MEKINIST 2 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Mekinist®0.5mg film-coated tablets

Mekinist®2mg film-coated tablets

trametinib

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

1. What is Mekinist and what is it used for

Mekinist is a medicine that contains the active substance trametinib. It is used alone or in combination with another medicine 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 by surgery.

Mekinist in combination with dabrafenib can also be used to prevent the recurrence of melanoma after it has been removed by 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 medicine works on the proteins produced by the mutated gene and slows down or stops the development of cancer.

2. What you need to know before you take Mekinist

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

If your doctor decides that you should take the combination treatment of Mekinist and dabrafenib, read the dabrafenib package leaflet carefully as well as this leaflet.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

Do not take Mekinist

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

Talk to your doctor if you think this may apply to you.

Warnings and precautions

Talk to your doctor before starting to take this medicine. Your doctor needs to know if you:

• have liver problems. While you are taking this medicine, your doctor may take blood samples to check how well your liver is working.
• have or have ever had kidney problems.
• have or have ever had breathing 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 should check your heart function before and during treatment.
• have eye problems, such as blockage of the veins that supply the eye (retinal vein occlusion) or swelling of the eye that may be due to a blockage of fluid (chorioretinopathy).

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

• have had another type of cancer other than melanoma or NSCLC, as you may be at a higher risk of developing other non-skin cancers while taking Mekinist.

Talk to your doctorif you think any of the above applies to you.

Conditions to look out for

Some people taking Mekinist develop other conditions that can be serious. You need to know what symptoms to look out for while taking this medicine.

Bleeding

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

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

Tell your doctor as soon as possibleif you experience these symptoms.

Fever

Treatment with Mekinist or the combination of Mekinist with dabrafenib can cause fever, although it is more likely if you take the combination (see also section 4). In some cases, people with fever develop low blood pressure, dizziness, and other symptoms.

Tell your doctor immediatelyif your temperature is over 38°C or if you feel feverish while taking this medicine.

Heart problems

Mekinist can cause heart problems or make existing heart problems worse (see section 4 of this leaflet “Heart problems”) in people taking Mekinist in combination with dabrafenib.

Tell your doctor if you have any heart problems. Before starting treatment and during treatment with this medicine, your doctor will perform tests to check if your heart is working properly. Tell your doctor immediately if you feel that: your heart is beating strongly, your heart is racing, or beating irregularly, if you feel dizzy, feel tired, feel faint, are short of breath, or your legs are swollen. If necessary, your doctor may decide to interrupt or stop treatment.

Changes in the skin that may indicate a new skin cancer

Your doctor will check your skin before starting treatment with this medicine and regularly while you are taking it. Tell your doctor immediatelyif you notice any changes in your skin while taking this medicine or after treatment (see also section 4).

Eye problems

Your doctor should examine your eyes while you are taking this medicine.

Talk to your doctor immediatelyif you have redness and irritation of the eyes, blurred vision, eye pain, or other changes in vision during treatment (see also section 4).

Mekinist can cause eye problems, including blindness. Mekinist is not recommended if you have ever had a blockage in the veins that drain the eyes (retinal vein occlusion). Tell your doctor immediately if you experience any of the following symptoms related to eye problems during treatment: 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 stop treatment.

Liver problems

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

• loss of appetite
• feeling unwell (nausea)
• feeling sick (vomiting)
• stomach pain (abdomen)
• yellowing of your skin or the whites of your eyes (jaundice)
• dark-colored urine
• itching of the skin

Tell your doctor as soon as possibleif you experience these symptoms.

Breathing or lung problems

Tell your doctor if you have breathing or lung problems, including difficulty breathing, frequent dry cough, shortness of breath, and fatigue. Your doctor may ask you to have your lung function checked before starting to take this medicine.

Muscle pain

Mekinist can cause muscle damage (rhabdomyolysis). Tell your doctoras soon as possible if you notice any of these symptoms:

• muscle pain
• dark urine due to kidney damage

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

• Read the information on ‘Serious side effects’ in section 4 of this leaflet.

