BRAFTOVI Hard capsule Ref.[8687] Active ingredients: Encorafenib

Encorafenib treatment in combination with binimetinib should be initiated and supervised under the responsibility of a physician experienced in the use of anticancer medicinal products.

Posology

The recommended dose of encorafenib is 450 mg (six 75 mg capsules) once daily, when used in combination with binimetinib.

Dose modification

The management of adverse reactions may require dose reduction, temporary interruption or treatment discontinuation (see Tables 1 and 2).

Dose reduction recommendations for encorafenib are presented in Table 1.

Table 1. Recommended dose modifications for encorafenib (when used in combination with binimetinib):

Administration of encorafenib at a dose of 450 mg once daily as a single agent is not recommended. If binimetinib is temporarily interrupted, encorafenib should be reduced at 300 mg once daily during the time of binimetinib dose interruption (see section 4.2 of binimetinib Summary of Product Characteristics [SmPC]) 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 Table 2), binimetinib should be interrupted. If encorafenib is permanently discontinued, then binimetinib should be discontinued.

For information on the posology and recommended dose modifications of binimetinib, see section 4.2 of binimetinib SmPC.

Dose modifications in case of adverse reactions are provided below and in Table 2.

For new primary cutaneous malignancies: No dose modifications are required for encorafenib.

For new primary non-cutaneous RAS mutation-positive malignancies: it should be considered to discontinue encorafenib and binimetinib permanently.

If treatment-related toxicities occur, then encorafenib and binimetinib should be simultaneously dose reduced, interrupted or discontinued. Exceptions where dose modifications are necessary for binimetinib only (adverse reactions primarily related to binimetinib) are: retinal pigment epithelial detachment (RPED), retinal vein occlusion (RVO), interstitial lung disease/pneumonitis, cardiac dysfunction, creatine phosphokinase (CK) elevation and rhabdomyolysis, and venous thromboembolism (VTE).

If one of these toxicities occurs, see section 4.2 of binimetinib SmPC for dose modification instructions for binimetinib.

Table 2. Recommended dose modifications for encorafenib (used in combination with binimetinib) for selected adverse reactions:

Table 3. Recommended dose modifications for encorafenib (used in combination with binimetinib) for other adverse reactions:

Duration of treatment

Treatment should continue until the patient no longer derives benefit or the development of unacceptable toxicity.

Missed doses

If a dose of encorafenib is missed, the patient should only take the missed dose if it is more than 12 hours until the next scheduled dose.

Vomiting

In case of vomiting after administration of encorafenib, the patient should not take an additional dose and should take the next scheduled dose.

Special populations

Elderly patients

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

Hepatic impairment

Patients with mild to severe hepatic impairment may have increased encorafenib exposure (see section 5.2).

Administration of encorafenib should be undertaken with caution at a reduced dose of 300 mg once daily in patients with mild hepatic impairment (Child-Pugh Class A). No dosing recommendation can be made in patients with moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment.

Renal impairment

No dose adjustment is required for patients with mild or moderate renal impairment based on a population pharmacokinetics (PK) analysis. There are no clinical data with encorafenib in patients with severe renal impairment. Therefore, the potential need for dose adjustment cannot be determined. Encorafenib should be used with caution in patients with severe renal impairment (see sections 4.4 and 5.2).

Paediatric population

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

Method of administration

Braftovi is for oral use. The capsules are to be swallowed whole with water. They may be taken with or without food. The concomitant administration of encorafenib with grapefruit juice should be avoided (see sections 4.4 and 4.5).

Symptoms

At doses of encorafenib between 600 to 800 mg once daily, renal dysfunction (Grade 3 hypercreatinaemia) was observed in 3 out of 14 patients. The highest administered dose occurred as a dosing error in one patient who took encorafenib at a dose of 600 mg twice daily for 1 day (total dose 1200 mg). Adverse reactions reported by this patient were Grade 1 events of nausea, vomiting and blurred vision; all subsequently resolved.

Management

There is no specific treatment for overdose. Since encorafenib is moderately bound to plasma proteins, haemodialysis is likely to be ineffective in the treatment of overdose with encorafenib. There is no known antidote for encorafenib. In the event of an overdose, encorafenib treatment should be interrupted and renal function must be monitored as well as adverse reactions. Symptomatic treatment and supportive care should be provided as needed.

Shelf life: 3 years.

Store below 30°C.

Store in the original package in order to protect from moisture.

Braftovi 50 mg hard capsules:

Polyamide/aluminum/PVC/aluminum blister containing 4 capsules.

Each pack contains either 28 or 112 hard capsules.

Not all pack sizes may be marketed.

Braftovi 75 mg hard capsules:

Polyamide/aluminum/PVC/aluminum blister containing 6 capsules.

Each pack contains either 42 or 168 hard capsules.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.