Prescribing Information for the Patient

Mekinist®0.5Coated Tablets

Mekinist®2Coated Tablets

trametinib

Read the entire prescribing information carefully before starting this medication, as it contains important information for you.

• Keep this prescribing information, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you, and you should not give it to others who have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse,even if they are not listed in this prescribing information. See section4.

Mekinist is a medication that contains the active ingredient trametinib. It is used alone or in combination with another medication that contains dabrafenib to treat a type of skin cancer called melanoma that has spread to other parts of the body, or cannot be removed through surgery.

Mekinist in combination with dabrafenib can also be used to prevent the recurrence of melanoma after it has been removed through surgery.

Mekinist in combination with dabrafenib is also used to treat a type of lung cancer called non-small cell lung cancer (NSCLC).

Both types of cancer have a specific change (mutation) in a gene called BRAF at position V600. This mutation in the gene may have caused the development of cancer. This medication acts on the proteins produced by the mutated gene and slows down or stops the development of cancer.

Mekinist can only be used to treat melanomas and CPNM that present BRAF mutation. Therefore, before starting treatment, your doctor will check if you have this mutation.

If your doctor decides that you take the combined treatment of Mekinist and dabrafenib,read carefully the dabrafenib prospect as well as this prospect.

If you have additional questions about the use of this medication, ask your doctor, pharmacist, or nurse.

Do not take Mekinist

• if you are allergic to trametinib or to any of the other components of this medication (including in section6).

Consult with your doctor if you think this may happen.

Warnings and precautions

Consult your doctor before starting to take this medication. Your doctor needs to know if you:

• haveliver problems. While taking this medication, your doctor may take blood samples to check the functioning of your liver.
• have or have hadkidney problems
• have or have hadrespiratory or lung problems
• have heart problems such as heart failure (which can cause shortness of breath, difficulty breathing when lying down, swelling of the feet or legs) or problems with the way your heart beats. Your doctor must control your cardiac function before and during treatment.
• have eye problems, such as blockage of the veins that irrigate the eye (retinal vein occlusion) or swelling of the eye that may be due to fluid blockage (choroideretinitis).

Before taking Mekinist in combination with dabrafenib, your doctor must know if you:

• have had another type of cancer other than melanoma or CPNM, as you may have a higher risk of developing other cancers that are not skin-related while taking Mekinist.

Consult with your doctorif you think any of the above circumstances may affect you.

Conditions to pay attention to

Some people who take Mekinist develop other conditions that can be serious. You need to know what symptoms to pay attention to while taking this medication.

Bleeding

Taking Mekinist or Mekinist in combination with dabrafenib may cause severe bleeding in the brain, digestive system (such as stomach, rectum, or intestine), lungs, and other organs, which can cause death. The symptoms may be:

• headache, dizziness, or feeling weak
• passing blood in the stool or black stools
• passing blood in the urine
• stomach pain
• coughing up or vomiting blood

Inform your doctor as soon as possibleif you feel these symptoms.

Fever

The treatment with Mekinist or the combination of Mekinist with dabrafenib may cause fever, although it is more likely if you take the combination (see also section4). In some cases, people with fever develop low blood pressure, dizziness, and other symptoms.

Inform your doctor immediatelyif your temperature is over 38°C or if you have a feeling of fever while taking this medication.

Heart disorder

Mekinist may cause problems in the heart, or may make existing problems worse (see in section4 of this prospect “Heart problems”) in people who take Mekinist in combination with dabrafenib.

Inform your doctor if you experience any heart problems. Before starting treatment and during treatment with this medication, your doctor will perform tests to check if your heart is functioning properly. Inform your doctor immediately if you feel that: your heart beats strongly, your heart rate accelerates, or beats irregularly, if you feel dizzy, tired, short of breath, or if your legs swell. If necessary, your doctor may decide to interrupt or suspend treatment.

