Mekinist
trametinib
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor, nurse or pharmacist.
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 get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.
What Mekinist is and what it is used for
What you need to know before you take Mekinist
How to take Mekinist
Possible side effects
How to store Mekinist
Contents of the pack and other information
Mekinist is a medicine that contains the active substance trametinib. It is used either on its own 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 is also used to prevent melanoma from coming back 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 cancers have a particular change (mutation) in a gene called BRAF at the V600 position. This mutation in the gene may have caused the cancer to develop. Your medicine targets proteins made from this mutated gene and slows down or stops the development of your cancer.
Mekinist should only be used to treat melanomas and NSCLC with the BRAF mutation. Therefore, before starting treatment your doctor will test for this mutation.
If your doctor decides that you will receive treatment with the combination of Mekinist and dabrafenib, read the dabrafenib leaflet carefully as well as this leaflet.
If you have any further questions on the use of this medicine, ask your doctor, nurse or pharmacist.
if you are allergic to trametinib or any of the other ingredients of this medicine (listed in section 6).
Check with your doctor if you think this applies to you.
Talk to your doctor before taking your medicine. Your doctor needs to know if you:
have any liver problems. Your doctor may take blood samples to monitor your liver function while you are taking this medicine.
have or have ever had kidney problems.
have or have ever had lung or breathing problems.
have heart problems such as heart failure (which can cause shortness of breath, difficulty in 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 including blockage of the vein draining the eye (retinal vein occlusion) or swelling in the eye which may be caused by fluid blockage (chorioretinopathy).
Some people taking Mekinist develop other conditions which can be serious. You need to know about important symptoms to look out for.
Bleeding
Taking Mekinist or the combination of Mekinist and dabrafenib can cause serious bleeding including in your brain, the digestive system (such as stomach, rectum or intestine), lungs, and other organs, and
can lead to death. Symptoms may include:
headaches, dizziness, or feeling weak
passing blood in the stools or passing black stools
passing blood in the urine
stomach pain
coughing / vomiting up blood
Fever
Taking Mekinist or the combination of Mekinist and dabrafenib may cause fever, although it is more likely if you are taking the combination treatment (see also section 4). In some cases, people with
fever may develop low blood pressure, dizziness or other symptoms.
Heart disorder
Mekinist can cause heart problems, or make existing heart problems worse (see also “Heart conditions” in section 4) in people taking Mekinist in combination with dabrafenib.
tiredness, light-headedness, shortness of breath or swelling in the legs. If necessary, your doctor may decide to interrupt your treatment or to stop it altogether.
Changes in your skin which may indicate new skin cancer
Your doctor will check your skin before you start taking this medicine and regularly while you are taking it. Tell your doctor immediately if you notice any changes to your skin while taking this
medicine or after treatment (see also section 4).
Eye problems
Mekinist can cause eye problems including blindness. Mekinist is not recommended if you have ever had blockage of the vein draining the eye (retinal vein occlusion). Tell your doctor immediately if you get the following symptoms of eye problems: blurred vision, loss of vision or other vision changes,
coloured dots in your vision or halos (seeing blurred outline around objects) during your treatment. If necessary, your doctor may decide to interrupt your treatment or to stop it altogether.
Liver problems
Mekinist, or the combination with dabrafenib, can cause problems with your liver which may develop into serious conditions such as hepatitis and liver failure, which may be fatal. Your doctor will monitor
you periodically. Signs that your liver may not be working properly may include:
loss of appetite
feeling sick (nausea)
being sick (vomiting)
pain in your stomach (abdomen)
yellowing of your skin or the whites of your eyes (jaundice)
dark-coloured urine
itching of your skin
Lung or breathing problems
your lung function before you start taking your medicine.
Muscle pain
Mekinist can result in the breakdown of muscle (rhabdomyolysis), Tell your doctor as soon as possible if you get any of these symptoms:
muscle pain
dark urine due to kidney damage
If necessary, your doctor may decide to interrupt your treatment or to stop it altogether.
→ Read the information “Possible serious side effects” in section 4 of this leaflet.
Hole in the stomach or intestine (perforation)
Taking Mekinist or the combination of Mekinist and dabrafenib may increase the risk of developing holes in the gut wall. Tell your doctor as soon as possible if you have severe abdominal pain.
Serious skin reactions
Serious skin reactions have been reported in people taking Mekinist in combination with dabrafenib. Tell your doctor immediately if you notice any changes to your skin (see section 4 for symptoms to be
aware of).
