Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Pierre Fabre Médicament, 45, place Abel Gance, 92100, Boulogne-Billancourt, France
Binimetinib in combination with encorafenib is indicated for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation (see sections 4.4 and 5.1).
Binimetinib treatment in combination with encorafenib should be initiated and supervised under the responsibility of a physician experienced in the use of anticancer medicinal products.
The recommended dose of binimetinib is 45 mg (three 15 mg tablets) twice daily, corresponding to a total daily dose of 90 mg approximately 12 hours apart.
The management of adverse reactions may require dose reduction, temporary interruption or treatment discontinuation (see below, Table 1 and Table 2).
For patients receiving 45 mg binimetinib twice daily, the recommended reduced dose of binimetinib is 30 mg twice daily. Dose reduction below 30 mg twice daily is not recommended. Therapy should be discontinued if the patient is not able to tolerate 30 mg orally twice daily.
If the adverse reaction that resulted in a dose reduction is under effective management, dose re-escalation to 45 mg twice daily may be considered. Dose re-escalation to 45 mg twice daily is not recommended if the dose reduction is due to left ventricular dysfunction (LVD) or any Grade 4 toxicity.
Dose modifications recommendations in case of adverse reactions are presented below and in Tables 1 and 2.
If treatment-related toxicities occur when binimetinib is used in combination with encorafenib, then both treatments should be simultaneously dose reduced, interrupted or discontinued. Exceptions where dose reductions are necessary for encorafenib only (adverse reactions primarily related to encorafenib) are: palmar-plantar erythrodysaesthesia syndrome (PPES), uveitis including iritis and iridocyclitis and QTc prolongation.
If one of these toxicities occurs, see section 4.2. of encorafenib Summary of Product Characteristics (SmPC) for dose modification instructions for encorafenib.
If binimetinib is temporarily interrupted, encorafenib should be reduced to 300 mg once daily during the time of binimetinib dose interruption (see Tables 1 and 2) as encorafenib is not well-tolerated at the dose of 450 mg as a single agent. If binimetinib is permanently discontinued, encorafenib should be discontinued.
If encorafenib is temporarily interrupted (see section 4.2 of encorafenib SmPC), binimetinib should be interrupted. If encorafenib is permanently discontinued, then binimetinib should be discontinued. For information on the posology and recommended dose modifications of encorafenib, see section 4.2 of encorafenib SmPC.
Table 1. Recommended dose modifications for binimetinib (used in combination with encorafenib) for selected adverse reaction:
Table 2. Recommended dose modifications for binimetinib (used in combination with encorafenib) for other adverse reactions:
Treatment should continue until the patient no longer derives benefit or the development of unacceptable toxicity.
If a dose of binimetinib is missed, it should not be taken if it is less than 6 hours until the next dose is due.
In case of vomiting after administration of binimetinib, the patient should not re-take the dose and should take the next scheduled dose.
No dose adjustment is required for patients aged 65 years and older (see section 5.2).
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).
No dose adjustment is recommended for patients with renal impairment (see section 5.2).
The safety and efficacy of binimetinib in children and adolescents have not yet been established. No data are available.
Mektovi is for oral use.
The tablets are to be swallowed whole with water. They may be taken with or without food.
The highest dose of binimetinib evaluated as single agent in clinical studies was 80 mg administered orally twice daily and was associated with ocular (chorioretinopathy) and skin toxicities (dermatitis acneiform).
There is no specific treatment of overdose. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary. Since binimetinib is highly bound to plasma proteins, haemodialysis is likely to be ineffective in the treatment of overdose with binimetinib.
Shelf life: 3 years.
This medicinal product does not require any special storage conditions.
PVC/PVDC/Alu blister containing 12 tablets. Each pack contains either 84 or 168 tablets.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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