Dosing & Uses
Dosage Forms & Strengths
capsule (Cometriq)
- 20mg
- 80mg
tablet (Cabometyx)
- 20mg
- 40mg
- 60mg
Medullary Thyroid Cancer
Cometriq only
Indicated for treatment of progressive, metastatic medullary thyroid cancer (MTC)
140 mg PO qDay
Continue until disease progression or unacceptable toxicity occurs
Renal Cell Carcinoma
Cabometyx only
Combination with nivolumab
- Indicated in combination with nivolumab for first-line treatment of advanced renal cell carcinoma (RCC)
- Cabozantinib 40 mg PO qDay PLUS nivolumab 240 mg IV q2Weeks or 480 mg IV q4Weeks
- Continue until disease progression or unacceptable toxicity
- Nivolumab only: Continue for up to 2 years
Single agent
- Indicated for advanced RC
- 60 mg PO qDay
- Continue until disease progression or unacceptable toxicity occurs
Hepatocellular Carcinoma
Cabometyx only
Indicated for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib
60 mg PO qDay
Continue until disease progression or unacceptable toxicity occurs
Differentiated Thyroid Cancer
Indicated for locally advanced or metastatic differentiated thyroid cancer (DTC) in adults who have progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible
BSA >1.2 m2: 60 mg PO qDay
Continue until disease progression or unacceptable toxicity
Dosage Modifications
Dosage reductions (Cabometyx)
-
Monotherapy with BSA >1.2 m2
- First dose reduction: 40 mg PO qDay
- Second dose reduction: 20 mg PO qDay
- Previously receiving 20 mg qDay: Resume at same dose
- Unable to tolerate 20 mg qDay: Discontinue treatment
-
In combination with nivolumab
- First dose reduction: 20 mg PO qDay
- Second dose reduction: 20 mg PO every other day
- Previously receiving 20 mg every other day: Resume at same dose
- Unable to tolerate 20 mg every other day: Discontinue treatment
Withhold dose until Grade ≤1 or until complete resolution
- Resume at reduced dose
- Grade ≥2 diarrhea
- Grade 3 or intolerable grade 2 palmar-plantar erythrodysesthesia
- Grade 2 or 3 proteinuria
- Any grade osteonecrosis of jaw (ONJ)
- Grade ≥3 or intolerable grade 2 other adverse reactions
Withhold dose until Grade ≤1
-
Cabometyx
- Consider corticosteroid therapy if withheld or discontinued when administered in combination with nivolumab
- ALT or AST >3x ULN but ≤10x ULN with concurrent total bilirubin [TB] <2x ULN
- After recovery, consider rechallenge with one or both of Cabometyx and nivolumab
- If rechallenging with nivolumab with or without Cabometyx, refer to nivolumab prescribing information
Withhold dose until adequately controlled at Grade ≤2
- Resume at reduced dose
- Grade 3 hypertension and hypertensive crisis
Permanently discontinue
- Grades 3 or 4 hemorrhage
- Any grade gastrointestinal perforation
- Grade 4 fistula
- Any grade acute myocardial infarction
- Grade ≥2 cerebral infarction
- Grade 3 or 4 arterial thromboembolic events
- Grade 4 venous thromboembolic events
- Grade 4 hypertension or uncontrolled hypertensive crisis
- Nephrotic syndrome
- Reversible posterior leukoencephalopathy syndrome (RPLS)
- ALT or AST >10x ULN or >3x ULN with concurrent TB ≥2x ULN; permanently discontinue both nivolumab and Cabometyx
CYP3A4 inhibitors
- Avoid coadministration with strong CYP3A4 inhibitors
- Cometriq: If strong CYP3A4 inhibitor required, decrease cabozantinib dose by 40 mg/day (eg, from 140 mg to 100 mg qDay)
- Cabometyx: If strong CYP3A4 inhibitor required, decrease cabozantinib dose by 20 mg/day (eg, from 60 mg to 40 mg qDay)
- Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued
CYP3A4 inducers
- Avoid coadministration of strong CYP3A4 inducers
- Cometriq: If strong CYP3A4 inducer required, increase dose by 40 mg/day (eg, from 140 mg to 180 mg qDay); do not exceed 180 mg/day
- Cabometyx: If strong CYP3A4 inducer required, increase dose by 20 mg/day (eg, from 60 mg to 80 mg qDay); do not exceed 80 mg/day
- Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued
Hepatic impairment
-
Cometriq
- Mild-to-moderate (Child-Pugh A or B): Reduce starting dose to 80 mg/day
- Moderate (Child-Pugh C): Not recommended
-
Cabometyx
- Mild (Child-Pugh A): No dosage adjustment necessary
- Moderate (Child-Pugh B): Reduce starting dose to 40 mg/day
- Severe (Child-Pugh C): Avoid use
Renal impairment
- Mild-to-moderate (CrCl ≥30 mL/min): No dosage adjustment necessary
- Severe (CrCl <30 mL/min): No experience
Dosage Forms & Strengths
tablet (Cabometyx)
- 20mg
- 40mg
- 60mg
