MEKTOVI 45 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Mektovi 15 mg film-coated tablets

Mektovi 45 mg film-coated tablets

binimetinib

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Mektovi and what is it used for

Mektovi is a cancer medicine that contains binimetinib as the active substance. It is used in adults, in combination with another medicine that contains 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 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.

Mutations in the BRAF gene can produce proteins that cause cancer to grow. Mektovi works on another protein called "MEK" that stimulates the growth of cancer cells. When Mektovi is used in combination with encorafenib (which works on the altered "BRAF" protein), the combination slows down or even stops the growth of the cancer.

2. What you need to know before you take Mektovi

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

Since Mektovi is used in combination with encorafenib, read the encorafenib package leaflet carefully, in addition to this leaflet.

Do not take Mektovi:

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

Warnings and precautions

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

• heart problems
• bleeding problems or if you are taking any medicine that may cause bleeding
• eye problems, including glaucoma or increased pressure in the eye
• muscle problems
• high blood pressure
• blood clots
• lung or breathing problems
• liver problems

Tell your doctor if you have ever had a blockage of the vein that drains the eye (retinal vein occlusion), as Mektovi is not recommended in these cases.

Tell your doctor if you have had any other cancer other than melanoma or NSCLC, as binimetinib, when taken with encorafenib, may worsen other types of cancer.

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

• Heart problems: Mektovi may affect how well your heart works, or make existing heart problems worse. Your doctor will check that your heart is working properly before, during, and after treatment with this medicine. Tell 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: Mektovi may cause serious bleeding problems. Tell 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, tell your doctor if you have a headache, dizziness, or weakness.

• Eye problems: Mektovi may cause serious eye problems. Tell 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 to detect any vision problems while you are taking Mektovi.

• Muscle problems: Mektovi may cause the destruction of muscle fibers (rhabdomyolysis). Your doctor will ask you to have blood tests to detect and/or monitor muscle problems before and during treatment. As a precaution, drink plenty of fluids during treatment. Tell your doctor immediately if you have muscle pain, cramps, stiffness, spasms, or dark urine.

• High blood pressure: Mektovi may increase your blood pressure. Your doctor or nurse will check your blood pressure before and during treatment with Mektovi. Tell your doctor immediately if you have severe headaches, feel dizzy, faint, or if your blood pressure is much higher than usual.

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

• Lung or breathing problems: this medicine may cause lung or breathing problems, such as inflammation of the lungs (pneumonitis or interstitial lung disease); the signs and symptoms may be cough, shortness of breath, or tiredness. If necessary, your doctor may interrupt or permanently stop treatment.

• Skin changes: Mektovi, when taken with encorafenib, may cause other types of skin cancer, such as squamous cell carcinoma of the skin. Your doctor will examine your skin before starting treatment, every 2 weeks while on treatment, and up to 6 months after stopping these medicines, to check for any new skin cancer. Tell 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 need to examine your head, neck, mouth, and lymph nodes to detect squamous cell carcinoma of the skin, and regular CT scans are recommended. This is a precaution in case squamous cell carcinoma develops in your body. Genital (in women) and anal examinations are also recommended before starting and after stopping treatment.

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

If you experience the following symptoms, contact your doctor immediately, as it may be a potentially life-threatening disorder: 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 cause changes in 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

Tell 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 increase the risk of side effects. In particular, tell your doctor if you are taking any of the following medicines or any other:

• medicines to treat bacterial infections such as rifampicin, ciprofloxacin.
• medicines typically used to treat epilepsy such as phenobarbital, phenytoin, carbamazepine.
• medicines to treat HIV such as indinavir, atazanavir.
• a medicine to treat carcinoma called sorafenib.
• a herbal treatment for depression: St. John's Wort.
• medicines used to treat depression such as duloxetine.
• medicines typically used to treat high cholesterol such as pravastatin.
• a medicine used to treat respiratory problems, theophylline.

Pregnancy

Mektovi is not recommended during pregnancy. It may cause permanent damage to the fetus or 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 Mektovi and continue to use it for at least 1 month after taking the last dose. Tell 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 think you may want to breast-feed, ask your doctor for advice before taking this medicine.

Driving and using machines

Mektovi may affect your ability to drive or use machines. Do not drive or use 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 Mektovi. Ask your doctor if you are unsure about driving.

Mektovi contains lactose

If your doctor has told you that you have an intolerance to some sugars, contact them before taking this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per dose, which is essentially "sodium-free".

