Note: Do not substitute cabozantinib tablets (Cabometyx) and capsules (Cometriq). Cabozantinib is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea/vomiting (ASCO [Hesketh 2020]). Withhold cabozantinib treatment for at least 3 weeks prior to scheduled surgery (including dental surgery or invasive dental procedures); do not administer cabozantinib for at least 2 weeks after major surgery and until adequate wound healing. Do not use cabozantinib in patients with a recent history of hemorrhage (including hemoptysis, hematemesis, or melena). Do not initiate cabozantinib in patients with uncontrolled hypertension.
Hepatocellular carcinoma, advanced: Cabometyx: Oral: 60 mg once daily until disease progression or unacceptable toxicity (Abou-Alfa 2018).
Renal cell carcinoma, advanced, first-line combination therapy (Cabometyx):
Note: May be used in combination with nivolumab regardless of risk stratification (Choueiri 2021).
Oral: 40 mg once daily (in combination with nivolumab); continue until disease progression or unacceptable toxicity (Choueiri 2021).
Renal cell carcinoma, advanced, single-agent therapy (Cabometyx):
Note: May be used in patients who are ineligible for (or who decline) initial treatment with immunotherapy-based combinations, as well as in those with progression after initial immunotherapy-based options or other VEGFR tyrosine kinase inhibitors (Choueiri 2016; George 2022; McGregor 2020).
Oral: 60 mg once daily until disease progression or unacceptable toxicity (Choueiri 2015; Choueiri 2017).
Thyroid cancer, differentiated, locally advanced or metastatic: Cabometyx: Oral: 60 mg once daily until disease progression or unacceptable toxicity (Brose 2021).
Thyroid cancer, medullary, metastatic: Cometriq: Oral: 140 mg once daily until disease progression or unacceptable toxicity (Schlumberger 2017).
Missed doses: Do not take a missed dose within 12 hours of the next dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Renal impairment prior to treatment initiation :
Note: The estimated glomerular filtration rate (eGFR) is estimated using MDRD (modification of diet in renal disease) equation.
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <30 mL/minute/1.73 m2 or dialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Renal toxicity during treatment:
Proteinuria, grade 2 or 3: Withhold cabozantinib until improvement to ≤ grade 1 proteinuria, then resume at a reduced dose.
Nephrotic syndrome: Permanently discontinue cabozantinib.
Hepatic impairment prior to treatment initiation:
Mild impairment (Child-Pugh class A):
Cabometyx: No dosage adjustment is necessary
Cometriq: Reduce the initial dose to 80 mg once daily.
Moderate impairment (Child-Pugh class B):
Cabometyx:
Initial dose 60 mg once daily: Reduce dose to 40 mg once daily.
Initial dose 40 mg once daily: Reduce dose to 20 mg once daily.
Cometriq: Reduce the initial dose to 80 mg once daily.
Severe impairment (Child-Pugh class C): Avoid use (has not been studied).
Hepatotoxicity during treatment (when used in combination with nivolumab [Cabometyx]):
ALT or AST >3 to ≤10 times ULN with concurrent total bilirubin <2 times ULN: Withhold both cabozantinib and nivolumab; consider corticosteroid therapy. Upon recovery to grade 0 or 1, may consider rechallenging with cabozantinib (at a reduced dose based on the severity) and/or nivolumab.
ALT or AST >10 times ULN or >3 times ULN with concurrent total bilirubin ≥2 times ULN: Permanently discontinue both cabozantinib and nivolumab; consider corticosteroid therapy.
(For additional information see "Cabozantinib: Pediatric drug information")
Note: Do not substitute cabozantinib tablets (Cabometyx) and capsules (Cometriq). Antiemetics are recommended as clinically appropriate for the prophylaxis and treatment of nausea and vomiting (Brose 2021). Withhold cabozantinib treatment for at least 3 weeks prior to scheduled surgery (including dental surgery or invasive dental procedures); do not administer cabozantinib for at least 2 weeks after major surgery and until adequate wound healing. Do not use cabozantinib in patients with a recent history of hemorrhage (including hemoptysis, hematemesis, or melena).
Thyroid cancer, differentiated, locally advanced or metastatic:
Cabometyx: Children ≥12 years and Adolescents:
BSA <1.2 m2: Oral: 40 mg once daily until disease progression or unacceptable toxicity.
BSA ≥1.2 m2: Oral: 60 mg once daily until disease progression or unacceptable toxicity.
