Mekinist 2 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the patient

Mekinist® 0.5 mg film-coated tablets

Mekinist® 2 mg film-coated tablets

trametinib

Read the entire 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 questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you. It may harm them.
• If you experience any adverse reactions, talk to your doctor, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

What this leaflet contains

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

1. What Mekinist is and what it is used for

Mekinist is a medicine that contains the active substance trametinib. It is used alone or in combination with another medicine containing 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 may 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 genetic change (mutation) in a gene called BRAF at position V600. This gene mutation may have caused the development of the cancer. This medicine acts on the proteins produced by the mutated gene and slows down or stops the progression of the cancer.

2. What you need to know before starting Mekinist

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

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

If you have any further questions about 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 may cause shortness of breath, difficulty breathing when lying down, swelling of the feet or legs), or problems with your heartbeat. Your doctor should monitor your heart function before and during treatment.
• have eye problems, such as blockage of the veins supplying the eye (retinal vein occlusion) or swelling of the eye that may be due to fluid buildup (chorioretinopathy).

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

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

Talk to your doctor if you think any of the above situations may apply to you.

Conditions to pay attention to

Some people taking Mekinist develop other conditions that may be serious. You need to know which symptoms to watch for while taking this medicine.

Bleeding

Taking Mekinist or Mekinist in combination with dabrafenib may cause serious bleeding in the brain, gastrointestinal tract (such as stomach, rectum, or intestines), lungs, and other organs, which could lead to death. Symptoms may include:

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

Inform your doctor as soon as possible if you experience these symptoms.

Fever

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

Inform your doctor immediately if your temperature is above 38°C or if you feel feverish while taking this medicine.

Heart disorders

Mekinist may cause heart problems or worsen existing heart conditions (see section 4 of this leaflet, “Heart conditions”) 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 that your heart is functioning properly. Inform your doctor immediately if you experience: strong or rapid heartbeat, irregular heartbeat, dizziness, fatigue, lightheadedness, shortness of breath, or swelling in your legs. If necessary, your doctor may decide to interrupt or stop treatment.

Skin changes that may indicate a new skin cancer

Your doctor will examine your skin before starting treatment with this medicine and regularly during treatment. Inform your doctor immediately if you notice any skin changes while on treatment or after treatment (see also section 4).

Eye problems

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

Contact your doctor immediately if you experience eye redness and irritation, blurred vision, eye pain, or other vision changes during treatment (see also section 4).

Mekinist may cause eye problems, including blindness. Mekinist is not recommended if you have ever had a blockage in the veins draining the eyes (retinal vein occlusion). Inform your doctor immediately if you develop any of the following eye-related symptoms during treatment: blurred vision, vision loss, other vision changes, seeing colored spots 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, may cause liver problems that could lead to conditions such as hepatitis or liver failure, which may be fatal. Your doctor will monitor you periodically. Signs that your liver is not working properly include:

• loss of appetite
• general discomfort (nausea)
• feeling sick (vomiting)
• stomach (abdominal) pain
• yellowing of the skin or whites of the eyes (jaundice)
• dark-colored urine
• itchy skin

Inform your doctor as soon as possible if you experience these symptoms.

Breathing or lung problems

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

Muscle pain

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

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

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

• Read the information ‘Possible serious side effects’ in section 4 of this leaflet.

Perforation of the stomach or intestine

Taking Mekinist or Mekinist in combination with dabrafenib may increase the risk of developing a perforation in the wall of the intestine. If you experience severe abdominal 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. Inform your doctor immediately if you notice any skin changes (see section 4 for symptoms to watch for).

Inflammatory disease mainly affecting the skin, lungs, eyes, and lymph nodes

An inflammatory disease mainly affecting the skin, lungs, eyes, or lymph nodes (sarcoidosis). Common symptoms of sarcoidosis may include cough, shortness of breath, swollen lymph nodes, vision disturbances, fever, fatigue, pain, joint swelling, or painful lumps (nodules) on the skin. If you experience any of these symptoms, contact your doctor.

