Cabozantinib is an oral multi-tyrosine kinase inhibitor. Cometriq (cabozantinib capsules) is indicated for the treatment of progressive, metastatic medullary thyroid cancer. Cabometyx (cabozantinib tablets) is indicated for the treatment of advanced renal cell carcinoma as monotherapy and in combination with nivolumab, for the treatment of hepatocellular carcinoma in patients who have been previously treated with sorafenib, and in adults and pediatric patients 12 and older with locally advanced or metastatic differentiated thyroid cancer that has progressed after VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible. Patients should not receive cabozantinib for at least 3 weeks before elective surgery due to wound healing complications that may be associated with treatment; do not administer cabozantinib for at least 2 weeks after major surgery and until adequate wound healing has occurred.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 1
-NIOSH (Draft) 2020 List: Table 2
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use gloves. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure.
Emetic Risk
-Moderate/High
-Administer routine antiemetic prophylaxis prior to treatment.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Do not substitute cabozantinib tablets with cabozantinib capsules.
-Take cabozantinib on an empty stomach; do not eat for at least 2 hours before and at least 1 hour after taking cabozantinib.
-Swallow capsules and tablets whole; do not open or crush.
-Do not take cabozantinib with grapefruit juice or nutritional supplements that are known to inhibit CYP450.
-Do not take a missed dose within 12 hours of the next dose. If the next dose is in 12 hours or more, take the missed dose; if the next dose is in less than 12 hours, skip the missed dose and take the next dose at the scheduled time.
Gastrointestinal adverse events that have been reported in clinical trials in patients who received cabozantinib include nausea (24% to 50%; grade 3 or 4, 0.6% to 4%), vomiting (14% to 32%; grade 3 or 4, 2% or less), abdominal pain (27% or less; grade 3 or 4, 4% or less), and dyspepsia including gastroesophageal reflux (15% or less; grade 3 or 4, less than 1%); the incidence was similar when cabozantinib was administered as tablets (60 mg per day) or capsules (140 mg per day) as monotherapy, or as tablets (40 mg per day) in combination with nivolumab. Anorexia or decreased appetite was reported in 23% to 48% (grade 3 or 4, 1.9% to 6%) of patients receiving cabozantinib as monotherapy or in combination with nivolumab. Additional GI adverse reactions reported with cabozantinib treatment in various clinical trials include constipation (27% or less; grade 3 or 4, 1% or less), dysphagia (13% or less; grade 3 or 4, 4% or less), xerostomia (10% or less; grade 3 or 4, 1% or less), and hemorrhoids (9% or less).
Severe bleeding has been reported in 3% to 5% of patients who received cabozantinib therapy in clinical trials. Bleeding including GI bleeding and hemoptysis resulting in death has occurred. Discontinue cabozantinib at least 3 weeks prior to elective surgery. Monitor patients for signs and symptoms of bleeding. Permanently discontinue therapy in patients who develop severe bleeding. Grade 3 or higher bleeding was reported in 3% of patients with metastatic medullary thyroid cancer who received cabozantinib capsules 140 mg/day (n = 214) in a randomized, placebo-controlled trial. Grade 3 or higher bleeding occurred in 5% of patients with renal cell carcinoma or hepatocellular carcinoma who received cabozantinib tablets 60 mg/day in randomized trials. One patient with hepatocellular carcinoma died due to upper GI bleeding.
Venous (6% to 7%) and arterial (2%) thromboembolism have been reported in patients who received cabozantinib therapy in clinical trials; some cases were fatal. Permanently discontinue cabozantinib in patients who develop a serious thromboembolic event (e.g., cerebral infarction, myocardial infarction) or any other thromboembolic complication that requires medical intervention. Pulmonary embolism (PE) occurred in 2% to 5% of patient with renal cell cancer (RCC), hepatocellular cancer (HCC), or thyroid cancer treated with cabozantinib monotherapy in 3 clinical trials; PE occurred in at least 2% of RCC patients treated with cabozantinib in combination with nivolumab in another clinical trial. Two patients with HCC died due to thrombosis; 1 patient due to a PE and 1 patient who had portal vein thrombosis.
Wound complications such as impaired wound healing and wound dehiscence have been reported with cabozantinib use. Therefore, temporary suspension of therapy is recommended at least 3 weeks before elective surgery; do not administer cabozantinib for at least 2 weeks following major surgery and until adequate wound healing. Wound complications occurred in 2% of patients with advanced renal cell carcinoma who received cabozantinib tablets 60 mg/day (n = 331) in a randomized trial.
Rash occurred in 19% to 23% (grade 3 or 4, 2% or less) and xerosis in 19% or fewer patients treated with cabozantinib tablets or capsules as monotherapy. The incidence of rash was higher in RCC patients receiving cabozantinib tablets in combination with nivolumab (36%; grade 3 or 4, 3.1%). The term rash included dermatitis acneiform/acneiform rash, bullous dermatitis, follicular rash, maculopapular rash, contact dermatitis, genital rash, exfoliative dermatitis, pustular rash, pruritic rash, and vesicular rash. Additionally, hair discoloration (depigmentation, color changes, and graying) (34%), alopecia (16%), erythema (11%; grade 3 or 4, 1%), and hyperkeratosis (7%) were reported in patients who received cabozantinib capsules as monotherapy. Grade 3 or 4 skin ulcer was reported in 3% of patients who received cabozantinib tablets as monotherapy in a small randomized trial and pruritus was reported in 19% (grade 3 or 4, 0.3%) of patients who received cabozantinib in combination with nivolumab. Palmar-plantar erythrodysesthesia (hand and foot syndrome) occurred in 40% to 50% (grade 3 or 4, 8% to 17%) of patients treated with cabozantinib as monotherapy or in combination with nivolumab in clinical trials; an interruption of therapy and a dose reduction may be necessary.
Hypertension was reported in 37% (grade 3, 16%; grade 4, less than 1%) of patients treated with cabozantinib in clinical trials; some patients developed hypertensive crisis. Monitor blood pressure prior to and regularly during cabozantinib treatment. Hold therapy in hypertensive patients not adequately controlled with medical management; resume therapy at a reduced cabozantinib dose. Permanently discontinue therapy if patients develop malignant hypertension, hypertensive crisis, or persistent uncontrolled hypertension despite optimal management. The incidence of hypertension (30% to 39%; grade 3 or 4, 8% to 28%) was similar in patients with medullary thyroid cancer receiving cabozantinib capsules at a dose of 60 mg per day and in patients with renal cell cancer (RCC), hepatocellular cancer, or differentiated thyroid cancer receiving cabozantinib tablets at a dose of 60 mg per day; the term hypertension included increased blood pressure, blood pressure fluctuation, and hypertensive crisis. The incidence of hypertension was also similar when cabozantinib tablets were given to patients with RCC at a dose of 40 mg per day in combination with nivolumab (36%; grade 3 or 4, 13%). Hypotension was reported in 7% (grade 3 or 4, 1%) of patients with medullary thyroid cancer receiving cabozantinib monotherapy with capsules (140 mg per day); one patient in this study died due to cardiac arrest. Grade 3 or 4 hypotension (5%), and angiopathy (1%) were reported in patients with advanced renal cell carcinoma who received cabozantinib tablets (60 mg per day) in another small randomized trial.
Grade 3 or 4 lung infection was reported in 1% of patients with advanced renal cell carcinoma (RCC) who received cabozantinib tablets at a monotherapy dose of 60 mg/day (n = 78) in a randomized trial. Additionally, pneumonia and septicemia resulting in death occurred in patients with metastatic medullary thyroid cancer who received cabozantinib capsules at a monotherapy dose of 140 mg/day (n = 214) in another randomized, placebo-controlled trial. Upper respiratory infections including nasopharyngitis, pharyngitis, and rhinitis were reported in 20% of patients with RCC treated with cabozantinib 40 mg/day given in combination with nivolumab in another clinical trial (grade 3 or 4, 0.3%); serious cases of pneumonia and urinary tract infection occurred in at least 2% of patients in this trial.
Osteonecrosis of the jaw (ONJ) has been reported in 1% or less of cabozantinib-treated patients. Symptoms suggestive of ONJ include jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache/dental pain, gingival ulceration or erosion, slow healing, or persistent jaw pain following dental surgery. An oral examination should be performed prior to and then periodically during cabozantinib therapy. Hold cabozantinib therapy in patients who develop ONJ until the it completely resolves and then resume treatment at a reduced dose.
Proteinuria was reported in 2% of patients who received cabozantinib capsules (140 mg per day) and in 8% of patients who received cabozantinib tablets (60 mg per day) across clinical trials; 1 patient with medullary thyroid cancer who received cabozantinib capsules developed nephrotic syndrome. Monitor urine protein regularly; an interruption of therapy or dose reduction may be necessary for grade 2 or higher proteinuria. Permanently discontinue cabozantinib in patients who develop nephrotic syndrome. In individual trials of patients receiving cabozantinib tablets, proteinuria occurred in 12% (grade 3 or 4, 2% to 3%) of patients with renal cell cancer in 2 clinical trials and in 15% (grade 3 or 4, 1%) of patients with differentiated thyroid cancer in 1 clinical trial.
In patients with renal cell cancer (RCC), hepatotoxicity occurred in 44% (grade 3 or 4, 11%) of patients receiving cabozantinib plus nivolumab, including transaminitis, autoimmune hepatitis, increased bilirubin, and hepatic failure. Grade 3 and 4 transaminitis may be more common when cabozantinib is administered in combination with nivolumab compared to cabozantinib alone. Monitor hepatic function at baseline and periodically during treatment; consider more frequent monitoring when administered in combination with nivolumab. An interruption or discontinuation of therapy may be necessary; treatment with systemic corticosteroids may also be necessary when coadministered with nivolumab. Avoid the use of cabozantinib in patients with severe hepatic disease (Child-Pugh C). Elevated hepatic enzymes commonly occurred in treatment with cabozantinib as monotherapy or in combination with nivolumab, including increased ALT (66% to 86%; grade 3 or 4, 2% to 9.8%), increased AST (74% to 86%; grade 3 or 4, 1% to 7.9%), and increased GGT (27% or less; grade 3 or 4, 5% or less); increased alkaline phosphatase also occurred in 34% to 52% (grade 3 or 4, 3% or less) of patients. The overall incidence of increased ALT (73%), increased AST (73%), and increased alkaline phosphatase (43%) were similar in patients with hepatocellular (HCC) cancer treated with cabozantinib monotherapy; however, the incidence of grade 3 or 4 increases in ALT (12%), AST (24%), and alkaline phosphatase (8%) were higher in this population. Hyperbilirubinemia occurred in 12% to 25% (grade 3 or 4, 2% or less) of patients with advanced thyroid cancer treated with cabozantinib monotherapy. Hypoalbuminemia was reported in 19% to 51% (grade 3 or 4, 1% to 2%) of who received cabozantinib monotherapy. Cholestatic hepatitis occurred in less than 1% of patients treated with cabozantinib.