Inflammatory disease mainly affecting the skin, lung, eyes and lymph nodes
An inflammatory disease mainly affecting the skin, lung, eyes and lymph nodes (sarcoidosis). Common symptoms of sarcoidosis may include coughing, shortness of breath, swollen lymph nodes,
visual disturbances, fever, fatigue, pain and swelling in the joints and tender bumps on your skin. Tell
your doctor if you get any of these symptoms.
Mekinist is not recommended for children and adolescents since the effects of Mekinist in people younger than 18 years old are not known.
Before starting treatment, tell your doctor, nurse or pharmacist if you are taking, have recently taken or might take any other medicines. This includes medicines obtained without a prescription. Keep a list of the medicines you take, so you can show it to your doctor, nurse or pharmacist when you get a new medicine.
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. Mekinist can harm the unborn baby.
If you are a woman who could become pregnant, you must use reliable birth control (contraception) while you are taking Mekinist and for at least 16 weeks after you stop taking it.
Birth control using hormones (such as pills, injections or patches) may not work as well if you are taking Mekinist in combination with dabrafenib. You need to use another effective method of birth control so you do not become pregnant while you are taking this combination of medicines. Ask your doctor, nurse or pharmacist for advice.
If you do become pregnant while you are taking Mekinist, tell your doctor immediately.
It is not known whether the ingredients of Mekinist can pass into breast milk.
If you are breast-feeding, or planning to breast-feed, you must tell your doctor. It is recommended that you do not breast-feed while you are taking Mekinist. You and your doctor will decide whether you
will take Mekinist or breast-feed.
Mekinist may impair fertility in both men and women.
Taking Mekinist with dabrafenib: Dabrafenib may permanently reduce male fertility. In addition, men who are taking dabrafenib may have a reduced sperm count, and their sperm count may not return to normal levels after they stop taking this medicine.
Prior to starting treatment with dabrafenib, talk to your doctor about options to improve your chances to have children in the future.
If you have any further questions on the effect of this medicine on fertility, ask your doctor, nurse or pharmacist.
Mekinist can have side effects that may affect your ability to drive or use machines. Avoid driving or using machines if you feel tired or weak, if you have problems with your vision or if your energy levels are low.
Descriptions of these effects can be found in other sections (see sections 2 and 4). Read all the information in this leaflet for guidance.
Discuss with your doctor, nurse or pharmacist if you are unsure about anything. Your disease symptoms and treatment situation may also affect your ability to drive or use machines.
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium- free’.
Always take this medicine exactly as your doctor, nurse or pharmacist has told you. Check with your doctor, nurse or pharmacist if you are not sure.
The usual dose of Mekinist either used alone or in combination with dabrafenib is one 2 mg tablet once a day. The recommended dose of dabrafenib, when used in combination with Mekinist, is 150 mg twice daily.
Your doctor may decide to lower the dose if you get side effects.
Swallow the tablet whole, with 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). This means that:
after taking Mekinist, you must wait at least 1 hour before eating, or
after eating, you must wait at least 2 hours before taking Mekinist. Take Mekinist at about the same time each day.
If you take too many tablets of Mekinist, contact your doctor, nurse or pharmacist for advice. If possible, show them the Mekinist pack and this leaflet.
If the missed dose is less than 12 hours late, take it as soon as you remember.
If the missed dose is more than12 hours late, skip that dose and take your next dose at the usual time. Then carry on taking your tablets at regular times as usual.
Do not take a double dose to make up for a forgotten dose.
Take Mekinist for as long as your doctor recommends. Do not stop unless your doctor advises you to. If you have any further questions on the use of this medicine, ask your doctor, nurse or pharmacist.
Take Mekinist in combination with dabrafenib exactly as your doctor, nurse or pharmacist tells you. Do not change your dose or stop Mekinist or dabrafenib unless your doctor, nurse or pharmacist tells you to.
Take Mekinist once daily and take dabrafenib twice daily. It may be good for you to get into the habit of taking both medicines at the same times each day. Mekinist should be taken with either the morning dose of dabrafenib or the evening dose of dabrafenib. The dabrafenib doses should be about 12 hours apart.
Take Mekinist and dabrafenib on an empty stomach, at least one hour before or two hours after a meal. Take 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 missed doses and just take your next dose at your regular time:
If it is less than 12 hours to your next scheduled dose of Mekinist, which is taken once daily.
If it is less than 6 hours to your next scheduled dose of dabrafenib, which is taken twice daily.