Perforation of the stomach or intestine

Taking Mekinist or Mekinist in combination with dabrafenib can increase the risk of developing a hole in the wall of the intestine. If you feel severe stomach pain, tell your doctor as soon as possible.

Severe skin reactions

Severe skin reactions have been reported in people taking Mekinist in combination with dabrafenib. Tell your doctor immediately if you notice any changes in your skin (see section 4 for symptoms to look out for).

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 cough, shortness of breath, swelling of the lymph nodes, vision changes, fever, fatigue, pain, joint inflammation, or painful lumps (bumps) on the skin. If you experience any of these symptoms, contact a doctor.

Immune system disorders

Mekinist in combination with dabrafenib can rarely cause a disease (hemophagocytic lymphohistiocytosis or HLH) in which the immune system produces too many cells to fight infections, called histiocytes and lymphocytes. The symptoms can include enlargement of the liver or spleen, skin rash, enlargement of the lymph nodes, breathing problems, tendency to bruise, kidney problems, and heart problems. Tell your doctor immediately if you experience several symptoms, such as fever, swelling of the lymph nodes, bruising, or skin rash, at the same time.

Tumor lysis syndrome

If you experience the following symptoms, tell your doctor immediately, as it may be a life-threatening condition: nausea, difficulty breathing, irregular heartbeats, muscle cramps, seizures, cloudy urine, decreased urine production, and fatigue. These can 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 or TLS) and can 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 18 years of age are not known.

Other medicines and Mekinist

Before starting treatment, tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines. This includes medicines obtained without a prescription. Make a list of the medicines you are taking and show it to your doctor, pharmacist, or nurse if you start taking a new medicine.

Using Mekinist with food and drinks

It is important to take Mekinist on an empty stomachbecause food can affect the absorption of this medicine (see section 3).

Pregnancy, breastfeeding, and fertility

The use of Mekinist is not recommended during pregnancy.

• If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine. Mekinist may harm your unborn baby.
• If you are a woman who is able to become pregnant, you must use a reliable method of contraception while taking Mekinist and for at least 16 weeks after stopping treatment.
• 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 method of contraception to prevent pregnancy during treatment with this combination of medicines. Ask your doctor, pharmacist, or nurse for advice.
• If you become pregnant while taking Mekinist, tell your doctor immediately.

Mekinist is not recommended during breastfeeding

It is not known whether the components of this medicine can pass into breast milk.

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

Fertility in men and women

Mekinist may affect fertility in men and women.

If you take Mekinist with dabrafenib: dabrafenib may permanently reduce fertility in men. Also, men taking dabrafenib may have a reduced sperm count and it may not return to normal levels until after they have stopped taking this medicine.

Talk to your doctor about the options for having children in the future before starting treatment with dabrafenib.

If you have any further questions about the effects of this medicine on fertility, ask your doctor, pharmacist, or nurse.

Driving and using machines

Mekinist can 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 leaflet (see sections 2 and 4). Read all the information included in this leaflet.

If you are not sure, talk to your doctor, pharmacist, or nurse. Your ability to drive or use machines may be affected by your disease, symptoms, or treatment.

Mekinist contains sodium

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

3. How to take Mekinist

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 1 tablet of 2 mg once a day. The recommended dose of dabrafenib, when used in combination with Mekinist, is 150 mg 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 this could increase the risk of having 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 1 hour before a meal or 2 hours after a meal). That is:

• once you have taken Mekinist, you must wait at least 1 hour before eating.

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

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

Do not take a double dose to make up for forgotten 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 indicates it.
• Take Mekinist once a dayand take dabrafenib twice a day. It would be good for you to have the habit of taking both medications together every day. You must take Mekinist with either the morning dose of dabrafenib orthe evening dose of dabrafenib. The doses of dabrafenib should be taken with a 12-hour difference.
• Take Mekinist and dabrafenib on an empty stomach, at least 1 hour before or 2 hours after a meal. Swallow 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 make up for the forgotten dose and take the next dose when it is due:
• • If there are less than 12 hours left until the next dose of Mekinist, which is taken once a day
  • If there are less than 6 hours left 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. Take the Mekinist tablets and dabrafenib capsules with you if you can. If possible, show the packaging of Mekinist and dabrafenib 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.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Possible Serious Adverse Effects

Heart Conditions

Mekinist may affect your heart's functioning. It is more likely to affect people with an existing heart problem. During treatment with Mekinist, you will undergo 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 consider them to be worsening.

