Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

MEKINIST (NDA-217513)

(TRAMETINIB)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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03/26/2026 (SUPPL-11)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

…

Table 14. Adverse Reactions (greater than or equal to 20%) in Adult Patients Treated with MEKINIST Plus Dabrafenib in Study BRF117019

…

Clinically relevant adverse reactions for MEKINIST in Study BRF117019 observed in less than 20% of patients who received MEKINIST in combination with dabrafenib were: peripheral neuropathy (9%), decreased ejection fraction (8%), atrioventricular block (2.9%), uveitis (1.9%), hypersensitivity (1.9%), Guillain-Barré syndrome(< 1%), and sarcoidosis (< 1%).

…

04/07/2025 (SUPPL-9)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

…

Other clinically important adverse reactions for MEKINIST across the COMBI-d and COMBI-v studies (N = 559) observed in less than 10% of patients who received MEKINIST in combination with dabrafenib were:

…

Nervous System: Peripheral neuropathy, Guillain-Barré syndrome

…

Other clinically important adverse reactions for MEKINIST in the COMBI-AD study observed in less than 20% of patients who received MEKINIST in combination with dabrafenib were: blurred vision (6%), decreased ejection fraction (5%), peripheral neuropathy (2.5%), rhabdomyolysis (< 1%), atrioventricular block (< 1%), Guillain-Barré syndrome (< 1%), and sarcoidosis (< 1%).

…

03/19/2025 (SUPPL-8)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

BRAF V600E Mutation-Positive Unresectable or Metastatic Solid Tumors and LGG

The safety and effectiveness of MEKINIST in combination with dabrafenib have been established in pediatric patients 1 year of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options; or with LGG with BRAF V600E mutation who require systemic therapy. Use of MEKINIST in combination with dabrafenib for these indications is supported by evidence from studies X2101 and G2201 that enrolled 171 patients (1 to < 18 years of age) with BRAF V600 mutation-positive advanced solid tumors, of which 4 (2.3%) patients were 1 to < 2 years of age, 39 (23%) patients were 2 to < 6 years of age, 54 (32%) patients were 6 to < 12 years of age, and 74 (43%) patients were 12 to < 18 years of age [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.6, 14.7)].

. . .

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

. . .

Administration

Instruct patients to take MEKINIST tablets on an empty stomach (at least 1 hour before or 2 hours after a meal) [see Dosage and Administration (2.3)].
When administering MEKINIST for oral solution as a single agent, instruct patients to take the oral solution with a low-fat meal or on an empty stomach [see Dosage and Administration (2.3)].
When coadministering with dabrafenib, instruct patients to take the MEKINIST oral solution on an empty stomach (at least 1 hour before or 2 hours after a meal). Breastfeeding and/or baby formula may be given on demand if a pediatric patient is unable to tolerate the fasting conditions [see Dosage and Administration (2.3)].

PATIENT INFORMATION

Additions and/or revisions underlined:

. . .

How should I take or give MEKINIST?

. . .

MEKINIST tablets:

Take MEKINIST 1 time each day, at the same time each day, about every 24 hours.
Take MEKINIST on an empty stomach (at least 1 hour before or 2 hours after a meal).
Take MEKINIST tablets whole. Do not crush or break MEKINIST tablets.
If MEKINIST tablets are prescribed for your child weighing at least 57 pounds (26 kg), your child’s healthcare provider will adjust their dose as your child grows.
Tell your healthcare provider if you or your child is not able to swallow MEKINIST tablets whole.

MEKINIST for oral solution:

MEKINIST for oral solution should only be given by a caregiver.
If MEKINIST for oral solution is prescribed for your child, your child’s healthcare provider will adjust their dose as your child grows.
See the “Instructions for Use” that comes with the medicine for instructions on how to correctly give a dose of MEKINIST.
MEKINIST for oral solution can be given using an oral syringe or feeding tube (4 French gauge or larger).
Give the MEKINIST oral solution 1 time each day, at the same time each day, about every 24 hours.
Give the MEKINIST oral solution with a low-fat meal or on an empty stomach when giving MEKINIST alone.
When giving MEKINIST in combination with dabrafenib, give the MEKINIST oral solution on an empty stomach (at least 1 hour before or 2 hours after a meal). If necessary, breastfeeding or baby formula may be given on demand.

. . .

