Cabometyx

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Cabometyx

Classes

Small Molecule Antineoplastic Multikinase Inhibitors

Administration

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.

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.

Adverse Reactions
Severe

hypertension / Early / 8.0-28.0
elevated hepatic enzymes / Delayed / 1.0-24.0
palmar-plantar erythrodysesthesia (hand and foot syndrome) / Delayed / 8.0-17.0
lymphopenia / Delayed / 0-16.0
diarrhea / Early / 7.0-16.0
hypocalcemia / Delayed / 0-12.0
fatigue / Early / 6.0-10.0
hypophosphatemia / Delayed / 3.0-9.0
hyponatremia / Delayed / 0-8.0
thromboembolism / Delayed / 2.0-7.0
asthenia / Delayed / 0-7.0
hypomagnesemia / Delayed / 1.0-7.0
neutropenia / Delayed / 2.0-7.0
anorexia / Delayed / 3.0-6.0
hypokalemia / Delayed / 0-6.0
GI bleeding / Delayed / 0-5.0
bleeding / Early / 3.0-5.0
pulmonary embolism / Delayed / 2.0-5.0
hypotension / Rapid / 0-5.0
syncope / Early / 0-5.0
weight loss / Delayed / 1.0-5.0
anemia / Delayed / 2.5-5.0
stomatitis / Delayed / 2.0-5.0
oral ulceration / Delayed / 0-5.0
nausea / Early / 1.0-4.0
dysphagia / Delayed / 0-4.0
abdominal pain / Early / 0-4.0
back pain / Delayed / 0-4.0
depression / Delayed / 0-4.0
dehydration / Delayed / 0-4.0
hypertriglyceridemia / Delayed / 0-4.0
tracheoesophageal fistula / Delayed / 0-4.0
renal failure (unspecified) / Delayed / 0-4.0
skin ulcer / Delayed / 0-3.0
proteinuria / Delayed / 0-3.0
bone pain / Delayed / 0-3.0
dyspnea / Early / 0-3.0
GI perforation / Delayed / 0-3.0
vomiting / Early / 0-2.0
wound dehiscence / Delayed / 0-2.0
rash / Early / 0-2.0
hyperbilirubinemia / Delayed / 0-2.0
hypoalbuminemia / Delayed / 0-2.0
headache / Early / 0-2.0
hyperglycemia / Delayed / 0-2.0
thrombocytopenia / Delayed / 0-2.0
hyperamylasemia / Delayed / 0-2.0
glossitis / Early / 0-2.0
xerostomia / Early / 0-1.0
constipation / Delayed / 0-1.0
dyspepsia / Early / 0-1.0
erythema / Early / 0-1.0
infection / Delayed / 0-1.0
osteonecrosis / Delayed / 0-1.0
nephrotic syndrome / Delayed / 0-1.0
arthralgia / Delayed / 0-1.0
musculoskeletal pain / Early / 0-1.0
muscle cramps / Delayed / 0-1.0
cough / Delayed / 0-1.0
dysphonia / Delayed / 0-1.0
hyperkalemia / Delayed / 0-1.0
leukopenia / Delayed / 0-1.0
leukoencephalopathy / Delayed / 0-1.0
seizures / Delayed / 0-1.0
pancreatitis / Delayed / 0-1.0
hypothyroidism / Delayed / 0-1.0
gastrointestinal fistula / Delayed / 0-1.0
thrombosis / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
cardiac arrest / Early / Incidence not known
hepatic failure / Delayed / Incidence not known
visual impairment / Early / Incidence not known
aortic dissection / Delayed / Incidence not known

Moderate

hemorrhoids / Delayed / 0-9.0
peripheral neuropathy / Delayed / 0-7.0
hepatitis / Delayed / 0-1.0
confusion / Early / 0-1.0
hemoptysis / Delayed / Incidence not known
impaired wound healing / Delayed / Incidence not known
contact dermatitis / Delayed / Incidence not known
osteomyelitis / Delayed / Incidence not known
hypoglycemia / Early / Incidence not known
adrenocortical insufficiency / Delayed / Incidence not known
pneumonitis / Delayed / Incidence not known

Mild

hair discoloration / Delayed / 0-34.0
dysgeusia / Early / 12.0-34.0
xerosis / Delayed / 0-19.0
alopecia / Delayed / 0-16.0
dizziness / Early / 0-14.0
anxiety / Delayed / 0-9.0
hyperkeratosis / Delayed / 0-7.0
paresthesias / Delayed / 0-7.0
gastroesophageal reflux / Delayed / Incidence not known
vesicular rash / Delayed / Incidence not known
acneiform rash / Delayed / Incidence not known
pruritus / Rapid / Incidence not known
maculopapular rash / Early / Incidence not known
dental pain / Delayed / Incidence not known

Common Brand Names

Cabometyx, COMETRIQ

Dea Class

Rx

Description

Multi-tyrosine kinase inhibitor
Used for certain types of thyroid cancer, advanced renal cell carcinoma, hepatocellular carcinoma
Do not give cabozantinib for at least 3 weeks before elective surgery or for at least 2 weeks after major surgery and until adequate wound healing has occurred

Dosage And Indications
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 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 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 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.[63362] [60738]

Dosing Considerations
Hepatic Impairment

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.[52506]
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.[60738]
 
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.

Renal Impairment

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.

Drug Interactions

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 releva

nce 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%.

How Supplied

Cabometyx Oral Tab: 20mg, 40mg, 60mg
COMETRIQ Oral Cap: 20mg, 20-80mg

Maximum Dosage
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.

Mechanism Of Action

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.

Pharmacokinetics

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.

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.

Pregnancy And Lactation
Pregnancy

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.

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.