Dosage adjustment for toxicity: Cabometyx:
|
Initial Dosage |
First Dosage Reduction |
Second Dosage Reduction |
|---|---|---|
|
a If previously receiving the lowest dose, resume at the same dose. If lowest dose is not tolerated, discontinue cabozantinib. | ||
|
40 mg once daily |
20 mg once daily |
20 mg every other daya |
|
60 mg once daily |
40 mg once daily |
20 mg once dailya |
|
Adverse Reaction |
Severity |
Cabometyx Dosage Modification |
|---|---|---|
|
GI toxicity: Diarrhea |
Any grade |
Manage with antidiarrheals as indicated. |
|
Grades 2, 3, or 4 |
Withhold cabozantinib until ≤ grade 1, then resume at a reduced dose. | |
|
GI toxicity: Perforation or fistulas |
GI perforation (any grade) or grade 4 fistula |
Permanently discontinue cabozantinib. |
|
Hemorrhage |
Grade 3 or 4 |
Permanently discontinue cabozantinib. |
|
Hypertension |
Grade 3 |
Withhold cabozantinib until hypertension is adequately controlled to ≤ grade 2, then resume at a reduced dose. Permanently discontinue cabozantinib for hypertension that cannot be controlled. |
|
Grade 4 |
Permanently discontinue cabozantinib. | |
|
Hypertensive crisis |
Permanently discontinue cabozantinib. | |
|
Hypocalcemia |
Any |
Replace calcium as necessary during treatment. Depending on the severity, withhold cabozantinib and resume at a reduced dose upon recovery or permanently discontinue. |
|
Osteonecrosis of the jaw |
Any grade |
Withhold cabozantinib until complete resolution, then resume at a reduced dose. |
|
Palmar-plantar erythrodysesthesia |
Grade 2 (intolerable) or grade 3 |
Withhold cabozantinib until ≤ grade 1, then resume at a reduced dose. |
|
Reversible posterior leukoencephalopathy syndrome |
Any grade |
Permanently discontinue cabozantinib. |
|
Thromboembolic events |
Acute myocardial infarction (any grade), cerebral infarction (≥ grade 2), arterial thromboembolic events (grade 3 or 4), venous thromboembolic events (grade 4) |
Permanently discontinue cabozantinib. |
|
Thyroid dysfunction |
Any |
Manage thyroid dysfunction as clinically indicated. |
|
Wound healing complications |
Any |
Withhold cabozantinib treatment for at least 3 weeks prior to scheduled surgery (including dental surgery or invasive dental procedures); do not administer cabozantinib for at least 2 weeks after major surgery and until adequate wound healing. The safety of resuming cabozantinib after resolution of wound healing complications has not been established. |
|
Other adverse reactions |
Grade 2 (intolerable), grade 3 or 4 |
Withhold cabozantinib until ≤ grade 1 or baseline, then resume at a reduced dose. |
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Renal impairment prior to treatment initiation :
Children ≥12 years and Adolescents: Cabometyx: Oral:
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <30 mL/minute/1.73 m2 or dialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Renal toxicity during treatment:
Proteinuria, grade 2 or 3: Withhold cabozantinib until improvement to ≤ grade 1 proteinuria, then resume at a reduced dose.
Nephrotic syndrome: Permanently discontinue cabozantinib.
Hepatic impairment prior to treatment initiation: Cabometyx: Children ≥12 years and Adolescents: Oral:
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B):
BSA <1.2 m2: Reduce initial dose to 20 mg once daily.
BSA ≥1.2 m2: Reduce initial dose to 40 mg once daily.
Severe impairment (Child-Pugh class C): Avoid use (has not been studied).
