BRAFTOVI 75 mg HARD CAPSULES

2. What you need to know before you take Braftovi

Before starting treatment, your doctor will check for the BRAF mutation.

Since Braftovi is used in combination with binimetinib to treat melanoma and NSCLC, read the package leaflet of binimetinib carefully, in addition to this leaflet.

Since Braftovi is used in combination with cetuximab to treat colorectal cancer, read the package leaflet of cetuximab carefully, in addition to this leaflet.

Do not take Braftovi

• if you are allergic to encorafenib or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Tell your doctor, pharmacist, or nurse before starting treatment with Braftovi, and inform them of all your health problems, especially if you have:

• heart problems, such as changes in heart electrical activity (prolongation of the QT interval)
• bleeding problems or if you are taking any medicine that may cause bleeding
• eye problems
• liver or kidney problems

Tell your doctor if you have had any other cancer apart from melanoma, colorectal cancer, or NSCLC, as Braftovi may worsen other types of cancer.

Get in touch with your doctor, pharmacist, or nurse immediately if you experience any of the following while taking this medicine:

• Heart problems: Braftovi, when taken with binimetinib, may affect your heart's functioning, alter the heart's electrical activity called "prolongation of the QT interval", or worsen existing heart problems. Your doctor will check that your heart is working properly before, during, and after treatment with these medicines. Contact your doctor immediately if you have any symptoms of heart problems, such as dizziness, tiredness, fainting, shortness of breath, if your heart beats strongly, rapidly, or irregularly, or if you have swelling in your legs.

• Bleeding problems: Braftovi may cause serious bleeding problems. Contact your doctor immediately if you have any signs of bleeding, such as coughing up blood, blood clots, vomiting blood or what looks like coffee grounds, red or black stools, blood in your urine, stomach pain, or unusual vaginal bleeding. Also, inform your doctor if you have a headache, dizziness, or weakness.

• Eye problems: Braftovi, when taken with binimetinib, may cause serious eye problems. Contact your doctor immediately if you have blurred vision, loss of vision, or other changes in your vision (such as seeing colored dots), halos (seeing blurry outlines of objects). Your doctor will examine your eyes for any vision problems while you are taking Braftovi.

• Skin changes: Braftovi may cause other types of skin cancer, such as squamous cell carcinoma of the skin. New melanomas can also occur while taking Braftovi. Your doctor will examine your skin for new skin cancers before treatment, every 2 weeks while on treatment, and for up to 6 months after stopping Braftovi. Contact your doctor immediately if you notice any changes in your skin during and after treatment, such as new warts, skin ulcers, or red bumps that bleed or do not heal, or changes in the size or color of a mole. Additionally, your doctor will examine you for squamous cell carcinoma of the skin in the head, neck, mouth, and lymph nodes, and you will have regular CT scans. This is a precaution in case you develop a new squamous cell carcinoma inside your body. Genital (in women) and anal examinations are also recommended before and after treatment.

• Liver problems: Braftovi may cause changes in blood tests related to your liver function (elevated liver enzymes). Your doctor will ask you to have blood tests to check your liver before and during treatment.

• Kidney problems: Braftovi may affect your kidney function (often shown by changes in blood tests and, less commonly, as dehydration and vomiting). Your doctor will ask you to have blood tests to check your kidney function before and during treatment. Drink plenty of fluids during treatment. Contact your doctor immediately if you vomit and become dehydrated.

If you experience the following symptoms, contact your doctor immediately, as it may be a life-threatening condition: nausea, difficulty breathing, irregular heartbeats, muscle cramps, seizures, cloudy urine, decreased urine production, and tiredness. These may be caused by a group of metabolic complications that can occur during cancer treatment and are caused by the breakdown products of dying cancer cells (tumor lysis syndrome (TLS)) and may affect kidney function (see also section 4: Possible side effects).

Children and adolescents

Braftovi is not recommended for children and adolescents under 18 years of age. This medicine has not been studied in this age group.

Other medicines and Braftovi

Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.

Some medicines may affect how Braftovi works or increase the risk of side effects.