Immune system disorders

Mekinist in combination with dabrafenib may rarely cause a condition (hemophagocytic lymphohistiocytosis or HLH) in which the immune system produces too many cells to fight infections, called histiocytes and lymphocytes. Symptoms may include enlargement of the liver or spleen, skin rash, enlarged lymph nodes, breathing problems, tendency to bruise easily, kidney abnormalities, and heart problems. Inform your doctor immediately if you experience several symptoms at once, such as fever, swollen lymph nodes, bruising, or rash.

Tumor lysis syndrome

If you experience the following symptoms, inform your doctor immediately, as this may be a potentially life-threatening condition: nausea, difficulty breathing, irregular heartbeat, muscle cramps, seizures, cloudy urine, reduced urine output, and fatigue. These may be caused by a group of metabolic complications that can occur during cancer treatment due to the breakdown products of dying cancer cells (tumor lysis syndrome or TLS) and may lead to changes in kidney function (see also section 4).

Children and adolescents

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

Other medicines and Mekinist

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

Use of Mekinist with food and drink

It is important that you take Mekinist on an empty stomach because food may 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 plan to become pregnant, consult your doctor before using this medicine. Mekinist may cause harm to the unborn baby.
• If you are a woman of childbearing potential, you must use a reliable method of contraception while taking Mekinist and for at least 16 weeks after stopping treatment.
• Hormonal contraceptive methods (birth control pills, injections, or contraceptive patches) may not be effective during treatment with Mekinist in combination with dabrafenib. It is recommended to use an additional effective contraceptive method to prevent pregnancy during treatment with this combination of medicines. Consult your doctor, pharmacist, or nurse for advice.
• If you become pregnant while taking Mekinist, inform your doctor immediately.

It is not recommended to use Mekinist while breastfeeding

It is unknown whether the components of this medicine pass into breast milk.

If you are breastfeeding or plan to breastfeed, you must inform your doctor. Breastfeeding is not recommended while you are 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 both men and women.

If you take Mekinist with dabrafenib: dabrafenib may permanently reduce fertility in men. In addition, men taking dabrafenib may experience reduced sperm count, and sperm levels may not return to normal until after stopping treatment.

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

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 may cause side effects that affect your ability to drive or operate machinery.

Avoid driving or operating machinery if you feel tired or weak, have vision problems, or feel low on energy.

Descriptions of these side effects can be found in other sections of this leaflet (see sections 2 and 4). Read all the information provided in this leaflet.

If you are unsure, talk to your doctor, pharmacist, or nurse. Your ability to drive and use machines may be affected not only by this medicine, but also by the disease itself, its symptoms, or the treatment.

Mekinist contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet; hence, essentially "sodium-free".

3. How to take Mekinist

Follow exactly the instructions for administering this medicine as given by your doctor, pharmacist, or nurse. If you are unsure, 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 daily. The recommended dose of dabrafenib, when used in combination with Mekinist, is 150 mg twice daily.

Your doctor will decide whether it is necessary to reduce the dose based on any adverse effects you may experience.

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

How to take it

Swallow the tablets whole with a full glass of water.

Take Mekinist once daily on an empty stomach (at least 1 hour before a meal or 2 hours after a meal). This means:

• After taking Mekinist, you must wait at least 1 hour before eating.
• If you have already eaten, you must wait at least 2 hours before taking Mekinist.

Take Mekinist at the same time each 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 time you were supposed to take Mekinist, take it as soon as you remember.

If more than 12 hours have passed since the usual time you were supposed to take Mekinist, skip this dose and take the next dose at your usual time. Then continue taking the tablets at your usual time.

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

If you stop taking Mekinist

Take Mekinist for as long as your doctor has recommended. Do not stop taking this medicine unless your doctor advises you to do so.