|
Initial dose |
First dose reduction |
Second dose reduction |
|---|---|---|
|
a If previously receiving the lowest dose, resume at the same dose. If lowest dose is not tolerated, discontinue cabozantinib. | ||
|
Cabometyx | ||
|
60 mg once daily |
40 mg once daily |
20 mg once dailya |
|
40 mg once daily (in combination with nivolumab) |
20 mg once daily |
20 mg every other daya |
|
Cometriq | ||
|
140 mg once daily |
100 mg once daily |
60 mg once dailya |
|
Adverse reaction |
Severity |
Cabobetyx dosage modification |
|---|---|---|
|
Adrenal insufficiency (when used in combination with nivolumab) |
≥ grade 2 |
Initiate symptomatic treatment (including hormone replacement therapy as clinically indicated). Withhold cabozantinib (and/or nivolumab); resume cabozantinib at a reduced dose depending on the severity. |
|
GI toxicity: Diarrhea |
Any grade |
Manage with antidiarrheals as indicated. |
|
Grade 2, 3, or 4 |
Withhold cabozantinib until ≤ grade 1, then resume at a reduced dose. | |
|
GI toxicity: Perforation or fistulas |
GI perforation (any grade) or grade 4 fistula |
Permanently discontinue cabozantinib. |
|
Hematologic toxicity (Cometriq) |
Grade 4 |
Withhold cabozantinib; upon return to baseline or improvement to grade 1, resume at a reduced dose. |
|
Hemorrhage |
Grade 3 or 4 |
Permanently discontinue cabozantinib. |
|
Hypertension |
Grade 3 |
Withhold cabozantinib until hypertension is adequately controlled to ≤ grade 2, then resume at a reduced dose. Permanently discontinue cabozantinib for hypertension that cannot be controlled. |
|
Grade 4 |
Permanently discontinue cabozantinib. | |
|
Hypertensive crisis |
Permanently discontinue cabozantinib. | |
|
Hypocalcemia |
Any |
Replace calcium as necessary during treatment. Depending on the severity, withhold cabozantinib and resume at a reduced dose upon recovery or permanently discontinue. |
|
Osteonecrosis of the jaw |
Any grade |
Withhold cabozantinib until complete resolution, then resume at a reduced dose. |
|
Palmar-plantar erythrodysesthesia |
Grade 2 (intolerable) or grade 3 |
Withhold cabozantinib until ≤ grade 1, then resume at a reduced dose. |
|
Reversible posterior leukoencephalopathy syndrome |
Any grade |
Permanently discontinue cabozantinib. |
|
Thromboembolic events |
Acute myocardial infarction (any grade), cerebral infarction (≥ grade 2), arterial thromboembolic events (grade 3 or 4), venous thromboembolic events (grade 4) |
Permanently discontinue cabozantinib. |
|
Thyroid dysfunction |
Any |
Manage thyroid dysfunction as clinically indicated. |
|
Wound healing complications |
Any |
Withhold cabozantinib treatment for at least 3 weeks prior to scheduled surgery (including dental surgery or invasive dental procedures); do not administer cabozantinib for at least 2 weeks after major surgery and until adequate wound healing. The safety of resuming cabozantinib after resolution of wound healing complications has not been established. |
|
Other adverse reactions |
Grade 2 (intolerable), 3, or 4 |
Withhold cabozantinib until ≤ grade 1 or baseline, then resume at a reduced dose. |
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Kit, Oral:
Cometriq (100 MG Daily Dose): Capsules: 100 mg daily-dose: 80 mg (7s) and 20 mg (7s)
Cometriq (140 MG Daily Dose): Capsules: 140 mg daily-dose: 80 mg (7s) and 20 mg (21s)
Cometriq (60 MG Daily Dose): Capsules: 60 mg daily-dose: 20 mg (21s)
Tablet, Oral:
Cabometyx: 20 mg, 40 mg, 60 mg
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Cabometyx: 20 mg, 40 mg, 60 mg
Contact Exelixus Access Services for information on obtaining cabozantinib (855-253-3273).
Oral: Do not administer with food; administer on an empty stomach (at least 1 hour before or 2 hours after eating). Note: The prescribing information (for Cometriq) describes when to give food with respect to cabozantinib; no food should be consumed for at least 2 hours before or for at least 1 hour after the cabozantinib dose. Swallow whole; do not open capsules or crush tablets. Do not substitute cabozantinib tablets and capsules.
Cabozantinib is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea/vomiting (ASCO [Hesketh 2020]).
Oral: Administer on an empty stomach (at least 1 hour before or 2 hours after eating). Swallow whole; do not crush tablets. Do not substitute cabozantinib tablets and capsules. Antiemetics are recommended as clinically appropriate for the prophylaxis and treatment of nausea and vomiting (Brose 2021).
Missed doses: Do not take a missed dose within 12 hours of the next dose.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Hepatocellular carcinoma, advanced (Cabometyx): Treatment of hepatocellular carcinoma (HCC) in patients who have previously been treated with sorafenib.
According to guidelines from the American Society of Clinical Oncology for systemic therapy for advanced HCC, cabozantinib is a potential second-line therapy option in patients who received atezolizumab and bevacizumab as first-line therapy, although sorafenib or lenvatinib are preferred in this setting. Cabozantinib is also a second-line therapy option in patients who received first-line therapy with sorafenib or lenvatinib (ASCO [Gordan 2020]).