Nervous system adverse events including dysgeusia (10% to 34%), headache (18% or less; grade 3 or 4, 2% or less), and dizziness (14% or less) have been reported in patients treated with cabozantinib as monotherapy or in combination with nivolumab; grade 3 or 4 syncope occurred in 5% or fewer patients who received cabozantinib tablets as monotherapy (60 mg per day). Dysgeusia occurred more often with cabozantinib capsules (140 mg per day) compared with cabozantinib tablets (60 mg per day). Paresthesias (7%), peripheral sensory neuropathy (7%), and peripheral neuropathy (5%) were also reported in patients who received cabozantinib capsules (140 mg per day).
Musculoskeletal system adverse events including arthralgia (14% or less; grade 3 or 4, 1% or less), muscle cramps/spasms (8% to 13%; grade 3 or 4, less than 1%), and extremity pain (14% or less; grade 3 or 4, 3% or less) have been reported in patients who received cabozantinib monotherapy (capsules, 140 mg/day; tablets, 60 mg/day) in clinical trials. Additionally, musculoskeletal pain at the chest was reported in 9% of patients with metastatic medullary thyroid cancer who received cabozantinib capsules 140 mg/day (n = 214) in a randomized, placebo-controlled trial (grade 3 or 4, 1%). Grade 3 or 4 pain (5%), back pain (4%), and bone pain (3%) were reported in patients with advanced renal cell carcinoma (RCC) who received cabozantinib tablets 60 mg/day (n = 78) in a randomized trial. Musculoskeletal pain including back pain, bone pain, musculoskeletal chest pain, myalgia, neck pain, extremity pain, and spinal pain was also reported in 33% of patients with RCC treated with cabozantinib tablets at a dose of 40 mg/day in combination with nivolumab (grade 3 or 4, 3.8%); arthralgia was reported in 18% of these patients (grade 3 or 4, 0.3%).
Fatigue, including asthenia, occurred in 41% to 56% (grade 3 or 4, 6% to 10%) of patients who received cabozantinib as monotherapy or in combination with nivolumab in clinical trials. Asthenia was separately reported in 19% to 22% (grade 3 or 4, 4% to 7%) of patients treated with cabozantinib monotherapy in 3 clinical trials.
Weight loss/decreased weight occurred in 17% to 31% (grade 3 or 4, 1% to 4%) of patients treated with cabozantinib tablets as monotherapy (60 mg per day) in several clinical trials. Decreased weight was reported in 48% (grade 3 or 4, 5%) in patients who received cabozantinib capsules as monotherapy (140 mg per day) in another clinical trial.
Anxiety occurred in 9% of patients with metastatic medullary thyroid cancer who received cabozantinib capsules 140 mg/day (n = 214) in a randomized, placebo-controlled trial. Grade 3 or 4 depression (4%) and confusion (1%) were reported in patients with advanced renal cell carcinoma who received cabozantinib tablets 60 mg/day (n = 78) in a randomized trial.
Dysphonia occurred in 10% to 20% (grade 3 or 4, 1% or less) of patients with renal cell cancer (RCC), hepatocellular cancer, or thyroid cancer treated with cabozantinib as monotherapy or in combination with nivolumab; the incidence was similar in patients who received capsules or tablets. Dyspnea occurred in 12% to 19% of patients who received cabozantinib tablets at a monotherapy dose of 60 mg/day (grade 3 or 4, 1% to 3%). Cough was reported in 18% (grade 3 or 4, less than 1%) of RCC patients who received cabozantinib 60 mg/day as monotherapy and in 20% of patients with RCC who received cabozantinib tablets at a dose of 40 mg/day in combination with nivolumab in separate clinical trials.
Hypocalcemia was more common in patients with thyroid cancer treated with cabozantinib capsules as monotherapy (52%; grade 3 or 4, 12%) and in patients with renal cell cancer (RCC) who received cabozantinib plus nivolumab (54%; grade 3 or 4, 1.9%) compared to those with RCC who received cabozantinib tablets as monotherapy (8% to 36%; grade 3 or 4, 2% to 9%). Monitor blood calcium concentrations and replete as necessary during treatment. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary depending on the severity of hypocalcemia. The lowest incidence of hypophosphatemia (25% to 28%; grade 3 or 4, 3% to 9%), hypomagnesemia (19% to 25%; grade 3 or 4, 1% to 3%), and hyponatremia (10% to 15%; grade 3 or 4, 2% or less) was in patients with thyroid cancer or hepatocellular cancer who received cabozantinib monotherapy. Hypophosphatemia (48% to 69%; grade 3 or 4, 8% to 28%), hypomagnesemia (31% to 47%; grade 3 or 4, 1.3% to 7%), and hyponatremia (30% to 43; grade 3 or 4, 8% to 11%) were more common in patients with RCC who received cabozantinib as monotherapy or in combination with nivolumab. Hypokalemia was reported in 18% to 23% (grade 3 or 4, 1% to 6%) of cabozantinib-treated patients with thyroid cancer or hepatocellular cancer. Hyperkalemia was reported in 35% (grade 3 or 4, 4.7%) of RCC patients who received cabozantinib with nivolumab; grade 3 or 4 hyperkalemia was also reported in 1% or fewer RCC patients who received cabozantinib monotherapy. Hyperglycemia was also reported in 37% to 44% (grade 3 or 4, 2% to 3.5%) of patients with RCC who received cabozantinib as monotherapy or combination therapy; hypoglycemia occurred in 26% (grade 3 or 4, 0.8%) of those who received combination therapy. Increased LDH occurred in 90% (grade 3 or 4, 10%) of patients with thyroid cancer who received cabozantinib tablets compared with 32% (grade 3 or 4, 3%) of those who received placebo in 1 clinical trial. Finally, dehydration was reported in 7% (grade 3 or 4, 2%) of patients with thyroid cancer who received cabozantinib capsules in 1 clinical trial; grade 3 or 4 dehydration also occurred in 4% of RCC patients who received cabozantinib tablets as monotherapy in another trial.
Lymphopenia was more common in patients with medullary thyroid cancer treated with cabozantinib capsules as monotherapy (53%; grade 3 or 4, 16%) or renal cell cancer (RCC) treated with cabozantinib plus nivolumab (42%; grade 3 or 4, 6.6%) compared to patients with RCC receiving cabozantinib tablets as monotherapy (25%; grade 3 or 4, 1% to 7%). Anemia (17% to 37%; grade 3 or 4, 5% or less), neutropenia (31% to 43%; grade 3 or 4, 7% or less), thrombocytopenia (25% to 41%; grade 3 or 4, 1% or less), and leukopenia (35% to 37%; grade 3 or 4, less than 1%) have also been reported with cabozantinib therapy. Decreases from baseline in leukocytes (38%; grade 3 or 4, 2%), neutrophils (31%; grade 3 or 4, 2%), and platelets (26%) have been reported in patients with differentiated thyroid cancer who received cabozantinib tablets as monotherapy. Decreased platelets (54%; grade 3 or 4, 10%) and increased hemoglobin (8%) were reported in patients with hepatocellular cancer who received cabozantinib tablets as monotherapy.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS), which is a syndrome of subcortical vasogenic edema also known as Posterior Reversible Encephalopathy Syndrome (PRES), has been reported in less than 1% of patients who received cabozantinib capsules (140 mg/day) in clinical trials. Convulsions/seizures occurred in less than 1% of patients with advanced renal cell carcinoma who received cabozantinib tablets 60 mg/day (n = 331) in a randomized trial. Symptoms of RPSL include seizures, headache, visual impairment/disturbances, confusion, and altered mental status. Discontinue cabozantinib therapy if RPLS is suspected or diagnosed; this syndrome may be confirmed on magnetic resonance imaging.
Pancreatitis occurred in less than 1% of patients with advanced renal cell carcinoma (RCC) who received cabozantinib tablets 60 mg/day (n = 331) in a randomized trial. Increased amylase level/hyperamylasemia was reported in 16% (grade 3 or 4, 2%) of patients with hepatocellular carcinoma who received cabozantinib tablets 60 mg/day (n = 467) in another randomized, placebo-controlled trial. Increased lipase (41%; grade 3 or 4, 14%) and amylase (41%; grade 3 or 4, 10%) levels were more common in patients with RCC treated with cabozantinib tablets at a dose of 40 mg/day in combination with nivolumab. Pancreatitis and increased lipase levels that resulted in treatment discontinuation also occurred in patients with metastatic medullary thyroid cancer who received cabozantinib capsules 140 mg/day (n = 214) in a randomized, placebo-controlled trial.
Thyroid dysfunction occurred in 19% (grade 3, 0.4%) of patients treated with cabozantinib tablets in clinical trials. Assess patients for signs of thyroid dysfunction at baseline as well as during treatment. Test thyroid function as clinically indicated and manage any thyroid dysfunction as appropriate. Hypothyroidism occurred in 8% to 21% (grade 3 or 4, less than 1%) of patients with renal cell cancer or hepatocellular cancer treated with cabozantinib monotherapy and in 34% (grade 3 or 4, 0.3%) of patients who received cabozantinib in combination with nivolumab. In patients with metastatic medullary thyroid cancer, Increased thyroid stimulating hormone (TSH) levels was reported in 57% of those who received cabozantinib monotherapy.
Hypertriglyceridemia occurred in 53% of patients with advanced renal cell carcinoma who received cabozantinib tablets 60 mg/day (n = 331) in a randomized trial; grade 3 or 4 hypertriglyceridemia was reported in 4% of patients.