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

How to take Mekinist in combination with dabrafenib

• Take Mekinist in combination with dabrafenib exactly as directed by your doctor, pharmacist, or nurse. Do not change the dose or stop taking Mekinist or dabrafenib unless instructed by your doctor, pharmacist, or nurse.
• Take Mekinist once daily and take dabrafenib twice daily. It may be helpful for you to take both medicines together each day. You should take Mekinist either with the morning dose of dabrafenib or with the evening dose of dabrafenib. The doses of dabrafenib should be taken 12 hours apart.
• 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 miss a dose of Mekinist or dabrafenib, take it as soon as you remember. Do not make up for the missed dose; take the next dose at the scheduled time:
  • If there are less than 12 hours until the next dose of Mekinist (taken once daily)
  • If there are less than 6 hours until the next dose of dabrafenib (taken twice daily)
• If you take more Mekinist or dabrafenib than prescribed, contact your doctor, pharmacist, or nurse immediately. Bring the Mekinist tablets and dabrafenib capsules with you if possible. If possible, show the Mekinist and dabrafenib packaging along with the leaflet.
• If you experience adverse effects, your doctor may decide to prescribe a lower dose of Mekinist and dabrafenib. Take the dose of Mekinist exactly as directed by your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Serious possible adverse effects

Heart problems

Mekinist can affect the way your heart works. This is more likely to occur in people who already have a pre-existing heart condition. During treatment with Mekinist, you will undergo heart tests. Signs and symptoms related to heart problems include:

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

If you experience any of these symptoms, inform your doctor as soon as possible, whether they are new or worsening.

High blood pressure

Mekinist can increase blood pressure (hypertension) or worsen existing hypertension. Your doctor or nurse will monitor your blood pressure during treatment with Mekinist. Contact your doctor or nurse immediately if you develop high blood pressure, if your blood pressure worsens, or if you experience severe headaches, feel lightheaded, or dizzy.

Bleeding problems

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

• headache, dizziness, or weakness
• coughing up blood or coughing up blood clots
• vomiting blood or vomit that looks like “coffee grounds”
• red stools or black, tar-like stools.

Eye problems (vision)

Mekinist can cause eye problems. Mekinist is not recommended if you have ever had a blockage in the veins draining the eyes (retinal vein occlusion). Your doctor will advise you to have an eye examination 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 any vision-related signs or symptoms, including:

• loss of vision
• redness and irritation in the eyes
• seeing colored spots
• seeing halos (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 spots on the trunk that are circular or target-shaped, with central blisters. Skin peeling. Mouth, throat, nose, genital, or eye ulcers. These serious skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome)

• widespread rash, fever, and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).

• Stop taking the medicine and seek immediate medical attention.

Up to 3 out of every 100 people taking Mekinist in combination with dabrafenib may develop a different type of skin cancer called Cutaneous Squamous Cell Carcinoma (cuSCC). Others may develop a type of cancer called Basal Cell Carcinoma (BCC). Typically, these changes affect only the skin locally and can be surgically removed, allowing treatment with Mekinist and dabrafenib to continue without interruption.

Some people taking Mekinist in combination with dabrafenib may also develop new melanomas. These melanomas are usually removed surgically, and treatment with Mekinist and dabrafenib can continue without interruption.

Your doctor will examine your skin before starting treatment with dabrafenib, monthly during treatment, and for 6 months after treatment ends. These checks are performed to detect new cancerous skin lesions.

Your doctor will also examine your head, neck, mouth, and lymph nodes and will perform regular scans (Computed Tomography) of the chest and abdominal area. Blood tests may also be performed. These checks help detect whether you have developed other cancers, including squamous cell carcinoma. Pelvic and anal examinations are recommended at the beginning and end of treatment (in women).

Mekinist, both as monotherapy and in combination with dabrafenib, may cause rash or acne-like rash. Follow your doctor’s instructions on how to prevent rash development. 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 immediately if you develop a severe skin rash accompanied by any of the following symptoms: skin blisters, mouth blisters or sores, skin peeling, fever, facial redness or swelling, blisters on the soles of the feet.