Changes in the skin that may indicate a new skin cancer

Your doctor will check your skin before starting treatment with this medication, and regularly while taking it.Inform your doctor immediatelyif you notice any changes in your skin while taking this medication or after treatment (see also section4).

Eye problems

Your doctor must examine your eyes while taking this medication.

Consult your doctor immediatelyif you have eye redness and irritation, blurred vision, eye pain, or other changes in vision during treatment (see also section4).

Mekinist may cause eye problems, even blindness. Mekinist is not recommended if you have ever had a blockage in the veins that drain the eye (retinal vein occlusion). Inform your doctor immediately if during treatment you experience the following symptoms related to eye problems: blurred vision, loss of vision, or other changes in vision, if you see colored dots or halos (blurred vision around objects). If necessary, your doctor may decide to interrupt or suspend treatment.

Liver problems

Mekinist, or the combination with dabrafenib, may cause liver problems that can develop diseases such as hepatitis or liver failure, which can be fatal. Your doctor will monitor you periodically. The signs that your liver is not functioning properly are:

• loss of appetite
• general discomfort (nausea)
• feeling sick (vomiting)
• stomach pain (abdomen)
• yellowing of your skin or the white of your eyes (jaundice)
• dark urine
• skin itching

Inform your doctor as soon as possibleif you feel these symptoms.

Respiratory or lung problems

Inform your doctor if you have respiratory or lung problems, including frequent difficulty breathing accompanied by dry cough, shortness of breath, and fatigue. Your doctor may ask you to have your pulmonary function checked before starting to take this medication.

Muscle pain

Mekinist may cause muscle deterioration (rhabdomyolysis).Inform your doctoras soon as possible if you notice any of the following symptoms:

• muscle pain
• dark urine due to kidney damage

If necessary, your doctor may decide to interrupt or suspend treatment.

• Read the information “Possible severe side effects” in section4 of this prospect.

Intestinal perforation

Taking Mekinist or Mekinist in combination with dabrafenib may increase the risk of developing intestinal wall perforation. If you experience severe abdominal pain, inform your doctor as soon as possible.

Severe skin reactions

Severe skin reactions have been reported in people who have taken Mekinist in combination with dabrafenib. Inform your doctor immediately if you notice any changes in your skin (see section4 to know the symptoms to pay attention to).

Inflammatory disease that mainly affects the skin, lungs, eyes, and lymph nodes

An inflammatory disease that mainly affects the skin, lungs, eyes, or lymph nodes (sarcoidosis). Common symptoms of sarcoidosis may include coughing, shortness of breath, lymph node inflammation, visual disturbances, fever, fatigue, pain, joint inflammation, or painful skin nodules. If you experience any of these symptoms, contact a doctor.

Immune system disorders

Mekinist in combination with dabrafenib may cause, in rare cases, a disease (hemophagocytic lymphohistiocytosis or LHH) in which the immune system produces too many cells to fight infections, called histiocytes and lymphocytes. The symptoms may consist of liver or spleen enlargement, skin rash, lymph node enlargement, respiratory problems, tendency to form bruises, renal abnormalities, and heart problems. Inform your doctor immediately if you experience several symptoms, such as fever, lymph node inflammation, bruises, or skin rash, at the same time.

Tumor lysis syndrome

If you experience the following symptoms, inform your doctor immediately, as it 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 or TLS) and may cause changes in kidney function (see also section 4).

Children and adolescents

Mekinist is not recommended in children and adolescents because the effects of Mekinist in people under 18years of age are unknown.

Other medications and Mekinist

Before starting treatment, inform your doctor, pharmacist, or nurse if you are taking,have taken recentlyor may need to take any other medication. This includes over-the-counter medications. Make a list of the medications you are taking, and show it to your doctor, pharmacist, or nurse if you start taking a new medication.

Use of Mekinist with food and drinks

It is essential to take Mekinist on an empty stomachbecause food may affect the absorption of this medication (see section3).

