Mektovi

Package leaflet: Information for the patient

Mektovi 15 mg film-coated tablets, 45 mg film-coated tablets

binimetinib
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 their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Mektovi is and what it is used for

Mektovi is an anticancer medicine that contains the active substance binimetinib. It is used in adults in combination with another medicine containing encorafenib to treat a type of skin cancer called melanoma or a type of lung cancer called non-small cell lung cancer (NSCLC), when the tumour:
has a specific alteration (mutation) in a gene called BRAF, and
has spread to other parts of the body or cannot be surgically removed.
Mutations in the BRAF gene can produce proteins that cause tumour growth. Mektovi acts on another protein called "MEK" which stimulates the growth of cancer cells. When Mektovi is used in combination with encorafenib, which targets the protein produced by the altered BRAF gene, the combination slows down or blocks tumour progression.

2. What you need to know before taking Mektovi

Before starting treatment, your doctor will check for the presence of the BRAF mutation.
Since Mektovi must be used in combination with encorafenib, please read carefully both the package leaflet for encorafenib and this leaflet.

Do not take Mektovi
if you are allergic to binimetinib or to any of the other ingredients of this medicine (listed in section 6).

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

• heart problems
• bleeding problems or if you are taking medicines that may cause bleeding
• eye problems including glaucoma or increased intraocular pressure
• muscle problems
• high blood pressure
• blood clots
• lung or breathing problems
• liver problems

Inform your doctor if you have ever had a blockage in the vein that drains blood away from the eye (retinal vein occlusion), as Mektovi is not recommended in this case.

Inform your doctor if you have had a type of cancer other than melanoma or non-small cell lung cancer, as binimetinib taken with encorafenib may worsen certain other types of tumours.

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

Heart problems: Mektovi may reduce the heart's ability to function properly or worsen existing heart problems. Your doctor will check that your heart is working correctly before and during treatment with this medicine. Contact your doctor immediately if you experience any symptoms of heart problems such as dizziness, fatigue, lightheadedness, shortness of breath, a sensation of rapid or irregular heartbeat, or swelling in the legs.

Bleeding problems: Mektovi may cause serious bleeding problems. Inform your doctor immediately if you experience any symptoms of bleeding such as coughing up blood, blood clots, vomiting blood or material resembling "coffee grounds", red or black tarry stools, blood in the urine, abdominal pain, or unusual vaginal bleeding. Also inform your doctor if you experience headache, dizziness, or weakness.

Eye problems: Mektovi may cause serious eye problems. Contact your doctor immediately if you experience blurred vision, loss of vision, or other visual disturbances (e.g. coloured spots in your vision), or halos (blurred outlines of objects). Your doctor will monitor your eyes for any vision problems during treatment with Mektovi.

Muscle problems: Mektovi may cause muscle breakdown (rhabdomyolysis). Your doctor will perform blood tests to monitor for muscle problems before and during treatment. As a precaution, drink plenty of fluids during treatment. Contact your doctor immediately if you experience muscle pain, cramps, stiffness, spasms, or dark urine.

High blood pressure: Mektovi may increase blood pressure. Your doctor or nurse will monitor your blood pressure before and during treatment with Mektovi. Inform your doctor immediately if you experience severe headache, dizziness, lightheadedness, or if your home blood pressure monitor shows a significantly higher than normal reading.

Blood clots: Mektovi may cause blood clots in the arms or legs, and if a clot travels to the lungs it may be fatal. Inform your doctor immediately if you experience chest pain, sudden shortness of breath, difficulty breathing, leg pain with or without swelling, swelling in arms and legs, or pale arm or leg.
If necessary, your doctor may temporarily interrupt or permanently discontinue treatment.

Lung or breathing problems: This medicine may cause lung or breathing problems, including inflammation of the lungs (pneumonitis or interstitial lung disease). Signs and symptoms may include cough, shortness of breath, or fatigue. If necessary, your doctor may temporarily interrupt or permanently discontinue treatment.

Skin changes: Mektovi, when taken with encorafenib, may cause other types of skin cancer such as cutaneous squamous cell carcinoma. Your doctor will examine your skin before starting treatment, every two months during treatment, and for up to 6 months after stopping the medicine, to check for any new skin tumours. Inform your doctor immediately if you notice any skin changes during or after treatment, including: a new wart, painful skin, or a red bump that bleeds or does not heal, or any change in size or colour of a mole.

