Drug Detail:Cabometyx (Cabozantinib [ ka-boe-zan-ti-nib ])
Generic Name: cabozantinib s-malate 60mg
Dosage Form: tablet
Drug Class: Multikinase inhibitors VEGF/VEGFR inhibitors
Important Dosage Information
- Stop treatment with CABOMETYX at least 3 weeks prior to scheduled surgery, including dental surgery [see Warnings and Precautions (5.1, 5.10, 5.11)].
- Do not substitute CABOMETYX tablets with cabozantinib capsules.
Recommended Dosage for Renal Cell Carcinoma
The recommended dosage of CABOMETYX as a single agent is 60 mg once daily until disease progression or unacceptable toxicity administered as recommended [see Dosage and Administration (2.9)].
The recommended dosage of CABOMETYX in combination with nivolumab is provided in the following table:
| Recommended Dosage | Duration of Therapy |
|---|---|
| CABOMETYX 40 mg once daily without food | until disease progression or unacceptable toxicity |
| Nivolumab 240 mg every 2 weeks (30-minute intravenous infusion) or 480 mg every 4 weeks (30- minute intravenous infusion) | until disease progression or unacceptable toxicity for up to 2 years |
Recommended Dosage for Hepatocellular Carcinoma
The recommended dosage of CABOMETYX as a single agent is 60 mg once daily until disease progression or unacceptable toxicity administered as recommended [see Dosage and Administration (2.9)].
Recommended Dosage for Differentiated Thyroid Cancer
The recommended dosage of CABOMETYX as a single agent for adult and pediatric patients 12 years of age and older with BSA greater than or equal to 1.2 m2 is 60 mg once daily until disease progression or unacceptable toxicity administered as recommended [see Dosage and Administration (2.9), Clinical Pharmacology (12.3)].
The recommended dosage of CABOMETYX as a single agent in pediatric patients 12 years of age and older with BSA less than 1.2 m2 is 40 mg once daily until disease progression or unacceptable toxicity administered as recommended [see [see Dosage and Administration (2.9), Clinical Pharmacology (12.3)].
Dosage Modifications for Adverse Reactions
Withhold CABOMETYX for:
- Intolerable Grade 2 adverse reactions
- Grade 3 or 4 adverse reactions
- Osteonecrosis of the jaw
Upon resolution/improvement (i.e., return to baseline or resolution to Grade 1) of an adverse reaction, reduce the dose as follows:
| Recommended Dosage | First Dosage Reduction To | Second Dosage Reduction To |
|---|---|---|
|
||
| CABOMETYX 60 mg daily in adult and pediatric patients with BSA greater than or equal to 1.2 m2 | 40 mg daily | 20 mg daily* |
| CABOMETYX 40 mg daily in pediatric patients with BSA less than 1.2 m2 | 20 mg daily | 20 mg every other day* |
| CABOMETYX 40 mg daily in combination with nivolumab | 20 mg daily | 20 mg every other day* |
| Adverse Reaction | Severity* | CABOMETYX Dosage Modification |
|---|---|---|
|
||
| Hemorrhage [see Warnings and Precautions (5.1)] | Grade 3 or 4 |
|
| Perforations and Fistulas [see Warnings and Precautions (5.2)] | Any grade gastrointestinal perforation or Grade 4 fistula |
|
| Thrombotic Events [see Warnings and Precautions (5.3)] | Any grade acute myocardial infarction or Grade 2 or higher cerebral infarction or Grade 3 or 4 arterial thromboembolic events or Grade 4 venous thromboembolic events |
|
| Hypertension and Hypertensive Crisis [see Warnings and Precautions (5.4)] | Grade 3 |
|
| Grade 4 |
|
|
| Diarrhea [see Warnings and Precautions (5.5)] | Grade 2, Grade, or Grade 4 |
|
| Palmar-Plantar Erythrodysesthesia [see Warnings and Precautions (5.6)] | Intolerable Grade 2 or Grade 3 |
|
| Proteinuria [see Warnings and Precautions (5.9)] | Grade 2 or 3 |
|
| Osteonecrosis of the jaw (ONJ) [see Warnings and Precautions (5.10)] | Any grade |
|
| Reversible Posterior Leukoencephalopathy Syndrome [see Warnings and Precautions (5.12)] | Any grade |
|
| Other Adverse Reactions [see Adverse Reactions (6.1)] | Intolerable Grade 2, or Grade 3, or Grade 4 |
|
The following table represents dosage modifications for the drug administered in combination that are different from those described above for CABOMETYX or in the Full Prescribing Information:
|
||
| CABOMETYX in combination with nivolumab | ALT or AST >3 times ULN but ≤10 times ULN with concurrent total bilirubin <2 times ULN | Withhold* both CABOMETYX and nivolumab until adverse reactions recover† to Grades 0 or 1 |
| ALT or AST >10 times ULN or >3 times ULN with concurrent total bilirubin ≥2 times ULN | Permanently discontinue both CABOMETYX and nivolumab | |
When administering CABOMETYX in combination with nivolumab for the treatment of advanced RCC, refer to the nivolumab prescribing information.
Dosage Modifications for Coadministration with Strong CYP3A4 Inhibitors
Reduce the daily CABOMETYX dose by 20 mg (for example, from 60 mg to 40 mg daily or from 40 mg to 20 mg daily or from 20 mg daily to 20 mg every other day in pediatric patients with BSA less than 1.2 m2). Resume the dose that was used prior to initiating the strong CYP3A4 inhibitor 2 to 3 days after discontinuation of the strong inhibitor [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].
Dosage Modifications for Coadministration with Strong CYP3A4 Inducers
Increase the daily CABOMETYX dose by 20 mg (for example, from 60 mg to 80 mg daily or from 40 mg to 60 mg daily) as tolerated. Resume the dose that was used prior to initiating the strong CYP3A4 inducer 2 to 3 days after discontinuation of the strong inducer. Do not exceed a daily dose of 80 mg [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].
Dosage Modifications for Patients with Moderate and Severe Hepatic Impairment
Reduce the starting dose of CABOMETYX 60 mg daily to 40 mg daily or 40 mg daily to 20 mg daily (for pediatric patients with BSA less than 1.2 m2) in patients with moderate hepatic impairment (Child-Pugh B) [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Administration
Do not administer CABOMETYX with food. Administer at least 1 hour before or at least 2 hours after eating [see Clinical Pharmacology (12.3)].
- Swallow CABOMETYX tablets whole. Do not crush CABOMETYX tablets.
- Do not take a missed dose within 12 hours of the next dose.
- Modify the CABOMETYX dose for patients taking drugs known to strongly induce or inhibit CYP3A4 and for patients with moderate hepatic impairment [see Dosage and Administration (2.6, 2.7, 2.8)].