If you develop a skin rash or if it worsens**, inform your doctor or nurse as soon as possible.**

Muscle pain

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

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

Respiratory or lung problems

Mekinist can cause lung inflammation (pneumonitis or interstitial lung disease). Inform your doctor or nurse if you develop new symptoms or worsening symptoms related to breathing difficulties 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. This could be a sign of a condition in which the immune system produces excessive cells to fight infections, known as histiocytes and lymphocytes, which may 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 heartbeat, muscle cramps, seizures, cloudy urine, reduced urine output, and fatigue. These may be signs of a condition caused by the rapid breakdown of cancer cells, which can be fatal in some people (tumor lysis syndrome or TLS); see section 2 (unknown frequency).

Possible adverse effects in patients taking Mekinist alone

Adverse effects that may occur 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 may be mild or severe
• cough
• shortness of breath
• diarrhea
• feeling sick (nausea), discomfort (vomiting)
• constipation
• stomach pain
• dry mouth
• skin rash, acne-like rash, facial redness, dry or itchy skin (see also section 4 “Skin changes”)
• unusual hair loss or thinning hair
• lack of energy, weakness, fatigue
• swelling of hands or feet (peripheral edema)
• fever

Very common adverse effects that may appear in blood tests:

• abnormal blood test results related to the liver

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

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

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

Adverse effects with unknown frequency (cannot be estimated from available data):

• irregular heartbeat (atrioventricular block)

Adverse effects when Mekinist is taken with dabrafenib

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

You may also experience new adverse effects due to taking dabrafenib together with Mekinist, listed below.

Inform your doctor as soon as possible if you notice symptoms appearing for the first time or worsening.

Read the dabrafenib package leaflet for more details about adverse effects that may occur while taking this medicine.

Adverse effects that may occur while taking Mekinist in combination with dabrafenib include:

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

• nasal and throat inflammation
• decreased appetite
• headache
• dizziness
• elevated blood pressure (hypertension)
• bleeding in different parts of the body, which may be mild or severe (hemorrhage)
• cough
• stomach pain
• constipation
• diarrhea
• feeling sick (nausea), discomfort (vomiting)
• rash, dry skin, itching, skin redness
• 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 blood liver function test results

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

• urinary tract infection
• skin effects including skin infection (cellulitis), inflammation of hair follicles, nail changes such as nail bed changes, nail pain, infection and inflammation of cuticles, pus-filled skin rashes, squamous cell skin cancer (a type of skin cancer), papilloma (a usually non-harmful tumor), wart growth, increased skin sensitivity to sunlight (see also section 4 “Skin changes”)
• dehydration (low levels of water or fluids)
• blurred vision, vision problems, eye inflammation (uveitis)
• less efficient heart pumping
• low blood pressure (hypotension)
• localized tissue swelling
• shortness of breath
• dry mouth
• mouth ulcers or pain, mucosal inflammation
• acne-like problems
• thickening of the outer skin layer (hyperkeratosis), patches of thickened, scaly, or hardened skin (actinic keratosis), cracked or fissured skin
• increased sweating, night sweats
• unusual hair loss or thinning
• redness, pain in hands and feet
• inflammation of the fat layer under the skin (panniculitis)
• mucosal inflammation
• facial swelling
• nerve problems that may cause pain, loss of sensation, or tingling in 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 to clot), and a type of white blood cell (leukopenia)
• low levels of sodium (hyponatremia) or phosphate (hypophosphatemia) 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):

• development of a new skin cancer (melanoma)
• skin markings
• allergic reactions (hypersensitivity)
• eye changes such as swelling due to fluid accumulation (chorioretinopathy), separation of the light-sensitive membrane in the back of the eye (retina) from its supporting layers (retinal detachment), and swelling around the eyes
• slower than normal heart rate and/or decreased heart rate
• lung inflammation (pneumonitis)
• pancreas inflammation
• intestine inflammation (colitis)
• kidney failure
• kidney inflammation
• inflammatory disease mainly affecting the skin, lungs, eyes, and lymph nodes (sarcoidosis)
• irregular heartbeat (atrioventricular block)
• raised, painful, red to dark purple skin spots or sores, mainly on arms, legs, face, and neck, with fever (signs of febrile neutrophilic dermatosis)

