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
Ocular
Grade 2-3 retinal pigment epithelial detachments (RPED)
Withhold Mekinist for up to 3 weeks
Grade 2-3 RPED that improves to Grade 0-1 within 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
Retinal vein occlusion
Grade 2-3 RPED that does not improve to at least Grade 1 within 3 weeks
Permanently discontinue Mekinist
Pulmonary
Interstitial lung disease/pneumonitis
Permanently discontinue Mekinist
Other
Grade 3 adverse reaction
Withhold Mekinist for up to 3 weeks
If Grade 3 adverse reaction improves to Grade 0-1 following interruption of Mekinist within 3 weeks
Reduce dose of Mekinist by 0.5 mg or discontinue Mekinist in patients taking Mekinist 1 mg daily
Grade 4 adverse reaction
Grade 3 adverse reaction that does not improve to Grade 0-1 within 3 weeks
Permanently discontinue Mekinist
a Note: The intensity of clinical adverse events graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Dosage Forms and Strengths
0.5 mg Tablets: Yellow, modified oval, biconvex, film-coated tablets with ‘GS’ debossed on one face and ‘TFC’ on the opposing face.
1 mg Tablets: White, round, biconvex, film-coated tablets with ‘GS’ debossed on one face and ‘LHE’ on the opposing face.
2 mg Tablets: Pink, round, biconvex, film-coated tablets with ‘GS’ debossed on one face and ‘HMJ’ on the opposing face.
Contraindications
None.
Warnings and Precautions
Cardiomyopathy
In Trial 1, cardiomyopathy [defined as cardiac failure, left ventricular dysfunction, or decreased left ventricular ejection fraction (LVEF)] occurred in 7% (14/211) o |
