2 DOSAGE AND ADMINISTRATION
2.1 Patient Selection
Confirm the presence of a BRAF V600E or V600K mutation in tumor specimens prior to initiating MEKTOVI [Clinical Studies (14)]. Information on FDA-approved tests for the detection of BRAF V600E and V600K mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.
2.2 Recommended Dosage
The recommended dosage of MEKTOVI is 45 mg orally taken twice daily, approximately 12 hours apart, in combination with encorafenib until disease progression or unacceptable toxicity. Refer to the encorafenib prescribing information for recommended encorafenib dosing information.
MEKTOVI may be taken with or without food [see Clinical Pharmacology (12.3)]. Do not take a missed dose of MEKTOVI within 6 hours of the next dose of MEKTOVI.
Do not take an additional dose if vomiting occurs after MEKTOVI administration but continue with the next scheduled dose.
2.3 Dosage Modifications for Adverse Reactions
If encorafenib is permanently discontinued, discontinue MEKTOVI.
Dose reductions for adverse reactions associated with MEKTOVI are presented in Table 1.
Action | Recommended Dose |
---|---|
First Dose Reduction | 30 mg orally twice daily |
Subsequent Modification | Permanently discontinue if unable to tolerate MEKTOVI 30 mg orally twice daily |
Dosage modifications for adverse reactions associated with MEKTOVI are presented in Table 2.
Severity of Adverse Reaction* | Dose Modification for MEKTOVI |
---|---|
| |
Cardiomyopathy [see Warnings and Precautions (5.1)] | |
| Withhold MEKTOVI for up to 4 weeks, evaluate LVEF every 2 weeks. Resume MEKTOVI at a reduced dose if the following are present:
|
| Permanently discontinue MEKTOVI. |
Venous Thromboembolism [see Warnings and Precautions (5.2)] | |
| Withhold MEKTOVI.
|
| Permanently discontinue MEKTOVI. |
Serous Retinopathy [see Warnings and Precautions (5.3)] | |
| Withhold MEKTOVI for up to 10 days.
|
Retinal Vein Occlusion (RVO) [see Warnings and Precautions (5.3)] | |
| Permanently discontinue MEKTOVI. |
Uveitis [see Warnings and Precautions (5.3)] | |
| If Grade 1 or 2 does not respond to specific ocular therapy, or for Grade 3 uveitis, withhold MEKTOVI for up to 6 weeks.
|
| Permanently discontinue MEKTOVI. |
Interstitial Lung Disease [see Warnings and Precautions (5.4)] | |
| Withhold MEKTOVI for up to 4 weeks.
|
| Permanently discontinue MEKTOVI. |
Hepatotoxicity [see Warnings and Precautions (5.5)] | |
| Maintain MEKTOVI dose.
|
| See Other Adverse Reactions. |
Rhabdomyolysis or Creatine Phosphokinase (CPK) elevations [see Warnings and Precautions (5.6)] | |
| Withhold MEKTOVI dose for up to 4 weeks.
|
Dermatologic | |
| If no improvement within 2 weeks, withhold MEKTOVI until Grade 0-1. Resume at same dose if first occurrence or reduce dose if recurrent. |
| Withhold MEKTOVI until Grade 0-1. Resume at same dose if first occurrence or reduce dose if recurrent. |
| Permanently discontinue MEKTOVI. |
Other Adverse Reactions (including: Hemorrhage [see Warnings and Precautions (5.7)])† | |
| Withhold MEKTOVI for up to 4 weeks.
|
| Permanently discontinue MEKTOVI, or Withhold MEKTOVI for up to 4 weeks.
|
| Consider permanently discontinuing MEKTOVI. |
| Permanently discontinue MEKTOVI. |
Refer to the encorafenib prescribing information for dose modifications for adverse reactions associated with encorafenib.
2.4 Dosage Modifications for Moderate or Severe Hepatic Impairment
For patients with moderate (total bilirubin greater than 1.5 and less than or equal to 3 × ULN and any AST) or severe (total bilirubin levels greater than 3 × ULN and any AST) hepatic impairment, the recommended dosage is 30 mg orally taken twice daily [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].