If you take too much Mekinist or dabrafenib, immediately contact your doctor, nurse or pharmacist. Take Mekinist tablets and dabrafenib capsules with you when possible. If possible, show them the Mekinist and dabrafenib pack with each leaflet.
If you get side effects your doctor may decide that you should take lower doses of Mekinist and dabrafenib. Take the doses of Mekinist and dabrafenib exactly as your doctor, nurse or pharmacist tells you.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Possible serious side effects
Heart conditions
Mekinist can affect how well your heart pumps blood. It is more likely to affect people who have an existing heart problem. You will be checked for any heart problems while you are taking Mekinist. Signs and symptoms of heart problems include:
feeling like your heart is pounding, racing, or beating irregularly
dizziness
tiredness
feeling light-headed
shortness of breath
swelling in the legs
High blood pressure
Mekinist can cause new or worsening high blood pressure (hypertension). Your doctor or nurse should check your blood pressure during treatment with Mekinist. Call your doctor or nurse right away if you develop high blood pressure, your blood pressure worsens, or you have severe headache,
light-headedness, or dizziness.
Bleeding problems
Mekinist can cause serious bleeding problems, especially in your brain or stomach. Call your doctor or nurse and get medical help right away if you have any unusual signs of bleeding, including:
headaches, dizziness, or weakness
coughing up of blood or blood clots
vomit containing blood or that looks like “coffee grounds”
red or black stools that look like tar
Eye (vision) problems
Mekinist can cause eye problems. Mekinist is not recommended if you have ever had a blockage of the vein draining the eye (retinal vein occlusion). Your doctor may advise an eye examination before you
take Mekinist and while you are taking it. Your doctor may ask you to stop taking Mekinist or refer
you to a specialist, if you develop signs and symptoms in your vision that include:
loss of vision
eye redness and irritation
coloured dots in your vision
halo (seeing a blurred outline around objects)
blurred vision
Changes in your skin
Serious skin reactions have been reported in people taking Mekinist in combination with dabrafenib (frequency not known). If you notice any of the following:
reddish patches on the trunk that are circular or target-shaped, with central blisters. Skin peeling. Ulcers of mouth, throat, nose, genitals and eyes. These serious skin rashes can be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome).
widespread rash, fever, and enlarged lymph nodes (DRESS-syndrome or drug hypersensitivity syndrome).
➔ stop using the medicine and seek medical attention immediately
Up to 3 in 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 skin cancer called basal cell carcinoma (BCC). Usually, these skin changes remain local and can be removed with surgery and treatment with Mekinist and dabrafenib can be continued without interruption.
Some people taking Mekinist in combination with dabrafenib may also notice that new melanomas have appeared. These melanomas are usually removed by surgery and treatment with Mekinist and dabrafenib can be continued without interruption.
Your doctor will check your skin before you start taking dabrafenib, then check it again every month while you are taking dabrafenib and for 6 months after you stop taking it. This is to look for any new skin cancers.
Your doctor will also check your head, neck, mouth and lymph glands and you will have scans of your chest and stomach area (called CT scans) regularly. You may also have blood tests. These checks are to detect if any other cancer, including squamous cell carcinoma, develops inside your body. Pelvic examinations (for women) and anal examinations are also recommended before and at the end of your treatment.
Mekinist as monotherapy or in combination with dabrafenib can cause rash or acne-like rash. Follow your doctor’s instructions for what to do to help prevent rash. Tell your doctor or nurse as soon as possible if you get any of these symptoms for the first time or if they get worse.