Rare adverse effects (may affect up to 1 in 1000 people):

• a hole (perforation) in the wall of the stomach or intestines

Adverse effects with unknown frequency (cannot be estimated from available data):

• inflammation of the heart muscle (myocarditis), which may cause difficulty breathing, fever, palpitations, and chest pain
• inflamed, scaly skin (exfoliative dermatitis)
• localized skin reactions at tattoo sites

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the national reporting system included in Appendix V. By reporting adverse effects, you can help provide 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 expiry date stated on the label of the bottle and on the outer packaging, following the abbreviation CAD. The expiry date refers to the last day of the month indicated.

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

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

Before opening: This medicine does not require any special storage temperature.

After opening: Store below 30 °C. Use within 30 days after opening.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Mekinist

• The active substance 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 core: mannitol (E421), microcrystalline cellulose (E460), hypromellose (E464), sodium croscarmellose (E468), magnesium stearate (E470b), sodium lauryl sulfate, and colloidal anhydrous 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).

Appearance of the product and contents of the pack

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

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

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

The bottles contain a silica gel desiccant in a small cylindrical container. The desiccant must be kept inside the bottle and must not be 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

Glaxo Wellcome, S.A.
Avda. Extremadura, 3
09400, Aranda de Duero
Burgos
Spain

Novartis Pharma GmbH
Sophie-Germain-Strasse 10
90443 Nuremberg
Germany

Further information on this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder:

Belgium/Belgium/Belgium Novartis Pharma N.V. Tel/Tel: +32 2 246 16 11	Lithuania SIA Novartis Baltics Lithuania Branch Tel: +370 5 269 16 50
	Luxembourg/Luxembourg Novartis Pharma N.V. Tel/Tel: +32 2 246 16 11
Czech Republic Novartis s.r.o. Tel: +420 225 775 111	Hungary Novartis Hungária Kft. Tel.: +36 1 457 65 00
Denmark Novartis Healthcare A/S Tlf.: +45 39 16 84 00	Malta Novartis Pharma Services Inc. Tel: +356 2122 2872
Germany Novartis Pharma GmbH Tel: +49 911 273 0	Netherlands Novartis Pharma B.V. Tel: +31 88 04 52 555
Estonia SIA Novartis Baltics Estonia Branch Tel: +372 66 30 810	Norway Novartis Norge AS Tlf: +47 23 05 20 00
Greece Novartis (Hellas) A.E.B.E. Tel: +30 210 281 17 12	Austria Novartis Pharma GmbH Tel: +43 1 86 6570
Spain Novartis Farmacéutica, S.A. Tel: +34 93 306 42 00	Poland Novartis Poland Sp. z o.o. Tel.: +48 22 375 4888
France Novartis Pharma S.A.S. Tél: +33 1 55 47 66 00	Portugal Novartis Farma - Produtos Farmacêuticos, S.A. Tel: +351 21 000 8600
Croatia Novartis Hrvatska d.o.o. Tel. +385 1 6274 220	Romania Novartis Pharma Services Romania SRL Tel: +40 21 31299 01
Ireland Novartis Ireland Limited Tel: +353 1 260 12 55	Slovenia Novartis Pharma Services Inc. Tel: +386 1 300 75 50
Iceland Vistor hf. Tel: +354 535 7000	Slovakia Novartis Slovakia s.r.o. Tel: +421 2 5542 5439
Italy Novartis Farma S.p.A. Tel: +39 02 96 54 1	Finland/Suomi Novartis Finland Oy Puh/Tel: +358 (0)10 6133 200
Cyprus Novartis Pharma Services Inc. Tel: +357 22 690 690	Sweden Novartis Sverige AB Tel: +46 8 732 32 00
Latvia SIA Novartis Baltics Tel: +371 67 887 070

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Other sources of information

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

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