In particular, tell your doctor if you are taking any of the following medicines or any other:

• certain medicines for fungal infections (such as itraconazole, posaconazole, fluconazole)
• certain medicines for bacterial infections (such as rifampicin, clarithromycin, telithromycin, erythromycin, penicillin)
• medicines used to treat epilepsy (seizures) (such as phenytoin, carbamazepine)
• medicines used to treat cancer (such as methotrexate, imatinib)
• medicines used to treat high cholesterol (such as rosuvastatin, atorvastatin)
• a herbal treatment for depression: St. John's Wort
• certain medicines for HIV (such as ritonavir, amprenavir, raltegravir, dolutegravir)
• hormonal contraceptives
• medicines used to treat high blood pressure (such as diltiazem, bosentan, furosemide)
• a medicine used to treat an irregular heartbeat: amiodarone

Taking Braftovi with food and drinks

Do not drink grapefruit juice while taking Braftovi. This is because it may increase the side effects of Braftovi.

Pregnancy

Braftovi is not recommended during pregnancy. It may harm the unborn baby or cause birth defects.

If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

If you are a woman who can become pregnant, you must use a reliable method of contraception while taking Braftovi and for at least 1 month after taking the last dose. Hormonal contraceptives (such as the pill, injections, patches, implants, and certain intrauterine devices (IUDs) that release hormones) may not be effective while you are taking Braftovi. You should use another reliable method of contraception, such as a barrier method (e.g., condom), to prevent pregnancy while taking this medicine. Talk to your doctor, pharmacist, or nurse.

Contact your doctor immediately if you become pregnant while taking Braftovi.

Breast-feeding

Braftovi is not recommended during breast-feeding. It is not known whether Braftovi passes into breast milk. If you are breast-feeding or think you may want to breast-feed, ask your doctor for advice before taking this medicine.

Fertility

Braftovi may reduce the number of sperm, which could affect your ability to father a child. Talk to your doctor if this is a concern for you.

Driving and using machines

Braftovi may affect your ability to drive or use machines. Avoid driving or using machines if you have vision problems or any other side effect that may affect your ability to drive or use machines (see section 4), while taking Braftovi. Talk to your doctor if you are unsure about driving.

3. How to take Braftovi

How much to take

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, check with your doctor or pharmacist.

For the treatment of melanoma and NSCLC

The recommended dose of Braftovi is 6 capsules of 75 mg once daily (which corresponds to a daily dose of 450 mg). You will also receive treatment with another medicine, binimetinib.

For the treatment of colorectal cancer

The recommended dose of Braftovi for the treatment of colorectal cancer is 4 capsules of 75 mg once daily (which corresponds to a daily dose of 300 mg). You will also receive treatment with another medicine, cetuximab.

If you have liver or kidney problems, your doctor may prescribe a lower dose.

If you experience serious side effects (such as heart, eye, or bleeding problems), your doctor may reduce the dose or stop treatment temporarily or permanently.

How to take Braftovi

Instructions for opening the blister:

• Do not press the capsule through the blister.
• Separate one of the blister units by folding and gently breaking it along the perforated line.
• Carefully peel off the blister lid, starting from the corner marked with an arrow.
• Gently remove the capsule.

Swallow the capsules whole with water. Braftovi can be taken with or without food.

If you vomit

If you vomit at any time after taking Braftovi, do not take an additional dose.

Take the next dose when you were supposed to.

If you take more Braftovi than you should

If you take more capsules than you should, contact your doctor, pharmacist, or nurse immediately. Some side effects of Braftovi, such as nausea, vomiting, dehydration, and blurred vision, may worsen. If possible, show them this leaflet and the medicine pack.

If you forget to take Braftovi

If you miss a dose of Braftovi, take it as soon as you remember. However, if it is more than 12 hours since the time you should have taken the dose, skip the missed dose and take the next dose when you were supposed to. Then, continue taking the capsules as usual.

Do not take a double dose to make up for a forgotten dose.

If you stop taking Braftovi

It is important that you take Braftovi for the time your doctor has prescribed. Do not stop taking this medicine unless your doctor tells you to.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Severe Adverse Effects

Braftovi may cause severe adverse effects. Consult your doctor immediatelyif you experience any of the following adverse effects for the first time or if existing ones worsen (see also section 2):

Heart problems: Braftovi, when taken with binimetinib, may affect the way your heart works (decrease in left ventricular ejection fraction); signs and symptoms may include:

• feeling dizzy, tired, or disoriented
• shortness of breath
• feeling that the heart is beating strongly, quickly, or irregularly
• swollen legs

Eye problems: Braftovi, when taken with binimetinib, may cause severe eye problems, such as fluid loss under the retina, which can cause detachment of some layers (retinal pigment epithelial detachment). Contact your doctor immediately if you experience the following eye symptoms:

• blurred vision, loss of vision, or other changes (such as seeing colored spots)
• halos (blurred outlines of objects)
• eye pain, swelling, or redness

