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Mekinist

"This week the U.S. Food and Drug Administration approved Mekinist (trametinib) in combination with Tafinlar (dabrafenib) to treat patients with advanced melanoma that is unresectable (cannot be removed by surgery) or metastatic (late-stage).

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Mekinist

Indications
Dosage
How Supplied

INDICATIONS

MEKINIST™ as a single agent 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].

MEKINIST, in combination with dabrafenib, 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. This indication is based on the demonstration of durable response rate [see Clinical Studies]. Improvement in disease-related symptoms or overall survival has not been demonstrated for MEKINIST in combination with dabrafenib.

Limitation of use

MEKINIST as a single agent is not indicated for treatment of patients who have received prior BRAF-inhibitor therapy [see Clinical Studies].

DOSAGE AND ADMINISTRATION

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]. Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.

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]. 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.

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 104°F
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 the Full Prescribing Information for dabrafenib.

HOW SUPPLIED

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.

Storage And Handling

0.5-mg Tablets: Yellow, modified oval, biconvex, film-coated tablets with 'GS' debossed on one face and 'TFC' on the opposing face and are available in bottles of 30 (NDC 0173-0849-13).

1-mg Tablets: White, round, biconvex, film-coated tablets with 'GS' debossed on one face and 'LHE' on the opposing face and are available in bottles of 30 (NDC 0173-0858-13).

2-mg Tablets: Pink, round, biconvex, film-coated tablets with 'GS' debossed on one face and 'HMJ' on the opposing face and are available in bottles of 30 (NDC 0173-0848-13).

Store refrigerated at 2° to 8°C (36° to 46°F). Do not freeze. Dispense in original bottle. Do not remove desiccant. Protect from moisture and light. Do not place medication in pill boxes.

GlaxoSmithKline, Research Triangle Park, NC 27709. Revised: January 2014

Last reviewed on RxList: 1/22/2014
This monograph has been modified to include the generic and brand name in many instances.

Indications
Dosage
How Supplied
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