Serious gastrointestinal (GI) events including GI perforation (3% or less), gastrointestinal fistula (1%), and non-GI fistula including tracheoesophageal fistula (4% or less) have been reported with cabozantinib therapy in clinical trials; fatal cases have been reported. Monitor patients for signs and symptoms of GI perforation and fistulas, including for signs of abscess or sepsis. Permanently discontinue cabozantinib tablets in patients who develop a grade 4 fistula or a GI perforation; permanently discontinue cabozantinib capsules in all patients who develop a perforation or fistula. GI perforation (3%), GI fistula (1%), and non-GI fistula including tracheoesophageal fistula (4%) were reported in patients with metastatic medullary thyroid cancer who received cabozantinib capsules 140 mg/day (n = 214) in a randomized, placebo-controlled trial; 1 patient with a GI fistula and 2 patients with a tracheoesophageal fistula died. Fistulas (1%) and GI perforation (1%) occurred in patients with advanced renal cell carcinoma or hepatocellular carcinoma who received cabozantinib tablets 60 mg/day in randomized trials. GI perforation resulting in death was reported in 2 patients with advanced renal cell carcinoma and 1 patient with hepatocellular carcinoma died because of an esophagobronchial fistula.
Diarrhea occurred in 62% (grade 3, 10%) of patients treated with cabozantinib in clinical trials. Monitor patients and manage using antidiarrheals as indicated. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary depending upon the severity. In individual clinical trials, the incidence was similar in patients receiving cabozantinib capsules (140 mg per day) or tablets (60 mg per day) as monotherapy, or cabozantinib tablets (40 mg per day) in combination with nivolumab (51% to 74%; grade 3 or 4, 7% to 16%).
Stomatitis occurred in 13% to 26% (grade 3 or 4, 5% or less) of patients treated with cabozantinib tablets as monotherapy (60 mg per day) in clinical trials; in some trials, mucosal inflammation was separately reported in 14% to 19% (grade 3 or 4, 2% or less) of cabozantinib-treated patients. The incidence of stomatitis (including mucosal inflammation, aphthous ulcer, and oral ulceration) was higher when cabozantinib 40 mg was administered in combination with nivolumab (37%; grade 3 or 4, 3.4%). The incidence of stomatitis (51%; grade 3 or 4, 5%) and oral pain (36%; grade 3 or 4, 2%) was highest in patients received cabozantinib capsules as monotherapy (140 mg per day) in 1 clinical trial. The stomatitis term included aphthous stomatitis, mouth/oral ulceration, mucosal inflammation; the oral pain term included oropharyngeal pain, glossitis, burning mouth syndrome, and glossodynia.
Increased serum creatinine (SCr) level occurred in 58% of patients with advanced renal cell carcinoma RCC) who received cabozantinib tablets 60 mg/day (n = 331) in a randomized trial; grade 3 or 4 increased SCr level was reported in less than 1% of these patients. The incidence was similar in patients with RCC treated with cabozantinib tablets at a dose of 40 mg/day in combination with nivolumab (39%; grade 3 or 4, 1.3%). Grade 3 or 4 renal failure (unspecified) (4%) and increased Scr level (3%) were reported in patients with advanced renal cell carcinoma who received cabozantinib tablets 60 mg/day (n = 78) in a randomized trial.
Arterial (including aortic) aneurysms, dissections (aortic dissection), and rupture have occurred in postmarketing experience with cabozantinib.
Primary or secondary adrenocortical insufficiency has been reported with cabozantinib when administered in combination with nivolumab therapy. Initiate symptomatic treatment including hormone replacement therapy for grade 2 or higher adrenal insufficiency as clinically indicated. Both cabozantinib and nivolumab may need to be interrupted or discontinued depending on severity; treatment with systemic corticosteroids may also be necessary. Adrenal insufficiency occurred in 4.7% (grade 3, 2.2%) of patients with renal cell cancer who received cabozantinib in combination with nivolumab. Of these patients, 80% received hormone replacement therapy including systemic corticosteroids; adrenal insufficiency resolved in 27% of patients.
Serious cases of pneumonitis occurred in at least 2% of patients with renal cell cancer treated with cabozantinib tablets at a dose of 40 mg/day in combination with nivolumab.
Serious GI perforation and fistula have been reported with cabozantinib use; one patient death was attributed to a GI fistula. Fatal non-GI fistulas (i.e., tracheal/esophageal fistulas) have also occurred in cabozantinib-treated patients. Monitor patients for signs and symptoms of GI perforations and fistulas, including abscess and sepsis. Permanently discontinue cabozantinib in patients who develop a GI perforation or grade 4 fistula.
Severe bleeding has been reported with cabozantinib use; some cases were fatal. Discontinue cabozantinib at least 3 weeks prior to elective surgery. Monitor patients for signs and symptoms of bleeding. Do not use cabozantinib in patients who have a recent history of bleeding including hemoptysis, hematemesis, or melena. Permanently discontinue therapy in patients who develop grade 3 or 4 bleeding.
Serious arterial and venous thromboembolism has been reported with cabozantinib use; some cases were fatal. Permanently discontinue cabozantinib in patients who develop an acute myocardial infarction or arterial or venous thromboembolic events that require medical intervention.
Impaired wound healing has occurred in patients treated with cabozantinib. Discontinue cabozantinib at least 3 weeks prior to elective surgery; do not administer cabozantinib for at least 2 weeks following major surgery and until adequate wound healing. The safety of resuming cabozantinib after resolution of wound healing complications has not been established.
Do not initiate cabozantinib therapy in patients with uncontrolled hypertension as treatment-emergent hypertension has occurred with cabozantinib use. Monitor blood pressure regularly during cabozantinib treatment. Hold therapy in hypertensive patients not adequately controlled with medical management; resume therapy at a reduced cabozantinib dose. Permanently discontinue therapy for severe hypertension unable to be controlled with antihypertensive therapy and for hypertensive crisis.
An oral examination should be performed prior to starting cabozantinib therapy to evaluate patients for dental disease; good oral hygiene practices should be encouraged. Temporary suspension of therapy is recommended at least 3 weeks before invasive dental work. Osteonecrosis of the jaw (ONJ) has been reported in cabozantinib-treated patients. If ONJ develops, hold cabozantinib therapy until it completely resolves and then resume treatment at a reduced dose.
Skin disease, specifically palmar-plantar erythrodysesthesia (hand and foot syndrome), has been reported with cabozantinib use. Hold therapy in patients who develop intolerable grade 2, or grade 3 or 4 hand and foot syndrome. Cabozantinib may be resumed at a reduced dose when toxicity has improved to grade 1.
Proteinuria has been reported with cabozantinib use; one cabozantinib-treated patient developed nephrotic syndrome. Monitor urine protein regularly; an interruption of therapy and dose reduction may be necessary for grade 2 or higher proteinuria. Permanently discontinue cabozantinib in patients who develop nephrotic syndrome.
Severe diarrhea has been reported with cabozantinib treatment. Monitor patients and manage using antidiarrheals as indicated. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS), which is a syndrome of subcortical vasogenic edema also known as Posterior Reversible Encephalopathy Syndrome (PRES), has been reported with cabozantinib use. Symptoms of RPSL include seizures, headache, visual disturbances, confusion, and altered mental status. Discontinue cabozantinib therapy if RPLS is suspected or diagnosed; this syndrome may be confirmed on magnetic resonance imaging.
Avoid the use of cabozantinib in patients with severe hepatic disease (Child-Pugh C). Cabozantinib can cause elevated hepatic enzymes. Hepatotoxicity including grade 3 and 4 transaminitis is more common when cabozantinib is administered in combination with nivolumab compared to cabozantinib alone. Monitor hepatic function at baseline and periodically during treatment; consider more frequent monitoring when administered in combination with nivolumab. An interruption or discontinuation of therapy may be necessary; treatment with systemic corticosteroids may also be necessary when coadministered with nivolumab.
Primary or secondary adrenal insufficiency can occur in patients treated with cabozantinib in combination with nivolumab. Initiate symptomatic treatment including hormone replacement therapy for grade 2 or higher adrenal insufficiency as clinically indicated. Both cabozantinib and nivolumab therapy may need to be interrupted or discontinued depending on severity; treatment with systemic corticosteroids may also be necessary.
Use cabozantinib with caution in patients with a history of thyroid disease. Thyroid dysfunction, primarily hypothyroidism, has been observed with cabozantinib treatment. Assess patients for signs of thyroid dysfunction at baseline as well as during treatment. Test thyroid function as clinically indicated and manage any thyroid dysfunction as appropriate.
Hypocalcemia has been reported in patients treated with cabozantinib in clinical trials. Monitor blood calcium concentrations and replete as necessary during treatment. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary depending on the severity of hypocalcemia.
Monitor physeal and longitudinal growth in children with open growth plates. Physeal widening has been observed in these patients when treated with cabozantinib; there are limited data available on the effects of cabozantinib on longitudinal growth.
Although there are no adequate and well-controlled studies in pregnant women, fetal harm may occur if cabozantinib is administered during pregnancy based on animal studies. Females of reproductive potential should avoid becoming pregnant during cabozantinib therapy. Women who become pregnant while receiving cabozantinib should be apprised of the potential hazard to the fetus. Toxicities reported in pregnant rats included loss of pregnancy (at Cometriq exposures less than 1% and Cabometyx less than 0.12-fold those achieved with recommended dosing), delayed fetal ossifications, and skeletal variations (at Cometriq exposures less than 0.03% and Cabometyx less than 0.04-fold those achieved with recommended dosing). Visceral malformations, reduced spleen size, and missing lung lobe were reported in pregnant rabbits who received cabozantinib doses (3 mg/kg) that achieved about 11% Cometriq exposure and 1.1-fold Cabometyx exposure at the recommended human doses.