Your doctor will also need to monitor for the development of cutaneous squamous cell carcinoma on the head, neck, mouth, and lymph nodes, 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 starting and at the end of treatment.

Liver problems: Mektovi may cause changes in liver blood test results (increased liver enzyme levels). Your doctor will perform blood tests to monitor liver function before and during treatment.

Contact your doctor immediately if you experience the following symptoms, as they may indicate a life-threatening condition: nausea, laboured breathing, 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
Mektovi 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 Mektovi
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.

• Some medicines may affect how Mektovi 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 medicines:
• certain antibiotics used to treat bacterial infections, such as rifampicin, ciprofloxacin
• medicines commonly used to treat epilepsy, such as phenytoin, phenobarbital, carbamazepine
• certain medicines used to treat HIV, such as indinavir, atazanavir
• a medicine used to treat cancer called sorafenib
• a herbal treatment for depression: St John's wort (Hypericum perforatum)
• a medicine used to treat depression, such as duloxetine
• medicines commonly used to treat high cholesterol, such as pravastatin
• a medicine used to treat breathing problems, theophylline

Pregnancy
Mektovi is not recommended during pregnancy. It may cause permanent 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 before taking this medicine.
If you are a woman of childbearing potential, you must use an effective method of contraception while taking Mektovi and continue using an effective method of contraception for at least 1 month after the last dose. Contact your doctor immediately if you become pregnant while taking Mektovi.

Breast-feeding
Mektovi is not recommended during breast-feeding. It is not known whether Mektovi passes into breast milk. If you are breast-feeding or planning to breast-feed, consult your doctor before taking this medicine.

Driving and using machines
Mektovi may affect your ability to drive or use machines. Avoid driving vehicles 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 Mektovi. Talk to your doctor if you are unsure whether you can drive safely.

Mektovi contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, speak with your doctor before taking this medicine.
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e. essentially 'sodium-free'.

3. How to take Mektovi

How much to take
Always take this medicine exactly as instructed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
The recommended dose of Mektovi is 45 mg (3 tablets of 15 mg or one 45 mg tablet) twice daily, approximately 12 hours apart, corresponding to a total daily dose
of 90 mg. You will also be given another medicine, encorafenib.
If you experience severe side effects (such as problems with the heart, eyes or skin), your doctor
may decide to reduce the dose or temporarily or permanently discontinue treatment.

How to take Mektovi
Swallow the tablets whole with water. Mektovi can be taken with food or between meals.
If you are unable to swallow the tablets whole, you may disperse the 15 mg Mektovi tablets in a small glass (approximately 10 mL, about 2 teaspoons) of water, orange juice, or apple juice and take immediately. The glass should then be rinsed with an additional 10 mL (approximately 2 teaspoons) of water, orange juice, or apple juice, and the rinse liquid should be drunk immediately.
If the mixture is not used within 30 minutes, discard it and prepare a fresh mixture.

In case of vomiting
If you vomit at any time after taking Mektovi, do not take another dose of the medicine. Take the next dose as scheduled.

If you take more Mektovi than you should
If you take more tablets than you should, contact your doctor, pharmacist, or nurse immediately. If possible, show them this leaflet and the medicine packaging.

If you forget to take Mektovi
If you forget a dose of Mektovi, take it as soon as you remember. However, if more than 6 hours have passed, skip that dose and take the next dose at the usual time. Then continue taking the tablets regularly as usual.
Do not take a double dose to make up for a forgotten dose.