Pregnancy, breastfeeding, and fertility

The use of Mekinist is not recommended during pregnancy.

• If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor before using this medication. Mekinist may cause fetal damage.
• If you are a fertile woman, you must use a reliable contraceptive method while taking Mekinist, and for at least 16weeks after stopping it.
• Hormonal contraceptives (birth control pills, injections, or patches) may not be effective during treatment with Mekinist in combination with dabrafenib. It is recommended to use an additional effective contraceptive method to avoid pregnancy during treatment with this combination of medications. Consult your doctor, pharmacist, or nurse for advice.
• If you become pregnant during treatment with Mekinist, inform your doctor immediately.

It is not recommended to use Mekinist during breastfeeding

The components of this medication are unknown to pass into breast milk.

If you are breastfeeding or plan to breastfeed, inform your doctor. It is recommended not to breastfeed while taking Mekinist. You and your doctor will decide whether to take this medication or to breastfeed.

Fertility of men and women

Mekinist may alter the fertility of men and women.

When taking Mekinist with dabrafenib: dabrafenib may permanently reduce male fertility. Men taking dabrafenib may experience reduced sperm count, and their sperm may not return to normal levels until they stop taking this medication.

Before starting treatment with dabrafenib, discuss your options for having children in the future with your doctor.

If you have additional questions about the effects of this medication on fertility, ask your doctor, pharmacist, or nurse.

Driving and using machines

Mekinist may cause side effects that affect your ability to drive or use machines.

Avoid driving or using machines if you feel tired or weak, if you have vision problems, or if you feel lacking in energy.

The description of these side effects can be found in other sections of this prospect (see sections2 and4.). Read all the information included in this prospect.

If you are unsure, consult your doctor, pharmacist, or nurse. Your ability to drive and use machines may be affected even by the disease, symptoms, or treatment itself.

Mekinist contains sodium

This medication contains less than 1mmol sodium (23mg) per tablet; this is, essentially “sodium-free”.

Follow exactly the administration instructions of this medication indicated by your doctor, pharmacist or nurse. In case of doubt, consult your doctor, pharmacist or nurse again.

How much to take

The recommended dose of Mekinist, whether used alone or in combination with dabrafenib, is 1tablet of 2mg once a day. The recommended dose of dabrafenib, when used in combination with Mekinist, is 150mg twice a day.

Your doctor will decide if it is necessary to reduce the dose based on the adverse effects you have.

Do not take more Mekinist than your doctor has recommended,as it could increase the risk of adverse effects.

How to take it

Swallow the tablets whole with the help of a full glass of water.

Take Mekinist once a day, on an empty stomach (at least 1hour before eating or 2hours after eating). That is:

• once you have taken Mekinist, you must wait at least 1hour before eating.
• if you have already eaten, you must wait at least 2hours before taking Mekinist.

Take Mekinist at the same time of day, every day.

If you take more Mekinist than you should

If you take too many Mekinist tablets, contact your doctor, pharmacist or nurse. If possible, show them the Mekinist packaging along with this leaflet.

If you forget to take Mekinist

If less than 12hours have passed since the usual time when you should have taken Mekinist, take it as soon as you remember.

If more than 12hours have passed since the usual time when you should have taken Mekinist, skip this dose and take the next one at your usual time. Then, continue taking the tablets at your usual time.

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

If you interrupt treatment with Mekinist

Take Mekinist for the time your doctor has recommended. Do not stop taking this medication unless your doctor recommends it.

If you have any other questions about the use of this medication, ask your doctor, pharmacist or nurse.