Differentiated Thyroid Cancer
Indicated for locally advanced or metastatic differentiated thyroid cancer (DTC) in pediatric patients aged ≥12 years who have progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible
BSA <1.2 m2: 40 mg PO q Day
BSA >1.2 m2: 60 mg PO qDay
Continue until disease progression or unacceptable toxicity
Dosage Modifications
Dosage reductions (Cabometyx)
-
Monotherapy with BSA >1.2 m2
- First dose reduction: 40 mg PO qDay
- Second dose reduction: 20 mg PO qDay
- Previously receiving 20 mg qDay: Resume at same dose
- Unable to tolerate 20 mg qDay: Discontinue treatment
-
Monotherapy with BSA <1.2 m2
- First dose reduction: 20 mg PO qDay
- Second dose reduction: 20 mg PO every other day
- Previously receiving 20 mg every other day: Resume at same dose
- Unable to tolerate 20 mg every other day: Discontinue treatment
Withhold dose until Grade ≤1 or until complete resolution
- Resume at reduced dose
- Grade ≥2 diarrhea
- Grade 3 or intolerable grade 2 palmar-plantar erythrodysesthesia
- Grade 2 or 3 proteinuria
- Any grade osteonecrosis of jaw (ONJ)
- Grade ≥3 or intolerable grade 2 other adverse reactions
Withhold dose until adequately controlled at Grade ≤2
- Resume at reduced dose
- Grade 3 hypertension and hypertensive crisis
Permanently discontinue
- Grades 3 or 4 hemorrhage
- Any grade gastrointestinal perforation
- Grade 4 fistula
- Any grade acute myocardial infarction
- Grade ≥2 cerebral infarction
- Grade 3 or 4 arterial thromboembolic events
- Grade 4 venous thromboembolic events
- Grade 4 hypertension or uncontrolled hypertensive crisis
- Nephrotic syndrome
- Reversible posterior leukoencephalopathy syndrome (RPLS)
CYP3A4 inhibitors
- Avoid coadministration with strong CYP3A4 inhibitors
- Cometriq: If strong CYP3A4 inhibitor required, decrease cabozantinib dose by 40 mg/day (eg, from 140 mg to 100 mg qDay)
- Cabometyx: If strong CYP3A4 inhibitor required, decrease cabozantinib dose by 20 mg/day (eg, from 60 mg to 40 mg qDay)
- Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued
CYP3A4 inducers
- Avoid coadministration of strong CYP3A4 inducers
- Cometriq: If strong CYP3A4 inducer required, increase dose by 40 mg/day (eg, from 140 mg to 180 mg qDay); do not exceed 180 mg/day
- Cabometyx: If strong CYP3A4 inducer required, increase dose by 20 mg/day (eg, from 60 mg to 80 mg qDay); do not exceed 80 mg/day
- Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued
Hepatic impairment
-
Cometriq
- Mild-to-moderate (Child-Pugh A or B): Reduce starting dose to 80 mg/day
- Moderate (Child-Pugh C): Not recommended
-
Cabometyx
- Mild (Child-Pugh A): No dosage adjustment necessary
- Moderate (Child-Pugh B): Reduce starting dose to 40 mg/day
- Severe (Child-Pugh C): Avoid use
Renal impairment
- Mild-to-moderate (CrCl ≥30 mL/min): No dosage adjustment necessary
- Severe (CrCl <30 mL/min): No experience
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (57)
- apalutamide
apalutamide will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
- armodafinil
armodafinil will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- atazanavir
atazanavir will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- bosentan
bosentan will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- carbamazepine
carbamazepine will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- ceritinib
ceritinib will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- chloramphenicol
chloramphenicol will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- clarithromycin
clarithromycin will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- clobazam
clobazam will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- cobicistat
cobicistat will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- conivaptan
conivaptan will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- dabrafenib
dabrafenib will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- darunavir
darunavir will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- dexamethasone
dexamethasone will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- efavirenz
efavirenz will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- enzalutamide
enzalutamide will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- etravirine
etravirine will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- fexinidazole
fexinidazole will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.