High Blood Pressure

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

Bleeding Problems

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

• headache, dizziness, or weakness
• coughing up blood or coughing up blood clots
• vomiting blood or if your vomit looks like "coffee grounds"
• having red or black, tar-like stools

Eyelid 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 in your vision, including:

• vision loss
• redness and irritation in the eyes
• seeing colored 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 not known). If you notice any of the following:

• red patches on the torso that are circular or target-shaped, with central blisters. Skin peeling. Ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin rashes can be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome)
• widespread rash, fever, and swollen lymph nodes (DRESS or drug hypersensitivity syndrome)

• Stop taking the medicine and seek immediate medical attention.

Up to 3 out of 100 people taking Mekinist in combination with dabrafenib may develop a different type of skin cancer called Squamous Cell Carcinoma (SCC). 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 treatment with Mekinist and dabrafenib can continue without interruption.

Some people taking Mekinist in combination with dabrafenib may also notice that they have new melanomas. These melanomas are usually removed by surgery, and treatment with Mekinist and dabrafenib can continue without interruption.

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

Your doctor will also examine your head, neck, mouth, and lymph nodes and will regularly perform a scanner (Computed Tomography) of the chest and abdominal area. You may also have blood tests. These reviews serve 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 a rash or acne-like rash. Follow your doctor's instructions on 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 have a skin rash 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 feel 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 inflammation of the lungs (pneumonitis or interstitial lung disease). Inform your doctor or nurse if you have new symptoms or worsening symptoms associated with breathing problems or lung problems, including:

• shortness of breath
• cough
• fatigue

Immune System Disorders

If you experience several symptoms simultaneously, such as fever, swollen lymph nodes, bruising, 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 the rapid breakdown of cancer cells that in some people can be fatal (tumor lysis syndrome or TLS), see section 2 (unknown frequency).

Possible Adverse Effects in Patients Taking Mekinist Alone

Adverse Effects that May be Observed While Taking Mekinist Alone:

Very Common Adverse 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
• cough
• shortness of breath
• diarrhea
• feeling of dizziness (nausea), discomfort (vomiting)
• constipation
• stomach pain
• dry mouth
• skin rash, acne-like rash, redness in the face, dry skin, or itching of the skin (see also in section 4 "Skin Changes")
• unusual hair loss or thinning hair
• lack of energy, weakness, fatigue
• swelling of the hands or feet (peripheral edema)
• fever

Very Common Adverse Effects that May Appear in Blood Tests:

• blood tests with altered liver function results

Common Adverse Effects (may affect up to 1 in 10 people):

• inflammation of the hair follicles on the skin
• disorders of the nails, such as changes in the nail bed, nail pain, infection, and swelling of the cuticles
• skin infection (cellulitis)
• skin rash with pus-filled blisters (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
• vision 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 Conditions")
• heart rate is lower than normal and/or decreased heart rate
• localized tissue inflammation
• lung inflammation (pneumonitis or interstitial lung disease)
• ulcers or sores in the mouth, inflammation of the mucous membranes
• redness, cracks, or fissures in the skin
• redness, pain in hands and feet
• swelling of the face
• mucous membrane inflammation
• feeling of weakness
• nerve problems that can cause pain, numbness, or tingling in the hands and feet and/or muscle weakness (peripheral neuropathy)

Common Adverse Effects that May Appear in Blood Tests:

• decreased red blood cells (anemia), abnormal creatine phosphokinase results, an enzyme found mainly in the heart, brain, and skeletal muscle

Uncommon Adverse Effects (may affect up to 1 in 100 people):