How to take Mekinist in combination with dabrafenib

• Take Mekinist in combination with dabrafenib exactly as your doctor, pharmacist or nurse has told you. Do not change the dose or stop taking Mekinist or dabrafenib unless your doctor, pharmacist or nurse tells you to.
• TakeMekinist once a dayand takedabrafenib twice a day. It would be good for you to have the habit of taking the two medications at the same time every day. You should take Mekinist with the morning dose of dabrafeniborwith the evening dose of dabrafenib. The doses of dabrafenib should be taken with a 12hour difference.
• Take Mekinist and dabrafenib on an empty stomach, at least one hour before or two hours after a meal. Take them whole with a full glass of water.
• If you forget a dose of Mekinist or dabrafenib, take it as soon as you remember. Do not compensate for the missed dose and take the next dose when it is due:
• • If there are less than 12hours until the next dose of Mekinist, which is taken once a day
  • If there are less than 6hours until the next dose of dabrafenib, which is taken twice a day
• If you take more Mekinist or dabrafenib, contact your doctor, pharmacist or nurse immediately. Bring the Mekinist tablets and dabrafenib capsules if you can. If possible, show them the Mekinist packaging and dabrafenib packaging along with the leaflet.
• If you experience adverse effects, your doctor may decide to give you a lower dose of Mekinist and dabrafenib. Take the dose of Mekinist exactly as your doctor, pharmacist or nurse has told you.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Possible serious side effects

Heart problems

Mekinist may affect the functioning of your heart. It is more likely to affect people with an existing heart problem. During treatment with Mekinist, you will have heart tests. Among the signs and symptoms related to heart problems are:

• palpitations, increased heart rate, or irregular heartbeats
• dizziness
• fatigue
• feeling dizzy
• shortness of breath
• swollen legs

If you experience any of these symptoms,inform your doctoras soon as possible, whether you experience them for the first time or if you think they are getting worse.

High blood pressure

Mekinist may increase blood pressure (hypertension) or worsen it. Your doctor or nurse must check your blood pressure during treatment with Mekinist. Contact your doctor or nurse immediately if you have high blood pressure, if your blood pressure worsens, or if you experience severe headaches, feel dizzy, or feel nauseous.

Bleeding problems

Mekinist may cause severe bleeding problems, especially in the brain or stomach. Contact your doctor or nurse, and seek immediate medical attention if you experience unusual signs of bleeding, including:

• headache, dizziness, or weakness
• coughing up blood or coughing up blood clots
• vomiting blood or if the vomit looks like "coffee grounds"
• having stools that are red or black with a tar-like appearance.

Eye problems (vision)

Mekinist may cause eye problems. It is not recommended to take Mekinist if you have ever had a blockage in the veins that drain the eyes (retinal vein occlusion). Your doctor will advise you to have an eye check before starting treatment with Mekinist and during treatment. Your doctor may ask you to stop taking Mekinist or refer you to a specialist if you experience signs and symptoms of vision problems, including:

• loss of vision
• redness and irritation in the eyes
• seeing spots
• seeing a halo (blurred vision around objects)
• blurred vision.

Skin changes

Severe skin reactions have been reported in people taking Mekinist in combination with dabrafenib (frequency unknown). If you notice any of the following:

• manches rojizas en el tronco que son circulares o con forma de diana, con ampollas centrales. Descamación de la piel. Úlceras en la boca, garganta, nariz, genitales y ojos. Estas erupciones cutáneas graves pueden estar precedidas de fiebre y síntomas gripales (síndrome de Stevens-Johnson)
• erupción generalizada, fiebre y ganglios linfáticos hinchados (síndrome DRESS o síndrome de la hipersensibilidad a medicamentos).

• Stop taking the medicine and seek medical attention immediately.

Up to 3 out of 100 people who take Mekinist in combination with dabrafenib may develop a different type of skin cancer called Cutaneous Squamous Cell Carcinoma (CSCC). Others may develop a type of cancer called Basal Cell Carcinoma (BCC). Normally, these changes only affect the skin locally and can be removed with surgery and continue treatment with Mekinist and dabrafenib without interrupting it.

Some people who take Mekinist in combination with dabrafenib may also notice that they have new melanomas. These melanomas are usually removed with surgery and treatment with Mekinist and dabrafenib can continue without interrupting it.

