Braftovi

Package leaflet: Information for the patient

Braftovi 50 mg hard capsules, 75 mg hard capsules

encorafenib
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. 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. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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 the active substance encorafenib. Changes
(mutations) in the BRAF gene can produce proteins that cause tumour growth. Braftovi targets the
proteins produced by this mutated BRAF gene.
It is used in combination with another medicine containing binimetinib for the treatment of adult
patients with a type of skin cancer called melanoma or with a type of lung cancer called non-small
cell lung cancer (NSCLC), when the tumour:
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 surgically removed.
When Braftovi is used in combination with binimetinib, which targets another protein that promotes
tumour cell growth, the combination slows down or blocks tumour progression.
Braftovi is also used in combination with another medicine, cetuximab, for the treatment of adult
patients with a type of colorectal cancer that:
has a specific alteration (mutation) in a gene responsible for producing a protein called BRAF, and
has spread to other parts of the body in patients previously treated with other anticancer medicines.
When Braftovi is used in combination with cetuximab (which binds to the epidermal growth factor
receptor (EGFR), a protein found on the surface of certain tumour cells), the combination slows down
or blocks tumour progression.

2. What you should know before taking Braftovi

Before starting treatment, your doctor will check for the presence of the BRAF mutation.
Since Braftovi must be used in combination with binimetinib for the treatment of melanoma and
non-small cell lung cancer, please read carefully both the binimetinib package leaflet and
this leaflet.
Since Braftovi must be used in combination with cetuximab for the treatment of colorectal
cancer, please read carefully both the cetuximab package leaflet and this leaflet.

Do not take Braftovi

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

Warnings and precautions
Before taking Braftovi, talk to your doctor, pharmacist, or nurse about your medical
conditions, especially if any of the following apply to you:

• heart problems, including disturbances in the heart's electrical activity (prolonged QT interval)
• bleeding problems or if you are taking medicines that may cause bleeding
• eye problems
• liver or kidney problems

Inform your doctor if you have had another type of tumour different from melanoma, colorectal
cancer, or non-small cell lung cancer, as Braftovi could worsen certain other types of tumours.
Immediately inform your doctor, pharmacist, or nurse if you experience any of the following
conditions while taking this medicine:

• Heart problems: Braftovi, when taken with binimetinib, may impair heart function, alter the heart's electrical activity known as “prolonged QT interval,” or worsen existing heart problems. Your doctor will check that your heart is functioning properly before and during treatment with these medicines. Contact your doctor immediately if you have any symptoms of heart problems, such as dizziness, fatigue, lightheadedness, shortness of breath, a sensation of your heart beating strongly, rapidly, or irregularly, or swelling in your legs.
• Bleeding problems: Braftovi can cause serious bleeding problems. Contact your doctor immediately if you have any symptoms of bleeding, such as coughing up blood, blood clots, vomiting blood or material that looks like “coffee grounds,” red or black tarry stools, blood in the urine, abdominal pain, or unusual vaginal bleeding. Also inform your doctor if you have headache, dizziness, or weakness.
• Eye problems: Braftovi, when taken in combination with binimetinib, may cause serious eye problems. Contact your doctor immediately if you experience blurred vision, loss of vision, or other visual disturbances (e.g., colored spots in vision), halos (blurred outlines of objects). Your doctor will examine your eyes to check for any vision problems during Braftovi treatment.
• Skin changes: Braftovi may cause other types of skin cancer, such as cutaneous squamous cell carcinoma. New melanomas may also occur during Braftovi treatment. Your doctor will examine your skin to detect any new skin tumours

before treatment, every two months during treatment, and for up to 6 months after you stop
taking Braftovi. Immediately inform your doctor if you notice any skin changes during or
after treatment, including: a new wart, painful skin, or a red, bleeding, or non-healing lesion, or changes in the size or colour of a mole. Your doctor will also examine your head, neck, mouth, and lymph nodes to detect squamous cell carcinoma, and you will undergo regular CT scans. This is a precaution in case squamous cell carcinoma develops inside your body. A pelvic examination (for women) and an anal examination are also recommended before and at the end of treatment.

• Liver problems: Braftovi may cause changes in blood tests related to liver function (increased liver enzyme levels). Your doctor will perform blood tests to monitor your liver before and during treatment.
• Kidney problems: Braftovi may affect kidney function (frequent changes in blood tests, less commonly dehydration and vomiting). Your doctor will perform blood tests to monitor your kidneys before and during treatment. Drink plenty of fluids during treatment. Inform your doctor immediately if you vomit and become dehydrated.

Contact your doctor immediately if you experience any of the following symptoms, as they may indicate a life-threatening condition: nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, cloudy urine, reduced urine output, and fatigue.
These symptoms may be caused by a group of metabolic complications that can occur during cancer treatment, possibly due to breakdown products from dying tumour cells (Tumour Lysis Syndrome (TLS)), which may lead to impaired 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
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicine.
Some medicines may affect how Braftovi works or make it more likely that you experience side effects. In particular, inform your doctor if you are taking any of the following medicines or any other medicine:

• 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 tumours (such as methotrexate, imatinib)
• medicines commonly used to lower cholesterol (such as rosuvastatin, atorvastatin)
• a herbal treatment for depression: St. John’s wort (Hypericum perforatum)
• certain HIV medicines 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.