• swelling of the eyes due to fluid loss (chorioretinopathy) (see also at the beginning of section 4 "Eye Problems (Vision)")
• inflammation of the nerves in the back of the eye (papilledema) (see also at the beginning of section 4 "Eye Problems (Vision)")
• separation of the light-sensitive membrane from 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)")
• the heart pumps blood less efficiently, causing difficulty breathing, extreme fatigue, and swelling in the ankles and legs (heart failure)
• a hole (perforation) in the stomach or intestinal wall
• inflammation of the intestines (colitis)
• muscle damage that can cause muscle pain and kidney damage (rhabdomyolysis)

Adverse Effects of Unknown Frequency (cannot be estimated from available data):

• irregular heartbeats (atrioventricular block)

Adverse Effects when Mekinist is Taken with Dabrafenib

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

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

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

Read the dabrafenib package insert for more information on adverse effects that may occur while taking this medicine.

The adverse effects that may occur while taking Mekinist in combination with dabrafenib are as follows:

Very Common Adverse 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, which can be mild or severe (hemorrhage)
• cough
• stomach pain
• constipation
• diarrhea
• feeling of dizziness (nausea), discomfort (vomiting)
• rash, dry skin, itching, redness of the skin
• joint pain, muscle pain, or pain in hands or feet
• muscle spasms
• lack of energy, feeling weak
• chills
• swollen hands and feet (peripheral edema)
• fever
• flu-like symptoms

Very Common Adverse Effects that May Appear in Blood Tests:

• abnormal liver function test results in blood

Common Adverse Effects (may affect up to 1 in 10 people):

• urinary tract infection
• skin effects, including skin infection (cellulitis), inflammation of the hair follicles on the skin, nail disorders, such as changes in the nail bed, nail pain, infection, and swelling of the cuticles, skin rash with pus-filled blisters, skin cancer (squamous cell carcinoma), papilloma (a type of non-cancerous tumor), wart growth, increased sensitivity of the skin to the sun (see also in section 4 "Skin Changes")
• dehydration (low water or fluid levels)
• blurred vision, vision problems, eye inflammation (uveitis)
• less efficient heart pumping
• low blood pressure (hypotension)
• localized tissue swelling
• shortness of breath
• dry mouth
• ulcers or mouth pain, mucous membrane inflammation
• acne-like rash
• thickening of the outer layer of the skin (hyperkeratosis), thickened skin patches, with scales or hardening (actinic keratosis), cracked or fissured skin
• increased sweating, night sweats
• unusual hair loss or thinning hair
• redness, pain in hands and feet
• inflammation of the fatty tissue under the skin (panniculitis)
• mucous membrane inflammation
• swelling of the face
• nerve problems that can cause pain, numbness, or tingling in the hands and feet and/or muscle weakness (peripheral neuropathy)

Common Adverse Effects that May Appear in Blood Tests:

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

Uncommon Adverse Effects (may affect up to 1 in 100 people):

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

Rare Adverse Effects (may affect up to 1 in 1,000 people):

• a hole (perforation) in the stomach or intestinal wall

Adverse 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 (exfoliative dermatitis)

Reporting of 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 package insert. 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 Mekinist

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

Do not use this medicine after the expiration date that appears on the label of the bottle and on the packaging, after the abbreviation EXP. The expiration date is the last day of the month indicated.

This medicine does not require any special storage temperature.

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

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

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

Medicines should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Container contents and additional information

Mekinist composition

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

• Tablet: mannitol (E421), microcrystalline cellulose (E460), hypromellose (E464), sodium croscarmellose (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 0.5 mg tablets), polysorbate 80 (E433), and red iron oxide (E172) (for the 2 mg tablets).

Product appearance and container contents

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

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

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

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

Marketing authorization holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Manufacturer

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 medication by contacting the local representative of the marketing authorization holder:

Date of last revision of this leaflet:

Other sources of information

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

On the European Medicines Agency website, you can find this leaflet in all languages of the European Union/European Economic Area.