Muscle pain
Mekinist can result in the breakdown of muscle (rhabdomyolysis). Tell your doctor or nurse if you have any new or worsening symptoms, including:
muscle pain
dark urine due to kidney damage
Lung or breathing problems
Mekinist can cause inflammation of the lung (pneumonitis or interstitial lung disease). Tell your doctor or nurse if you have any new or worsening symptoms of lung or breathing problems, including:
shortness of breath
cough
fatigue
The side effects that you may see when you take Mekinist alone are as follows:
Very common side effects (may affect more than 1 in 10 people):
High blood pressure (hypertension)
Bleeding, at various sites in the body, which may be mild or serious
Cough
Shortness of breath
Diarrhoea
Feeling sick (nausea), being sick (vomiting)
Constipation
Stomach ache
Dry mouth
Skin rash, acne-like rash, redness of the face, dry or itching skin (see also “Changes in your skin” earlier in section 4)
Unusual hair loss or thinning
Lack of energy or feeling weak or tired
Swelling of the hands or feet (oedema peripheral)
Fever
Very common side effects that may show up in your blood tests
Abnormal blood test results related to the liver
Common side effects (may affect up to 1 in 10 people):
Inflammation of hair follicles in the skin
Nail disorders such as nail bed changes, nail pain, infection and swelling of the cuticles
Infection of the skin (cellulitis)
Skin rash with pus-filled blisters (see also “Changes in your skin” earlier in section 4)
Allergic reaction (hypersensitivity)
Dehydration (low levels of water or fluid)
Blurred vision
Swelling around the eyes
Eyesight problems (see also “Eye (vision) problems” earlier in section 4)
Changes in how the heart pumps blood (left ventricular dysfunction) (see also “Heart conditions” earlier in section 4)
Heart rate that is lower than the normal range and/or a decrease in heart rate
Localised tissue swelling
Inflammation of the lung (pneumonitis or interstitial lung disease)
Sore mouth or mouth ulcers, inflammation of mucous membranes
Reddening, chapping or cracking of the skin
Red, painful hands and feet
Swelling of the face
Inflammation of the mucosa
Feeling weak
Common side effects that may show up in your blood tests:
Decreased red blood cells (anaemia), abnormal test related to creatine phosphokinase, an enzyme found mainly in heart, brain, and skeletal muscle
Uncommon side effects (may affect up to 1 in 100 people):
Swelling in the eye caused by fluid leakage (chorioretinopathy) (see also “Eye (vision) problems” earlier in section 4)
Swelling of nerves at the back of the eye (papilloedema) (see also “Eye (vision) problems” earlier in section 4)
Separation of the light-sensitive membrane in the back of the eye (the retina) from its supporting layers (retinal detachment) (see also “Eye (vision) problems” earlier in section 4).
Blockage of the vein draining the eye (retinal vein occlusion) (see also “Eye (vision) problems” earlier in section 4)
Heart pumping less efficiently, causing shortness of breath, extreme tiredness and swelling in ankles and legs (heart failure)
A hole (perforation) in the stomach or intestines
Inflammation of the intestines (colitis)
Breakdown of muscle which can cause muscle pain and kidney damage (rhabdomyolysis)
Side effects when Mekinist and dabrafenib are taken together
When you take Mekinist and dabrafenib together you may get any of the side effects given in the lists above, although the frequency may change (increase or decrease).
You may also get additional side effects due to taking dabrafenib at the same time as Mekinist in the list below.
Tell your doctor as soon as possible if you get any of these symptoms, either for the first time or if they get worse.
The side effects that you may see when you take Mekinist in combination with dabrafenib are as follows:
Very common side effects (may affect more than 1 in 10 people):
Nasal and throat inflammation
Decreased appetite
Headache
Dizziness
High blood pressure (hypertension)
Bleeding, at various sites in the body, which may be mild or serious (haemorrhage)
Cough
Stomach ache
Constipation
Diarrhoea
Feeling sick (nausea), being sick (vomiting)
Rash, dry skin, itching, skin reddening
Joint pain, muscle pain, or pain in the hands or feet
Muscle spasms
Lack of energy, feeling weak
Chills
Swelling of the hands or feet (oedema peripheral)
Fever
Flu-like illness
Very common side effects that may show up in your blood tests
Abnormal blood test results related to the liver
Common side effects (may affect up to 1 in 10 people):
Infection of the urinary system
Skin effects including infection of the skin (cellulitis), inflammation of hair follicles in the skin, nail disorders such as nail bed changes, nail pain, infection and swelling of the cuticles, skin rash with pus-filled blisters, cutaneous squamous cell carcinoma (a type of skin cancer), papilloma (a type of skin tumour which is usually not harmful), wart-like growths, increased sensitivity of the skin to sun (see also “Changes in your skin” earlier in section 4)
Dehydration (low levels of water or fluid)
Blurred vision, eyesight problems, inflammation of the eye (uveitis)
Heart pumping less efficiently
Low blood pressure (hypotension)
Localised tissue swelling
Shortness of breath
Dry mouth
Sore mouth or mouth ulcers, inflammation of mucous membranes
Acne-like problems
Thickening of the outer layer of the skin (hyperkeratosis), patches of thick, scaly, or crusty skin (actinic keratosis), chapping or cracking of the skin
Increased sweating, night sweats
Unusual hair loss or thinning
Red, painful hands and feet
Inflammation of the fatty layer under the skin (panniculitis)
Inflammation of the mucosa
Swelling of the face
Common side effects that may show up in your blood tests
Low levels of white blood cells
Decrease in number of red blood cells (anaemia), blood platelets (cells that help blood to clot), and a type of white blood cells (leukopenia)
Low levels of sodium (hyponatraemia) or phosphate (hypophosphataemia) in the blood
Increase in blood sugar level
Increase in creatine phosphokinase, an enzyme found mainly in heart, brain, and skeletal muscle
Increase in some substances (enzymes) produced by the liver
Uncommon side effects (may affect up to 1 in 100 people):
Appearance of new skin cancer (melanoma)
Skin tags
Allergic reactions (hypersensitivity)
Eye changes including swelling in the eye caused by fluid leakage (chorioretinopathy), separation of the light-sensitive membrane in the back of the eye (the retina) from its supporting layers (retinal detachment) and swelling around the eyes
Heart rate that is lower than the normal range and/or a decrease in heart rate
Inflammation of the lung (pneumonitis)
Inflammation of pancreas
Inflammation of the intestines (colitis)
Kidney failure
Inflammation of the kidneys
Inflammatory disease mainly affecting the skin, lung, eyes and lymph nodes (sarcoidosis)
Rare side effects (may affect up to 1 in 1000 people)
A hole (perforation) in the stomach or intestines
Not known (frequency cannot be estimated from the available data):
Inflammation of the heart muscle (myocarditis) which can result in breathlessness, fever, palpitations and chest pain.
