resume CABOMETYX at a reduced dose.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. 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 of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during CABOMETYX treatment and for 4 months after the last dose.

ADVERSE REACTIONS

The most commonly reported (≥25%) adverse reactions were: diarrhea, fatigue, nausea, decreased appetite, hypertension, PPE, weight decreased, vomiting, dysgeusia, and stomatitis.

DRUG INTERACTIONS

Strong CYP3A4 Inhibitors: If concomitant use with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage.

Strong CYP3A4 Inducers: If concomitant use with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage.

USE IN SPECIFIC POPULATIONS

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

Hepatic Impairment: In patients with mild to moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.

Please see accompanying full Prescribing Information.

References: 1. CABOMETYX® (cabozantinib) Prescribing Information. Exelixis, Inc, 2017. 2. Data on file. Exelixis, Inc.