FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE
MEKINIST™ is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test [see Clinical Studies (14.1)].

Limitation of use: MEKINIST is not indicated for treatment of patients who have received prior BRAF-inhibitor therapy [see Clinical Studies (14.2)].
2 DOSAGE AND ADMINISTRATION
2.1 Patient Selection
Select patients for treatment of unresectable or metastatic melanoma with MEKINIST based on presence of BRAF V600E or V600K mutation in tumor specimens [see Clinical Studies (14.1)]. 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 Dosing
The recommended dose is 2 mg orally once daily until disease progression or unacceptable toxicity. Take at least 1 hour before or 2 hours after a meal. Do not take a missed dose within 12 hours of the next dose.
2.3 Dose Modifications
Table 1. Recommended Dose Modifications for MEKINIST 
Target Organ 
Adverse Reactiona 
Dose Modification
 
Cutaneous 
Grade 2 rash 
Reduce dose of MEKINIST by 0.5 mg or discontinue MEKINIST in patients taking MEKINIST 1 mg daily
 
Intolerable Grade 2 rash that does not improve within 3 weeks following dose reduction
 
Grade 3 or 4 rash 
Withhold MEKINIST for up to 3 weeks
 
If improved within 3 weeks, resume MEKINIST at a lower dose (reduced by 0.5 mg) or discontinue MEKINIST in patients taking MEKINIST 1 mg daily
 
Intolerable Grade 2, or Grade 3 or 4 rash that does not improve within 3 weeks despite interruption of dosing of MEKINIST 
Permanently discontinue MEKINIST
 
Cardiac 
Asymptomatic, absolute decrease in LVEF of 10% or greater from baseline and is below institutional lower limits of normal (LLN) from pretreatment value 
Withhold MEKINIST for up to 4 weeks
 
Asymptomatic, absolute decrease in LVEF of 10% or greater from baseline and is below LLN that improves to normal LVEF value within 4 weeks following interruption of MEKINIST 
If improved within 4 weeks, resume MEKINIST at a lower dose (reduced by 0.5 mg) or discontinue MEKINIST in patients taking MEKINIST 1 mg daily
 
Symptomatic congestive heart failure
 
Absolute decrease in LVEF of greater than 20% from baseline that is below LLN
 
Absolute decrease in LVEF of 10% or greater from baseline and is below LLN that does not improve to normal LVEF value within 4 weeks following interruption of MEKINIST 
Permanently discontinue MEKINIST
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