3. How to take Mektovi

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.

The recommended dose of Mektovi is 45 mg (three 15 mg tablets or one 45 mg tablet) twice a day, approximately 12 hours apart, which corresponds to a total daily dose of 90 mg. You will also receive treatment with another medicine, encorafenib.

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

How to take Mektovi

Swallow the tablets whole with water. Mektovi can be taken with or without food.

If you vomit

If you vomit at any time after taking Mektovi, do not take an additional dose. Take the next dose when it is due.

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 pack.

If you forget to take Mektovi

If you miss a dose of Mektovi, take it as soon as you remember. However, if it is more than 6 hours since the time you should have taken the missed dose, skip it and take the next dose when it is due. Then, continue taking the tablets as usual.

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

If you stop taking Mektovi

It is important that you take Mektovi for as long as your doctor has prescribed it. 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

Mektovi 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: Mektovi may affect the way your heart works (decrease in left ventricular ejection fraction); signs and symptoms may be:

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

Increased blood pressure: Mektovi may increase blood pressure. Consult your doctor immediately if you have severe headache, feel dizzy, or if you usually take your blood pressure at home with a blood pressure device and it is much higher than normal.

Blood clots: Mektovi may cause blood clots (venous thromboembolism, including pulmonary embolism); signs and symptoms may be:

• chest pain
• sudden shortness of breath or difficulty breathing
• pain in the legs, with or without swelling
• swollen arms and legs
• a cold and pale arm or leg

Eye problems: Mektovi may cause fluid loss under the retina, which can lead to detachment of some layers (retinal pigment epithelial detachment), which could lead to:

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

Muscle problems: Mektovi may cause muscle fiber destruction (rhabdomyolysis), which can cause kidney damage and be fatal; signs and symptoms may be:

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

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

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

Other skin cancers: When Mektovi is taken with encorafenib, the patient may suffer from different types of skin cancer, such as squamous cell carcinoma of the skin. These skin cancers usually affect a small area and can be removed with surgery, and treatment with Mektovi (and encorafenib) can continue without interruption.

Tumor Lysis Syndrome: Mektovi 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.

Adverse Effects when Mektovi is taken with Encorafenib

In addition to the severe adverse effects mentioned above, people who take Mektovi with encorafenib may also experience the following adverse effects.

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

• decrease in red blood cell count (anemia)
• nerve problems, causing pain, numbness, or tingling in hands and feet
• headache
• dizziness
• bleeding in different parts of the body
• vision problems (visual impairment)
• stomach pain
• diarrhea
• vomiting
• nausea
• constipation
• itching
• dry skin
• hair loss or weakening (alopecia)
• skin rash of various types
• thickening of the outer layers of the skin
• joint pain (arthralgia)
• muscle disorders
• back pain
• pain in the limbs
• 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, indicating heart and skeletal muscle damage

Common(may affect up to 1 in 10 people)

• certain types of skin tumors, such as cutaneous papilloma
• allergic reaction that can include swelling of the face and difficulty breathing
• changes in taste
• eye inflammation (uveitis)
• 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 of the skin, 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 skin sensitivity 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

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Mektovi

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

Do not use this medicine after the expiration date that appears on the blister pack and carton after CAD. The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

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

Mektovi Composition

• The active ingredient is binimetinib.

Mektovi 45 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.

• The other ingredients are:

• Tablet core: lactose monohydrate, microcrystalline cellulose (E460i), colloidal anhydrous silica (E551), sodium croscarmellose (E468), and magnesium stearate (E470b). See section 2 "Mektovi contains lactose".
• Tablet 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), and talc (E533b).

Product Appearance and Package Contents

Mektovi 15 mg film-coated tablets

The film-coated tablets are oval, yellow to dark yellow, biconvex, and have no score, with an "A" engraved on one side and "15" on the other.

Mektovi 15 mg film-coated tablets are dispensed in cartons of 84 tablets (7 blisters of 12 tablets each) or 168 tablets (14 blisters of 12 tablets each).

Only certain package sizes may be marketed.

Mektovi 45 mg film-coated tablets

The film-coated tablets are oval, white to off-white, biconvex, and have no score, with a "45" engraved on one side.

Mektovi 45 mg film-coated tablets are dispensed in cartons of 28 tablets (2 blisters of 14 tablets each) or 56 tablets (4 blisters of 14 tablets each).

Only certain package 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 Prospectus:

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