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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.
3 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.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Cardiomyopathy
In Trial 1, cardiomyopathy [defined as cardiac failure, left ventricular dysfunction, or decreased left ventricular ejection fraction (LVEF)] occurred in 7% (14/211) of patients treated with MEKINIST; no chemotherapy-treated patient in Trial 1 developed cardiomyopathy. The median time to onset of cardiomyopathy in patients treated with MEKINIST was 63 days (range: 16 to 156 days); cardiomyopathy was identified within the first month of treatment with MEKINIST in five of these 14 patients. Four percent of patients in Trial 1 required discontinuation (4/211) and/or dose reduction (7/211) of MEKINIST. Cardiomyopathy resolved in 10 of these 14 (71%) patients.
Across clinical trials of MEKINIST at the recommended dose (N = 329), 11% of patients developed evidence of cardiomyopathy (decrease in LVEF below institutional lower limits of normal with an absolute decrease in LVEF ≥10% below baseline) and 5% demonstrated a decrease in LVEF below institutional lower limits of normal with an absolute decrease in LVEF of ≥20% below baseline.
Assess LVEF by echocardiogram or multigated acquisition (MUGA) scan before initiation of MEKINIST, one month after initiation of MEKINIST, and then at 2- to 3-month intervals while on treatment. Withhold treatment if absolute LVEF value decreases by 10% from pre-treatment values and is less than the lower limit of normal. Permanently discontinue MEKINIST for symptomatic cardiomyopathy or persistent, asymptomatic LVEF dysfunction that does not resolve within 4 weeks [see Dosage and Administration (2.3)].
5.2 Retinal Pigment Epithelial Detachment (RPED)
Retinal pig