- fosamprenavir
fosamprenavir will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- fosphenytoin
fosphenytoin will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- idelalisib
idelalisib will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- imatinib
imatinib will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- indinavir
indinavir will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- isoniazid
isoniazid will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- itraconazole
itraconazole will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- ivosidenib
ivosidenib will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
- ketoconazole
ketoconazole will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- levoketoconazole
levoketoconazole will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- lonafarnib
lonafarnib will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.
- lopinavir
lopinavir will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- lumacaftor/ivacaftor
lumacaftor/ivacaftor will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- mitotane
mitotane will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- nafcillin
nafcillin will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- nefazodone
nefazodone will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- nelfinavir
nelfinavir will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- nevirapine
nevirapine will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- nicardipine
nicardipine will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- oxcarbazepine
oxcarbazepine will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- palifermin
palifermin increases toxicity of cabozantinib by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.
- pentobarbital
pentobarbital will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- phenobarbital
phenobarbital will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- phenytoin
phenytoin will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- posaconazole
posaconazole will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- primidone
primidone will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- quinidine
quinidine will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- rifabutin
rifabutin will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- rifampin
rifampin will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- rifapentine
rifapentine will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- ritonavir
ritonavir will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- saquinavir
saquinavir will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- St John's Wort
St John's Wort will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.
- tipranavir
tipranavir will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- tucatinib
tucatinib will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.
- voriconazole
voriconazole will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.
- voxelotor
voxelotor will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.
Monitor Closely (53)
- abacavir
abacavir will increase the level or effect of cabozantinib by Other (see comment). Use Caution/Monitor. MRP2 inhibitors increase cabozantinib toxicity
- adefovir
adefovir will increase the level or effect of cabozantinib by Other (see comment). Use Caution/Monitor. MRP2 inhibitors increase cabozantinib toxicity
- amiodarone
amiodarone will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- aprepitant
aprepitant will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- belzutifan
belzutifan will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.
- bicalutamide
bicalutamide will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- cenobamate
cenobamate will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
- cidofovir
cidofovir will increase the level or effect of cabozantinib by Other (see comment). Use Caution/Monitor. MRP2 inhibitors increase cabozantinib toxicity
- cimetidine
cimetidine will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- crizotinib
crizotinib will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- crofelemer
crofelemer increases levels of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.
- cyclosporine
cyclosporine will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dichlorphenamide
dichlorphenamide and cabozantinib both decrease serum potassium. Use Caution/Monitor.
- diltiazem
diltiazem will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- doxycycline
doxycycline will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dronedarone
dronedarone will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- duvelisib
duvelisib will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. will increase the level or effect of
- elagolix
elagolix will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.
