Mektovi 15 mg comprimidos recubiertos con pelicula

Prescribing Information for the Patient

Mektovi 15 mg Film-Coated Tablets

Mektovi 45 mg Film-Coated Tablets

binimetinib

Read this entire prescribing information carefully before starting to take this medicine, as 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 only for you, and you should 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.

Mektovi is a cancer medication that contains binimetinib as the active ingredient. It is used in adults, combined with another medication 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 growth. Mektovi acts on another protein called “MEK” that stimulates the growth of cancer cells. When Mektovi is used in combination with encorafenib (which acts on the altered BRAF protein), the combination slows down or even stops cancer growth.

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

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

Do not take Mektovi::

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

Warnings and precautions

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

• heart problems

• bleeding problems or if you are taking any medication that may cause bleeding

• eye problems, including glaucoma or increased intraocular pressure

• muscle problems

• high blood pressure

• blood clots

• lung or respiratory problems

• liver problems

Inform 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.

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

Immediately contact your doctor, pharmacist, or nurse if you experience any of the following conditions while taking this medication:

• Heart problems: Mektovi may cause your heart to function poorly, or worsen existing heart problems. Your doctor will check that your heart is functioning correctly, before, during, and after treatment with this medication. Immediately consult your doctor if you experience any symptoms of heart problems such as dizziness, fatigue, confusion, shortness of breath, if your heart beats strongly, accelerates, beats irregularly, or if you have swelling in your legs.

• Bleeding problems: Mektovi may cause severe bleeding problems. Immediately consult your doctor if you experience any signs of bleeding such as coughing up blood, blood clots, vomiting that contains blood or appears "coffee ground," black or red stools, blood in your urine, abdominal pain, unusual vaginal bleeding. Also inform your doctor if you experience headache, dizziness, or weakness.

• Eye problems: Mektovi may cause severe eye problems. Immediately consult your doctor 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 Mektovi.

• Muscle problems: Mektovi may cause the destruction of muscle fibers (rhabdomyolysis). Your doctor will request that you undergo blood tests to detect and/or control muscle problems before and during treatment. As a precaution, drink plenty of liquids during treatment. Immediately consult your doctor if you experience muscle pain, cramps, stiffness, spasms, 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. Immediately consult your doctor if you experience severe headaches, dizziness, confusion, or, if you are accustomed to taking your blood pressure at home with a blood pressure device, it is much higher than what is normally expected.

• Blood clots: Mektovi may cause blood clots in your legs or arms, if a clot travels to your lungs it could be fatal. Immediately consult your doctor if you experience 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 discontinue treatment.

• Lung or respiratory problems: this medication may cause lung or respiratory problems, such as inflammation of the lungs (pneumonitis or interstitial lung disease); symptoms may include coughing, shortness of breath, fatigue. If necessary, your doctor may interrupt or discontinue treatment.

• Skin changes: Mektovi, when taken with encorafenib, may cause other types of skin cancer, such as squamous cell skin carcinoma. Your doctor will examine your skin before starting treatment, every 2 weeks during treatment, and up to 6 months after stopping these medications, to check if any new skin cancer develops. Immediately consult your doctor 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 any moles.

In addition, your doctor will need to examine you, your head, neck, mouth, and lymph nodes, to detect squamous cell skin carcinoma, and regular CT scans are recommended. This is a precaution, in case squamous cell skin carcinoma develops in your body. Women are also recommended to undergo genital and anal examinations before starting treatment and after stopping it.

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

If you experience the following symptoms, contact your doctor immediately, as they may be a potentially fatal condition: 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 may occur during cancer treatment and are caused by the breakdown products of dying cancer cells (tumor lysis syndrome) and may cause changes in kidney function (see section 4: Possible side effects).

Children and adolescents

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

Other medications and Mektovi

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 Mektovi works or increase the risk of adverse effects. Especially, consult your doctor if you are taking any medication from this list or any other:

• medications to treat bacterial infections such as rifampicin, ciprofloxacin.

• medications typically used to treat epilepsy such as phenobarbital, phenytoin, carbamazepine.
• medications to treat HIV such as indinavir, atazanavir

• a medication to treat cancer called sorafenib.

• a herbal treatment for depression: St. John's Wort.

• medications typically used to treat depression such as duloxetine.

• medications typically used to treat high cholesterol such as pravastatin.

• a medication used to treat respiratory problems, theophylline.