Counsel patients about the reproductive risk and contraception requirements during cabozantinib treatment. Cabozantinib can be teratogenic if taken by the mother during pregnancy. Females of reproductive potential should avoid pregnancy and use effective contraception during and for at least 4 months after the last dose. These patients should undergo pregnancy testing prior to initiation of cabozantinib tablets. Women who become pregnant while receiving cabozantinib should be apprised of the potential hazard to the fetus. In addition, based on animal data, cabozantinib may cause impaired fertility or infertility in both males and females. Decreased sperm count and reduced reproductive organ weight were reported in male rats at cabozantinib doses (2.5 mg/kg or higher) about equal to the Cometriq exposure and 13-fold greater than Cabometyx exposures observed with recommended human doses. A decrease in live embryos and significant pre- and post-implantation losses occurred in female rats at cabozantinib doses (1 mg/kg or higher) that achieved about 50% of the Cometriq exposure and 5-fold greater Cabometyx exposure than is observed with recommended human doses. In a 6-month repeat dose study, hypospermia and absence of corpus lutea were reported in male and female dogs at cabozantinib doses that resulted in AUC values equal to 6% and 3% of recommended human doses of Cometriq, respectively, and 0.5-fold (males) and less than0.1-fold (females) of the expected Cabometyx exposures in humans based on the recommended dose. Ovarian necrosis occurred in female rats who received cabozantinib at doses (5 mg/kg/day X 14 days) that achieved exposure about equal to that observed with recommended human doses.
It is not known if cabozantinib or cabozantinib metabolites are excreted into human milk. Due to the potential for serious adverse reactions in the nursing infant, women should avoid breast-feeding during treatment and for 4 months after the last dose.
For the treatment of thyroid cancer:
-for the treatment of progressive, metastatic medullary thyroid cancer:
Oral dosage (Cometriq [capsules] only; do not substitute with Cabometyx [tablets]):
Adults: 140 mg orally once daily on an empty stomach until disease progression or unacceptable toxicity occurs. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Treatment with cabozantinib led to a significantly improved median progression-free survival time (11.2 months vs. 4 months) and objective response rate (27% vs. 0%) compared with placebo in 330 patients with progressive metastatic medullary thyroid cancer in a multinational, randomized, double-blind, phase 3 trial. All responses in the cabozantinib arm were partial responses and the median duration of response was 14.7 months. Overall survival was not significantly different between treatment arms at a planned interim analysis. In this study, 92% of patients had undergone a thyroidectomy, 48% of patients had the RET mutation, and 25% of patients had previously received 2 or more systemic therapies (including a tyrosine kinase inhibitor in 21% of patients).
-for the treatment of locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy in patients who are radioactive iodine-refractory or ineligible:
Oral dosage (Cabometyx [tablets] only; do not substitute with Cometriq [capsules]):
Adults: 60 mg PO once daily on an empty stomach until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, randomized, phase 3 clinical trial (COSMIC-311), patients who were at least 16 years of age with locally advanced or metastatic DTC that had progressed following prior VEGFR-targeted therapy and were radioactive iodine-refractory or ineligible were randomized to treatment with cabozantinib tablets or placebo until disease progression or unacceptable toxicity. After a median follow-up of 6.2 months, treatment with cabozantinib significantly improved the median progression-free survival (PFS) compared with placebo (not reached vs. 1.9 months); an updated analysis without formal statistical testing reported a PFS of 11 months for cabozantinib-treated patients compared with 1.9 months for those who received placebo. The overall response rate was 15% on patients treated with cabozantinib compared with 0% in those who received placebo.
Children and Adolescents 12 years and older with BSA 1.2 m2 or higher: 60 mg PO once daily on an empty stomach until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Use of cabozantinib tablets in pediatric patients 12 years and older with DTC is supported by well-controlled studies in adults with additional population pharmacokinetic data demonstrating similar exposure at the recommended dose in adults and pediatric patients 12 years and older. In a multicenter, randomized, phase 3 clinical trial (COSMIC-311), patients who were at least 16 years of age with locally advanced or metastatic DTC that had progressed following prior VEGFR-targeted therapy and were radioactive iodine-refractory or ineligible were randomized to treatment with cabozantinib tablets or placebo until disease progression or unacceptable toxicity. After a median follow-up of 6.2 months, treatment with cabozantinib significantly improved the median progression-free survival (PFS) compared with placebo (not reached vs. 1.9 months); an updated analysis without formal statistical testing reported a PFS of 11 months for cabozantinib-treated patients compared with 1.9 months for those who received placebo. The overall response rate was 15% on patients treated with cabozantinib compared with 0% in those who received placebo.
Children and Adolescents 12 years and older with BSA less than 1.2 m2: 40 mg PO once daily on an empty stomach until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Use of cabozantinib tablets in pediatric patients 12 years and older with DTC is supported by well-controlled studies in adults with additional population pharmacokinetic data demonstrating similar exposure at the recommended dose in adults and pediatric patients 12 years and older. In a multicenter, randomized, phase 3 clinical trial (COSMIC-311), patients who were at least 16 years of age with locally advanced or metastatic DTC that had progressed following prior VEGFR-targeted therapy and were radioactive iodine-refractory or ineligible were randomized to treatment with cabozantinib tablets or placebo until disease progression or unacceptable toxicity. After a median follow-up of 6.2 months, treatment with cabozantinib significantly improved the median progression-free survival (PFS) compared with placebo (not reached vs. 1.9 months); an updated analysis without formal statistical testing reported a PFS of 11 months for cabozantinib-treated patients compared with 1.9 months for those who received placebo. The overall response rate was 15% on patients treated with cabozantinib compared with 0% in those who received placebo.
For the treatment of advanced or metastatic renal cell cancer:
-for the first-line treatment of metastatic renal cell cancer:
Oral dosage (tablets only; do not substitute with cabozantinib capsules):
Adults: 60 mg by mouth once daily until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. First-line treatment with cabozantinib significantly improved median progression free survival (PFS) over sunitinib in intermediate- or poor-risk patients with metastatic renal cell cancer in a multicenter, randomized, open-label, phase 2 clinical trial (8.6 months vs. 5.6 months). The secondary endpoint of ORR was also improved (46% vs. 18%); overall survival data were not mature (30.3 months vs. 21.8 months). Treatments were similarly tolerated.
-for the first-line treatment of advanced renal cell cancer, in combination with nivolumab:
Oral dosage (tablets only; do not substitute with cabozantinib capsules):
Adults: 40 mg PO once daily without food until disease progression or unacceptable toxicity. Administer in combination with nivolumab 240 mg IV over 30 minutes every 2 weeks OR 480 mg IV over 30 minutes every 4 weeks, until disease progression, unacceptable toxicity, or for up to 2 years in patients without disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. First-line treatment with nivolumab plus cabozantinib significantly improved median progression-free survival (16.6 months vs. 8.3 months) compared with sunitinib in a randomized, open-label study. The median overall survival was also significantly improved in the nivolumab plus cabozantinib arm (37.7 months vs. 34.3 months); in an exploratory analysis, these findings were not significant in patients with IMDC favorable or intermediate risk. The objective response rate was 55.7% (complete response, [8%]) versus 27.1% (CR, 4.6%), respectively.
-for the treatment of relapsed or refractory advanced renal cell cancer:
Oral dosage (tablets only; do not substitute with cabozantinib capsules):
Adults: 60 mg by mouth once daily on an empty stomach until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, randomized, open-label clinical trial of patients with advanced renal cell cancer who had received at least 1 prior anti-angiogenic therapy, the primary outcome of median progression-free survival (PFS) by blinded independent radiology review in the first 375 patients randomized to the study was significantly improved in patients treated with cabozantinib (n = 187) compared with everolimus (n = 188) (7.4 months vs. 3.8 months). In the total study population, median overall survival (21.4 months vs. 16.5 months) and confirmed objective response rate (ORR) (17% vs. 3%) were also significantly improved in cabozantinib-treated patients (n = 330) compared with those who received everolimus (n = 328).
For the treatment of hepatocellular cancer in patients who have been previously treated with sorafenib:
Oral dosage (tablets only; do not substitute with cabozantinib capsules):
Adults: 60 mg by mouth once daily until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a randomized phase 3 clinical trial, treatment with cabozantinib significantly improved median overall survival and median progression-free survival compared with placebo in patients with advanced hepatocellular cancer that progressed on or after sorafenib therapy. Patients in the cabozantinib arm experienced approximately twice as many serious adverse reactions compared with placebo.
Therapeutic Drug Monitoring:
Dosage Adjustments due to Treatment-Related Toxicities
Cometriq capsules
-First dose reduction: 100 mg PO once daily.
-Second dose reduction: 60 mg PO once daily. For patients already receiving 60 mg once daily, resume therapy at that dose; if 60 mg once daily is not tolerated, discontinue cabozantinib.
Cabometyx tablets
-First dose reduction (monotherapy): 40 mg PO once daily for adults and pediatric patients with a BSA of 1.2 m2 or higher receiving an initial dose of 60 mg; 20 mg PO once daily for pediatric patients with a BSA less than 1.2 m2 receiving an initial dose of 40 mg.
-First dose reduction (in combination with nivolumab): 20 mg PO once daily.
-Second dose reduction (monotherapy): 20 mg PO once daily for adults and pediatric patients with a BSA of 1.2 m2 or higher; 20 mg PO every other day for pediatric patients with a BSA less than 1.2 m2. For patients already receiving the lowest dose, resume therapy at that dose; if the lowest dose is not tolerated, discontinue cabozantinib.
-Second dose reduction (in combination with nivolumab): 20 mg PO every other day. For patients already receiving the lowest dose, resume therapy at that dose; if the lowest dose is not tolerated, discontinue cabozantinib.
Adrenal Insufficiency
-TABLETS, Grade 2 or higher: Initiate symptomatic treatment, including hormone replacement, as clinically indicated. Hold cabozantinib and/or nivolumab and resume cabozantinib at a reduced dose depending on severity. For patients already receiving the lowest dose, resume at the same dose; if the lowest dose is not tolerated, discontinue therapy.
Diarrhea
-TABLETS, Grade 2 or higher: Hold cabozantinib therapy and use antidiarrheals as indicated. When diarrhea resolves to grade 1 or less, resume therapy at a reduced dose. For patients already receiving the lowest dose, resume at the same dose; if the lowest dose is not tolerated, discontinue therapy.