Renal cell carcinoma, advanced (Cabometyx):
First-line treatment (in combination with nivolumab) of advanced renal cell carcinoma (RCC).
Treatment (monotherapy) of advanced RCC.
Thyroid cancer, differentiated, locally advanced or metastatic (Cabometyx): Treatment of locally advanced or metastatic differentiated thyroid cancer that has progressed following VEGFR-targeted therapy in adults and pediatric patients ≥12 years of age who are radioactive iodine-refractory or ineligible.
Thyroid cancer, medullary (Cometriq): Treatment of progressive, metastatic medullary thyroid cancer.
Cabozantinib may be confused with axitinib, bosutinib, cabazitaxel, capecitabine, capmatinib, ceritinib, cobimetinib, crizotinib, dasatinib, imatinib, lenvatinib, nilotinib, ponatinib, regorafenib, ruxolitinib, vandetanib, vemurafenib.
Cabometyx may be confused with Cometriq, Copiktra.
Cometriq may be confused with CoQ10 (abbreviation often used for coenzyme Q10).
This medication is in a class the Institute for Safe Medical Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Cabozantinib tablets (Cabometyx) and capsules (Cometriq) are NOT interchangeable; do NOT substitute.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions report in adults.
>10%:
Cardiovascular: Hypertension (30% to 61%, including hypertensive crisis)
Dermatologic: Alopecia (16%), erythema of skin (11%), hair discoloration (34%), palmar-plantar erythrodysesthesia (42% to 50%), skin rash (19% to 23%), xeroderma (11% to 19%)
Endocrine & metabolic: Hyperglycemia (37%), hypoalbuminemia (19% to 51%), hypocalcemia (8% to 52%), hypokalemia (18% to 23%), hypomagnesemia (19% to 31%), hyponatremia (10% to 30%), hypophosphatemia (25% to 48%), hypothyroidism (8% to 21%), increased gamma-glutamyl transferase (26% to 27%), increased lactate dehydrogenase (84% to 90%), increased serum triglycerides (53%), weight loss (17% to 48%)
Gastrointestinal: Abdominal pain (23% to 27%), constipation (25% to 27%), decreased appetite (23% to 48%), diarrhea (51% to 74%; grades 3/4: 7% to 11%), dysgeusia (10% to 34%), dyspepsia (10% to 12%), dysphagia (13%), increased serum amylase (16%), mucosal swelling (14% to 19%), nausea (24% to 50%; grades 3/4: 2% to 4%), stomatitis (13% to 51%; grades 3/4: 2% to 5%), vomiting (14% to 32%; grades 3/4: ≤2%)
Genitourinary: Proteinuria (2% to 15%)
Hematologic & oncologic: Anemia (17% to 31%; grades 3/4: 4% to 5%), leukopenia (35%; grades 3/4: <1%), lymphocytopenia (25% to 53%; grades 3/4: 7% to 16%), neutropenia (31% to 43% grades 3/4: 2% to 7%), thrombocytopenia (25% to 35%; grades 3/4: <1%)
Hepatic: Hyperbilirubinemia (12% to 25%), increased serum alanine aminotransferase (66% to 86%), increased serum alkaline phosphatase (34% to 52%), increased serum aspartate aminotransferase (73% to 86%)
Nervous system: Dizziness (11% to 14%), fatigue (41% to 56%), headache (10% to 18%), mouth pain (36%), voice disorder (10% to 20%)
Neuromuscular & skeletal: Arthralgia (11% to 14%), asthenia (19% to 22%), limb pain (9% to 14%), muscle spasm (8% to 13%)
Renal: Increased serum creatinine (58%)
Respiratory: Cough (18%), dyspnea (12% to 19%)
1% to 10%:
Cardiovascular: Arterial thromboembolism (2%), hypotension (7%), pulmonary embolism (4% to 5%), venous thromboembolism (6% to 7%)
Dermatologic: Hyperkeratosis (7%)
Endocrine & metabolic: Dehydration (7%)
Gastrointestinal: Gastrointestinal fistula (1%), gastrointestinal perforation (1% to 3%), hemorrhoids (9%), xerostomia (10%)
Hematologic & oncologic: Hemorrhage (grades ≥3: 3% to 5%)
Nervous system: Anxiety (9%), paresthesia (7%), peripheral neuropathy (5%), peripheral sensory neuropathy (7%)
Neuromuscular & skeletal: Musculoskeletal chest pain (9%), osteonecrosis of the jaw (≤1%)
Respiratory: Pleural effusion (≥2%)
Miscellaneous: Fistula (nongastrointestinal: 1% to 4%; includes transesophageal fistula), postoperative wound complication (2%)
<1%:
Gastrointestinal: Pancreatitis
Hepatic: Cholestatic hepatitis
Nervous system: Reversible posterior leukoencephalopathy syndrome, seizure
Frequency not defined: Genitourinary: Nephrotic syndrome
Postmarketing: Cardiovascular: Aneurysm (arterial), aortic aneurysm, aortic dissection, coronary artery dissection, myocardial rupture (arterial rupture and aortic rupture)
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to cabozantinib or any component of the formulation.
