Braftovi 50 mg hard capsules

Patient Information Leaflet

Introduction

Package leaflet: Information for the patient

Braftovi 50 mg hard capsules

Braftovi 75 mg hard capsules

encorafenib

Read the entire leaflet carefully before you start taking this medicine, as it contains important information for you.

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

Leaflet contents

1. What Braftovi is and what it is used for
2. What you need to know before taking Braftovi
3. How to take Braftovi
4. Possible side effects
5. How to store Braftovi
6. Contents of the pack and other information

1. What Braftovi is and what it is used for

Braftovi is an anticancer medicine that contains encorafenib as the active substance.

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

It is used in combination with another medicine 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 medicine containing cetuximab to treat adult patients with a type of colorectal cancer when:

• it has a specific alteration (mutation) in a gene responsible for producing a protein called BRAF, and
• it has spread to other parts of the body in patients who have previously been treated with other anticancer medicines.

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 the growth of their cancer.

2. What you need to know before starting 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, carefully read the binimetinib package leaflet in addition to this one.

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

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

Talk to your doctor, pharmacist, or nurse before starting Braftovi, and inform them about all your health conditions, especially if you have:

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

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

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

• Heart problems: Braftovi, when taken with binimetinib, may cause your heart to function less effectively, alter the heart's electrical activity known as "QT interval prolongation," or worsen existing heart problems. Your doctor will check that your heart is functioning properly before, during, and after treatment with these medicines. Seek immediate medical advice if you experience any symptoms of heart problems such as dizziness, fatigue, lightheadedness, shortness of breath, strong or rapid heartbeat, irregular heartbeat, or swelling in the legs.

• Bleeding problems: Braftovi can cause serious bleeding problems. Contact your doctor immediately if you notice any signs of bleeding such as coughing up blood, blood clots, vomiting blood or material that looks like "ground coffee," red or black, tarry stools, blood in the urine, abdominal pain, unusual vaginal bleeding. Also inform your doctor if you experience headache, dizziness, or weakness.

• Eye problems: Braftovi, when taken with binimetinib, may cause serious eye problems. Contact your doctor immediately if you experience blurred vision, vision loss, or other changes in vision (e.g., seeing colored spots), halos (seeing blurred outlines around 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 cutaneous squamous cell carcinoma. New melanomas may also develop while you are taking Braftovi. Your doctor will examine your skin for new skin cancers before treatment, every 2 weeks during treatment, and for up to 6 months after stopping Braftovi. Contact your doctor immediately if you notice skin changes during or after treatment, such as new warts, skin ulcers, or red, bleeding, or non-healing bumps, or changes in size or color of moles. In addition, your doctor will examine you for cutaneous squamous cell carcinoma in the head, neck, mouth, and lymph nodes, and you will undergo regular CT scans. This is precautionary in case a new squamous cell carcinoma develops inside your body. Genital (in women) and anal examinations are also recommended before starting and after completing treatment.

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

• Kidney problems: Braftovi may affect kidney function (often shown by abnormalities in blood tests and, more rarely, as dehydration and vomiting). Your doctor will request blood tests to monitor kidney function before and during treatment. Drink plenty of fluids during treatment. Contact your doctor immediately if you experience vomiting and become dehydrated.

If you experience the following symptoms, contact your doctor immediately, as they may indicate a potentially life-threatening condition: nausea, difficulty breathing, irregular heartbeat, muscle cramps, seizures, cloudy urine, decreased urine output, and fatigue. These may be caused by a group of metabolic complications that can occur during cancer treatment, resulting from the breakdown products of dying cancer cells (tumor lysis syndrome (TLS)), which may lead to changes in kidney function (see also section 4: Possible side effects).

Children and adolescents

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

Other medicines and Braftovi

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

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

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

• certain antifungal medicines (such as itraconazole, posaconazole, fluconazole)
• certain antibiotics (such as rifampicin, clarithromycin, telithromycin, erythromycin, penicillin)
• medicines commonly used to treat epilepsy (seizures) (such as phenytoin, carbamazepine)
• medicines commonly used to treat cancer (such as methotrexate, imatinib)
• medicines commonly used to treat high cholesterol (such as rosuvastatin, atorvastatin)
• a herbal remedy for depression: St. John’s wort
• certain HIV treatments (such as ritonavir, amprenavir, raltegravir, dolutegravir)
• hormonal contraceptives
• medicines commonly used to treat high blood pressure (such as diltiazem, bosentan, furosemide)
• a medicine used to treat irregular heartbeat: amiodarone.

Taking Braftovi with food and drink

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

Pregnancy

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

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

If you are a woman of childbearing potential, you must use a reliable method of contraception while taking Braftovi, and continue using it for at least 1 month after taking the last dose. Hormonal contraceptives (such as pills, injections, patches, implants, and certain hormone-releasing intrauterine devices (IUDs)) may not be effective while 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. Consult your doctor, pharmacist, or nurse.

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

Breast-feeding

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

Fertility

Braftovi may reduce sperm count, 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 operating machinery if you experience vision problems or any other side effects that may impair your ability to drive or use machines (see section 4) while taking Braftovi. Consult your doctor if you are unsure whether you can drive safely.

3. How to take Braftovi

How much to take

Follow exactly the instructions given by your doctor or pharmacist for taking this medicine. If you are unsure, consult your doctor or pharmacist again.

For treatment of melanoma and NSCLC

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

For treatment of colorectal cancer

The recommended dose of Braftovi for treating colorectal cancer is 4 capsules of 75 mg once daily (corresponding 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 advise you to start treatment at a lower dose.