Pregnancy

Mektovi is not recommended during pregnancy. It may cause permanent damage to the fetus or congenital 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 who may become pregnant, you must use a reliable contraceptive method while taking Mektovi, and you must continue to use it for at least 1 month after taking the last dose. Immediately consult your doctor if you become pregnant while taking Mektovi.

Breastfeeding

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

Driving and operating machinery

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

Mektovi contains lactose

If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

This medication contains less than 1 mmol of sodium (23 mg) per dose; it is essentially "sodium-free."

How much to take

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

The recommended dose of Mektovi is 45 mg (three 15 mg tablets or one 45 mg tablet) taken twice a day, approximately with a 12-hour interval between doses, which corresponds to a total daily dose of 90 mg. You will also receive treatment with another medication, encorafenib.

If you experience severe side effects (such as heart, eye, or skin problems), your doctor may reduce your 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 have vomiting

If you vomit at any time after taking Mektovi, do not take an additional dose. 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 packaging of the medication.

If you forget to take Mektovi

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

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

If you interrupt treatment with Mektovi

It is essential to take Mektovi for the time prescribed by your doctor. 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

Mektovi may cause severe side effects. Consult your doctor immediatelyif you haveany of the following side effects for the first time or if they worsen existing ones (see also section 2):

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

• feeling dizzy, tired, or disoriented

• shortness of breath

• feeling like your heart is beating strongly, quickly, or irregularly

• swollen legs

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

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

• chest pain

• sudden shortness of breath or difficulty breathing

• leg pain, with or without swelling

• swollen arms and legs

• an arm or leg that is cold and pale

Eye problems: Mektovi may cause fluid loss from the eye under the retina, which may lead to the detachment of some layers (pigmentary retinal detachment), which could result in:

• 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 may lead to kidney damage and be fatal; the 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 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

Other skin cancers: When Mektovi is taken with encorafenib, the patient may develop different types of skin cancer, such as squamous cell skin carcinoma. These skin cancers (see section 2) 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 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.

Severe side effects when Mektovi is taken with encorafenib

In addition to the severe side effects mentioned above, people taking Mektovi with encorafenib may also experience the following side effects.

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

• decreased red blood cell count (anemia)
• nerve problems, causing pain, numbness, or tingling in hands and feet
• headaches
• dizziness
• bleeding in various parts of the body
• vision problems (visual impairment)
• abdominal pain
• diarrhea
• vomiting
• nausea
• constipation
• itching
• dry skin
• hair loss or thinning (alopecia)
• various types of skin rash
• skin thickening
• joint pain (arthralgia)
• 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 blood test results related to creatine kinase, indicating heart and skeletal muscle 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)
• inflammation of the colon (colitis)
• skin redness, cracking, or rupture
• inflammation of the subcutaneous fat layer, with symptoms such as soft nodules under the skin

• skin rash with flat spots or protuberances like acne (acneiform dermatitis)

• skin redness, peeling, or blistering on the hands and feet (erythema palmoplantar or hand-foot syndrome)
• renal 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

Rare(may affect up to 1 in 100 people)

• some types of skin tumors, such as basal cell carcinoma
• facial muscle weakness and paralysis

• pancreatitis, which causes severe abdominal pain

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information about 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 blister pack and the box after CAD. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. By doing so, you will help protect the environment.

Composition of Mektovi

• The active ingredient is binimetinib.

Mektovi 45film-coated tablets: Each film-coated tablet contains 15mg of binimetinib.

Mektovi 45film-coated tablets: Each film-coated tablet contains 45mg of binimetinib.

• The other components are:

• Core of the tablet: lactose monohydrate, microcrystalline cellulose (E460i), anhydrous colloidal silica (E551), sodium croscarmellose (E468) and magnesium stearate (E470b).See section 2 “Mektovi contains lactose”.
• Coating of the tablet:

Mektovi 15mg film-coated tablets: polyvinyl alcohol (E1203), macrogol 3350 (E1521), titanium dioxide (E171), talc (E533b), yellow iron oxide (E172) and black iron oxide (E172).

• Mektovi 45mg film-coated tablets: alcohol polivinílico (E1203), macrogol 4000 (E1521), calcium carbonate (E170), talc (E533b).

Appearance of the product and contents of the pack

Mektovi 15mg film-coated tablets

The film-coated tablets are oval-shaped, yellow to dark yellow, biconvex, unnotched tablets with an “A” engraved on one face and “15” on the other.

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

Only some pack sizes may be marketed.

Mektovi 45mg film-coated tablets

The film-coated tablets are oval-shaped, white to off-white, biconvex, unnotched tablets with a “45” engraved on one face.

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

Only some pack sizes may 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 revision 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.