- encorafenib
encorafenib, cabozantinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
- erythromycin base
erythromycin base will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- erythromycin stearate
erythromycin stearate will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fedratinib
fedratinib will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
- fluconazole
fluconazole will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fosaprepitant
fosaprepitant will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- furosemide
furosemide will increase the level or effect of cabozantinib by Other (see comment). Use Caution/Monitor. MRP2 inhibitors increase cabozantinib toxicity
- grapefruit
grapefruit will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Do not ingest grapefruit or grapefruit juice while taking caboznatinib
- haloperidol
haloperidol will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- iloperidone
iloperidone increases levels of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.
- istradefylline
istradefylline will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
- lamivudine
lamivudine will increase the level or effect of cabozantinib by Other (see comment). Use Caution/Monitor. MRP2 inhibitors increase cabozantinib toxicity
- lapatinib
lapatinib will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lenacapavir
lenacapavir will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- lidocaine
lidocaine will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lorlatinib
lorlatinib will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- metronidazole
metronidazole will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- mifepristone
mifepristone will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If concomitant use necessary, reduce dose of cabozantinib; for patients taking cabozantinib tablets, reduce dose by 20 mg (eg, 60 mg/day to 40 mg/day; 40 mg/day to 20 mg/day); for patients taking cabozantinib capsules, reduce dose by 40 mg (eg, 140 mg/day to 100 mg/day or 100 mg/day to 60 mg/day); resume cabozantinib dose that was used prior to initiating treatment with mifepristone 2 to 3 days after discontinuation of mifepristone
- nevirapine
nevirapine will increase the level or effect of cabozantinib by Other (see comment). Use Caution/Monitor. MRP2 inhibitors increase cabozantinib toxicity
- probenecid
probenecid will increase the level or effect of cabozantinib by Other (see comment). Use Caution/Monitor. MRP2 inhibitors increase cabozantinib toxicity
- ribociclib
ribociclib will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ritonavir
ritonavir will increase the level or effect of cabozantinib by Other (see comment). Use Caution/Monitor. MRP2 inhibitors increase cabozantinib toxicity
- rucaparib
rucaparib will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
- saquinavir
saquinavir will increase the level or effect of cabozantinib by Other (see comment). Use Caution/Monitor. MRP2 inhibitors increase cabozantinib toxicity
- sertraline
sertraline will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- siponimod
siponimod and cabozantinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- stiripentol
stiripentol, cabozantinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
- tazemetostat
tazemetostat will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tecovirimat
tecovirimat will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
- tenofovir AF
tenofovir AF will increase the level or effect of cabozantinib by Other (see comment). Use Caution/Monitor. MRP2 inhibitors increase cabozantinib toxicity
- tetracycline
tetracycline will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ticagrelor
