Package Insert: Information for the Patient

Tafinlar®50mg Hard Capsules

Tafinlar®75mg Hard Capsules

dabrafenib

Read this package insert carefully before starting to take this medication, as it contains important information for you.

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

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

Tafinlar in combination with trametinib may also be used to prevent the recurrence of melanoma after it has been removed through surgery.

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

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

Tafinlar can only be used to treat melanomas and CPNM with the BRAF gene mutation.

Therefore, before starting treatment, your doctor will check if you have this mutation.

If your doctor decides that you should take the combined treatment of Tafinlar and trametinib, read the trametinib prospectus as well as this prospectus carefully.

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

Do not take Tafinlar

• if you are allergicto dabrafenib or to any of the other components of this medication (including those listed in section6).

If you think this applies to you, consult your doctor.

Warnings and precautions

Consult your doctor before starting to take Tafinlar. Your doctor needs to know if:

• you haveliver problems.
• you have or have ever hadkidney problems.

You may need to have blood samples taken while you are being treated with Tafinlar to check how your liver and kidneys are working.

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

Before taking Tafinlar in combination with trametinib, your doctor must know:

• if you have heart problems such as heart failure or problems with the way your heart beats.
• if you have eye problems, such as blockage of the blood vessels that supply the eye (retinal vein occlusion) or swelling of the eye that may be due to fluid blockage (chorioretinopathy).
• if you have or have ever had breathing or lung problems, such as frequent difficulty breathing accompanied by dry cough, shortness of breath, and fatigue.
• if you have or have ever had gastrointestinal problems such as diverticulitis (inflamed pouches in the colon) or metastases in the gastrointestinal tract.

Consult your doctorif you think any of the above circumstances apply to you.

Conditions to be aware of

Some people who take Tafinlar develop other diseases that can be serious. You need to know what signs and symptoms to look out for while taking this medication. In this section, some of these symptoms (bleeding, fever, skin changes, and eye problems) are briefly mentioned, but you will find more detailed information in section4, “Adverse reactions”.

Bleeding

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

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

Inform your doctor as soon as possibleif you experience these symptoms

Fever

Treatment with Tafinlar or the combination of Tafinlar and trametinib can cause fever, although it is more likely if you take the combination (see also section4). In some cases, people with fever develop low blood pressure, dizziness, and other symptoms.

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

Heart problems

Tafinlar can cause heart problems, or make existing problems worse (see section4 “Heart problems”) in people taking Tafinlar with trametinib.

Inform your doctor if you experience any heart problems. Before starting treatment and during treatment with Tafinlar in combination with trametinib, your doctor will perform tests to check if your heart is working properly. Inform your doctor immediately if you feel your heart is beating strongly, your heart is racing, or beating irregularly, if you experience dizziness, fatigue, shortness of breath, or swelling in your legs. If necessary, your doctor may decide to interrupt or suspend treatment.

Changes in the skin that may indicate a new skin cancer

Your doctor will check your skin before starting treatment with this medication, and regularly while you are taking it.

Consult your doctor immediatelyif you notice any changes in your skin while taking this medication or after treatment (see also section4).

Eye problems

Your doctor must examine your eyes while you are taking this medication.

Consult 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).

Tafinlar when given in combination with trametinib can cause eye problems, including blindness. Trametinib is not recommended if you have ever had blockage of the blood vessels that drain the eye (retinal vein occlusion). Inform your doctor immediately if during treatment you experience the following symptoms related to eye problems: blurred vision, loss of vision, or other changes in vision, if you see colored dots or halos (blurred vision around objects). If necessary, your doctor may decide to interrupt or suspend treatment.

• Read the information on fever, skin changes, and eye problems in section 4 of this prospectus. Inform your doctor, pharmacist, or nurse if you experience any of these signs or symptoms.

Liver problems

Tafinlar in combination with trametinib can cause liver problems that may develop into diseases such as hepatitis or liver failure, which can be fatal. Your doctor will monitor you periodically. The signs that your liver is not working properly are:

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

Inform your doctor as soon as possibleif you experience these symptoms

Muscle pain

Tafinlar in combination with trametinib can cause muscle deterioration (rhabdomyolysis).Inform your doctoras 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 suspend treatment.