If you stop treatment with Mektovi
It is important that you continue taking Mektovi for the entire duration prescribed by your doctor. Do not stop unless your doctor tells you to do so.
If you have any questions about using this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Serious side effects
Mektovi 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: Mektovi can affect how the heart works (reduction in left ventricular ejection fraction); signs and symptoms may include:

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

High blood pressure: Mektovi can increase blood pressure. Inform your doctor immediately if you have severe headaches, feel dizzy or lightheaded, or if your blood pressure measured with a home monitoring device is much higher than normal.
Blood clots: Mektovi can cause blood clots (venous thromboembolism including pulmonary embolism); signs and symptoms may include:

• chest pain
• sudden shortness of breath or trouble breathing
• leg pain with or without swelling
• swelling in the arms and legs
• if one arm or leg feels cold, pale or weak

Eye problems: Mektovi can cause fluid buildup under the retina of the eye, leading to separation of layers in the eye (retinal pigment epithelial detachment), which may result in the following symptoms:

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

Muscle problems: Mektovi can 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

Bleeding problems: Mektovi can cause serious bleeding problems. Inform your doctor immediately if you have unusual bleeding or signs of bleeding, including:

• headache, 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

Other skin cancers: When Mektovi is taken with encorafenib, you may develop different types of skin cancer such as cutaneous squamous cell carcinoma. Usually, these skin tumors (see also section 2) are localized to a small area and can be removed surgically, and treatment with Mektovi (and encorafenib) can continue uninterrupted.
Tumor lysis syndrome: Treatment with Mektovi can cause rapid breakdown of tumor cells, which may be fatal in some people. Symptoms may include nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, cloudy urine, reduced urine output, and fatigue.
Other side effects when Mektovi and encorafenib are taken together
In addition to the serious side effects listed above, people taking Mektovi and encorafenib together may also experience the following side effects.
Very common (may affect more than 1 in 10 people)

• reduced red blood cell count (anaemia)
• nerve problems causing pain, numbness or tingling in hands and feet
• headache
• dizziness
• bleeding in various parts of the body
• visual 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 layers of the skin
• joint pain (arthralgia)
• muscle disorders
• back pain
• limb pain
• fever
• swelling of the hands or feet (peripheral oedema), localized swelling
• fatigue
• abnormal liver function laboratory test results
• abnormal creatine kinase laboratory test results, indicating heart or muscle damage

Common (may affect up to 1 in 10 people)

• certain types of skin cancer such as skin papilloma
• allergic reaction which may include facial swelling and difficulty breathing
• changes in taste perception
• eye inflammation (uveitis)
• colon inflammation (colitis)
• redness, fissures or cracks in the skin
• inflammation of the fat layer beneath the skin; symptoms include soft skin nodules
• skin rash with flat discolored 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
• abnormal kidney laboratory test results (increased creatinine)
• abnormal liver function laboratory test results (alkaline phosphatase)
• abnormal pancreatic function laboratory test results (amylase, lipase)
• increased sensitivity of the skin to sunlight

Uncommon (may affect up to 1 in 100 people)

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

Reporting of side effects
If you experience any side effect, 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 Mektovi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and carton after
Exp./EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Mektovi contains
­ The active substance is binimetinib.
Mektovi 15 mg film-coated tablets: each film-coated tablet contains 15 mg of binimetinib.
Mektovi 45 mg film-coated tablets: each film-coated tablet contains 45 mg of binimetinib.
­ Other components are:

• Tablet core: lactose monohydrate, microcrystalline cellulose (E460i), anhydrous colloidal silica (E551), sodium croscarmellose (E468) and magnesium stearate (E470b). See section 2 “Mektovi contains lactose”.
• Film coating: Mektovi 15 mg film-coated tablets: polyvinyl alcohol (E1203), macrogol 3350 (E1521), titanium dioxide (E171), talc (E533b), yellow iron oxide (E172) and black iron oxide (E172). Mektovi 45 mg film-coated tablets: polyvinyl alcohol (E1203), macrogol 4000 (E1521), calcium carbonate (E170), talc (E533b).

Description of the appearance of Mektovi and package contents
Mektovi 15 mg film-coated tablets
The film-coated tablets are yellow to dark yellow, biconvex, smooth, ovaloid film-coated tablets, marked with “A” on one side and “15” on the other.
Mektovi 15 mg film-coated tablets are available in packs of 84 tablets (7 blisters containing 12 tablets each) or 168 tablets (14 blisters containing 12 tablets each).
Mektovi 45 mg film-coated tablets
The film-coated tablets are white to off-white, biconvex, smooth, ovaloid film-coated tablets, marked with “45” on one side.
Mektovi 45 mg film-coated tablets are available in packs of 28 tablets (2 blisters containing 14 tablets each) or 56 tablets (4 blisters containing 14 tablets each).
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.