Cabometyx

— THERAPEUTIC CATEGORIES —
  • Bladder, kidney, and other urologic cancers
  • Colorectal and other GI cancers
  • Pancreatic, thyroid, and other endocrine cancers

Cabometyx Generic Name & Formulations

General Description

Cabozantinib 20mg, 40mg, 60mg; tabs.

Pharmacological Class

Kinase inhibitor.

How Supplied

Tabs—30

Manufacturer

Generic Availability

NO

Mechanism of Action

Cabozantinib has shown in in vitro biochemical and/or cellular assays to inhibit the tyrosine kinase activity of MET, VEGFR-1, -2 and -3, AXL, RET, ROS1, TYRO3, MER, KIT, TRKB, FLT-3, and TIE-2. These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, drug resistance, and maintenance of the tumor microenvironment.

Cabometyx Indications

Indications

As a single agent for advanced renal cell carcinoma (RCC). In combination with nivolumab for first-line treatment of advanced RCC.

Cabometyx Dosage and Administration

Adult

Swallow whole. Take at least 1hr before or 2hrs after food. As a single agent: 60mg once daily. In combination with nivolumab: 40mg once daily. Continue until disease progression or unacceptable toxicity. Concomitant strong CYP3A4 inhibitors: if unavoidable, reduce daily dose by 20mg; resume dose used prior to starting inhibitor 2–3 days after discontinuation of inhibitor. Concomitant strong CYP3A4 inducers: if unavoidable, increase daily dose by 20mg (max 80mg daily); resume dose used prior to starting inducer 2–3 days after discontinuation of inducer. Moderate hepatic impairment (Child-Pugh B): reduce starting dose by 20mg. Dose modifications for adverse reactions: see full labeling.

Children

Not established.

Cabometyx Contraindications

Not Applicable

Cabometyx Boxed Warnings

Not Applicable

Cabometyx Warnings/Precautions

Warnings/Precautions

Not substitutable with cabozantinib caps. Permanently discontinue if the following occurs: GI perforation, GI fistula (Grade 4), severe hemorrhage (Grade 3/4), acute MI, serious thromboembolic events that require medical intervention, hypertensive crisis or severe hypertension despite optimal medical management, nephrotic syndrome, reversible posterior leukoencephalopathy syndrome; with nivolumab: if AST or AST >10×ULN or >3×ULN with total bilirubin ≥2×ULN. Withhold for intolerable Grade 2 reactions, Grade 3/4 reactions, or osteonecrosis of the jaw; with nivolumab: for ALT or AST >3×ULN but ≤10×ULN with total bilirubin <2×ULN. Recent history of hemorrhage (including hemoptysis, hematemesis, melena): do not administer. Monitor for GI perforations/fistulas. Monitor BP regularly; withhold for hypertension inadequately controlled with medical management; resume at reduced dose when resolved. Higher risk of hepatotoxicity (with nivolumab); monitor liver enzymes prior to initiation and more frequently during treatment; withhold (consider corticosteroid therapy) and resume at reduced dose based on severity. Risk of adrenal insufficiency (with nivolumab); withhold therapy based on severity. Withhold therapy if intolerable Grade 2 diarrhea, unmanageable Grade 3/4 diarrhea, or intolerable Grade 2/3 palmar-plantar erythrodysesthesia (PPE) develops until improvement to Grade 1; resume at reduced dose. Monitor urine protein regularly. Perform oral exam prior to initiation and periodically during therapy. Impaired wound healing: withhold for ≥3 weeks prior to elective surgery (including dental); do not give for ≥2 weeks after major surgery and until adequate healing. Monitor for thyroid dysfunction prior to initiation and during therapy; perform thyroid function tests and manage as clinically indicated. Monitor blood calcium levels during therapy; withhold and resume at reduced dose upon recovery or permanently discontinue based on severity. Severe hepatic impairment (Child-Pugh C): avoid. Severe renal impairment. Embryo-fetal toxicity. Advise females of reproductive potential to use effective contraception during and for 4 months after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 4 months after the last dose).

Cabometyx Pharmacokinetics

Absorption

Median time to peak cabozantinib concentrations: ranged 3–4 hours post-dose. Cabozantinib Cmax and AUC increased by 41% and 57%, respectively, following a high-fat meal relative to fasted conditions.

Distribution

Volume of distribution: ~319 L. Plasma protein bound: ≥99.7%.

Metabolism

Hepatic (CYP3A4).

Elimination

Fecal (~54%). Renal (~27%). Half-life (predicted): ~99 hours. Clearance at steady-state: ~2.2 L/hr.

Cabometyx Interactions

Interactions

Avoid concomitant strong CYP3A4 inhibitors (eg, ketoconazole, grapefruit or grapefruit juice) and strong CYP3A4 inducers (eg, rifampin, St. John's wort); if unavoidable, see Adult dose.

Cabometyx Adverse Reactions

Adverse Reactions

Diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, vomiting, weight decreased, constipation; also with nivolumab: hepatotoxicity, stomatitis, rash, hypothyroidism, musculoskeletal pain, dysgeusia, abdominal pain, cough, upper RTI.