Bleeding problems: Braftovi may cause severe bleeding problems. Consult your doctor immediately if you notice any unusual signs of bleeding, such as:

• headaches, dizziness, or weakness
• coughing up blood or clots
• vomiting blood or coffee-ground-like material
• black or tarry stools
• blood in the urine
• abdominal pain
• unusual vaginal bleeding

Muscle problems: Braftovi, when taken with binimetinib, may cause muscle fiber destruction (rhabdomyolysis) that can lead to kidney damage and be fatal; signs and symptoms may include:

• muscle pain, cramps, stiffness, or spasms
• dark-colored urine

Other skin cancers: Treatment with Braftovi may cause other types of skin cancer, such as squamous cell carcinoma of the skin. These skin changes usually affect a small area and can be removed with surgery, and treatment with Braftovi can continue without interruption. Some people taking Braftovi may also develop new melanomas. These melanomas are usually removed with surgery, and treatment with Braftovi can continue without interruption.

Tumor Lysis Syndrome: Braftovi may cause rapid breakdown of cancer cells, which can be fatal in some people. Symptoms may include nausea, difficulty breathing, irregular heartbeats, muscle cramps, seizures, cloudy urine, decreased urine production, and fatigue.

Other Adverse Effects

In addition to the severe adverse effects mentioned above, people taking Braftovi may also experience other adverse effects.

Adverse Effects when Braftovi is taken with Binimetinib for the treatment of melanoma or CPNM

Very Common(may affect more than 1 in 10 people):

• decrease in red blood cell count (anemia)

• nervous system problems, causing pain, numbness, or tingling in hands and feet
• headache
• dizziness
• bleeding in different parts of the body
• high blood pressure
• vision problems (visual impairment)
• stomach pain
• diarrhea
• vomiting
• nausea
• constipation
• itching
• dry skin
• hair loss or thinning (alopecia)
• skin rash of various types
• thickening of the outer layers of the skin
• joint pain (arthralgia)
• muscle disorders
• back pain
• limb pain
• fever
• swelling of the hands or feet (peripheral edema), localized swelling
• fatigue
• abnormal blood test results for liver function
• abnormal blood test results related to creatine kinase (an enzyme in the blood that can indicate inflammation or muscle damage)

Common(may affect up to 1 in 10 people)

• certain types of skin tumors, such as seborrheic keratosis
• allergic reaction that can include facial swelling and difficulty breathing
• changes in taste
• eye inflammation (uveitis)
• blood clots
• colon inflammation (colitis)
• redness, cracking, or breaking of the skin

• inflammation of the fatty layer under the skin, with symptoms such as soft nodules under the skin
• skin rash with a flat or raised area like acne (acneiform dermatitis)
• redness, peeling, or blisters on the hands and feet (palmar-plantar erythrodysesthesia or hand-foot syndrome)
• kidney failure
• abnormal kidney function test results (increased creatinine)
• abnormal liver function blood test results (alkaline phosphatase)
• abnormal pancreatic function blood test results (amylase, lipase)
• increased sensitivity of the skin to the sun

Uncommon(may affect up to 1 in 100 people)

• certain types of skin tumors, such as basal cell carcinoma
• weakness and paralysis of the facial muscles
• pancreatitis (inflammation of the pancreas) that causes severe abdominal pain

Adverse Effects when Braftovi is used alone in clinical trialsconducted in

patients with melanoma

If you continue taking Braftovi alone while temporarily interrupting the other medication (binimetinib), based on your doctor's decision, you may experience some of the adverse effects listed below, although the frequency may change (increase or decrease).

Very Common(may affect more than 1 in 10 people)

• fatigue
• general discomfort (nausea)
• vomiting
• constipation
• skin rash of various types
• redness, peeling, or blisters on the hands and feet (palmar-plantar erythrodysesthesia or hand-foot syndrome)
• thickening of the outer layers of the skin (hyperkeratosis)
• dry skin
• itching
• hair loss or thinning (alopecia)
• redness, cracking, or breaking of the skin
• darkening of the skin
• loss of appetite
• difficulty sleeping (insomnia)
• headache
• nervous system problems, causing pain, numbness, or tingling in hands and feet
• changes in taste
• joint pain (arthralgia)
• muscle pain, spasms, or weakness
• limb pain
• back pain
• fever
• certain types of benign skin tumors, such as melanocytic nevus and seborrheic keratosis
• abnormal liver function blood test results