-CAPSULES, Intolerable grade 2, grade 3 that cannot be managed with standard antidiarrheal treatment, or any grade 4: Hold cabozantinib therapy. When diarrhea resolves to grade 1 or less, resume therapy at a reduced dose. For patients already receiving the lowest dose, resume at the same dose; if the lowest dose is not tolerated, discontinue therapy.
Fistula
-TABLETS AND CAPSULES, Grade 4: Permanently discontinue cabozantinib.
GI perforation
-TABLETS AND CAPSULES, Any grade: Permanently discontinue cabozantinib.
Hemorrhage
-TABLETS, Grade 3 or 4: Permanently discontinue cabozantinib.
-CAPSULES, Serious hemorrhage: Permanently discontinue cabozantinib.
Hypertension
-TABLETS, Grade 3 hypertension: Hold cabozantinib. When hypertension is controlled to grade 2 or less, resume therapy at a reduced dose. For patients already receiving the lowest dose, resume at the same dose; if the lowest dose is not tolerated, discontinue therapy. Permanently discontinue cabozantinib for hypertension that cannot be controlled.
-TABLETS, Grade 4: Permanently discontinue cabozantinib.
-CAPSULES, Severe hypertension that cannot be controlled with antihypertensive therapy or grade 4 hypertension: Permanently discontinue cabozantinib.
Hypocalcemia
-TABLETS: Hold cabozantinib therapy and resume at a reduced dose upon recovery or permanently discontinue therapy depending on the severity.
Osteonecrosis of the Jaw
-TABLETS AND CAPSULES, Any grade: Hold cabozantinib therapy. Upon complete resolution, restart cabozantinib at a reduced dose. For patients already receiving the lowest dose, resume at the same dose; if the lowest dose is not tolerated, discontinue therapy.
Palmar-Plantar Erythrodysesthesia (hand and foot syndrome)
-TABLETS, Intolerable grade 2 or 3: Hold cabozantinib therapy. When hand and foot syndrome resolves to grade 1 or less, resume therapy at a reduced dose. For patients already receiving the lowest dose, resume at the same dose; if the lowest dose is not tolerated, discontinue therapy.
Proteinuria
-TABLETS, Grade 2 or 3: Hold cabozantinib therapy. When proteinuria resolves to grade 1 or less, resume therapy at a reduced dose. For patients already receiving the lowest dose, resume at the same dose; if the lowest dose is not tolerated, discontinue therapy.
-TABLETS AND CAPSULES, Nephrotic syndrome: Permanently discontinue cabozantinib.
Reversible posterior leukoencephalopathy syndrome (RPLS)
-TABLETS AND CAPSULES, Any grade: Permanently discontinue cabozantinib.
Thrombosis
-TABLETS AND CAPSULES, Acute myocardial infarction: Permanently discontinue cabozantinib.
-TABLETS, Grade 2 or higher cerebral infarction: Permanently discontinue cabozantinib.
-TABLETS, Grade 3 or 4 arterial thromboembolic events: Permanently discontinue cabozantinib.
-TABLETS, Grade 4 venous thromboembolic events: Permanently discontinue cabozantinib.
-CAPSULES, Any arterial or venous thromboembolic events that require medical intervention: Permanently discontinue cabozantinib.
Other
-TABLETS AND CAPSULES, Intolerable grade 2 or any grade 3 or 4 adverse reactions: Hold cabozantinib therapy. Upon resolution to grade 1 or less (or baseline), resume therapy at a reduced dose. For patients already receiving the lowest dose, resume at the same dose; if the lowest dose is not tolerated, discontinue therapy.
Maximum Dosage Limits:
-Adults
Cometriq: 140 mg/day PO.
Cabometyx: 60 mg/day PO.
-Geriatric
Cometriq: 140 mg/day PO.
Cabometyx: 60 mg/day PO.
-Adolescents
Cabometyx: BSA 1.2 m2 or higher, 60 mg PO; BSA less than 1.2 m2, 40 mg PO.
-Children
Cabometyx, 12 years and older: BSA 1.2 m2 or higher, 60 mg PO; BSA less than 1.2 m2, 40 mg PO.
Less than 12 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Baseline Hepatic Impairment:
Cometriq capsules:
-Mild or moderate hepatic impairment (Child-Pugh class A or B): Reduce the starting dose of cabozantinib to 80 mg once daily.
-Severe hepatic impairment (Child-Pugh class C): Use not recommended.
Cabometyx tablets:
-Mild hepatic impairment (Child-Pugh class A): Specific guidelines for dosage adjustments in mild hepatic impairment are not available; it appears that no dosage adjustments are needed.
-Moderate hepatic impairment (Child-Pugh class B): Reduce the starting dose of cabozantinib 60 mg once daily to 40 mg once daily for adults and pediatric patients with a BSA of 1.2 m2 or higher. Reduce the starting dose of cabozantinib 40 mg once daily to 20 mg once daily for pediatric patients with a BSA less than 1.2 m2.
-Severe hepatic impairment (Child-Pugh class C): Use not recommended.
Treatment-Related Hepatotoxicity:
In combination with nivolumab (Cabometyx tablets):
-AST or ALT level of more than 3 to 10 times the ULN with concurrent total bilirubin level less than 2 times the ULN: Hold nivolumab and cabozantinib and consider the use of corticosteroid therapy. Upon recovery to grade 1 or less, consider rechallenge with one or both of nivolumab and cabozantinib.
-AST or ALT level more than 10 times the ULN or more than 3 times the ULN with concurrent total bilirubin level 2 times the ULN or more: Permanently discontinue nivolumab and cabozantinib; consider the use of corticosteroid therapy.
Patients with Renal Impairment Dosing
Baseline Renal Impairment:
Cometriq capsules and Cabometyx tablets: No cabozantinib dosage adjustment is recommended in patients with mild or moderate renal impairment. Cabozantinib clearance did not significantly change with creatinine clearance values 30 mL/min or higher in a population pharmacokinetic analysis. Specific guidelines for dosage adjustments in patients with severe renal impairment are not available.
*non-FDA-approved indication
Abacavir: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with abacavir is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and abacavir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Abacavir; Dolutegravir; Lamivudine: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with abacavir is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and abacavir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown. (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with lamivudine is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and lamivudine is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown. (Minor) Monitor for an increase in dolutegravir-related adverse reactions if coadministration with cabozantinib is necessary. Dolutegravir is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Abacavir; Lamivudine, 3TC: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with abacavir is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and abacavir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown. (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with lamivudine is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and lamivudine is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with abacavir is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and abacavir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown. (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with lamivudine is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and lamivudine is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Adagrasib: (Major) Avoid concomitant use of cabozantinib and adagrasib due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with adagrasib 2 to 3 days after discontinuation of adagrasib. Cabozantinib is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Adefovir: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with adefovir is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and adefovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Afatinib: (Moderate) If the concomitant use of cabozantinib and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of cabozantinib. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib.
Albuterol; Budesonide: (Minor) Monitor for an increase in budesonide-related adverse reactions if coadministration with cabozantinib is necessary. Budesonide is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid concomitant use of cabozantinib and clarithromycin due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with clarithromycin 2 to 3 days after discontinuation of clarithromycin. Cabozantinib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Apalutamide: (Major) Avoid coadministration of cabozantinib with apalutamide due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with apalutamide 2 to 3 days after discontinuation of apalutamide. Cabozantinib is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased single-dose cabozantinib exposure by 77%.
Atazanavir: (Major) Avoid concomitant use of cabozantinib and atazanavir due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with atazanavir 2 to 3 days after discontinuation of atazanavir. Cabozantinib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Atazanavir; Cobicistat: (Major) Avoid concomitant use of cabozantinib and atazanavir due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with atazanavir 2 to 3 days after discontinuation of atazanavir. Cabozantinib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%. (Major) Avoid concomitant use of cabozantinib and cobicistat due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with cobicistat 2 to 3 days after discontinuation of cobicistat. Cabozantinib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving cabozantinib. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving cabozantinib. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-glycoprotein (P-gp). Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Minor) Monitor for an increase in both cabozantinib- and tenofovir-related adverse reactions if coadministration is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and tenofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib. Cabozantinib is also P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as tenofovir. The clinical relevance of either of these interactions is unknown.
Budesonide: (Minor) Monitor for an increase in budesonide-related adverse reactions if coadministration with cabozantinib is necessary. Budesonide is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Budesonide; Formoterol: (Minor) Monitor for an increase in budesonide-related adverse reactions if coadministration with cabozantinib is necessary. Budesonide is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Budesonide; Glycopyrrolate; Formoterol: (Minor) Monitor for an increase in budesonide-related adverse reactions if coadministration with cabozantinib is necessary. Budesonide is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Carbamazepine: (Major) Avoid coadministration of cabozantinib with carbamazepine due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with carbamazepine 2 to 3 days after discontinuation of carbamazepine. Cabozantinib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased single-dose cabozantinib exposure by 77%.
Carvedilol: (Minor) Monitor for an increase in carvedilol-related adverse reactions if coadministration with cabozantinib is necessary. Carvedilol is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Ceritinib: (Major) Avoid concomitant use of cabozantinib and ceritinib due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with ceritinib 2 to 3 days after discontinuation of ceritinib. Cabozantinib is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Chloramphenicol: (Major) Avoid concomitant use of cabozantinib and chloramphenicol due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with chloramphenicol 2 to 3 days after discontinuation of chloramphenicol. Cabozantinib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cidofovir: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with cidofovir is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and cidofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Clarithromycin: (Major) Avoid concomitant use of cabozantinib and clarithromycin due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with clarithromycin 2 to 3 days after discontinuation of clarithromycin. Cabozantinib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Cobicistat: (Major) Avoid concomitant use of cabozantinib and cobicistat due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with cobicistat 2 to 3 days after discontinuation of cobicistat. Cabozantinib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Cobimetinib: (Minor) Monitor for an increase in cobimetinib-related adverse reactions if coadministration with cabozantinib is necessary. Cobimetinib is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Colchicine: (Major) Avoid concomitant use of colchicine and cabozantinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and cabozantinib is a P-gp inhibitor.
Cyclosporine: (Minor) Monitor for an increase in cabozantinib- and cyclosporine-related adverse events if concomitant use of is necessary; consider closer monitoring of cyclosporine serum concentrations. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and cyclosporine is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown. Cabozantinib is also a P-glycoprotein (P-gp) inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as cyclosporine; however, the clinical relevance of this finding is unknown.
