Braftovi (Capsules) Instructions for Use

Marketing Authorization Holder

Pierre Fabre Medicament (France)

Manufactured By

Catalent Pharma Solutions LLC (USA)

ATC Code

L01EC03 (Encorafenib)

Active Substance

Encorafenib (Rec.INN registered by WHO)

Dosage Form

Braftovi

Capsules 75 mg

Dosage Form, Packaging, and Composition

Capsules

6 pcs. – blisters (7 pcs.) – cardboard packs (42 pcs.) – By prescription

Clinical-Pharmacological Group

Antitumor drug. Protein kinase inhibitor

Pharmacotherapeutic Group

Antineoplastic agents, protein kinase inhibitors, serine-threonine kinase B-Raf (BRAF) inhibitors

Pharmacological Action

Antitumor drug, protein kinase inhibitors, serine-threonine kinase B-Raf (BRAF) inhibitor. Defects (mutations) in the BRAF gene can lead to the production of specific proteins that stimulate the growth of tumor cells. The target for encorafenib is precisely these proteins, which are formed as a result of a mutation in the BRAF gene.

The use of encorafenib in combination with binimetinib, which targets another protein that stimulates the growth of tumor cells, slows down or stops the growth of tumor cells.

The use of encorafenib in combination with cetuximab (which binds to the epidermal growth factor receptor [EGFR]) slows down or stops the growth of tumor cells.

Indications

In combination with binimetinib (which targets another protein that stimulates the growth of tumor cells) for the treatment of skin cancer (melanoma) in the presence of a mutation in the gene responsible for the production of the BRAF protein, with involvement of other organs and systems, or which cannot be removed surgically.

In combination with cetuximab (which binds to EGFR) for the treatment of colon cancer in the presence of a mutation in the gene responsible for the production of the BRAF protein, with involvement of other organs and systems in patients who have previously received treatment with other antitumor drugs.

ICD codes

Dosage Regimen

Take orally once daily.

Swallow capsules whole with water. Do not chew or crush.

The recommended dosage is 450 mg (six 75 mg capsules) once daily when used in combination with binimetinib.

The recommended dosage is 300 mg (four 75 mg capsules) once daily when used in combination with cetuximab.

Take at approximately the same time each day.

You may take with or without food.

If you vomit after taking a dose, do not take an additional dose. Take the next dose at the scheduled time.

If you miss a dose, take it as soon as you remember. If it is less than 12 hours until the next scheduled dose, skip the missed dose. Do not take a double dose to make up for a forgotten one.

Dosage modifications or interruptions may be required based on individual tolerance and the management of specific adverse reactions.

Assess renal function and hepatic function prior to initiation and during treatment. Use with caution in patients with pre-existing impairment; no specific starting dose adjustment is recommended for mild to moderate impairment.

Monitor electrocardiograms (ECGs) and electrolytes before treatment, during dose modification, and periodically throughout therapy, as encorafenib can prolong the QT interval.

Adverse Reactions

Adverse reactions occurring with the use of encorafenib as part of combination therapy

From the cardiovascular system frequent – decreased left ventricular ejection fraction (feeling of dizziness, fatigue or unsteadiness, shortness of breath, palpitations, arrhythmia, swelling in the legs), tachycardia.

From the organ of vision frequent – retinal pigment epithelial detachment, blurred vision, loss of vision or other vision changes (e.g., colored dots in the visual field), halo effect, eye pain, swelling or redness; infrequent – uveitis.

From the blood coagulation system frequent – bleeding of various locations.

From the musculoskeletal system very common – arthralgia, pain, spasm or weakness in muscles, pain in arms and legs, back pain, increased body temperature, joint pain; common – rhabdomyolysis (which can provoke kidney damage), signs of which are muscle pain, cramps, stiffness or spasms, dark urine, arthritis.

From the skin and subcutaneous tissues very common – skin rash of various types, redness, palmar-plantar erythrodysesthesia syndrome, hyperkeratosis, dry skin, itching, alopecia, redness, peeling or cracks on the skin, skin darkening; common – cutaneous squamous cell carcinoma, new melanomas; basal cell carcinoma of the skin, acneiform dermatitis, skin peeling, photosensitivity.

From the digestive system very common – nausea, vomiting, constipation, loss of appetite, increased activity of liver transaminases; common – deviations in laboratory parameters of pancreatic function.

From the nervous system very common – insomnia, headache, peripheral neuropathy, taste perversion; common – weakness and paralysis of facial muscles.

From the urinary system common – renal failure, increased creatinine concentration.

Other benign and malignant neoplasms very common – melanocytic nevus and papillomas.

Allergic reactions common – angioedema, urticaria.

General reactions very common – fatigue.

Contraindications

Hypersensitivity to encorafenib, pregnancy, breastfeeding period, children and adolescents under 18 years of age.

With caution

Cardiac disorders (including QT interval prolongation); bleeding disorders, use of drugs that may cause bleeding; visual disturbances; impaired liver and/or kidney function; history of malignant diseases.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Use with caution in patients with impaired liver function.

Use in Renal Impairment

Use with caution in patients with impaired renal function.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

Before starting treatment, the patient should be checked for the presence of a BRAF gene mutation.

In combination with binimetinib, Encorafenib can impair heart function and alter the electrical activity of the heart (QT interval prolongation). Before starting and during treatment, the patient should be examined to identify disorders of the cardiovascular system.

During and after treatment, the skin condition should be monitored to identify new warts, bleeding non-healing skin lesions or reddish blisters, changes in the size or color of moles. In addition, the physician should ensure the absence of squamous cell carcinoma on the head, neck, oral cavity and lymph nodes. For this purpose, CT scans should be performed regularly. Before and after completion of treatment, it is also recommended to examine the external genitalia (in women) and the anus.

Before starting and during treatment, liver and kidney function should be regularly monitored.

During treatment, the patient should consume plenty of fluids to avoid dehydration.

When combined with binimetinib or with cetuximab, the side effects of these drugs should be taken into account.

Effect on ability to drive vehicles and operate machinery

During treatment, patients should refrain from driving vehicles or operating machinery, especially if visual disturbances or any other side effects occur that may affect these activities.

Drug Interactions

Possible increased risk of adverse reactions with concurrent use of encorafenib with the following drugs: itraconazole, posaconazole, fluconazole; rifampicin, clarithromycin, telithromycin, erythromycin, penicillin; phenytoin, carbamazepine; methotrexate, imatinib; rosuvastatin, atorvastatin; St. John’s wort preparations; ritonavir, amprenavir, raltegravir, dolutegravir; hormonal contraceptives; diltiazem, bosentan, furosemide; amiodarone.

When consuming grapefruit/grapefruit juice concurrently during treatment with encorafenib, its undesirable reactions may be enhanced.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.