Prescribing Information for the Patient

Braftovi 50 mg Hard Capsules

Braftovi 75 mg Hard Capsules

encorafenib

Read this entire prescribing information carefully before starting to take this medicine, because

it contains important information for you.

• Keep this prescribing information, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed to you alone, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prescribing information. See section 4.

Braftovi is a cancer medication that contains encorafenib as its active ingredient.

Changes (mutations) in the BRAF gene can produce proteins that cause melanoma growth. Braftovi targets proteins synthesized from this modified BRAF gene.

It is used in combination with another medication containing binimetinib, to treat adult patients with a type of skin cancer called melanoma or a type of lung cancer called non-small cell lung cancer (NSCLC) when the cancer:

• has a specific alteration (mutation) in a gene responsible for producing a protein called BRAF, and
• has spread to other parts of the body or cannot be removed by surgery.

When Braftovi is used in combination with binimetinib, which targets another protein that stimulates cancer cell growth, the combination slows down or even stops cancer growth.

Braftovi is also used in combination with another medication containing cetuximab, to treat adult patients with a type of colorectal cancer when:

-has a specific alteration (mutation) in a gene responsible for producing a protein called BRAF, and

-has spread to other parts of the body of patients who have been previously treated with other cancer medications.

When Braftovi is used in combination with cetuximab (which binds to the epidermal growth factor receptor (EGFR), a protein on the surface of certain cancer cells), the combination slows down or stops cancer growth.

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

Since Braftovi is used in combination with binimetinib to treat melanoma and CPNM, read the prospectus for binimetinib carefully, in addition to this prospectus.

Since Braftovi is used in combination with cetuximab to treat colorectal cancer, read the prospectus for cetuximab carefully, in addition to this prospectus.

Do not take Braftovi

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

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take Braftovi, and inform them of all your health problems, especially if you have:

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

Inform your doctor if you have had any other type of cancer other than melanoma, colorectal cancer, or CPNM, as Braftovi may worsen other types of cancer.

Contact your doctor, pharmacist, or nurse immediately if you experience any of the following disorders while taking this medication:

• Heart problems: Braftovi, when taken with binimetinib, may cause your heart to function poorly, alter the electrical activity of the heart called "prolongation of the QT interval," or worsen existing heart problems. Your doctor will check that your heart is functioning correctly before, during, and after treatment with these medications. Consult your doctor immediately if you experience any symptoms of heart problems such as dizziness, fatigue, drowsiness, shortness of breath, if your heart beats strongly, accelerates, beats irregularly, or if you have swelling in your legs.

• Bleeding problems: Braftovi may cause severe bleeding problems. Consult your doctor immediately if you experience any signs of bleeding such as coughing up blood, blood clots, vomiting that contains blood or appears "mocha," bloody stools, urine that appears bloody, abdominal pain, unusual vaginal bleeding. Also inform your doctor if you experience headaches, dizziness, or weakness.

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

• Skin changes: Braftovi may cause other types of skin cancer, such as squamous cell skin carcinoma. New melanomas may also develop while taking Braftovi. Your doctor will examine your skin for new skin cancers before treatment, every 2 weeks during treatment, and up to 6 months after stopping Braftovi. Consult your doctor immediately if you notice any changes in your skin during treatment and after, such as new warts, skin ulcers, or red, bleeding, or non-healing bumps, or changes in size or color of a mole. Additionally, your doctor will examine you for squamous cell skin carcinoma in the head, neck, mouth, and lymph nodes, and you will undergo regular CT scans. This is a precaution in case a new squamous cell carcinoma develops in your body. Regular gynecological and anal examinations are also recommended (in women) before treatment and at the end of treatment.

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

• Kidney problems: Braftovi may alter kidney function (often manifested by abnormalities in blood tests and, less frequently, as dehydration and vomiting). Your doctor will ask you to have blood tests to monitor kidney function before and during treatment. Drink plenty of fluids during treatment. Consult your doctor immediately if you experience vomiting and dehydration.

If you experience the following symptoms, contact your doctor immediately, as they may be a potentially life-threatening disorder: nausea, difficulty breathing, irregular heartbeats, muscle cramps, seizures, cloudy urine, decreased urine production, and fatigue. 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 cause changes in kidney function (see section 4: Possible side effects).

Children and adolescents

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

Other medications and Braftovi

Inform your doctor, pharmacist, or nurse if you are taking, have taken recently, or may need to take any other medication.