ticagrelor will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- verapamil
verapamil will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
Minor (4)
- acetazolamide
acetazolamide will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
Adverse Effects
Adverse effects are for all grades unless otherwise specified
>10%
Cometriq
- AST, ALT increased (86%)
- Diarrhea (63%)
- Hypertension, treatment-emergent (61%)
- Increased TSH (57%)
- Lymphopenia (53%)
- ALP increased (52%)
- Hypocalcemia (52%)
- Stomatitis (51%)
- Palmar-plantar erythrodysesthesia syndrome (50%)
- Weight decreased (48%)
- Appetite decreased (46%)
- Nausea (43%)
- Fatigue (41%)
- Oral pain (36%)
- Neutropenia (35%)
- Thrombocytopenia (35%)
- Dysgeusia (34%)
- Hair color changes, depigmentation, graying (34%)
- Hypertension (33%)
- Hypophosphatemia (28%)
- Constipation (27%)
- Abdominal pain (27%)
- Hypobilirubinemia (25%)
- Vomiting (24%)
- Asthenia (21%)
- Dysphonia (20%)
- Rash (19%)
- Dry skin (19%)
- Hypomagnesemia (19%)
- Hypokalemia (18%)
- Headache (18%)
- Alopecia (16%)
- Dizziness (14%)
- Arthralgia (14%)
- Palmar-plantar erythrodysesthesia syndrome, Grade 3 or 4 (13%)
- Dysphagia (13%)
- Muscle spasms (12%)
- Dyspepsia (11%)
- Erythema (11%)
Cabometyx
- Diarrhea (74%)
- AST increased (74%)
- ALT increased (68%)
- Creatinine increased (58%)
- Fatigue (56%)
- Triglycerides increased (53%)
- Nauseas (50%)
- Hypophosphatemia (48%)
- Decreased appetite (46%)
- Palmar-plantar erythrodysesthesia syndrome (42%)
- Hypertension (39%)
- Hyperglycemia (37%)
- Hypoalbuminemia (36%)
- ALP increased (35%)
- WBCs decreased (35%)
- Vomiting (32%)
- Hypomagnesemia (31%)
- Weight decreased (31%)
- ANC decreased (31%)
- Hgb decreased (31%)
- Hyponatremia (30%)
- GGT increased (27%)
- Constipation (25%)
- Lymphocytes decreased (25%)
- Platelets decreased (25%)
- Dysgeusia (24%)
- Abdominal pain (23%)
- Rash (23%)
- Stomatitis (22%)
- Hypothyroidism (21%)
- Dysphonia (20%)
- Dyspnea (19%)
- Mucosal inflammation (19%)
- Asthenia (19%)
- Cough (18%)
- Anemia (17%)
- Hypertension, Grade 3-4 (16%)
- Muscle spasms (13%)
- Dyspepsia (12%)
- Proteinuria (12%)
- Diarrhea (11%)
- Dry skin, Grade 3-4 (11%)
- Headache (11%)
- Dizziness (11%)
- Arthralgia (11%)
All grades (DTC)
- LDH increased (90%)
- AST increased (77%)
- ALT increased (66%)
- Diarrhea (51%)
- Palmar-plantar erythrodysesthesia (46%)
- Fatigue (42%)
- Leukocytes decreased (38%)
- Hypocalcemia (36%)
- ALP increased (34%)
- Neutrophils decreased (31%)
- Hypertension (30%)
- GGT increased (26%)
- Stomatitis (26%)
- Platelets decreased (26%)
- Hypomagnesemia (25%)
- Nausea (24%)
- Decreased appetite (23%)
- Hypoalbuminemia (19%)
- Hypokalemia (18%)
- Weight decreased (18%)
- Proteinuria (15%)
- Hyponatremia (15%)
- Vomiting (14%)
- Hyperbilirubinemia (12%)
1-10%
Cometriq
- Hyponatremia (10%)
- Hemorrhoids (9%)
- Musculoskeletal chest pain (9%)
- Anxiety (9%)
- Paresthesia (7%)
- Peripheral sensory neuropathy (7%)
- Dehydration (7%)
- Hyperkeratosis (7%)
- Hypotension (7%)
- Venous thromboembolism (6%)
- Peripheral neuropathy (5%)
- Non-GI fistula (4%)
- GI perforation (3%)
- Arterial thromboembolism (2%)
- Proteinuria (2%)
- GI fistula (1%)
- Osteonecrosis of the jaw (1%)
Cabometyx
- Fatigue, Grade 3-4 (9%)
- Palmar-plantar erythrodysesthesia syndrome, Grade 3-4 (8%)
- Hyponatremia, Grade 3-4 (8%)
- Hypophosphatemia, Grade 3-4 (8%)
- Hypomagnesemia, Grade 3-4 (7%)
- Lymphocytes decreased, Grade 3-4 (7%)
- Anemia, Grade 3-4 (5%)
- GGT decreased, Grade 3-4 (5%)
- Nausea, Grade 3-4 (4%)
- Asthenia, Grade 3-4 (4%)
- Abdominal pain, Grade 3-4 (4%)
- Hgb decreased, Grade 3-4 (4%)
- Triglycerides increased, Grade 3-4 (4%)
- ALT increased, Grade 3-4 (3%)