If you experience serious adverse 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 push the capsule through the blister.
• Separate one unit from the blister by bending and gently breaking along the perforated line.
• Carefully peel back the foil 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 cannot swallow the capsules whole, you may open them and disperse the contents in a small amount (approximately 20 mL, about 1 tablespoon) of apple puree, and immediately consume the entire mixture.

If the mixture is not used within 30 minutes, discard it and prepare a new one.

If you vomit

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

Take your next dose at the scheduled time.

If you take more Braftovi than you should

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

If you forget to take Braftovi

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

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

If you stop taking Braftovi

It is important that you take Braftovi for as long as your doctor has prescribed. Do not stop taking this medicine unless instructed by your doctor.

If you have any further questions about 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 everyone experiences them.

Serious adverse effects

Braftovi may cause serious adverse effects. Contact your doctor immediately if 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 how your heart functions (decreased left ventricular ejection fraction); signs and symptoms may include:

• feeling dizzy, tired, or lightheaded
• shortness of breath
• feeling that your heart is beating strongly, rapidly, or irregularly
• swollen legs

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

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

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

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

Muscle problems: Braftovi, when taken with binimetinib, may cause the breakdown of muscle fibers (rhabdomyolysis), which in turn can lead to kidney damage and may 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 cutaneous squamous cell carcinoma. Typically, these skin changes (see also section 2) affect a small area and can be surgically removed, and treatment with Braftovi can continue uninterrupted. Some people taking Braftovi may also develop new melanomas. These melanomas are usually surgically removed, and treatment with Braftovi can continue without interruption.

Tumor lysis syndrome: Braftovi may cause rapid breakdown of cancer cells, which in some people may be fatal. Symptoms may include nausea, difficulty breathing, irregular heartbeat, muscle cramps, seizures, cloudy urine, reduced urine output, and fatigue.

Other adverse effects

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

Adverse effects when Braftovi is taken together 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)
• nerve problems causing pain, loss of sensation, or tingling in hands and feet
• headache
• dizziness
• bleeding in various 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 may indicate muscle inflammation or damage)

Common (may affect up to 1 in 10 people):

• certain types of skin tumors, such as cutaneous papilloma
• allergic reaction that may include facial swelling and difficulty breathing
• changes in taste sensation
• eye inflammation (uveitis)
• blood clots
• inflammation of the colon (colitis)
• redness, cracking, or splitting of the skin
• inflammation of the fatty layer beneath the skin, with symptoms such as soft nodules under the skin
• skin rash with flat or raised acne-like spots (acneiform dermatitis)
• redness, peeling, or blisters on the hands and feet (hand-foot syndrome or palmar-plantar erythrodysesthesia)
• kidney failure
• abnormal kidney function test results (increased creatinine)
• abnormal liver function blood test results (alkaline phosphatase)
• abnormal blood test results for pancreatic function (amylase, lipase)
• increased skin sensitivity to sunlight

Uncommon (may affect up to 1 in 100 people):

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

Adverse effects when Braftovi was used alone in clinical trials conducted in patients with melanoma

If you continue taking Braftovi alone while temporarily interrupting the other medicine (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 (called hand-foot syndrome or palmar-plantar erythrodysesthesia)
• thickening of the outer layers of the skin (hyperkeratosis)
• dry skin
• itching
• abnormal hair loss or thinning (alopecia)
• redness, cracking, or splitting of the skin
• darkening of the skin
• loss of appetite
• difficulty sleeping (insomnia)
• headache
• nerve problems, which may cause pain, loss of sensation, or tingling in hands and feet
• changes in taste sensation
• joint pain (arthralgia)
• muscle pain, spasms, or weakness
• limb pain
• back pain
• fever
• certain types of benign skin tumors, such as melanocytic nevus and cutaneous papilloma
• abnormal blood test results related to the liver

Common (may affect up to 1 in 10 people):

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

Uncommon (may affect up to 1 in 100 people):

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

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

In addition to the serious adverse effects mentioned above, people taking Braftovi together 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)
• nerve problems causing pain, loss of sensation, or tingling in hands and feet
• headache
• bleeding in various parts of the body
• diarrhea
• stomach pain
• general discomfort (nausea)
• vomiting
• constipation
• skin rash with flat or raised acne-like spots (acneiform dermatitis)
• skin rash of various types
• dry skin
• itching
• joint pain (arthralgia) and muscle and/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 cutaneous papilloma
• allergic reaction that may include facial swelling and difficulty breathing
• dizziness
• changes in taste sensation
• increased heart rate
• darkening of the skin
• redness, peeling, or blisters on the hands and feet (hand-foot syndrome or palmar-plantar erythrodysesthesia)
• thickening of the outer layers of the skin (hyperkeratosis)
• redness, cracking, or splitting of the skin
• hair loss or thinning (alopecia)
• kidney failure
• abnormal kidney function test results (increased creatinine)
• abnormal blood test results related to the liver

Uncommon (may affect up to 1 in 100 people):

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

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect 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 help provide more information on the safety of this medicine.

5. Braftovi Storage

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

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

Store below 30 ºC. Keep 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 medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Braftovi

• The active substance 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:

• Capsule contents: 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), 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 pack

Braftovi 50 mg hard capsules

The hard capsule (capsule) has an opaque orange cap and an opaque beige 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 single-dose pre-cut blisters. Only some pack sizes may 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 available in packs of 42x1 capsules or 168x1 capsules in single-dose pre-cut blisters. Only some pack sizes may be marketed.

Marketing Authorization Holder

PIERRE FABRE MEDICAMENT

Les Cauquillous

81500 Lavaur

France

Manufacturer

PIERRE FABRE MEDICAMENT PRODUCTION

Progipharm site, Rue du Lycée

45500 GIEN

France

Date of the latest revision of this summary:

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