COTELLIC

The pharmacokinetics of cobimetinib was studied in healthy subjects and cancer patients. Cobimetinib exhibits linear pharmacokinetics in the dose range of 3.5 to 100 mg (i.e., 0.06 to 1.7 times the recommended dosage). Following oral administration of COTELLIC 60 mg once daily, steady-state was reached by 9 days with a mean accumulation ratio of 2.4-fold (44% CV).

AbsorptionFollowing oral dosing of 60 mg once daily in cancer patients, the median time to achieve peak plasma levels (T max ) was 2...

14.1 Unresectable or Metastatic Melanoma The safety and efficacy of COTELLIC was established in a multicenter, randomized (1:1), double-blinded, placebo-controlled trial conducted in 495 patients with previously untreated, BRAF V600 mutation-positive, unresectable or metastatic, melanoma. The presence of BRAF V600 mutation was detected using the cobas ® 4800 BRAF V600 mutation test. All patients received vemurafenib 960 mg orally twice daily on days 1–28 and were randomized to receive COTELLIC 60 mg or matching placebo orally once daily on days 1–21 of an every 28-day cycle. Randomization was ...

The following adverse reactions are discussed in greater detail in other sections of the label: New Primary Cutaneous Malignancies [see Warnings and Precautions (5.1) ] Hemorrhage [see Warnings and Precautions (5.2) ] Cardiomyopathy [see Warnings and Precautions (5.3) ] Serious Dermatologic Reactions [see Warnings and Precautions (5.4) ] Serous Retinopathy and Retinal Vein Occlusion [see Warnings and Precautions (5.5) ] Hepatotoxicity [see Warnings and Precautions (5.6) ] Rhabdomyolysis [see War...

None. None. ( 4 )

Review the Full Prescribing Information for vemurafenib for information on the serious risks of vemurafenib. New primary malignancies, cutaneous and non-cutaneous : Monitor patients for new malignancies prior to initiation of therapy, while on therapy, and for up to 6 months following the last dose of COTELLIC. ( 5.1 ) Hemorrhage : Major hemorrhagic events can occur with COTELLIC. Monitor for signs and symptoms of bleeding. ( 5.2 , 2.3 ) Cardiomyopathy : The risk of cardiomyopathy is increased i...

7 DRUG INTERACTIONS Avoid concomitant administration of COTELLIC with strong or moderate CYP3A inducers or inhibitors. ( 2.3 , 7.1 , 7.2 ) 7.1 Effect of Strong or Moderate CYP3A Inhibitors on COTELLIC Coadministration of COTELLIC with itraconazole (a strong CYP3A4 inhibitor) increased cobimetinib systemic exposure by 6.7-fold. Avoid concurrent use of COTELLIC and strong or moderate CYP3A inhibitor...