Mekinist

Mekinist Manufacturers

• Glaxosmithkline Llc
  

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  Mekinist | Glaxosmithkline Llc

  

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  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 dosage regimens of MEKINIST are:

  • 2 mg orally taken once daily as a single agent • 2 mg orally taken once daily in combination with dabrafenib 150 mg orally taken twice daily

  Continue treatment until disease progression or unacceptable toxicity occurs. Take MEKINIST as a single agent, or MEKINIST in combination with dabrafenib, at least 1 hour before or 2 hours after a meal [see Clinical Pharmacology (12.3)]. Do not take a missed dose of MEKINIST within 12 hours of the next dose of MEKINIST. When administered in combination with dabrafenib, take the once daily dose of MEKINIST at the same time each day with either the morning dose or the evening dose of dabrafenib.

  2.3 Dose Modifications

  For New Primary Cutaneous Malignancies: No dose modifications are required.

  For New Primary Non-Cutaneous Malignancies: No dose modifications are required for MEKINIST. If used in combination with dabrafenib, permanently discontinue dabrafenib in patients who develop RAS mutation-positive non-cutaneous malignancies.

  Table 1. Recommended Dose Reductions

  Dose Reductions for MEKINIST When Administered as a Single Agent or in Combination With Dabrafenib

  First Dose Reduction

  1.5 mg orally once daily

  Second Dose Reduction

  1 mg orally once daily

  Subsequent Modification

  Permanently discontinue if unable to tolerate MEKINIST 1 mg orally once daily

  Dose Reductions for Dabrafenib When Administered in Combination With MEKINIST

  First Dose Reduction

  100 mg orally twice daily

  Second Dose Reduction

  75 mg orally twice daily

  Third Dose Reduction

  50 mg orally twice daily

  Subsequent Modification

  Permanently discontinue dabrafenib if unable to tolerate 50 mg orally twice daily

  Table 2. Recommended Dose Modifications for MEKINIST as a Single Agent and for MEKINIST and Dabrafenib Administered in Combination

  Severity of Adverse Reactiona

  MEKINISTb

  Dabrafenib

  (When Used in Combination)b,c

  Febrile drug reaction

  • Fever of 101.3°F to 104oF

  Do not modify the dose of MEKINIST.

  Withhold dabrafenib until fever resolves. Then resume at same or lower dose level.

  • Fever higher than 104°F • Fever complicated by rigors, hypotension, dehydration, or renal failure

  Withhold MEKINIST until fever resolves. Then resume MEKINIST at same or lower dose level.

  • Withhold dabrafenib until fever resolves. Then resume at a lower dose level. 

  Or

  • Permanently discontinue dabrafenib.

  Cutaneous

  • Intolerable Grade 2 skin toxicity • Grade 3 or 4 skin toxicity

  Withhold MEKINIST for up to 3 weeks.

  • If improved, resume at a lower dose level. • If not improved, permanently discontinue.

  Withhold dabrafenib for up to 3 weeks.

  • If improved, resume at a lower dose level. • If not improved, permanently discontinue.

  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.

  • If improved to normal LVEF value, resume at a lower dose level. • If not improved to normal LVEF value, permanently discontinue.

  Do not modify the dose of dabrafenib.

  • Symptomatic congestive heart failure • Absolute decrease in LVEF of greater than 20% from baseline that is below LLN

  Permanently discontinue MEKINIST.

  Withhold dabrafenib, if improved, then resume at the same dose.

  Venous Thromboembolism

  • Uncomplicated DVT or PE

  Withhold MEKINIST for up to 3 weeks.

  • If improved to Grade 0-1, resume at a lower dose level. • If not improved, permanently discontinue.

  Do not modify the dose of dabrafenib.

  • Life Threatening PE

  Permanently discontinue MEKINIST.

  Permanently discontinue dabrafenib.

  Ocular Toxicities

  • Grade 2-3 retinal pigment epithelial detachments (RPED)

  Withhold MEKINIST for up to 3 weeks.

  • If improved to Grade 0-1, resume at a lower dose level. • If not improved, permanently discontinue.

  Do not modify the dose of dabrafenib.

  • Retinal vein occlusion

  Permanently discontinue MEKINIST.

  Do not modify the dose of dabrafenib.

  • Uveitis and Iritis

  Do not modify the dose of MEKINIST.

  Withhold dabrafenib for up to 6 weeks.

  • If improved to Grade 0-1, then resume at the same dose. • If not improved, permanently discontinue.

  Pulmonary

  • Interstitial lung disease/pneumonitis

  Permanently discontinue MEKINIST.

  Do not modify the dose of dabrafenib.

  Other

  • Intolerable Grade 2 adverse reactions • Any Grade 3 adverse reactions

  Withhold MEKINIST for up to 3 weeks.

  • If improved to Grade 0-1, resume at a lower dose level. • If not improved, permanently discontinue.

  Withhold dabrafenib

  • If improved to Grade 0-1, resume at a lower dose level. • If not improved, permanently discontinue. • First occurrence of any Grade 4 adverse reaction • Withhold MEKINIST until adverse reaction improves to Grade 0-1. Then resume at a lower dose level.

  Or

  • Permanently discontinue. • Withhold dabrafenib until adverse reaction improves to Grade 0-1. Then resume at a lower dose level.

  Or

  • Permanently discontinue. • Recurrent Grade 4 adverse reaction

  Permanently discontinue MEKINIST.

  Permanently discontinue dabrafenib.

    a National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.   b See Table 1 for recommended dose reductions of MEKINIST and dabrafenib.   c Refer to Full Prescribing Information for dabrafenib.

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