- AST increased, Grade 3-4 (3%)
- Dyspnea, Grade 3-4 (3%)
- Decreased appetite, Grade 3-4 (3%)
- Proteinuria, Grade 3-4 (2%)
- Vomiting, Grade 3-4 (2%)
- Stomatitis, Grade 3-4 (2%)
- ANC decreased, Grade 3-4 (2%)
- ALP decreased, Grade 3-4 (2%)
- Hypoalbuminemia, Grade 3-4 (2%)
- Hyperglycemia, Grade 3-4 (2%)
All grades (DTC)
- Dry mouth (10%)
- Dysgeusia (10%)
- Headache (10%)
- Dysphonia (10%)
- Pulmonary embolism (5%)
Grade 3 or 4 (DTC)
- LDH increased (10%)
- Fatigue (10%)
- Palmar-plantar erythrodysesthesia (10%)
- Hypertension (10%)
- Hypocalcemia (9%)
- Diarrhea (7%)
- Stomatitis (5%)
- Nausea (3%)
- Decreased appetite (3%)
- Headache (2%)
- Pulmonary embolism (2%)
- ALT increased (2%)
- GGT increased (2%)
- Hypomagnesemia (2%)
- Leukocytes decreased (2%)
- Vomiting (1%)
- Dry mouth (1%)
- Weight decreased (1%)
- Proteinuria (1%)
- AST increased (1%)
- Hypoalbuminemia (1%)
- Hypokalemia (1%)
- Neutrophils decreased (1%)
<1%
Reversible posterior leukoencephalopathy syndrome (RPLS)
Postmarketing Effects
Suprahepatic international normalized ratio and epistaxis (during concomitant use of warfarin)
Vascular disorders: Arterial (including aortic) aneurysms, dissections, and rupture
Thyroid dysfunction
Musculoskeletal and connective tissue disorders: Extremity pain
Warnings
Contraindications
None
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; discontinue therapy for Grade 3 or 4 hemorrhage; do not administer therapy to patients with a recent history of hemorrhage, including hemoptysis, hematemesis, or melena
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
Increases risk of treatment-emergent hypertension; do not initiate therapy in patients with uncontrolled hypertension; monitor blood pressure regularly during treatment; withhold therapy for hypertension that is not adequately controlled with medical management; when controlled, resume therapy at reduced dose; discontinue therapy for severe hypertension that cannot be controlled with anti-hypertensive therapy and for hypertensive crisis
Palmar-plantar erythrodysesthesia syndrome reported; withhold therapy until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE
Proteinuria may occur; monitor urine protein regularly during treatment; for grade 2 or 3 proteinuria, withhold treatment until improvement to ≤ grade 1 proteinuria; resume at reduced dose; discontinue in patients who develop nephrotic syndrome
Fetal harm may occur when administered to a pregnant woman (see Pregnancy)
Reversible posterior leukoencephalopathy syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, reported; perform evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function; discontinue therapy in patients who develop RPLS
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 and resume treatment at reduced dose 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
Physeal widening has been observed in children with open growth plates when treated with this medication; based on limited available data of the effects of therapy on longitudinal growth, physeal, and longitudinal growth monitoring is recommended in children with open growth plates
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
Osteonecrosis of the jaw
- Osteonecrosis of the jaw (ONJ) reported; 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 oral examination prior to initiation of therapy andperiodically during therapy; advise patients regarding good oral hygiene practices; withhold treatment for at least 3 weeks prior to scheduled dental surgery, or invasive dental procedures, if possible; withhold therapy for development of ONJ until complete resolution
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
Pregnancy
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
