Cotellic

2 DOSAGE AND ADMINISTRATION Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of COTELLIC with vemurafenib for patients with melanoma. ( 2.1 ) The recommended dose is 60 mg orally once daily for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity. Take COTELLIC with or without food. ( 2.2 ) 2.1 Patient Selection for Treatment of Melanoma Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of treatment with COTELLIC with vemurafenib. Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics . 2.2 Recommended Dosage The recommended dosage regimen of COTELLIC is 60 mg (three 20 mg tablets) orally taken once daily for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity [see Clinical Studies (14) ] . Take COTELLIC with or without food [see Clinical Pharmacology (12.3) ] . If a dose of COTELLIC is missed or if vomiting occurs when the dose is taken, resume dosing with the next scheduled dose. 2.3 Dose Modifications Concurrent CYP3A Inhibitors Do not take strong or moderate CYP3A inhibitors while taking COTELLIC. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking COTELLIC 60 mg, reduce COTELLIC dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume previous dose of COTELLIC 60 mg [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . Use an alternative to a strong or moderate CYP3A inhibitor in patients who are taking a reduced dose of COTELLIC (40 or 20 mg daily) [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . Adverse Reactions Review the Full Prescribing Information for vemurafenib for recommended dose modifications. Table 1. Recommended Dose Reductions for COTELLIC First Dose Reduction 40 mg orally once daily Second Dose Reduction 20 mg orally once daily Subsequent Modification Permanently discontinue COTELLIC if unable to tolerate 20 mg orally once daily Table 2. Recommended Dose Modifications for COTELLIC for Adverse Reactions Severity of Adverse Reaction National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0) Dose Modification for COTELLIC New Primary Malignancies (cutaneous and non-cutaneous) No dose modification is required. Hemorrhage Grade 3 Withhold COTELLIC for up to 4 weeks. If improved to Grade 0 or 1, resume at the next lower dose level. If not improved within 4 weeks, permanently discontinue. Grade 4 Permanently discontinue. Cardiomyopathy Asymptomatic, absolute decrease in LVEF from baseline of greater than 10% and less than institutional lower limit of normal (LLN) Withhold COTELLIC for 2 weeks; repeat LVEF. Resume at next lower dose if all of the following are present: LVEF is at or above LLN and Absolute decrease from baseline LVEF is 10% or less. Permanently discontinue if any of the following are present: LVEF is less than LLN or Absolute decrease from baseline LVEF is more than 10%. Symptomatic LVEF decrease from baseline Withhold COTELLIC for up to 4 weeks, repeat LVEF. Resume at next lower dose if all of the following are present: Symptoms resolve and LVEF is at or above LLN and Absolute decrease from baseline LVEF is 10% or less. Permanently discontinue if any of the following are present: Symptoms persist, or LVEF is less than LLN, or Absolute decrease from baseline LVEF is more than 10%. Dermatologic Reactions Grade 2 (intolerable), Grade 3 or 4 Withhold or reduce dose. Serous Retinopathy or Retinal Vein Occlusion Serous retinopathy Withhold COTELLIC for up to 4 weeks. If signs and symptoms improve, resume at the next lower dose level. If not improved or symptoms recur at the lower dose within 4 weeks, permanently discontinue. Retinal vein occlusion Permanently discontinue COTELLIC. Liver Laboratory Abnormalities and Hepatotoxicity First occurrence Grade 4 Withhold COTELLIC for up to 4 weeks. If improved to Grade 0 or 1, then resume at the next lower dose level. If not improved to Grade 0 or 1 within 4 weeks, permanently discontinue. Recurrent Grade 4 Permanently discontinue COTELLIC. Rhabdomyolysis and Creatine Phosphokinase (CPK) elevations Grade 4 CPK elevation Any CPK elevation and myalgia Withhold COTELLIC for up to 4 weeks. If improved to Grade 3 or lower, resume at the next lower dose level. If not improved within 4 weeks, permanently discontinue. Photosensitivity Grade 2 (intolerable), Grade 3 or Grade 4 Withhold COTELLIC for up to 4 weeks. If improved to Grade 0 or 1, resume at the next lower dose level. If not improved within 4 weeks, permanently discontinue. Other Grade 2 (intolerable) adverse reactions Any Grade 3 adverse reactions Withhold COTELLIC for up to 4 weeks. If improved to Grade 0 or 1, resume at the next lower dose level. If not improved within 4 weeks, permanently discontinue. First occurrence of any Grade 4 adverse reaction Withhold COTELLIC until adverse reaction improves to Grade 0 or 1. Then resume at the next lower dose level, OR Permanently discontinue. Recurrent Grade 4 adverse reaction Permanently discontinue COTELLIC.

See official label

1 INDICATIONS AND USAGE COTELLIC ® is a kinase inhibitor indicated: For the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with vemurafenib.