Inflamed, flaky skin (exfoliative dermatitis)
If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the bottle label and carton after EXP. The expiry date refers to the last day of that month.
This medicine does not require any special temperature storage conditions.
Store in the original package in order to protect from light and moisture.
Keep the bottle tightly closed with the dessicant inside (small cylinder shaped container). Once opened, the bottle may be stored for 30 days at not more than 30°C.
Do not throw away medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
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 ingredients are
Tablet: mannitol (E421), microcrystalline cellulose (E460), hypromellose (E464), croscarmellose sodium (E468), magnesium stearate (E470b), sodium laurilsulfate and
colloidal silicon dioxide (E551).
Film coating: hypromellose (E464), titanium dioxide (E171), polyethylene glycol, iron oxide yellow (E172) (for 0.5 mg tablets), polysorbate 80 (E433) and iron oxide red
(E172) (for 2 mg tablets).
The Mekinist 0.5 mg film-coated tablets are yellow, modified oval, biconvex, with the company logo debossed on one face and “TT” on the opposing face.
The Mekinist 2 mg film-coated tablets are pink, round, biconvex, with the company logo debossed on one face and “LL” on the opposing face.
The film-coated tablets are supplied in opaque white plastic bottles with threaded plastic closures. One bottle contains either 7 or 30 tablets.
The bottles also include a silica gel desiccant in a small cylinder shaped container. The desiccant must be kept inside the bottle and must not be eaten.
Novartis Europharm Limited Vista Building
Elm Park, Merrion Road
Dublin 4 Ireland
Lek Pharmaceuticals d.d. Verovskova ulica 57
1526, Ljubljana
Slovenia
Novartis Pharma GmbH Roonstraße 25
D-90429 Nuremberg
Germany
Glaxo Wellcome, S.A. Avda. Extremadura, 3 09400, Aranda de Duero Burgos
Spain
For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
SIA Novartis Baltics Lietuvos filialas Tel: +370 5 269 16 50
Novartis Bulgaria EOOD Тел: +359 2 489 98 28
Novartis s.r.o.
Tel: +420 225 775 111
Novartis Healthcare A/S Tlf: +45 39 16 84 00
Novartis Pharma Services Inc. Tel: +356 2122 2872
Novartis Pharma GmbH Tel: +49 911 273 0
Novartis Pharma B.V. Tel: +31 88 04 52 555
SIA Novartis Baltics Eesti filiaal Tel: +372 66 30 810
Novartis Norge AS Tlf: +47 23 05 20 00
Novartis (Hellas) A.E.B.E. Τηλ: +30 210 281 17 12
Novartis Pharma GmbH Tel: +43 1 86 6570
Novartis Farmacéutica, S.A. Tel: +34 93 306 42 00
Novartis Poland Sp. z o.o. Tel.: +48 22 375 4888
Novartis Pharma S.A.S. Tél: +33 1 55 47 66 00
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Vistor hf.
Sími: +354 535 7000
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Puh/Tel: +358 (0)10 6133 200
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SIA Novartis Baltics Tel: +371 67 887 070
Novartis Ireland Limited Tel: +44 1276 698370
This leaflet is available in all EU/EEA languages on the European Medicines Agency website.