Your doctor will examine your skin before starting treatment with dabrafenib, monthly while taking dabrafenib, and during the 6 months after treatment is completed. The reason for these reviews is to look for new skin cancer lesions.

Your doctor will also examine your head, neck, mouth, and lymph nodes and will perform regular chest and abdominal CT scans. They may also perform blood tests. These reviews are to detect if you have developed other cancers, including squamous cell carcinoma. It is recommended that both at the beginning and at the end of treatment, a pelvic exam (in women) and anal exam be performed.

Mekinist, both as monotherapy and in combination with dabrafenib, may cause acne-like rash or rash. Follow your doctor's instructions to know what to do to prevent the appearance of a rash. If you experience any of these symptoms for the first time or if they worsen, inform your doctor or nurse as soon as possible.

Contact your doctor immediatelyif you experience severe skin rash with any of the following symptoms: blisters on the skin, blisters or sores in the mouth, skin peeling, fever, redness or swelling in the face, blisters on the soles of the feet.

If you experience a rash on the skin or if it worsens, inform your doctor or nurse as soon as possible.

Muscle pain

Mekinist may cause muscle damage (rhabdomyolysis). Inform your doctor or nurse if you experience a new symptom or if any of the following symptoms worsen:

• muscle pain
• dark-colored urine due to kidney damage.

Respiratory or lung problems

Mekinist may cause lung inflammation (pneumonitis or interstitial lung disease). Inform your doctor or nurse if you experience new symptoms or worsening symptoms associated with breathing difficulties or lung problems, including:

• shortness of breath
• coughing
• fatigue

Immune system disorders

If you experience simultaneous symptoms, such as fever, swollen lymph nodes, bruises, or skin rash, inform your doctor immediately. It may be a sign of a disease in which the immune system produces too many cells to fight infections, called histiocytes and lymphocytes, which can cause various symptoms (known as hemophagocytic lymphohistiocytosis); see section 2 (rare frequency).

Tumor lysis syndrome

Inform your doctor immediately if you experience the following symptoms: nausea, difficulty breathing, irregular heartbeats, muscle cramps, seizures, cloudy urine, decreased urine production, and fatigue. These may be signs of a condition resulting from rapid cell breakdown in cancer cells that in some people can be fatal (tumor lysis syndrome or TLS), see section 2 (unknown frequency).

Possible side effects in patients taking Mekinist alone

Side effects that can be observed while taking only Mekinist:

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

• high blood pressure (hypertension)
• bleeding in different parts of the body, which can be mild or severe
• coughing
• shortness of breath
• diarrhea
• nausea, vomiting
• constipation
• stomach pain
• dry mouth
• skin rash, acne-like rash, redness on the face, dry skin, or itching on the skin (see also in section 4 “Skin changes”)
• unusual hair loss or fine hair
• fatigue, weakness, tiredness
• swelling of the hands or feet (peripheral edema)
• fever

Very common side effects that may appear in blood tests:

• blood test results with abnormal liver-related results

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

• inflammation of the skin follicles
• hair and nail disorders, such as changes in the nail bed, nail pain, infection, and inflammation of the cuticles
• skin infection (cellulitis)
• skin rash with blisters filled with pus (see also at the beginning of section 4 “Skin changes”)
• allergic reaction (hypersensitivity).
• dehydration (low water or fluid levels)
• blurred vision
• swelling around the eyes
• eye problems (see also in section 4 “Eye problems (vision)”)
• changes in how the heart pumps blood (left ventricular dysfunction) (see also in section 4 “Heart problems”).
• heart rate is slower than normal and/or decreased heart rate
• localized inflamed tissue
• inflammation in the lungs (pneumonitis or interstitial lung disease)
• mouth sores or ulcers, inflammation of the mucous membranes
• redness, cracks, or fissures in the skin
• redness, pain in the hands and feet
• swelling in the face
• inflammation of the mucous membranes
• feeling weak
• nerve problems that can cause pain, loss of sensation, or numbness in the hands and feet and/or muscle weakness (peripheral neuropathy)

