Mekinist Dosage

Generic name: trametinib
Dosage form: tablet, film coated

The information at Drugs.com is not a substitute for medical advice. ALWAYS consult your doctor or pharmacist.

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.

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.

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.

 
aNational Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
 
bSee Table 1 for recommended dose reductions of MEKINIST and dabrafenib.
 
cRefer to Full Prescribing Information for dabrafenib.
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