RESNIBEN

A population pharmacokinetic analysis of cabozantinib was performed using data collected from 289 patients with solid tumors including MTC following oral administration of 140 mg daily doses. Repeat daily dosing of COMETRIQ at 140 mg for 19 days resulted in 4- to 5-fold mean cabozantinib accumulation (based on AUC) compared to a single dose administration; steady state was achieved by Day 15.

AbsorptionFollowing oral administration of COMETRIQ, median time to peak cabozantinib plasma concentrat...

The safety and efficacy of COMETRIQ was assessed in an international, multi-center, randomized, double-blind, controlled trial (Study 1) of 330 patients with metastatic medullary thyroid carcinoma (MTC). Patients were required to have evidence of actively progressive disease within 14 months prior to study entry confirmed by an Independent Radiology Review Committee (IRRC) masked to treatment assignment (89%) or the treating physician (11%). Patients were randomized (2:1) to receive COMETRIQ 140 mg (n = 219) or placebo (n = 111) orally once daily, without food, until disease progression determ...

The following clinically significant adverse reactions are discussed elsewhere in the labeling: Perforations and Fistula [see Warnings and Precautions (5.1) ] Hemorrhage [see Warnings and Precautions (5.2) ] Thromboembolic Events [see Warnings and Precautions (5.3) ] Impaired Wound Healing [see Warnings and Precautions (5.4) ] Hypertension and Hypertensive Crisis [see Warnings and Precautions (5.5) ] Cardiac Failure [see Warnings and Precautions (5.6) ] Osteonecrosis of the Jaw [see Warnings and...

None None. ( 4 )

Perforations and Fistulas: Monitor for symptoms. Discontinue COMETRIQ for Grade 4 fistula or perforation. ( 5.1 ) Hemorrhage: Do not administer COMETRIQ if recent history of hemorrhage. ( 5.2 ) Thrombotic Events: Discontinue COMETRIQ for myocardial infarction or serious arterial or venous thromboembolic events. ( 5.3 ) Impaired Wound Healing: Withhold COMETRIQ for at least 3 weeks before elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound hea...

7 DRUG INTERACTIONS Strong CYP3A4 Inhibitors: Reduce the COMETRIQ dosage. ( 2.2 , 7.1 ) Strong CYP3A4 Inducers: Increase the COMETRIQ dosage. ( 2.2 , 7.2 ) 7.1 Effect of CYP3A4 Inhibitors Administration of a strong CYP3A4 inhibitor, ketoconazole to healthy subjects increased single-dose plasma cabozantinib exposure by 38%. Avoid taking a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, c...