Common side effects that may appear in blood tests:

• decreased red blood cells (anemia), abnormal results related to the heart, brain, and skeletal muscle (creatine phosphokinase)

Rare side effects (may affect up to 1 in 100 people):

• swelling in the eyes due to fluid loss (choroidoretinopathy) (see also at the beginning of section 4 “Eye problems (vision)”)
• inflammation of the nerves at the back of the eye (papilloedema) (see also at the beginning of section 4 “Eye problems (vision)”)
• separation of the light-sensitive membrane at the back of the eye (retinal detachment) (see also at the beginning of section 4 “Eye problems (vision)”)
• blockage of the veins that drain the eyes (retinal vein occlusion) (see also in section 4 “Eye problems (vision)”)
• heart pumps blood with less efficiency, causing difficulty breathing, extreme fatigue, and inflammation in the legs and feet (heart failure)
• hole (perforation) in the stomach or intestinal wall
• inflammation of the intestines (colitis)
• muscle damage that can cause muscle pain and kidney damage (rhabdomyolysis).

Side effects of unknown frequency (cannot be estimated from available data):

• irregular heartbeats (atrioventricular block)

Side effects when Mekinist is taken with dabrafenib

When Mekinist is taken with dabrafenib, you may experience any of the side effects listed above, although their frequency may change (increase or decrease)

You may also experience new side effects due to taking dabrafenib at the same time as Mekinist, which are listed below.

Inform your doctor as soon as possible if you noticeboth that the symptoms appear for the first time and if they worsen.

Read the dabrafenib prospectus for more details on side effects or that may appear while taking this medicine.

The side effects that may be seen while taking Mekinist in combination with dabrafenib are as follows:

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

• inflammation of the nose and throat
• decreased appetite
• headache
• dizziness
• high blood pressure (hypertension)
• bleeding in different parts of the body that can be mild or severe (hemorrhage)
• coughing
• stomach pain
• constipation
• diarrhea
• nausea, vomiting
• skin rash, dry skin, itching, redness on the skin
• joint pain, muscle pain, or pain in the hands or feet
• muscle spasms
• fatigue, feeling weak
• chills
• swollen hands and feet (peripheral edema)
• fever
• flu-like symptoms

Very common side effects that may appear in blood tests:

• abnormal liver test results

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

• urinary tract infection
• skin effects that include skin infection (cellulitis), inflammation of the skin follicles, nail changes, such as changes in the nail bed, nail pain, infection, and inflammation of the cuticles, skin rash with blisters filled with pus, skin cancer (squamous cell carcinoma), warts, increased skin sensitivity to the sun (see also in section 4 “Skin changes”)
• dehydration (low water or fluid levels)
• blurred vision, eye problems, inflammation of the eye (uveitis)
• heart pumps blood with less efficiency
• low blood pressure (hypotension)
• localized swelling
• breathing difficulties
• dry mouth
• mouth sores or ulcers, inflammation of the mucous membranes
• acne-like symptoms
• thickening of the outer layer of the skin (hyperkeratosis), patches of thickened skin with scales or hardness (actinic keratosis), cracked or fissured skin
• increased sweating, night sweats
• unusual hair loss or thinning
• redness, pain in the hands and feet
• inflammation of the fatty tissue under the skin (panniculitis)
• inflammation of the mucous membranes
• swelling in the face
• nerve problems that can cause pain, loss of sensation, or numbness in the hands and feet and/or muscle weakness (peripheral neuropathy)

Common side effects that may appear in blood tests:

• low white blood cell count
• decreased red blood cells (anemia), platelets in the blood (cells that help blood to clot) and a type of white blood cell (leucopenia)
• low sodium (hyponatremia) or phosphate (hypophosphatemia) levels in the blood
• high blood sugar levels
• high levels of creatine phosphokinase, an enzyme found mainly in the heart, brain, and skeletal muscle
• high levels of substances (enzymes) produced by the liver