Braftovi with food and drink
Do not drink grapefruit juice during treatment with Braftovi, as this may increase the risk of side effects from Braftovi.

Pregnancy
Braftovi is not recommended during pregnancy. It may cause harm or birth defects to the unborn baby.
If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your doctor or pharmacist before taking this medicine.
If you are a woman of childbearing potential, you must use an effective contraceptive method while taking Braftovi and continue using an effective contraceptive method for at least 1 month after taking the last dose. Hormonal contraceptives [e.g., pills, injections, patches, implants, and certain hormone-releasing intrauterine devices (IUDs)] may not work as expected while you are taking Braftovi. You must use another effective contraceptive method, such as a barrier method (e.g., condom), to avoid becoming pregnant while taking this medicine. Consult your doctor or pharmacist.
Contact your doctor immediately if you become pregnant while taking Braftovi.

Breastfeeding
Braftovi is not recommended during breastfeeding. It is not known whether Braftovi passes into breast milk. If you are breastfeeding or planning to breastfeed, consult your doctor before taking this medicine.

Fertility
Braftovi may reduce sperm count in males. This could affect the ability to have children. Talk to your doctor if you have concerns about this.

Driving and using machines
Braftovi may affect your ability to drive or operate machinery. Avoid driving or operating machinery if you have any vision problems or other side effects that may affect your ability to drive or use machines (see section 4) while taking Braftovi. Talk to your doctor if you are unsure whether you can drive safely.

3. How to take Braftovi

How much to take
Take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

For the treatment of melanoma and non-small cell lung cancer
The recommended dose of Braftovi is 6 capsules of 75 mg taken once daily (corresponding to a daily dose of 450 mg). You will also be given another medicine, binimetinib.

For the treatment of colorectal carcinoma
The recommended dose of Braftovi for the treatment of colorectal carcinoma is 4 capsules of 75 mg taken once daily (corresponding to a daily dose of 300 mg). You will also be given another medicine, cetuximab.

If you have liver or kidney problems, your doctor may prescribe a lower dose.
If you experience severe side effects (such as heart, eye or bleeding problems), your doctor may reduce the dose, temporarily suspend treatment or permanently discontinue it.

How to take Braftovi

Instructions for opening the blister pack:

• Do not push the capsule through the blister.
• Detach one blister cell by bending and gently tearing along the perforations.
• Carefully peel back the foil starting from the corner marked with an arrow.
• Gently remove the capsule.

Swallow the capsules whole with water. Braftovi can be taken with food or between meals.
If you have difficulty swallowing the capsules whole, you may open them and disperse the contents in a small amount of apple puree (approximately 20 mL, about 1 tablespoon), and take the mixture immediately.
If the mixture is not used within 30 minutes, discard it and prepare a fresh one.

In case of vomiting
If you vomit at any time after taking Braftovi, do not take another dose. Take your next scheduled dose as planned.

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

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, skip that dose and take the next dose at your usual time. Then continue taking the capsules at regular intervals 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 continue taking Braftovi for as long as your doctor has prescribed it. Do not stop unless your doctor tells you to do so.
If you have any questions about how to use this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects

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

Heart problems: Braftovi, when taken with binimetinib, may affect how the heart works (reduced left ventricular ejection fraction). Signs and symptoms may include:

• feeling dizzy, tired or lightheaded
• shortness of breath
• feeling like your heart is pounding, racing or beating irregularly
• swelling in the legs

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

• blurred vision, vision loss or other visual disturbances (such as colored spots in your vision)
• seeing halos (blurred edges around objects)
• eye pain, swelling or redness

Bleeding problems: Braftovi may cause serious bleeding issues. Inform your doctor immediately if you notice signs of unusual bleeding, including:

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

Muscle problems: Braftovi, when taken with binimetinib, may cause muscle breakdown (rhabdomyolysis), which 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 a type of skin tumour such as cutaneous squamous cell carcinoma. These skin changes (see also section 2) are usually confined to 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.

Tumour lysis syndrome: Treatment with Braftovi may cause rapid breakdown of tumour cells, which in some people may be fatal. Symptoms may include nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, cloudy urine, reduced urine output and fatigue.