Common(may affect up to 1 in 10 people)

• allergic reaction that can include facial swelling and difficulty breathing
• weakness and paralysis of the facial muscles
• increased heart rate
• skin rash with a flat or raised area like acne (acneiform dermatitis)
• peeling of the skin
• joint inflammation (arthritis)
• kidney failure
• abnormal kidney function test results (increased creatinine)
• increased sensitivity of the skin to the sun
• abnormal pancreatic function blood test results (lipase)

Uncommon(may affect up to 1 in 100 people)

• types of skin cancer, such as basal cell carcinoma
• eye inflammation (uveitis)
• pancreatitis (inflammation of the pancreas) that causes severe abdominal pain
• abnormal pancreatic function blood test results (amylase)

Adverse Effects when Braftovi is taken with Cetuximab for the treatment of colorectal cancer

In addition to the severe adverse effects mentioned above, people taking Braftovi with cetuximab may also experience the following adverse effects.

Very Common(may affect more than 1 in 10 people)

• new moles called "melanocytic nevus"
• loss of appetite
• difficulty sleeping (insomnia)
• nervous system problems, causing pain, numbness, or tingling in hands and feet

• headache
• bleeding in different parts of the body
• diarrhea
• stomach pain
• general discomfort (nausea)
• vomiting
• constipation
• skin rash with a flat or raised area like acne (acneiform dermatitis)

• skin rash of various types
• dry skin
• itching

• joint pain (arthralgia) and muscle or bone pain (musculoskeletal pain)
• muscle pain, weakness, or spasms
• limb pain
• back pain
• fatigue
• fever

Common(may affect up to 1 in 10 people)

• certain types of skin tumors, such as seborrheic keratosis
• allergic reaction that can include facial swelling and difficulty breathing
• dizziness
• changes in taste
• increased heart rate
• darkening of the skin
• redness, peeling, or blisters on the hands and feet (palmar-plantar erythrodysesthesia or hand-foot syndrome)
• thickening of the outer layers of the skin (hyperkeratosis)
• redness, cracking, or breaking of the skin
• hair loss or thinning (alopecia)
• kidney failure
• abnormal kidney function test results (increased creatinine)
• abnormal liver function blood test results

Uncommon(may affect up to 1 in 100 people)

• certain types of skin tumors, such as basal cell carcinoma
• pancreatitis (inflammation of the pancreas) that causes severe abdominal pain
• peeling of the skin
• abnormal pancreatic function blood test results (amylase, lipase)

Reporting of Adverse Effects

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet.

You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Braftovi

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date stated on the carton and blister after EXP. The expiration date is the last day of the month indicated.

Store below 30°C.

Store in the original packaging to protect from moisture.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Braftovi

• The active ingredient is encorafenib.

Braftovi 50 mg hard capsules: each hard capsule contains 50 mg of encorafenib

Braftovi 75 mg hard capsules: each hard capsule contains 75 mg of encorafenib

• Other ingredients are:

• Capsule content: copovidone (E1208), poloxamer 188, microcrystalline cellulose (E460i), succinic acid (E363), crospovidone (E1202), colloidal anhydrous silica (E551), magnesium stearate (E470b).
• Capsule shell: gelatin (E441), titanium dioxide (E171), red iron oxide (E172), yellow iron oxide (E172), black iron oxide (E172).
• Printing ink: shellac (E904), black iron oxide (E172), propylene glycol (E1520).

Appearance of the Product and Package Contents

Braftovi 50 mg hard capsules

The hard capsule (capsule) has an orange opaque cap and a flesh-colored opaque body, with an "A" printed on the cap and "LGX 50 mg" printed on the body.

Braftovi 50 mg is available in packs of 28x1 capsules or 112x1 capsules in precut unit-dose blisters. Not all pack sizes may be marketed.

Braftovi 75 mg hard capsules

The hard capsule (capsule) has a flesh-colored opaque cap and a white opaque body, with an "A" printed on the cap and "LGX 75 mg" printed on the body.

Braftovi 75 mg is available in packs of 42x1 capsules or 168x1 capsules in precut unit-dose blisters. Not all pack sizes may be marketed.

Marketing Authorization Holder

PIERRE FABRE MEDICAMENT

Les Cauquillous

81500 Lavaur

France

Manufacturer

PIERRE FABRE MEDICAMENT PRODUCTION

Site Progipharm, Rue du Lycée

45500 GIEN

France

Date of Last Revision of this Leaflet:

Detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu.