Drug Detail:Mekinist (Trametinib [ tra-me-ti-nib ])
Generic Name: TRAMETINIB DIMETHYL SULFOXIDE .5mg
Dosage Form: tablet, film coated
Drug Class: Multikinase inhibitors
Patient Selection
Melanoma
- Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of treatment with MEKINIST as a single agent or in combination with dabrafenib [see Clinical Studies (14.1, 14.2)].
- Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.
NSCLC
- Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with MEKINIST and dabrafenib [see Clinical Studies (14.3)].
- Information on FDA-approved tests for the detection of BRAF V600E mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.
ATC
- Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with MEKINIST and dabrafenib [see Clinical Studies (14.4)]. An FDA-approved test for the detection of BRAF V600E mutation in ATC is not currently available.
Solid Tumors
- Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with MEKINIST and dabrafenib [see Clinical Studies (14.6)]. An FDA-approved test for the detection of BRAF V600E mutation in solid tumors other than melanoma and NSCLC is not currently available.
Low-Grade Glioma
- Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with MEKINIST and dabrafenib [see Clinical Studies (14.7)]. An FDA-approved test for the detection of BRAF V600E mutation in LGG is not currently available.
Recommended Dosage
MEKINIST Tablets
Adult Patients
The recommended dosage for MEKINIST tablets in adult patients is 2 mg orally taken once daily [see Dosage and Administration (2.3)].
Pediatric Patients
The recommended dosage for MEKINIST tablets in pediatric patients who weigh at least 26 kg is based on body weight (Table 1) [see Dosage and Administration (2.3)]. A recommended dosage of MEKINIST tablets has not been established in patients who weigh less than 26 kg.
| Body Weight | Recommended Dosage |
| 26 to 37 kg | 1 mg orally once daily |
| 38 to 50 kg | 1.5 mg orally once daily |
| 51 kg or greater | 2 mg orally once daily |
MEKINIST for Oral Solution
The recommended dosage for MEKINIST for oral solution is based on body weight (Table 2) [see Dosage and Administration (2.3)].
| Body Weight | Recommended Dosage Total Volume of Oral Solution Once Daily (Trametinib Content) |
| 8 kg | 6 mL (0.3 mg) |
| 9 kg | 7 mL (0.35 mg) |
| 10 kg | 7 mL (0.35 mg) |
| 11 kg | 8 mL (0.4 mg) |
| 12 to 13 kg | 9 mL (0.45 mg) |
| 14 to 17 kg | 11 mL (0.55 mg) |
| 18 to 21 kg | 14 mL (0.7 mg) |
| 22 to 25 kg | 17 mL (0.85 mg) |
| 26 to 29 kg | 18 mL (0.9 mg) |
| 30 to 33 kg | 20 mL (1 mg) |
| 34 to 37 kg | 23 mL (1.15 mg) |
| 38 to 41 kg | 25 mL (1.25 mg) |
| 42 to 45 kg | 28 mL (1.4 mg) |
| 46 to 50 kg | 32 mL (1.6 mg) |
| ≥ 51 kg | 40 mL (2 mg) |
- The recommended duration of treatment for patients with unresectable or metastatic melanoma or solid tumors, metastatic NSCLC, or locally advanced or metastatic anaplastic thyroid cancer is until disease progression or unacceptable toxicity.
- The recommended duration of treatment in the adjuvant melanoma setting is until disease recurrence or unacceptable toxicity for up to 1 year.
- The recommended duration of treatment for pediatric patients with LGG is until disease progression or until unacceptable toxicity.
Refer to the dabrafenib prescribing information for recommended dabrafenib dosing information.
Administration
- Take MEKINIST at the same time each day, approximately 24 hours apart.
- Take MEKINIST 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.
- If vomiting occurs after MEKINIST administration, do not take an additional dose. Take the next dose at its scheduled time.
MEKINIST Tablets
- Do not crush or break MEKINIST tablets.
MEKINIST for Oral Solution
- MEKINIST for oral solution is intended for administration by a caregiver. Prior to use of the oral solution, ensure caregivers receive training on proper dosing and administration of MEKINIST for oral solution.
Preparation and Administration
- To prepare MEKINIST for oral solution, tap the bottle until powder flows freely. Add 90 mL distilled or purified water to the powder in the bottle and invert or gently shake the bottle with re-attached cap for up to 5 minutes until powder is fully dissolved yielding a clear solution. Separate the dosing adapter from the oral syringe. Insert dosing adapter into bottle neck after reconstitution of the solution. Write the discard after date. Once reconstituted, MEKINIST oral solution can be used for 35 days.