Cabometyx Clinical Trials

See Literature

Cabometyx Note

Not Applicable

Cabometyx Patient Counseling

See Literature

Cabometyx Generic Name & Formulations

General Description

Cabozantinib 20mg, 40mg, 60mg; tabs.

Pharmacological Class

Kinase inhibitor.

How Supplied

Tabs—30

Manufacturer

Generic Availability

NO

Mechanism of Action

Cabozantinib has shown in in vitro biochemical and/or cellular assays to inhibit the tyrosine kinase activity of MET, VEGFR-1, -2 and -3, AXL, RET, ROS1, TYRO3, MER, KIT, TRKB, FLT-3, and TIE-2. These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, drug resistance, and maintenance of the tumor microenvironment.

Cabometyx Indications

Indications

Hepatocellular carcinoma (HCC) in patients who have been previously treated with sorafenib.

Cabometyx Dosage and Administration

Adult

Swallow whole. Take at least 1hr before or 2hrs after food. As a single agent: 60mg once daily. In combination with nivolumab: 40mg once daily. Continue until disease progression or unacceptable toxicity. Concomitant strong CYP3A4 inhibitors: if unavoidable, reduce daily dose by 20mg; resume dose used prior to starting inhibitor 2–3 days after discontinuation of inhibitor. Concomitant strong CYP3A4 inducers: if unavoidable, increase daily dose by 20mg (max 80mg daily); resume dose used prior to starting inducer 2–3 days after discontinuation of inducer. Moderate hepatic impairment (Child-Pugh B): reduce starting dose by 20mg. Dose modifications for adverse reactions: see full labeling.

Children

Not established.

Cabometyx Contraindications

Not Applicable

Cabometyx Boxed Warnings

Not Applicable

Cabometyx Warnings/Precautions

Warnings/Precautions

Not substitutable with cabozantinib caps. Permanently discontinue if the following occurs: GI perforation, GI fistula (Grade 4), severe hemorrhage (Grade 3/4), acute MI, serious thromboembolic events that require medical intervention, hypertensive crisis or severe hypertension despite optimal medical management, nephrotic syndrome, reversible posterior leukoencephalopathy syndrome; with nivolumab: if AST or AST >10×ULN or >3×ULN with total bilirubin ≥2×ULN. Withhold for intolerable Grade 2 reactions, Grade 3/4 reactions, or osteonecrosis of the jaw; with nivolumab: for ALT or AST >3×ULN but ≤10×ULN with total bilirubin <2×ULN. Recent history of hemorrhage (including hemoptysis, hematemesis, melena): do not administer. Monitor for GI perforations/fistulas. Monitor BP regularly; withhold for hypertension inadequately controlled with medical management; resume at reduced dose when resolved. Higher risk of hepatotoxicity (with nivolumab); monitor liver enzymes prior to initiation and more frequently during treatment; withhold (consider corticosteroid therapy) and resume at reduced dose based on severity. Risk of adrenal insufficiency (with nivolumab); withhold therapy based on severity. Withhold therapy if intolerable Grade 2 diarrhea, unmanageable Grade 3/4 diarrhea, or intolerable Grade 2/3 palmar-plantar erythrodysesthesia (PPE) develops until improvement to Grade 1; resume at reduced dose. Monitor urine protein regularly. Perform oral exam prior to initiation and periodically during therapy. Impaired wound healing: withhold for ≥3 weeks prior to elective surgery (including dental); do not give for ≥2 weeks after major surgery and until adequate healing. Monitor for thyroid dysfunction prior to initiation and during therapy; perform thyroid function tests and manage as clinically indicated. Monitor blood calcium levels during therapy; withhold and resume at reduced dose upon recovery or permanently discontinue based on severity. Severe hepatic impairment (Child-Pugh C): avoid. Severe renal impairment. Embryo-fetal toxicity. Advise females of reproductive potential to use effective contraception during and for 4 months after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 4 months after the last dose).

Cabometyx Pharmacokinetics

Absorption

Median time to peak cabozantinib concentrations: ranged 3–4 hours post-dose. Cabozantinib Cmax and AUC increased by 41% and 57%, respectively, following a high-fat meal relative to fasted conditions.

Distribution

Volume of distribution: ~319 L. Plasma protein bound: ≥99.7%.

Metabolism

Hepatic (CYP3A4).

Elimination

Fecal (~54%). Renal (~27%). Half-life (predicted): ~99 hours. Clearance at steady-state: ~2.2 L/hr.

Cabometyx Interactions

Interactions

Avoid concomitant strong CYP3A4 inhibitors (eg, ketoconazole, grapefruit or grapefruit juice) and strong CYP3A4 inducers (eg, rifampin, St. John's wort); if unavoidable, see Adult dose.

Cabometyx Adverse Reactions

Adverse Reactions

Diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, vomiting, weight decreased, constipation; also with nivolumab: hepatotoxicity, stomatitis, rash, hypothyroidism, musculoskeletal pain, dysgeusia, abdominal pain, cough, upper RTI.