Rare side effects (may affect up to 1 in 100 people):

• new skin cancer (melanoma)
• skin marks
• allergic reactions (hypersensitivity)
• eye changes, such as swelling due to fluid accumulation (choroidoretinopathy), separation of the light-sensitive membrane at the back of the eye (retinal detachment), and swelling around the eyes
• slow heart rate and/or decreased heart rate
• inflammation of the lungs (pneumonitis)
• inflammation of the pancreas
• inflammation of the intestines (colitis)
• kidney failure
• inflammation of the kidneys
• inflammatory disease that mainly affects the skin, lungs, eyes, and lymph nodes (sarcoidosis)
• irregular heartbeats (atrioventricular block)
• raised, painful, red or dark purple spots or blisters that appear mainly on the arms, legs, face, and neck, with fever (signs of acute febrile neutrophilic dermatosis)

Rare side effects (may affect up to 1 in 1,000 people):

• hole (perforation) in the stomach or intestinal wall

Side effects of unknown frequency (cannot be estimated from available data):

• inflammation of the heart muscle (myocarditis) that can cause difficulty breathing, fever, palpitations, and chest pain
• inflamed, scaly skin (dermatitis exfoliativa)

Reporting side effects

If you experienceany type of side effect, consult your doctor, pharmacist, or nurse, even if it is apossibleside effect that does not appear in this prospectus.You can also report them directly through the national 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 label of the bottle and on the packaging, after the abbreviation CAD. The expiration date is the last day of the month indicated.

This medication does not require any special storage temperature.

Store in the original packaging to protect it from light and moisture.

Keep the container perfectly closed with the desiccant inside (small cylindrical container).

Once opened, the bottle can be stored for 30 days at a temperature below 30°C.

Medications should not be thrown down the drains or in the trash.Ask your pharmacist how to dispose ofthe containers and medications that you no longerneed.This will help protect the environment.

Composition of Mekinist

• The active ingredient is trametinib. Each film-coated tablet contains trametinib dimethyl sulfoxide equivalent to 0.5mg or 2mg of trametinib.
• The other components are:

• Tablet:mannitol (E421), microcrystalline cellulose (E460), hypromellose (E464), croscarmellose sodium (E468), magnesium stearate (E470b), sodium lauryl sulfate and anhydrous colloidal silica (E551).
• Film coating:hypromellose (E464), titanium dioxide (E171), polyethylene glycol, yellow iron oxide (E172) (for the 0.5mg tablets), polysorbate 80 (E433) and red iron oxide (E172) (for the 2mg tablets).

Appearance of the product and contents of the pack

Mekinist 0.5mg: the film-coated tablets are yellow, oval, biconvex, marked with the company logo on one face and ‘TT’ on the opposite face.

Mekinist 2mg: the film-coated tablets are pink, round, biconvex, marked with the company logo on one face and ‘LL’ on the opposite face.

The film-coated tablets are supplied in white opaque plastic bottles with plastic screw-top caps. A bottle contains 7 or 30tablets.

The bottles include a silica gel desiccant in a small cylindrical container. The desiccant should be kept inside the bottle and should not be ingested.

Marketing Authorisation Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Responsible for manufacturing

Lek Pharmaceuticals d.d.

Verovskova ulica 57

1526, Ljubljana

Slovenia

Novartis Pharmaceutical Manufacturing LLC

Verovskova ulica 57

1000, Ljubljana

Slovenia

Novartis Pharma GmbH

Roonstraße 25

D-90429 Nuremberg

Germany

Glaxo Wellcome, S.A.

Avda. Extremadura, 3

09400, Aranda de Duero

Burgos

Spain

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

You can request more information about this medicine by contacting the local representative of the marketing authorisation holder:

Last update of this leaflet:

Other sources of information

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

This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.