03/07/2025 (SUPPL-5)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.5 Cardiomyopathy

Additions and/or revisions underlined:

…

Assess LVEF by echocardiogram or multigated acquisition (MUGA) scan before initiation of MEKINIST as a single agent or with dabrafenib, one month after initiation, and then at 2- to 3-month intervals while on treatment. For an asymptomatic absolute decrease in LVEF of 10% or greater from baseline that is below the institutional LLN, withhold MEKINIST for up to 4 weeks. If improved to normal LVEF value, resume MEKINIST at a lower dose. If no improvement to normal LVEF value within 4 weeks, permanently discontinue MEKINIST. For symptomatic cardiomyopathy or an absolute decrease in LVEF of greater than 20% from baseline that is below the institutional LLN, permanently discontinue MEKINIST [see Dosage and Administration (2.4)].

10/01/2024 (SUPPL-7)

Approved Drug Label (PDF)

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT INFORMATION

Additions and/or revisions underlined:

How should I store MEKINIST?

MEKINIST tablets:

Store MEKINIST tablets at room temperature between 68°F to 77°F (20°C to 25°C).

…

07/11/2024 (SUPPL-4)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

…

Other clinically important adverse reactions for MEKINIST in a pool of MEKINIST monotherapy clinical studies observed in less than 10% of patients who received MEKINIST were:

…

Nervous System: Dizziness, dysgeusia, peripheral neuropathy

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Nervous System: Peripheral neuropathy

…

Other clinically important adverse reactions for MEKINIST in Study BRF113928 observed in less than 20% of patients who received MEKINIST administered with dabrafenib were:

Cardiac: Atrioventricular block

Nervous System: Peripheral neuropathy

…

03/29/2024 (SUPPL-3)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

…

Cardiac: Bradycardia, atrioventricular block, bundle branch block

Immune System: Sarcoidosis

Musculoskeletal and Connective Tissue: Rhabdomyolysis

Skin and Subcutaneous Tissue: Photosensitivity

…

Other clinically important adverse reactions for MEKINIST in Study BRF113928 observed in less than 20% of patients who received MEKINIST administered with dabrafenib were:

Cardiac: Atrioventricular block

…

Clinically relevant adverse reactions for MEKINIST in Study BRF117019 observed in less than 20% of patients who received MEKINIST in combination with dabrafenib were: decreased ejection fraction (8%), atrioventricular block (2.9%), uveitis (1.9%), and hypersensitivity (1.9%).

…

Clinically relevant adverse reactions for MEKINIST in Study X2101 observed in less than 20% of patients (N=48) who received MEKINIST in combination with dabrafenib were: atrioventricular block (2.1%).

6.2 Postmarketing Experience

Additions and/or revisions underlined:

…

Cardiac: Atrioventricular block complete. This adverse reaction was also observed with MEKINIST monotherapy.

Immune System: Hemophagocytic lymphohistiocytosis (HLH) [see Warnings and Precautions (5.12)]

Skin and Subcutaneous Tissue: SCAR (including DRESS and SJS) [see Warnings and Precautions (5.9)]

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT INFORMATION

Additions and/or revisions; please refer to label for complete information.

…

How should I take or give MEKINIST?

…

MEKINIST for oral solution:

…

MEKINIST for oral solution can be given using an oral syringe or feeding tube (4 French gauge or larger).
…
What are the possible side effects of MEKINIST?
MEKINIST may cause serious side effects, including:
…

heart problems, including heart failure. Your healthcare provider should check your heart function before and during treatment with MEKINIST. Call your healthcare provider right away if you have any of the following signs and symptoms of a heart problem:
- feeling like your heart is pounding, racing, or beating irregularly
- shortness of breath
- swelling of your ankles and feet
- feeling lightheaded
  …
  How should I store MEKINIST?
  …
  MEKINIST for oral solution:

Store MEKINIST for oral solution in the original amber bottle at room temperature below 77°F (25°C). Do not freeze.
Keep MEKINIST for oral solution in the carton it comes in and away from direct moisture and light.
Throw away unused MEKINIST for oral solution after the expiration or “discard after” date written on the amber bottle label.
…

02/27/2024 (SUPPL-2)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

…

MEKINIST with Dabrafenib

…

Other clinically important adverse reactions for MEKINIST observed in less than 10% of patients who received MEKINIST in combination with dabrafenib (N = 559) were:

…

Skin and Subcutaneous Tissue: Photosensitivity

…