Concerns related to adverse effects:
• Adrenal insufficiency: Primary and secondary adrenal insufficiency have occurred with the combination of cabozantinib and nivolumab, including cases of grade 2 to 3 adrenal insufficiency. The majority of patients received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in approximately one-fourth of patients. In cases where cabozantinib and nivolumab were withheld for adrenal insufficiency, most reinitiated treatment after symptom improvement with recurrence of adrenal insufficiency in some patients.
• Dermatologic toxicity: Palmar-plantar erythrodysesthesia syndrome occurred in nearly half of patients; grade 3 events were reported.
• GI toxicity: Diarrhea has been commonly observed in cabozantinib-treated patients; grade 3 and 4 diarrhea has occurred. GI perforations and fistulas (including fatal cases) have been reported with cabozantinib. Tracheal/esophageal fistulas were also noted; some cases were fatal.
• Hemorrhage: Severe and fatal hemorrhages have occurred with cabozantinib, including grade 3 or higher events.
• Hepatotoxicity: Increased frequencies of grade 3 and 4 ALT and AST elevations may occur when cabozantinib is administered in combination with nivolumab (compared to cabozantinib alone). ALT or AST elevations may recur when rechallenged with cabozantinib and/or nivolumab.
• Hypertension: Cabozantinib may increase the risk of treatment-emergent hypertension. Stage 1 and 2 hypertension were commonly seen in cabozantinib-treated patients; grade 3 and 4 hypertension has been reported.
• Hypocalcemia: Cabozantinib may cause hypocalcemia, including grade 3 and 4 events.
• Osteonecrosis of the jaw: Osteonecrosis of the jaw (ONJ) occurred rarely; manifestations may include 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.
• Proteinuria: Proteinuria occurred in some patients receiving cabozantinib; nephrotic syndrome was also reported (rare).
• Reversible posterior leukoencephalopathy syndrome: Reversible posterior leukoencephalopathy syndrome (RPLS), a syndrome of subcortical vasogenic edema (based on MRI findings), may occur with cabozantinib. Signs of RPLS include seizures, headache, visual disturbances, confusion, or altered mental function.
• Thromboembolic events: Cabozantinib is associated with an increased risk of thrombotic events. Venous thromboembolism (including pulmonary embolism) and arterial thromboembolism have been observed in cabozantinib-treated patients. Fatal thromboembolic events have occurred.
• Thyroid dysfunction: Thyroid dysfunction (primarily hypothyroidism) has been observed with cabozantinib, including grade 3 thyroid dysfunction.
• Wound healing impairment: Cabozantinib inhibits vascular endothelial growth factor receptors 1, 2, and 3; wound healing complications have been reported with therapy.
Dosage form specific issues:
• Formulations: Cabozantinib is available in tablets (Cabometyx) and capsules (Cometriq) which are NOT interchangeable; do NOT substitute.