Cabometyx Clinical Trials

See Literature

Cabometyx Note

Not Applicable

Cabometyx Patient Counseling

See Literature

Cabometyx Generic Name & Formulations

General Description

Cabozantinib 20mg, 40mg, 60mg; tabs.

Pharmacological Class

Kinase inhibitor.

How Supplied

Tabs—30

Manufacturer

Generic Availability

NO

Mechanism of Action

Cabozantinib has shown in in vitro biochemical and/or cellular assays to inhibit the tyrosine kinase activity of MET, VEGFR-1, -2 and -3, AXL, RET, ROS1, TYRO3, MER, KIT, TRKB, FLT-3, and TIE-2. These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, drug resistance, and maintenance of the tumor microenvironment.

Cabometyx Indications

Indications

As a single agent for patients with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible.

Cabometyx Dosage and Administration

Adult

Swallow whole. Take at least 1hr before or 2hrs after food. ≥12yrs (BSA ≥1.2m2): 60mg once daily; (BSA <1.2m2): 40mg once daily. Continue until disease progression or unacceptable toxicity. Concomitant strong CYP3A4 inhibitors: if unavoidable, reduce daily dose by 20mg; resume dose used prior to starting inhibitor 2–3 days after discontinuation of inhibitor. Concomitant strong CYP3A4 inducers: if unavoidable, increase daily dose by 20mg (max 80mg daily); resume dose used prior to starting inducer 2–3 days after discontinuation of inducer. Moderate hepatic impairment (Child-Pugh B): reduce starting dose by 20mg. Dose modifications for adverse reactions: see full labeling.

Children

<12yrs: not established.

Cabometyx Contraindications

Not Applicable

Cabometyx Boxed Warnings

Not Applicable

Cabometyx Warnings/Precautions

Warnings/Precautions

Not substitutable with cabozantinib caps. Permanently discontinue if the following occurs: GI perforation, GI fistula (Grade 4), severe hemorrhage (Grade 3/4), acute MI, serious thromboembolic events that require medical intervention, hypertensive crisis or severe hypertension despite optimal medical management, nephrotic syndrome, reversible posterior leukoencephalopathy syndrome; with nivolumab: if AST or AST >10×ULN or >3×ULN with total bilirubin ≥2×ULN. Withhold for intolerable Grade 2 reactions, Grade 3/4 reactions, or osteonecrosis of the jaw; with nivolumab: for ALT or AST >3×ULN but ≤10×ULN with total bilirubin <2×ULN. Recent history of hemorrhage (including hemoptysis, hematemesis, melena): do not administer. Monitor for GI perforations/fistulas. Monitor BP regularly; withhold for hypertension inadequately controlled with medical management; resume at reduced dose when resolved. Higher risk of hepatotoxicity (with nivolumab); monitor liver enzymes prior to initiation and more frequently during treatment; withhold (consider corticosteroid therapy) and resume at reduced dose based on severity. Risk of adrenal insufficiency (with nivolumab); withhold therapy based on severity. Withhold therapy if intolerable Grade 2 diarrhea, unmanageable Grade 3/4 diarrhea, or intolerable Grade 2/3 palmar-plantar erythrodysesthesia (PPE) develops until improvement to Grade 1; resume at reduced dose. Monitor urine protein regularly. Perform oral exam prior to initiation and periodically during therapy. Impaired wound healing: withhold for ≥3 weeks prior to elective surgery (including dental); do not give for ≥2 weeks after major surgery and until adequate healing. Monitor for thyroid dysfunction prior to initiation and during therapy; perform thyroid function tests and manage as clinically indicated. Monitor blood calcium levels during therapy; withhold and resume at reduced dose upon recovery or permanently discontinue based on severity. Severe hepatic impairment (Child-Pugh C): avoid. Severe renal impairment. Embryo-fetal toxicity. Advise females of reproductive potential to use effective contraception during and for 4 months after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 4 months after the last dose).

Cabometyx Pharmacokinetics

Absorption

Median time to peak cabozantinib concentrations: ranged 3–4 hours post-dose. Cabozantinib Cmax and AUC increased by 41% and 57%, respectively, following a high-fat meal relative to fasted conditions.

Distribution

Volume of distribution: ~319 L. Plasma protein bound: ≥99.7%.

Metabolism

Hepatic (CYP3A4).

Elimination

Fecal (~54%). Renal (~27%). Half-life (predicted): ~99 hours. Clearance at steady-state: ~2.2 L/hr.

Cabometyx Interactions

Interactions

Avoid concomitant strong CYP3A4 inhibitors (eg, ketoconazole, grapefruit or grapefruit juice) and strong CYP3A4 inducers (eg, rifampin, St. John's wort); if unavoidable, see Adult dose.

Cabometyx Adverse Reactions

Adverse Reactions

Diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, vomiting, weight decreased, constipation; also with nivolumab: hepatotoxicity, stomatitis, rash, hypothyroidism, musculoskeletal pain, dysgeusia, abdominal pain, cough, upper RTI.

Cabometyx Clinical Trials

See Literature

Cabometyx Note

Not Applicable

Cabometyx Patient Counseling

See Literature