Dabigatran: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with cabozantinib is necessary in patients with CrCL greater than 50 mL/minute. Avoid coadministration in patients with CrCL less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCL less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Cabozantinib is a P-glycoprotein (P-gp) inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as dabigatran; however, the clinical relevance of this finding is unknown.
Darunavir: (Major) Avoid concomitant use of cabozantinib and darunavir due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with darunavir 2 to 3 days after discontinuation of darunavir. Cabozantinib is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Darunavir; Cobicistat: (Major) Avoid concomitant use of cabozantinib and cobicistat due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with cobicistat 2 to 3 days after discontinuation of cobicistat. Cabozantinib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%. (Major) Avoid concomitant use of cabozantinib and darunavir due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with darunavir 2 to 3 days after discontinuation of darunavir. Cabozantinib is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concomitant use of cabozantinib and cobicistat due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with cobicistat 2 to 3 days after discontinuation of cobicistat. Cabozantinib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%. (Major) Avoid concomitant use of cabozantinib and darunavir due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with darunavir 2 to 3 days after discontinuation of darunavir. Cabozantinib is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%. (Minor) Monitor for an increase in both cabozantinib- and tenofovir-related adverse reactions if coadministration is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and tenofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib. Cabozantinib is also P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as tenofovir. The clinical relevance of either of these interactions is unknown.
Delavirdine: (Major) Avoid concomitant use of cabozantinib and delavirdine due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with delavirdine 2 to 3 days after discontinuation of delavirdine. Cabozantinib is a CYP3A substrate and delavirdine is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Desogestrel; Ethinyl Estradiol: (Minor) Monitor for an increase in ethinyl estradiol-related adverse reactions if coadministration with cabozantinib is necessary. Ethinyl estradiol is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Dextromethorphan; Quinidine: (Minor) Monitor for an increase in quinidine-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of quinidine may be necessary. Quinidine is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Digoxin: (Minor) Monitor for an increase in digoxin-related adverse reactions if coadministration with cabozantinib is necessary; monitor digoxin levels as clinically appropriate. Digoxin is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Docetaxel: (Minor) Monitor for an increase in docetaxel-related adverse reactions if coadministration with cabozantinib is necessary. Docetaxel is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Dolutegravir: (Minor) Monitor for an increase in dolutegravir-related adverse reactions if coadministration with cabozantinib is necessary. Dolutegravir is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Dolutegravir; Lamivudine: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with lamivudine is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and lamivudine is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown. (Minor) Monitor for an increase in dolutegravir-related adverse reactions if coadministration with cabozantinib is necessary. Dolutegravir is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Dolutegravir; Rilpivirine: (Minor) Monitor for an increase in dolutegravir-related adverse reactions if coadministration with cabozantinib is necessary. Dolutegravir is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Minor) Monitor for an increase in both cabozantinib- and tenofovir-related adverse reactions if coadministration is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and tenofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib. Cabozantinib is also P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as tenofovir. The clinical relevance of either of these interactions is unknown. (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with lamivudine is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and lamivudine is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Doxorubicin Liposomal: (Minor) Monitor for an increase in doxorubicin-related adverse reactions if coadministration with cabozantinib is necessary. Doxorubicin is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Doxorubicin: (Minor) Monitor for an increase in doxorubicin-related adverse reactions if coadministration with cabozantinib is necessary. Doxorubicin is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Drospirenone; Ethinyl Estradiol: (Minor) Monitor for an increase in ethinyl estradiol-related adverse reactions if coadministration with cabozantinib is necessary. Ethinyl estradiol is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Monitor for an increase in ethinyl estradiol-related adverse reactions if coadministration with cabozantinib is necessary. Ethinyl estradiol is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) Monitor for an increase in both cabozantinib- and tenofovir-related adverse reactions if coadministration is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and tenofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib. Cabozantinib is also P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as tenofovir. The clinical relevance of either of these interactions is unknown.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Minor) Monitor for an increase in both cabozantinib- and tenofovir-related adverse reactions if coadministration is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and tenofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib. Cabozantinib is also P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as tenofovir. The clinical relevance of either of these interactions is unknown. (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with lamivudine is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and lamivudine is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Eletriptan: (Minor) Monitor for an increase in eletriptan-related adverse events if concomitant use with cabozantinib is necessary, as plasma concentrations of eletriptan may be increased. Cabozantinib is a P-glycoprotein (P-gp) inhibitor and eletriptan is a substrate of P-gp; the clinical relevance of this finding is unknown.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concomitant use of cabozantinib and cobicistat due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with cobicistat 2 to 3 days after discontinuation of cobicistat. Cabozantinib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%. (Minor) Monitor for an increase in both cabozantinib- and tenofovir-related adverse reactions if coadministration is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and tenofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib. Cabozantinib is also P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as tenofovir. The clinical relevance of either of these interactions is unknown.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of cabozantinib and cobicistat due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with cobicistat 2 to 3 days after discontinuation of cobicistat. Cabozantinib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%. (Minor) Monitor for an increase in both cabozantinib- and tenofovir-related adverse reactions if coadministration is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and tenofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib. Cabozantinib is also P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as tenofovir. The clinical relevance of either of these interactions is unknown.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Minor) Monitor for an increase in both cabozantinib- and tenofovir-related adverse reactions if coadministration is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and tenofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib. Cabozantinib is also P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as tenofovir. The clinical relevance of either of these interactions is unknown.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Minor) Monitor for an increase in both cabozantinib- and tenofovir-related adverse reactions if coadministration is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and tenofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib. Cabozantinib is also P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as tenofovir. The clinical relevance of either of these interactions is unknown.
Emtricitabine; Tenofovir alafenamide: (Minor) Monitor for an increase in both cabozantinib- and tenofovir-related adverse reactions if coadministration is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and tenofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib. Cabozantinib is also P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as tenofovir. The clinical relevance of either of these interactions is unknown.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) Monitor for an increase in both cabozantinib- and tenofovir-related adverse reactions if coadministration is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and tenofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib. Cabozantinib is also P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as tenofovir. The clinical relevance of either of these interactions is unknown.
Encorafenib: (Major) Avoid coadministration of cabozantinib with encorafenib due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with encorafenib 2 to 3 days after discontinuation of encorafenib. Cabozantinib is a CYP3A substrate and encorafenib is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased single-dose cabozantinib exposure by 77%.
Enzalutamide: (Major) Avoid coadministration of cabozantinib with enzalutamide due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with enzalutamide 2 to 3 days after discontinuation of enzalutamide. Cabozantinib is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased single-dose cabozantinib exposure by 77%.
Erythromycin: (Minor) Monitor for an increase in erythromycin-related adverse reactions if coadministration with cabozantinib is necessary. Erythromycin is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Ethinyl Estradiol; Norelgestromin: (Minor) Monitor for an increase in ethinyl estradiol-related adverse reactions if coadministration with cabozantinib is necessary. Ethinyl estradiol is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Ethinyl Estradiol; Norethindrone Acetate: (Minor) Monitor for an increase in ethinyl estradiol-related adverse reactions if coadministration with cabozantinib is necessary. Ethinyl estradiol is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Ethinyl Estradiol; Norgestrel: (Minor) Monitor for an increase in ethinyl estradiol-related adverse reactions if coadministration with cabozantinib is necessary. Ethinyl estradiol is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Monitor for an increase in ethinyl estradiol-related adverse reactions if coadministration with cabozantinib is necessary. Ethinyl estradiol is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Etonogestrel; Ethinyl Estradiol: (Minor) Monitor for an increase in ethinyl estradiol-related adverse reactions if coadministration with cabozantinib is necessary. Ethinyl estradiol is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with cabozantinib is necessary. The dose of everolimus may need to be reduced. Everolimus is a P-glycoprotein (P-gp) substrate and cabozantinib is a P-gp inhibitor. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations.
Fosamprenavir: (Major) Avoid concomitant use of cabozantinib and fosamprenavir due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with fosamprenavir 2 to 3 days after discontinuation of fosamprenavir. Cabozantinib is a CYP3A substrate and fosamprenavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Fosphenytoin: (Major) Avoid coadministration of cabozantinib with fosphenytoin due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with fosphenytoin 2 to 3 days after discontinuation of fosphenytoin. Cabozantinib is a CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased single-dose cabozantinib exposure by 77%.
Furosemide: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with furosemide is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and furosemide is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Glecaprevir; Pibrentasvir: (Minor) Monitor for an increase in glecaprevir-related adverse reactions if coadministration with cabozantinib is necessary. Glecaprevir is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown. (Minor) Monitor for an increase in pibrentasvir-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of pibrentasvir may be necessary. Pibrentasvir is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Glyburide: (Minor) Monitor for an increase in glyburide-related adverse reactions, including hypoglycemia, if coadministration with cabozantinib is necessary. Glyburide is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Glyburide; Metformin: (Minor) Monitor for an increase in glyburide-related adverse reactions, including hypoglycemia, if coadministration with cabozantinib is necessary. Glyburide is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Grapefruit juice: (Major) Advise patients to avoid grapefruit and grapefruit juice during cabozantinib treatment due to the risk of increased cabozantinib exposure and adverse reactions. Cabozantinib is a CYP3A substrate and grapefruit juice is a strong CYP3A inhibitor.
Idelalisib: (Major) Avoid concomitant use of cabozantinib and idelalisib due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with idelalisib 2 to 3 days after discontinuation of idelalisib. Cabozantinib is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Indinavir: (Major) Avoid concomitant use of cabozantinib and indinavir due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with indinavir 2 to 3 days after discontinuation of indinavir. Cabozantinib is a CYP3A substrate and indinavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of cabozantinib with rifampin due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with rifampin 2 to 3 days after discontinuation of rifampin. Cabozantinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased single-dose cabozantinib exposure by 77%.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of cabozantinib with rifampin due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with rifampin 2 to 3 days after discontinuation of rifampin. Cabozantinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased single-dose cabozantinib exposure by 77%.
