cabozantinib (Rx)

Brand and Other Names:Cometriq, Cabometyx
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Dosing & Uses

AdultPediatric

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
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              Serious - Use Alternative (56)

              • abametapir

                abametapir will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

              • 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.

              • 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.

              • 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.

              • clozapine

                clozapine 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.

              • desipramine

                desipramine 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.

              • 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.

              • 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 (0)

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                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

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                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; do not administer Cabometyx to patients with risk for severe hemorrhage

                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

                Osteonecrosis of the jaw reported (rare); discontinue at least 28 days prior to invasive dental procedures

                Increases risk of treatment-emergent hypertension; discontinue for severe hypertension that cannot be controlled with antihypertensive therapy

                Palmar-plantar erythrodysesthesia syndrome reported; withhold treatment if needed (see Dosage Modifications)

                Proteinuria may occur

                Fetal harm may occur when administered to a pregnant woman (see Pregnancy)

                Reversible posterior leukoencephalopathy syndrome (RPLS) reported (rare)

                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 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

                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

                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
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                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.

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                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

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                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])

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                Images

                BRAND FORM. UNIT PRICE PILL IMAGE
                Cometriq oral
                -
                100 mg/day(80 mg x1-20 mg x1) capsule
                Cometriq oral
                -
                140 mg/day(80 mg x1-20 mg x3) capsule
                Cometriq oral
                -
                60 mg/day (20 mg x 3/day) capsule
                Cabometyx oral
                -
                40 mg tablet
                Cabometyx oral
                -
                20 mg tablet
                Cabometyx oral
                -
                60 mg tablet

                Copyright © 2010 First DataBank, Inc.

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                Patient Handout

                Patient Education
                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 persist or worsen, 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 worsen any current infections. Avoid contact with people who have infections that may spread to others (such as chickenpox, measles, flu). Consult your doctor if you have been exposed to an infection or for more details.Do not have immunizations/vaccinations without the consent of your doctor. 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 frequently 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. Your doctor may order a pregnancy test before starting this medication. You should not become pregnant while you are using cabozantinib. Cabozantinib may harm an unborn baby. 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 October 2021. Copyright(c) 2021 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.

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                Tier Description
                1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
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                5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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                NC NOT COVERED – Drugs that are not covered by the plan.
                Code Definition
                PA Prior Authorization
                Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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                Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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                Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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                Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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                Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.