Substrate of CYP2C9 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy
Bisphosphonate Derivatives: Angiogenesis Inhibitors (Systemic) may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Cabozantinib. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Cabozantinib. Management: Avoid use of strong CYP3A4 inducers with cabozantinib if possible. If combined, increase cabozantinib capsules (Cometriq) by 40 mg from previous dose, max 180 mg daily. Increase cabozantinib tablets (Cabometyx) by 20 mg from previous dose, max 80 mg daily Risk D: Consider therapy modification
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Cabozantinib. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Cabozantinib. Management: Avoid use of a strong CYP3A4 inhibitor with cabozantinib if possible. If combined, decrease cabozantinib capsules (Cometriq) by 40 mg from previous dose or decrease cabozantinib tablets (Cabometyx) by 20 mg from previous dose. Risk D: Consider therapy modification
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Grapefruit Juice: May increase the serum concentration of Cabozantinib. Risk X: Avoid combination
MRP2 Inhibitors: May increase the serum concentration of Cabozantinib. Risk C: Monitor therapy
Rifabutin: May decrease the serum concentration of Cabozantinib. Risk C: Monitor therapy
Rifapentine: May decrease the serum concentration of Cabozantinib. Risk C: Monitor therapy
Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy
St John's Wort: May decrease the serum concentration of Cabozantinib. Risk X: Avoid combination
A high-fat meal increased Cmax and AUC by 41% and 57%, respectively compared to the fasted state. Cabozantinib serum concentrations may be increased when taken with grapefruit or grapefruit juice. Management: Must be taken on an empty stomach, at least 1 hour before and 2 hours after food. Avoid concurrent use with grapefruit or grapefruit juice.
Evaluate pregnancy status prior to initiating therapy in patients who can become pregnant. Patients who can become pregnant should use effective contraception during therapy and for 4 months after the last cabozantinib dose.
Based on its mechanism of action and data from animal reproduction studies, adverse effects on pregnancy may be expected.
It is not known if cabozantinib is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends discontinuing breastfeeding during treatment and for 4 months after the last cabozantinib dose.
Avoid grapefruit and grapefruit juice throughout therapy.
Monitor renal function, liver function (at baseline and periodically; consider monitoring more frequently when cabozantinib is administered in combination with nivolumab), CBC with differential and platelets, serum electrolytes, including calcium (regularly during treatment), thyroid function testing (at baseline and as clinically indicated). Monitor urine protein (regularly during treatment). Consider monitoring urine protein/creatinine ratio (at baseline and as clinically indicated) (Brose 2021). Evaluate pregnancy status (prior to treatment in patients who can become pregnant). Monitor BP (regularly during therapy). Monitor for signs/symptoms of GI perforations or fistulas (including abscess and sepsis), bleeding/hemorrhage, palmar-plantar erythrodysesthesia syndrome, reversible posterior leukoencephalopathy syndrome (evaluate patients who present with seizures, headache, visual disturbances, confusion, or altered mental function), osteonecrosis of the jaw (perform oral examination prior to initiation and periodically during therapy), thyroid dysfunction (assess for signs of thyroid dysfunction at baseline; monitor for signs/symptoms during treatment), wound healing complications, diarrhea, and stomatitis, and for signs/symptoms of adrenal insufficiency (when used in combination with nivolumab). Assess patients for proper oral hygiene practices. Monitor adherence.
The American Society of Clinical Oncology hepatitis B screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends hepatitis B virus (HBV) screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Cabozantinib is a potent inhibitor of proinvasive receptor tyrosine kinases (RTKs), including AXL, FLT-3, KIT, MER, MET, RET, ROS1, TIE-2, TRKB, TYRO3, and VEGFR-1, -2, and -3; induces apoptosis of cancer cells and suppresses tumor growth, metastasis, and angiogenesis (Yakes 2011).
Distribution: Vd: ~349 L (Cometriq); ~319 L (Cabometyx)
Bioavailability: Following a single 140 mg dose, a 19% increase in the Cmax was observed with the tablet (compared to the capsule), although the difference in AUC was <10%.
Protein binding: ≥99.7% to plasma proteins
Metabolism: Hepatic via CYP3A4
Half-life elimination: ~55 hours (Cometriq); ~99 hours (Cabometyx)
Time to peak: 2 to 5 hours (Cometriq); 3 to 4 hours (Cabometyx)
Excretion: Feces (~54%; 43% as unchanged drug); urine (~27%)
Hepatic function impairment: Cabozantinib exposure was increased by 81% in subjects with mild impairment (Child-Pugh class A) and by 63% in subjects with moderate impairment (Child-Pugh class B), compared to subjects with normal liver function.
Kit (Cometriq (100 MG Daily Dose) Oral)
80 & 20 mg (per each): $377.99
Kit (Cometriq (140 MG Daily Dose) Oral)
3 x 20 MG &80 MG (per each): $188.99
Kit (Cometriq (60 MG Daily Dose) Oral)
20 mg (per each): $251.99
Tablets (Cabometyx Oral)
20 mg (per each): $931.50
40 mg (per each): $931.50
60 mg (per each): $931.50
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