Itraconazole: (Major) Avoid concomitant use of cabozantinib and itraconazole due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with itraconazole 2 to 3 days after discontinuation of itraconazole. Cabozantinib is a CYP3A substrate and itraconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Ketoconazole: (Major) Avoid concomitant use of cabozantinib and ketoconazole due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with ketoconazole 2 to 3 days after discontinuation of ketoconazole. Cabozantinib is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Coadministration with ketoconazole increased cabozantinib exposure by 38%.
Lamivudine, 3TC: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with lamivudine is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and lamivudine is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Lamivudine, 3TC; Zidovudine, ZDV: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with lamivudine is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and lamivudine is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Lamivudine; Tenofovir Disoproxil Fumarate: (Minor) Monitor for an increase in both cabozantinib- and tenofovir-related adverse reactions if coadministration is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and tenofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib. Cabozantinib is also P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as tenofovir. The clinical relevance of either of these interactions is unknown. (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with lamivudine is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and lamivudine is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of cabozantinib and clarithromycin due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with clarithromycin 2 to 3 days after discontinuation of clarithromycin. Cabozantinib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Lapatinib: (Moderate) Monitor for an increase in lapatinib-related adverse reactions if coadministration with cabozantinib is necessary. Lapatinib is a P-glycoprotein (P-gp) substrate and cabozantinib is a P-gp inhibitor. Increased plasma concentrations of lapatinib are likely.
Lefamulin: (Moderate) Monitor for lefamulin-related adverse effects if oral lefamulin is administered with cabozantinib as concurrent use may increase exposure from lefamulin tablets; an interaction is not expected with intravenous lefamulin. Lefamulin is a CYP3A4 and P-gp substrate and cabozantinib is a P-gp inhibitor.
Letermovir: (Moderate) Avoid coadministration of letermovir and cabozantinib in patients also receiving cyclosporine due to the risk of increased cabozantinib exposure; an interaction is not expected in patients taking letermovir and cabozantinib without cyclosporine. If concomitant use of cabozantinib with both letermovir and cyclosporine is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 40 mg/day; 40 mg/day to 20 mg/day); for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 100 mg/day or 100 mg/day to 60 mg/day). Resume the cabozantinib dose that was used prior to initiating treatment with letermovir and cyclosporine 2 to 3 days after discontinuation of either letermovir or cyclosporine. Cabozantinib is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased single-dose cabozantinib exposure by 38%.
Levoketoconazole: (Major) Avoid concomitant use of cabozantinib and ketoconazole due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with ketoconazole 2 to 3 days after discontinuation of ketoconazole. Cabozantinib is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Coadministration with ketoconazole increased cabozantinib exposure by 38%.
Levonorgestrel; Ethinyl Estradiol: (Minor) Monitor for an increase in ethinyl estradiol-related adverse reactions if coadministration with cabozantinib is necessary. Ethinyl estradiol is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Monitor for an increase in ethinyl estradiol-related adverse reactions if coadministration with cabozantinib is necessary. Ethinyl estradiol is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Minor) Monitor for an increase in ethinyl estradiol-related adverse reactions if coadministration with cabozantinib is necessary. Ethinyl estradiol is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Lonafarnib: (Major) Avoid concomitant use of cabozantinib and lonafarnib due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with lonafarnib 2 to 3 days after discontinuation of lonafarnib. Cabozantinib is a CYP3A substrate and lonafarnib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Loperamide: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with cabozantinib. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and cabozantinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with cabozantinib. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and cabozantinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lopinavir; Ritonavir: (Major) Avoid concomitant use of cabozantinib and ritonavir due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with ritonavir 2 to 3 days after discontinuation of ritonavir. Cabozantinib is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of cabozantinib with lumacaftor; ivacaftor due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with lumacaftor; ivacaftor 2 to 3 days after discontinuation of lumacaftor; ivacaftor. Cabozantinib is a CYP3A4 substrate and lumacaftor; ivacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased single-dose cabozantinib exposure by 77%.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of cabozantinib with lumacaftor; ivacaftor due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with lumacaftor; ivacaftor 2 to 3 days after discontinuation of lumacaftor; ivacaftor. Cabozantinib is a CYP3A4 substrate and lumacaftor; ivacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased single-dose cabozantinib exposure by 77%.
Maraviroc: (Minor) Monitor for an increase in maraviroc-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of maraviroc may be necessary. Maraviroc is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Mefloquine: (Minor) Monitor for an increase in mefloquine-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of mefloquine may be necessary. Mefloquine is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Mifepristone: (Major) Avoid concomitant use of cabozantinib and mifepristone due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with mifepristone 2 to 3 days after discontinuation of mifepristone. Cabozantinib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Mitotane: (Major) Avoid coadministration of cabozantinib with mitotane due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with mitotane 2 to 3 days after discontinuation of mitotane. Cabozantinib is a CYP3A4 substrate and mitotane is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased single-dose cabozantinib exposure by 77%.
Morphine: (Minor) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with cabozantinib is necessary; a dose adjustment of morphine may be necessary. Morphine is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold.
Morphine; Naltrexone: (Minor) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with cabozantinib is necessary; a dose adjustment of morphine may be necessary. Morphine is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold.
Naldemedine: (Minor) Monitor for an increase in naldemedine-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of naldemedine may be necessary. Naldemedine is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and cabozantinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and cabozantinib is a P-gp inhibitor.
Nefazodone: (Major) Avoid concomitant use of cabozantinib and nefazodone due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with nefazodone 2 to 3 days after discontinuation of nefazodone. Cabozantinib is a CYP3A substrate and nefazodone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Nelfinavir: (Major) Avoid concomitant use of cabozantinib and nelfinavir due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with nelfinavir 2 to 3 days after discontinuation of nelfinavir. Cabozantinib is a CYP3A substrate and nelfinavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Nirmatrelvir; Ritonavir: (Major) Avoid concomitant use of cabozantinib and ritonavir due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with ritonavir 2 to 3 days after discontinuation of ritonavir. Cabozantinib is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Monitor for an increase in ethinyl estradiol-related adverse reactions if coadministration with cabozantinib is necessary. Ethinyl estradiol is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Norethindrone; Ethinyl Estradiol: (Minor) Monitor for an increase in ethinyl estradiol-related adverse reactions if coadministration with cabozantinib is necessary. Ethinyl estradiol is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Monitor for an increase in ethinyl estradiol-related adverse reactions if coadministration with cabozantinib is necessary. Ethinyl estradiol is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Norgestimate; Ethinyl Estradiol: (Minor) Monitor for an increase in ethinyl estradiol-related adverse reactions if coadministration with cabozantinib is necessary. Ethinyl estradiol is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid coadministration of cabozantinib with rifabutin due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with rifabutin 2 to 3 days after discontinuation of rifabutin. Cabozantinib is a CYP3A4 substrate and rifabutin is a CYP3A4 inducer.
Paclitaxel: (Minor) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of paclitaxel may be necessary. Paclitaxel is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Pazopanib: (Minor) Monitor for an increase in pazopanib-related adverse reactions if coadministration of with cabozantinib is necessary; a dose adjustment of pazopanib may be necessary. Pazopanib is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Phenobarbital: (Major) Avoid coadministration of cabozantinib with phenobarbital due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with phenobarbital 2 to 3 days after discontinuation of phenobarbital. Cabozantinib is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased single-dose cabozantinib exposure by 77%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of cabozantinib with phenobarbital due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with phenobarbital 2 to 3 days after discontinuation of phenobarbital. Cabozantinib is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased single-dose cabozantinib exposure by 77%.
Phenytoin: (Major) Avoid coadministration of cabozantinib with phenytoin due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with phenytoin 2 to 3 days after discontinuation of phenytoin. Cabozantinib is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased single-dose cabozantinib exposure by 77%.
Posaconazole: (Major) Avoid concomitant use of cabozantinib and posaconazole due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with posaconazole 2 to 3 days after discontinuation of posaconazole. Cabozantinib is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Pralsetinib: (Major) Avoid concomitant use of cabozantinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and cabozantinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Prednisone: (Minor) Monitor for an increase in prednisone-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of prednisone may be necessary. Prednisone is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Primidone: (Major) Avoid coadministration of cabozantinib with primidone due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with primidone 2 to 3 days after discontinuation of primidone. Cabozantinib is a CYP3A4 substrate and primidone is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased single-dose cabozantinib exposure by 77%.
Probenecid: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with probenecid is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and probenecid is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and cabozantinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and cabozantinib is a P-gp inhibitor. (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with probenecid is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and probenecid is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Quinidine: (Minor) Monitor for an increase in quinidine-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of quinidine may be necessary. Quinidine is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Quinine: (Minor) Monitor for an increase in quinine-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of quinine may be necessary. Quinine is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Ranolazine: (Minor) Monitor for an increase in ranolazine-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of ranolazine may be necessary. Ranolazine is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Relugolix: (Major) Avoid concomitant use of relugolix and oral cabozantinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer cabozantinib at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and cabozantinib is a P-gp inhibitor.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral cabozantinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer cabozantinib at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and cabozantinib is a P-gp inhibitor.
Repotrectinib: (Major) Avoid coadministration of repotrectinib with cabozantinib due to increased repotrectinib exposure which may increase the risk for repotrectinib-related adverse effects. Repotrectinib is a P-gp substrate and cabozantinib is a P-gp inhibitor.
Ribociclib: (Major) Avoid concomitant use of cabozantinib and ribociclib due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with ribociclib 2 to 3 days after discontinuation of ribociclib. Cabozantinib is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Ribociclib; Letrozole: (Major) Avoid concomitant use of cabozantinib and ribociclib due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with ribociclib 2 to 3 days after discontinuation of ribociclib. Cabozantinib is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Rifabutin: (Major) Avoid coadministration of cabozantinib with rifabutin due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with rifabutin 2 to 3 days after discontinuation of rifabutin. Cabozantinib is a CYP3A4 substrate and rifabutin is a CYP3A4 inducer.
Rifampin: (Major) Avoid coadministration of cabozantinib with rifampin due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with rifampin 2 to 3 days after discontinuation of rifampin. Cabozantinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased single-dose cabozantinib exposure by 77%.
