No dose adjustment is required for patients aged 65 years and older (see section 5.2).

Hepatic impairment

No dose adjustment is required in patients with mild hepatic impairment (Child-Pugh A).

As encorafenib is not recommended in patients with moderate (Child Pugh B) or severe hepatic impairment (Child-Pugh C), administration of binimetinib is not recommended in these patients. (see section 4.2 of encorafenib SmPC).

Renal impairment

No dose adjustment is recommended for patients with renal impairment (see section 5.2).

Paediatric population

The safety and efficacy of binimetinib in children and adolescents have not yet been established. No data are available.

Method of administration

Mektovi is for oral use.

The tablets are to be swallowed whole with water. They may be taken with or without food.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Binimetinib is to be given in combination with encorafenib. For additional information on warnings and precautions associated with encorafenib treatment, see section 4.4 of encorafenib SmPC.

BRAF mutation testing

Before taking binimetinib in combination with encorafenib, patients must have BRAF V600 mutation confirmed by validated test. The efficacy and safety of binimetinib in combination with encorafenib have been established only in patients with tumours expressing BRAF V600E and V600K mutations. Binimetinib in combination with encorafenib should not be used in patients with wild type BRAF malignant melanoma.

Binimetinib in combination with encorafenib in patients who have progressed on a BRAF inhibitor

There are limited data for use of the combination of binimetinib with encorafenib in patients who have progressed on a prior BRAF inhibitor given for the treatment of unresectable or metastatic melanoma with BRAF V600 mutation. These data show that the efficacy of the combination would be lower in these patients.

Binimetinib in combination with encorafenib in patients with brain metastases

There are limited efficacy data with the combination of binimetinib and encorafenib in patients with a BRAF V600 mutant melanoma which have metastasised to the brain (see section 5.1).

Left ventricular dysfunction (LVD)

LVD defined as symptomatic or asymptomatic decreases in ejection fraction can occur when binimetinib is administered.

It is recommended that LVEF is assessed by echocardiogram or multi-gated acquisition (MUGA) scan before initiation of binimetinib, 1 month after initiation, and then at approximately 3-month intervals or more frequently as clinically indicated, while on treatment. The occurrence of LVEF decrease can be managed with treatment interruption, dose reduction or with treatment discontinuation (see section 4.2).

The safety of binimetinib in combination with encorafenib has not been established in patients with a baseline LVEF that is either below 50 % or below the institutional LLN. Therefore, in these patients, binimetinib should be used with caution and for any symptomatic left ventricular dysfunction, Grade 3-4 LVEF, or absolute decrease of LVEF from baseline of ≥ 10 %, binimetinib should be discontinued and LVEF should be eva luated every 2 weeks until recovery.

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