Some medications may affect how Braftovi works or increase the risk of adverse effects.

Particularly, consult your doctor if you are taking any medication from this list or any other:

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

Taking Braftovi with food and drinks

Do not take grapefruit juice during your treatment with Braftovi. This is because it may increase the side effects of Braftovi.

Pregnancy

Braftovi is not recommended during pregnancy. It may cause damage to the fetus or birth defects.

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medication.

If you are a woman with the possibility of becoming pregnant, you should use a reliable contraceptive method while taking Braftovi, and continue to use it for at least 1 month after taking the last dose. It is possible that hormonal contraceptives (such as pills, injections, patches, implants, and certain intrauterine devices (IUDs) that release hormones) may not be effective while taking Braftovi. You should use another reliable contraceptive method, such as a barrier method (e.g., condom), to avoid becoming pregnant while taking this medication. Consult your doctor, pharmacist, or nurse.

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

Breastfeeding

Braftovi is not recommended during breastfeeding. It is unknown whether Braftovi passes into breast milk. If you are breastfeeding or plan to breastfeed, consult your doctor before taking this medication.

Fertility

Braftovi may reduce the number of sperm, which may affect your ability to father children. Consult your doctor if this is a problem for you.

Driving and operating machines

Braftovi may affect your ability to drive or operate machines. Avoid driving or operating machines if you experience vision problems or any other side effect that may affect your ability to drive or operate machines (see section 4), while taking Braftovi. Consult your doctor if you are unsure if you can drive.

How much to take

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

For melanoma and CPNM treatment

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

For colorectal cancer treatment

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

If you have liver or kidney problems, your doctor may indicate that you start treatment at a lower dose.

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

How to take Braftovi

Instructions for opening the blister pack:

-Do not press the capsule through the blister pack.

-Separate one of the units of the blister pack by folding it and breaking it gently along the perforated line.

-Carefully remove the film from the blister pack starting from the corner marked with an arrow.

-Carefully remove the capsule.

Swallow the capsules whole with water. Braftovi can be taken with food or between meals.

If you vomit

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

Take the next dose as scheduled.

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 packaging of the medication.

If you forget to take Braftovi

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

Do not take a double dose to make up for the missed doses.

If you interrupt treatment with Braftovi

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

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Severe side effects

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

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

• feeling dizzy, tired, or disoriented
• shortness of breath
• feeling like your heart is beating too hard, too fast, or irregularly
• swollen legs

Eye problems: Braftovi, when taken with binimetinib, may cause serious eye problems, such as fluid loss under the retina, which can cause some layers to detach (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 dots)
• halos (seeing blurry outlines of objects)
• eye pain, swelling, or redness

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

• headaches, dizziness, or weakness
• coughing up blood or clots
• vomiting that contains blood or looks like "coffee grounds"
• black or tarry stools
• blood in the urine
• abdominal pain
• unusual vaginal bleeding

Muscle problems: Braftovi, when taken with binimetinib, may cause muscle destruction (rhabdomyolysis) that, in turn, may cause kidney damage and be fatal; the signs and symptoms may be:

• pain, cramps, stiffness, or spasms in the muscles
• dark-colored urine

Other skin cancers: Treatment with Braftovi may cause other types of skin cancer, such as squamous cell skin carcinoma. These skin changes (see also section 2) 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 that, in some people, can be fatal. The symptoms may include nausea, difficulty breathing, irregular heartbeats, muscle cramps, seizures, cloudy urine, decreased urine production, and fatigue.

Other side effects

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

Side effects when Braftovi is taken with binimetinib for the treatment of melanoma or NSCLC

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

• decreased red blood cell count (anemia)

• nerve problems, causing pain, numbness, or tingling in the hands and feet
• headaches
• dizziness
• bleeding in various parts of the body
• high blood pressure
• vision problems (visual impairment)
• abdominal pain
• diarrhea
• vomiting
• nausea
• constipation
• itching
• dry skin
• hair loss or thinning (alopecia)
• various types of skin rash
• thickening of the outer skin layers
• joint pain (arthritis)
• muscle problems
• back pain
• pain in the extremities
• fever
• swelling of the hands or feet (peripheral edema), localized swelling
• fatigue
• abnormal liver function test results
• abnormal creatine kinase blood test results (a blood test that may indicate muscle inflammation or damage)

Common(may affect up to 1 in 10 people)

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

• inflammation of the subcutaneous fat layer, with symptoms such as soft nodules under the skin
• skin rash with flat or raised areas like acne (acneiform dermatitis)
• skin redness, peeling, or blistering on the hands and feet (erythema palmoplantar or hand-foot syndrome)
• kidney failure
• abnormal kidney function test results (increased creatinine)
• abnormal liver function test results (alkaline phosphatase)
• abnormal pancreatic function test results (amylase, lipase)
• increased skin sensitivity to the sun.