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Tyrosine kinase inhibitor that targets RET, MET, VEGFR-1, -2, and -3, KIT, TrkB, FLT-3, AXL, and TIE-2 pathways; these tyrosine kinases are involved in both normal cellular function and pathologic processes (eg, oncogenesis, metastasis, tumor angiogenesis, and maintenance of tumor microenvironment)
Absorption
Peak plasma time: 2-5 hr; (Cometriq); 3-4 hr (Cabometyx)
Steady-state achieved: Day 15
A 19% increase in the peak plasma concentration of the tablet formulation (Cabometyx) compared with the capsule formulation (Cometriq)
Effects of food
- High fat meal increases Cmax and AUC by 41% and 57% respectively compared to fasted conditions
Distribution
Protein Bound: ≥99.7%
Vd: 349 L (Cometriq); 319 L (Cabometyx)
Metabolism
Metabolized via hepatic CYP3A4
Metabolites: XL184 N-oxide
CYP3A4 substrate; CYP2C8 inhibitor (noncompetitive), CYP2C9 and CYP2C19 inhibitor (mixed), CYP3A4 (weak competitive); CYP1A1 inducer
P-gp transport inhibitor
Elimination
Half-life: 55 hr (Cometriq); 99 hr (Cabometyx)
Clearance: 4.4 L/hr (Cometriq); 2.2 L/hr (Cabometyx)
Excretion (Cabometyx): 54% feces, 27% urine
Administration
Oral Administration
Do not substitute Cabometyx tablets and Cometriq capsules for one another
Take on empty stomach, do not eat for at least 2 hr before or 1 hr after administration
Swallow capsule or tablet whole; do not chew or empty contents of capsule; do not crush tablet
Do not take a missed dose within 12 hr of the next dose
Do not ingest foods (eg, grapefruit, grapefruit juice) or nutritional supplements known to affect CYP3A4 substrates (eg, St. John’s wort)
Storage
Tablets or capsules: Store at room temperature (20-25°C [68-77°F])
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Cometriq oral - | 100 mg/day(80 mg x1-20 mg x1) capsule |  | |
| Cometriq oral - | 60 mg/day (20 mg x 3/day) capsule |  | |
| Cometriq oral - | 140 mg/day(80 mg x1-20 mg x3) capsule | | |
| Cabometyx oral - | 20 mg tablet |  | |
| Cabometyx oral - | 60 mg tablet |  | |
| Cabometyx oral - | 40 mg tablet |  |
Copyright © 2010 First DataBank, Inc.
Patient Handout
cabozantinib oral
CABOZANTINIB - ORAL
(KA-boe-ZAN-ti-nib)
COMMON BRAND NAME(S): Cabometyx, Cometriq
USES: This medication is used to treat various types of cancer (including kidney, thyroid, liver cancer). Cabozantinib belongs to a class of drugs known as tyrosine kinase inhibitors. It works by slowing or stopping the growth of cancer cells.
HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start taking cabozantinib and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Since different forms of this medication (capsules, tablets) are used to treat different types of cancer, do not change forms of this medication unless directed by your doctor.Take this medication by mouth as directed by your doctor, usually once daily. Do not take with food. Take it on an empty stomach. Do not eat for at least 2 hours before your dose and at least 1 hour after taking it.Swallow this medication whole with a full glass of water (8 ounces/240 milliliters). Do not open or crush the capsules or tablets.Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit can increase the chance of side effects with this medicine. Ask your doctor or pharmacist for more details.Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day.The dosage is based on your medical condition, response to treatment, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products). For children, the dosage is based on their body size. Do not increase your dose or use this drug more often or for longer than prescribed. Your condition will not improve any faster, and your risk of side effects will increase.