Rifapentine: (Major) Avoid coadministration of cabozantinib with rifapentine due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with rifapentine 2 to 3 days after discontinuation of rifapentine. Cabozantinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased single-dose cabozantinib exposure by 77%.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with cabozantinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and cabozantinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with cabozantinib; concurrent use may increase rimegepant exposure. Rimegepant is a P-gp substrate and cabozantinib is a P-gp inhibitor.
Ritonavir: (Major) Avoid concomitant use of cabozantinib and ritonavir due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with ritonavir 2 to 3 days after discontinuation of ritonavir. Cabozantinib is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Romidepsin: (Minor) Monitor for an increase in romidepsin-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of romidepsin may be necessary. Romidepsin is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Saquinavir: (Major) Avoid concomitant use of cabozantinib and saquinavir due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with saquinavir 2 to 3 days after discontinuation of saquinavir. Cabozantinib is a CYP3A substrate and saquinavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Monitor for an increase in ethinyl estradiol-related adverse reactions if coadministration with cabozantinib is necessary. Ethinyl estradiol is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Silodosin: (Minor) Monitor for an increase in silodosin-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of silodosin may be necessary. Silodosin is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of cabozantinib. Coadministration may increase sirolimus concentrations and the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and cabozantinib is a P-gp inhibitor.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of cabozantinib with St. Johns Wort due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with St. Johns Wort 2 to 3 days after discontinuation of St. Johns Wort. Cabozantinib is a CYP3A4 substrate and St. Johns Wort is a strong CYP3A4 inducer, although the effect varies widely and is preparation-dependent. Coadministration with another strong CYP3A4 inducer decreased single-dose cabozantinib exposure by 77%.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with cabozantinib is necessary. Talazoparib is a P-gp substrate and cabozantinib is a P-gp inhibitor.
Temsirolimus: (Minor) Monitor for an increase in temsirolimus-related adverse reactions if coadministration with cabozantinib is necessary. Temsirolimus is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Tenofovir Alafenamide: (Minor) Monitor for an increase in both cabozantinib- and tenofovir-related adverse reactions if coadministration is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and tenofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib. Cabozantinib is also P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as tenofovir. The clinical relevance of either of these interactions is unknown.
Tenofovir Alafenamide: (Minor) Monitor for an increase in both cabozantinib- and tenofovir-related adverse reactions if coadministration is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and tenofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib. Cabozantinib is also P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as tenofovir. The clinical relevance of either of these interactions is unknown.
Tenofovir Disoproxil Fumarate: (Minor) Monitor for an increase in both cabozantinib- and tenofovir-related adverse reactions if coadministration is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and tenofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib. Cabozantinib is also P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as tenofovir. The clinical relevance of either of these interactions is unknown.
Ticagrelor: (Minor) Monitor for an increase in ticagrelor-related adverse reactions if coadministration with cabozantinib is necessary. Ticagrelor is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Tipranavir: (Major) Avoid concomitant use of cabozantinib and tipranavir due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with tipranavir 2 to 3 days after discontinuation of tipranavir. Cabozantinib is a CYP3A substrate and tipranavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Topotecan: (Major) Avoid coadministration of cabozantinib with oral topotecan due to increased topotecan exposure; cabozantinib may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp). Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone.
Trandolapril; Verapamil: (Minor) Monitor for an increase in verapamil-related adverse reactions if coadministration with cabozantinib is necessary. Verapamil is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Tucatinib: (Major) Avoid concomitant use of cabozantinib and tucatinib due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with tucatinib 2 to 3 days after discontinuation of tucatinib. Cabozantinib is a CYP3A substrate and tucatinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with cabozantinib. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of the P-gp drug transporter; cabozantinib is a P-gp inhibitor.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with cabozantinib due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of cabozantinib. Venetoclax is a P-glycoprotein (P-gp) substrate; cabozantinib is a P-gp inhibitor. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
Verapamil: (Minor) Monitor for an increase in verapamil-related adverse reactions if coadministration with cabozantinib is necessary. Verapamil is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Vincristine Liposomal: (Moderate) Monitor for an increase in vincristine-related adverse reactions, including neurotoxicity and severe constipation, if coadministration of with cabozantinib is necessary. Cabozantinib is a P-glycoprotein (P-gp) inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as vincristine; however, the clinical relevance of this finding is unknown. The effect of concomitant use of P-gp inhibitors with vincristine has not been investigated, but it is likely that these agents will alter the pharmacokinetics or pharmacodynamics of vincristine.
Vincristine: (Moderate) Monitor for an increase in vincristine-related adverse reactions, including neurotoxicity and severe constipation, if coadministration of with cabozantinib is necessary. Cabozantinib is a P-glycoprotein (P-gp) inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as vincristine; however, the clinical relevance of this finding is unknown. The effect of concomitant use of P-gp inhibitors with vincristine has not been investigated, but it is likely that these agents will alter the pharmacokinetics or pharmacodynamics of vincristine.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of cabozantinib and clarithromycin due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with clarithromycin 2 to 3 days after discontinuation of clarithromycin. Cabozantinib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Voriconazole: (Major) Avoid concomitant use of cabozantinib and voriconazole due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with voriconazole 2 to 3 days after discontinuation of voriconazole. Cabozantinib is a CYP3A substrate and voriconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Cabozantinib is an oral multi-tyrosine kinase inhibitor that works by blocking abnormal tyrosine kinase proteins (RET, MET, VEGFR-1, VEGFR-2, VEGFR-3, KIT, TRKB, FLT-3, AXL, TIE-2, ROS1, TYRO3, and MER) associated with the growth and development of medullary thyroid cancer (MTC) and renal cell carcinoma. Cabozantinib inhibits these receptor tyrosine kinases (RTK) that are responsible for the control of many cellular functions including cell migration, metabolism, proliferation, and differentiation, as well as maintenance of the tumor microenvironment. RTK mutations are common in MTC, occurring in 30 to 50% of sporadic cases and almost all of hereditary cases. The RET gene mutation activation is associated with a predisposition to certain cancers including MTC; increased levels of RTKs are also found in renal cell cancers. Cabozantinib inhibited MET and VEGFR-2 phosphorylation in vitro and in tumor models in vivo. In mouse models, cabozantinib led to decreased tumor and endothelial cell proliferation and increased apoptosis and inhibition of breast, lung, and glioma tumor growth.
Cabozantinib is administered orally. It is highly bound to human plasma proteins (99.7% or more). The mean volume of distribution (Vd) was 349 L, the mean clearance was 4.4 L/hour, and the predicted effective half-life was 55 hours following oral doses of cabozantinib (Cometriq) 140 mg/day administered to 289 patients with solid tumors including medullary thyroid cancer in a pharmacokinetic analysis. The manufacturer of Cabometyx reports the Vd as 319 L, clearance as 2.2 L/hour, and terminal half-life as 99 hours. Following a single oral dose of 14C-cabozantinib given to healthy subjects, about 81% of the total radioactivity was recovered, with 54% of the radioactivity in the feces (43% as unchanged drug) and 21% of the radioactivity in the urine. Unchanged cabozantinib was not detectable in the urine following a 72-hour collection.
Affected cytochrome P450 isoenzymes and drug transporters: CYP1A1, CYP2C8, CYP2C9, CYP2C19, CYP3A4, P-gp, MRP2
Cabozantinib is metabolized in the liver and is a substrate of CYP3A4 in vitro; inhibition of CYP3A4 reduced the formation of the oxidative metabolite by > 80%. While cabozantinib is also a CYP2C9 substrate, inhibition of CYP2C9 had a minimal effect on metabolite formation (less than 20%). Cabozantinib is a CYP2C8 inhibitor in vitro; however, the interaction was not found to be relevant in a clinical study. Because of this, less sensitive substrates of other pathways affected by cabozantinib in vitro (i.e., CYP2C9, CYP2C19, CYP3A4) were not evaluated and a clinically relevant effect is considered unlikely. Cabozantinib induces CYP1A1 mRNA; however, the clinical significance of this interaction is unknown. It is also a MRP2 substrate and P-glycoprotein (P-gp) inhibitor, but the clinical significance of these findings is unknown.
-Route-Specific Pharmacokinetics
Oral Route
Following a single cabozantinib oral dose, the median time to peak plasma concentration (Tmax) was 2 to 5 hours in 289 patients with solid tumors including medullary thyroid cancer in a pharmacokinetic analysis. Following repeat oral cabozantinib 140 mg/day dosing, steady state was achieved by day 15 and the AUC increased to 4 to 5 times the values achieved with single doses by day 19. When a single cabozantinib 140-mg dose was administered with a high-fat meal in healthy subjects, the Cmax and AUC values were increased by 41% and 57%, respectively. Therefore, cabozantinib should be taken on an empty stomach.
The Cmax of the tablet formulation of cabozantinib (Cabometyx) was 19% higher compared to the capsule formulation (Cometriq) after a single 140-mg dose; the AUC was less than 10% different between dosage forms. Do not substitute Cabometyx tablets with Cometriq capsules.
-Special Populations
Hepatic Impairment
Cabozantinib exposure increased by 81% and 63%, respectively, in patients with mild (Child-Pugh class A) and moderate (Child-Pugh class B) hepatic impairment. The pharmacokinetic parameters of cabozantinib have not been evaluated in patients with severe (Child-Pugh class C) hepatic impairment. Because cabozantinib is metabolized in the liver, its use in patients with severe hepatic impairment is not recommended.
Renal Impairment
Cabozantinib clearance did not significantly change in subjects with mild to moderate renal impairment (CrCL 30 mL/min or more) in a population pharmacokinetic analysis. The pharmacokinetics of cabozantinib in patients with severe renal impairment (CrCL less than 30 mL/min) or end-stage renal disease (ESRD) requiring dialysis is unknown.
Pediatrics
The systemic exposure to cabozantinib in pediatric patients 12 years and older at the recommended dosages are expected to be comparable to the exposure in adults at the dose of cabozantinib 60 mg (tablets) once daily.
Geriatric
Age (range, 20 to 86 years) did not affect the pharmacokinetic parameters of cabozantinib in a population pharmacokinetic analysis.
Gender Differences
Gender had no clinically significant impact on cabozantinib clearance in a population pharmacokinetic analysis.
Ethnic Differences
Ethnicity had no clinically significant impact on cabozantinib pharmacokinetics in a population pharmacokinetic analysis.