Uncommon(may affect up to 1 in 100 people)

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

Side effects when Braftovi was 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 side effects listed below, although the frequency may change (increase or decrease).

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

• fatigue
• general feeling of being unwell (nausea)
• vomiting
• constipation
• skin rash of various types
• skin redness, peeling, or blistering on the hands and feet (erythema palmoplantar or hand-foot syndrome)
• thickening of the outer skin layers (hyperkeratosis)
• dry skin
• itching
• abnormal hair loss or thinning (alopecia)
• skin redness, cracking, or breaking
• skin darkening
• loss of appetite
• difficulty sleeping (insomnia)
• headaches
• nerve problems, causing pain, numbness, or tingling in the hands and feet
• changes in taste
• joint pain (arthritis)
• muscle pain, weakness, or spasms
• pain in the extremities
• back pain
• fever
• some types of benign skin tumors, such as melanocytic nevus and cutaneous papilloma
• abnormal liver function test results

Common(may affect up to 1 in 10 people)

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

• inflammation of the pancreas (pancreatitis) that causes intense abdominal pain

Uncommon(may affect up to 1 in 100 people)

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

Side effects when Braftovi is taken with cetuximab for the treatment of colorectal cancer

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

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

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

hands and feet.

• headaches
• bleeding in various parts of the body
• diarrhea
• abdominal pain
• general feeling of being unwell (nausea)
• vomiting
• constipation
• skin rash of various types
• skin redness, peeling, or blistering on the hands and feet (erythema palmoplantar or hand-foot syndrome)
• thickening of the outer skin layers (hyperkeratosis)
• dry skin
• itching

• joint pain (arthritis) and muscle or bone pain (musculoskeletal pain)
• muscle pain, weakness, or spasms
• pain in the extremities
• back pain
• fatigue
• fever

Common(may affect up to 1 in 10 people)

• some types of skin tumors, such as cutaneous papilloma
• allergic reaction that may include facial swelling and difficulty breathing
• dizziness
• changes in taste
• increased heart rate
• skin darkening
• skin redness, peeling, or blistering on the hands and feet (erythema palmoplantar or hand-foot syndrome)
• thickening of the outer skin layers (hyperkeratosis)
• skin redness, cracking, or breaking
• abnormal hair loss or thinning (alopecia)
• kidney failure
• abnormal kidney function test results (increased creatinine)
• abnormal liver function test results

Uncommon(may affect up to 1 in 100 people)

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

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, nurse, or healthcare professional, even if it is a possible side effect that does not appear in this leaflet.

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

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

Do not use this medication after the expiration date that appears on the box and the blister pack

after CAD. The expiration date is the last day of the month indicated.

Store below 30 °C.

Store in the original packaging to protect it from moisture.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist

how to dispose of the packaging and the medication that you no longer need. In this way,

you will help protect the environment.

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

• The other components are:

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

Appearance of the product and contents of the packaging

Braftovi 50 mg hard capsules

The hard capsule (capsule) has an orange opaque cap and a beige opaque body, with an “A” printed on the cap and “LGX 50 mg” printed on the body.

Braftovi 50 mg is presented in blister packs of 28x1 capsules or 112x1 capsules in a single-dose pack. Some package sizes may only be marketed.

Braftovi 75 mg hard capsules

The hard capsule (capsule) has an opaque beige cap and an opaque white body, with an “A” printed on the cap and “LGX 75 mg” printed on the body.

Braftovi 75 mg is presented in blister packs of 42x1 capsules or 168x1 capsules in a single-dose pack. Some package sizes may only be marketed.

Marketing authorization holder

PIERRE FABRE MEDICAMENT

Les Cauquillous

81500 Lavaur

France

Responsible for manufacturing

PIERRE FABRE MEDICAMENT PRODUCTION

Site Progipharm, Rue du Lycée

45500 GIEN

France

Last review date of this leaflet:

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