SIDE EFFECTS: Dizziness, diarrhea, nausea, vomiting, mouth sores, constipation, stomach pain, tiredness, weakness, weight loss, decreased appetite, taste changes, hoarseness, and lightening of hair color may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Temporary hair loss may occur. Normal hair growth should return after treatment has ended.People using this medication may have serious side effects. However, you have been prescribed this drug because your doctor has judged that the benefit to you is greater than the risk of side effects. Careful monitoring by your doctor may decrease your risk.Cabozantinib may rarely cause serious, possibly fatal, stomach/abdominal side effects such as a hole in the gut wall (perforation) or an abnormal tunnel or connection in your body (fistula). It can also rarely cause serious, possibly fatal, bleeding. Do not take this medication if you have serious bleeding. Get medical help right away if you have unusual or easy bruising/bleeding, signs of stomach/intestinal bleeding (such as bloody/black/tarry stools, stomach/abdominal pain, bloody vomit, vomit that looks like coffee grounds), fever, chills, sudden/severe back pain, severe vomiting/diarrhea, or if you are coughing/gagging/choking when eating or drinking, or coughing up blood.This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high. Your doctor may control your blood pressure with medication.Tell your doctor right away if you have any serious side effects, including: redness/pain/swelling/blisters on the palms of your hands or soles of your feet, frothy urine, swelling of the hands/feet, cold intolerance, slow heartbeat, signs of a low calcium blood level (such as severe muscle spasms, mental/mood changes, seizures), symptoms of a jawbone problem (such as jaw pain, toothache, gum sores), poor wound healing, signs of liver problems (such as yellowing eyes/skin, dark urine).Cabozantinib may also rarely cause a serious brain condition. Get medical help right away if you develop headaches, seizures, vision changes, confusion, or problems thinking.This medication may rarely cause serious problems (such as heart attacks, strokes, deep vein thrombosis, pulmonary embolism) from blood clots. Get medical help right away if you have any very serious side effects, including: chest/jaw/left arm pain, unusual sweating, sudden/severe headache, weakness on one side of your body, confusion, trouble speaking, sudden vision changes (such as partial/complete blindness), pain/redness/swelling in your arms/legs, tingling/weakness/numbness in your face/arms/legs, trouble breathing, coughing up blood, sudden dizziness/fainting.This medication may lower your ability to fight infections. This may make you more likely to get a serious (rarely fatal) infection or make any infection you have worse. Tell your doctor right away if you have any signs of infection (such as sore throat that doesn't go away, fever, chills, cough).When used with the medication nivolumab, cabozantinib may cause your adrenal glands not to work well. Tell your doctor right away if you have any signs of your adrenal glands not working well (such as loss of appetite, unusual tiredness, weight loss).A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Before taking cabozantinib, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, recent bleeding (including coughing up/vomiting blood, bloody/black/tarry stools), high blood pressure, blood vessel problems (such as an aneurysm or a tear/break in the aorta or other blood vessels), open wounds.This drug may make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Cabozantinib can make you more likely to get infections or may make current infections worse. Stay away from anyone who has an infection that may easily spread (such as chickenpox, COVID-19, measles, flu). Talk to your doctor if you have been exposed to an infection or for more details.Tell your health care professional that you are using cabozantinib before having any immunizations/vaccinations. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).To lower the chance of getting cut, bruised, or injured, use caution with sharp objects like razors and nail cutters, and avoid activities such as contact sports.Pain or sores in the mouth and throat may occur. Brush your teeth carefully/gently, avoid using mouthwash that contains alcohol, and rinse your mouth often with cool water. It may also be best to eat soft, moist foods.Some people taking cabozantinib may have serious jawbone problems. Your doctor should check your mouth before you start this medication. Tell your dentist that you are taking this medication before you have any dental work done. To help prevent jawbone problems, have regular dental exams and learn how to keep your teeth and gums healthy. If you have jaw pain, tell your doctor and dentist right away.Before having any surgery (especially dental work), tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products). Your doctor or dentist may tell you to stop taking cabozantinib at least 3 or 4 weeks before surgery. This medication may cause wounds to heal more slowly. Follow all instructions about when to stop or restart this medication.Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while using cabozantinib. Cabozantinib may harm an unborn baby. Your doctor should order a pregnancy test before you start this medication. Ask about reliable forms of birth control while using this medication and for 4 months after the last dose. If you become pregnant, talk to your doctor right away about the risks and benefits of this medication.It is unknown if this drug passes into breast milk. Because of the possible risk to a nursing infant, breast-feeding while using this drug and for 4 months after the last dose is not recommended. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Other medications can affect the removal of cabozantinib from your body, which may affect how cabozantinib works. One example is St. John's wort, among others.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: Do not share this medication with others.Lab and/or medical tests (such as blood pressure, mouth exams, urine protein, liver/thyroid function, calcium blood levels) should be done before you start taking this medication and while you are taking it. Keep all medical and lab appointments. Consult your doctor for more details.
MISSED DOSE: If you miss a dose, take it as soon as you remember if it is more than 12 hours before the next dose. If it is less than 12 hours before the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.
STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
Information last revised May 2023. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