- Administer MEKINIST for oral solution from oral dosing syringe or feeding tube.
- After reconstitution, store in original bottle below 25°C (77°F) and do not freeze.
Dosage Modifications for Adverse Reactions
Dose reductions for adverse reactions associated with MEKINIST are presented in Tables 3 and 4.
| Recommended Dosage | 1 mg orally once daily | 1.5 mg orally once daily | 2 mg orally once daily |
| First dose reduction | 0.5 mg orally once daily | 1 mg orally once daily | 1.5 mg orally once daily |
| Second dose reduction | N/A | 0.5 mg orally once daily | 1 mg orally once daily |
| Subsequent modification | Permanently discontinue MEKINIST tablets if unable to tolerate a maximum of two dose reductions. | ||
| Body Weight (Recommended dosage) |
First Dose Reduction | Second Dose Reduction |
| 8 kg [6 mL (0.3 mg)] |
5 mL | 3 mL |
| 9 kg [7 mL (0.35 mg)] |
5 mL | 4 mL |
| 10 kg [7 mL (0.35 mg)] |
5 mL | 4 mL |
| 11 kg [8 mL (0.4 mg)] |
6 mL | 4 mL |
| 12 to 13 kg [9 mL (0.45 mg)] |
7 mL | 5 mL |
| 14 to 17 kg [11 mL (0.55 mg)] |
8 mL | 6 mL |
| 18 to 21 kg [14 mL (0.7 mg)] |
11 mL | 7 mL |
| 22 to 25 kg [17 mL (0.85 mg)] |
13 mL | 9 mL |
| 26 to 29 kg [18 mL (0.9 mg)] |
14 mL | 9 mL |
| 30 to 33 kg [20 mL (1 mg)] |
15 mL | 10 mL |
| 34 to 37 kg [23 mL (1.15 mg)] |
17 mL | 12 mL |
| 38 to 41 kg [25 mL (1.25 mg)] |
19 mL | 13 mL |
| 42 to 45 kg [28 mL (1.4 mg)] |
21 mL | 14 mL |
| 46 to 50 kg [32 mL (1.6 mg)] |
24 mL | 16 mL |
| ≥ 51 kg [40 mL (2 mg)] |
30 mL | 20 mL |
| Permanently discontinue MEKINIST for oral solution if unable to tolerate a maximum of two dose reductions. | ||
Dosage modifications for adverse reactions associated with MEKINIST are presented in Table 5.
| a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. b See Tables 3 and 4 for recommended dose reductions of MEKINIST. c Dose modifications are not recommended for MEKINIST when administered with dabrafenib for the following adverse reactions of dabrafenib: non-cutaneous malignancies and uveitis. Dose modification of MEKINIST is not required for new primary cutaneous malignancies. |
|
| Severity of Adverse Reactiona | Dosage Modification for MEKINISTb |
| Hemorrhage [see Warnings and Precautions (5.2)] | |
|
Withhold MEKINIST.
|
|
Permanently discontinue MEKINIST. |
| Venous Thromboembolic Events [see Warnings and Precautions (5.4)] | |
|
Withhold MEKINIST for up to 3 weeks.
|
|
Permanently discontinue MEKINIST. |
| Cardiomyopathy [see Warnings and Precautions (5.5)] | |
|
Withhold MEKINIST for up to 4 weeks.
|
|
Permanently discontinue MEKINIST. |
| Ocular Toxicities [see Warnings and Precautions (5.6)] | |
|
Withhold MEKINIST for up to 3 weeks.
|
|
Permanently discontinue MEKINIST. |
| Pulmonary [see Warnings and Precautions (5.7)] | |
|
Permanently discontinue MEKINIST. |
| Febrile Reactions [see Warnings and Precautions (5.8)] | |
|
Withhold MEKINIST until fever resolves, then resume MEKINIST at same or lower dose. |
|
|
| Skin Toxicities [see Warnings and Precautions (5.9)] | |
|
Withhold MEKINIST for up to 3 weeks.
|
|
Permanently discontinue MEKINIST. |
| Other Adverse Reactionsc | |
|
Withhold MEKINIST.
|
|
|
|
Permanently discontinue MEKINIST. |
Refer to the dabrafenib prescribing information for dose modifications for adverse reactions associated with dabrafenib.