Other side effects

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

Side effects when Braftovi and binimetinib are taken together for the treatment of melanoma or non-small cell lung cancer

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

• low red blood cell levels (anaemia)
• nerve problems causing pain, numbness or tingling in hands and feet
• headache
• dizziness
• bleeding in various parts of the body
• high blood pressure
• vision disturbances (impaired vision)
• stomach pain
• diarrhoea
• vomiting
• nausea
• constipation
• itching
• dry skin
• hair loss or thinning (alopecia)
• various types of skin rash
• thickening of the outer skin layers
• joint pain (arthralgia)
• muscle problems
• back pain
• limb pain
• fever
• swelling of the hands or feet (peripheral oedema), localized swelling
• fatigue
• abnormal laboratory test results for liver function
• abnormal laboratory test results for 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 cancer such as skin papilloma
• allergic reaction that may include facial swelling and difficulty breathing
• changes in taste perception
• eye inflammation (uveitis)
• blood clots
• inflammation of the colon (colitis)
• redness, cracking or chapping of the skin
• inflammation of the fat layer beneath the skin; symptoms include soft skin nodules
• skin rash with flat discoloured areas or acne-like raised bumps (acneiform dermatitis)
• redness, peeling or blisters on the hands and feet (palmar-plantar erythrodysesthesia or hand-foot syndrome)
• kidney problems (impaired kidney function)
• abnormal laboratory test results related to kidney function (increased creatinine)
• abnormal laboratory test results for liver function (alkaline phosphatase)
• abnormal laboratory test results for pancreatic function (amylase, lipase)
• increased sensitivity of the skin to sunlight

Uncommon (may affect up to 1 in 100 people)

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

Side effects when Braftovi was used alone in clinical studies conducted in patients with melanoma

If you continue taking Braftovi alone while the other medicine (binimetinib) has been temporarily suspended based on your doctor's decision, you may experience some of the side effects listed above, although their frequency may change (increase or decrease).

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

• fatigue
• nausea
• vomiting
• constipation
• various types of skin rash
• redness, peeling or blisters on the hands and feet (palmar-plantar erythrodysesthesia or hand-foot syndrome)
• thickening of the outer skin layer (hyperkeratosis)
• dry skin
• itching
• hair loss or abnormal thinning (alopecia)
• redness, cracking or chapping of the skin
• darkening of the skin
• loss of appetite
• difficulty sleeping (insomnia)
• headache
• nerve problems that may cause pain, numbness or tingling in hands and feet
• changes in taste perception
• joint pain (arthralgia)
• muscle pain, spasm or weakness
• limb pain
• back pain
• fever
• certain types of benign skin tumours such as melanocytic naevi and skin papillomas
• abnormal blood test results related to liver function

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
• paralysis or movement disturbances in the face
• rapid heartbeat
• skin rash with flat discoloured areas or acne-like raised bumps (acneiform dermatitis)
• skin peeling or scaly skin
• joint inflammation (arthritis)
• kidney problems (impaired kidney function)
• abnormal blood test results related to kidney function (increased creatinine)
• increased sensitivity of the skin to sunlight
• abnormal laboratory test results for pancreatic function (lipase)

Uncommon (may affect up to 1 in 100 people)

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

Side effects when Braftovi and cetuximab are taken together for the treatment of colorectal cancer

In addition to the adverse events described above, the following side effects may occur in patients taking Braftovi together with cetuximab.

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

• new moles called "melanocytic naevi"
• loss of appetite
• difficulty sleeping (insomnia)
• nerve problems that may cause pain, numbness or tingling in hands and feet
• headache
• bleeding in various parts of the body
• diarrhoea
• stomach pain
• nausea
• vomiting
• constipation
• skin rash with flat discoloured areas or acne-like raised bumps (acneiform dermatitis)
• various types of skin rash
• dry skin
• itching
• joint pain (arthralgia) and muscle and/or bone pain (musculoskeletal pain)
• muscle pain, spasm or weakness
• limb pain
• back pain
• fatigue
• fever

Common (may affect up to 1 in 10 people)

• certain types of skin tumours such as skin papilloma
• allergic reaction that may include facial swelling and difficulty breathing
• dizziness
• change in taste
• fast heartbeat
• darkening of the skin
• redness, peeling or blisters on the hands and feet (palmar-plantar erythrodysesthesia or hand-foot syndrome)
• thickening of the outer skin layer (hyperkeratosis)
• redness, cracking or chapping of the skin
• hair loss or thinning (alopecia)
• kidney problems
• abnormal blood test results related to kidney function (increased creatinine)
• abnormal blood test results for liver function

Uncommon (may affect up to 1 in 100 people)

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

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Braftovi

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./EXP. The expiry date refers to the last day of that month.
Store below 30 °C. Keep in the original packaging to protect the medicine from moisture.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What Braftovi contains

• 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 coating: 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)

Description of the appearance of Braftovi and package contents

Braftovi 50 mg hard capsules
The hard capsule (capsule) has an opaque orange cap and an opaque beige body, with a stylized “A” printed on the cap and “LGX50mg” on the body.
Braftovi 50 mg is available in packs of 28x1 capsules or 112x1 capsules in perforated blisters for unit dose.
Not all 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 a stylized “A” printed on the cap and “LGX75mg” on the body.
Braftovi 75 mg is available in packs of 42x1 capsules or 168x1 capsules in perforated blisters for unit dose.
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

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