Perforation in the stomach or intestine

Taking the combination of Tafinlar and trametinib may increase the risk of developing perforation in the intestinal wall. If you experience severe abdominal paininform your doctoras soon as possible.

Severe skin reactions

Severe skin reactions have been reported in people who have taken Tafinlar in combination with trametinib. Inform your doctor immediately if you notice any changes in your skin (see section4 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 coughing, shortness of breath, swollen lymph nodes, visual disturbances, fever, fatigue, pain, swollen joints, or painful lumps under the skin. If you experience any of these symptoms, contact a doctor.

Immune system disorders

Tafinlar in combination with trametinib may cause a rare disease (hemophagocytic lymphohistiocytosis or LHH) in which the immune system produces too many cells to fight infections, called histiocytes and lymphocytes. The symptoms may include enlarged liver or spleen, skin rash, swollen lymph nodes, respiratory problems, tendency to form bruises, kidney abnormalities, and heart problems. If you experience several symptoms simultaneously, such as fever, swollen lymph nodes, bruises, or skin rash, inform your doctor immediately.

Tumor lysis syndrome

If you experience the following symptoms, inform your doctor immediately, as they may be a potentially fatal condition: nausea, difficulty breathing, irregular heartbeats, muscle cramps, convulsions, cloudy urine, decreased urine production, and fatigue. These may 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 may cause changes in kidney function (see also section4).

Children and adolescents

Tafinlar is not recommended for children and adolescents. The effects of Tafinlar on people under 18 years old are unknown.

Other medications and Tafinlar

Before starting treatment, inform your doctor, pharmacist, or nurse if you are taking,have taken recentlyor may need to take any other medication. This includes medications purchased without a prescription.

Some medications may affect the way Tafinlar works, or make it more likely that you will experience adverse reactions. Tafinlar may also affect the way other medications work. These include:

• birth control medications(contraceptives) that contain hormones, such as the pill, injections, or patches
• warfarin and acenocoumarol, medications used to makeblood thinner
• digoxin, used to treatheart disease
• medications to treatfungus infections,such as ketoconazole, itraconazole, voriconazole, and posaconazole
• some calcium channel blockers, used to treathigh blood pressure, such as diltiazem, felodipine, nicardipine, nifedipine, or verapamil
• medications to treatcancer, such as cabazitaxel
• some medications thatlower cholesterolin the blood, such as gemfibrozil
• some medications to treat certainmental health disorders, such as haloperidol
• someantibiotics, such as clarithromycin, doxycycline, and telithromycin
• some medications used to treattuberculosis, such as rifampicin
• some medications to lowercholesterol, such as atorvastatin and simvastatin
• someimmunosuppressants, such as cyclosporine, tacrolimus, and sirolimus
• someanti-inflammatorymedications, such as dexamethasone and methylprednisolone
• some medications to treatHIV, such as ritonavir, amprenavir, indinavir, darunavir, delavirdine, efavirenz, fosamprenavir, lopinavir, nelfinavir, tipranavir, saquinavir, and atazanavir
• some medications used to relievepain, such as fentanyl or methadone
• medications to treatseizures(epileptic crises), such as phenytoin, phenobarbital, primidone, valproic acid, or carbamazepine
• antidepressants such as nefazodone and St. John's Wort (Hypericum perforatum).

• Consult your doctor, pharmacist, or nurseif you are taking any of these medications (or if you are unsure). Your doctor may consider adjusting your dose.

Keep a list of the medications you are taking to show to your doctor, pharmacist, or nurse.

Pregnancy, breastfeeding, and fertility

Tafinlar is not recommended during pregnancy.

• If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor, pharmacist, or nurse before using this medication. Tafinlar is not recommended during pregnancy, as it may harm the fetus.
• If you are a woman, and you may become pregnant, you must use a reliable method of birth control while taking Tafinlar and for 2weeks after stopping treatment and 16weeks after the last dose of trametinib when given in combination with Tafinlar.
• Birth control medications that contain hormones (such as the pill, injections, or patches) may not be as effective while taking Tafinlar or the combined treatment (Tafinlar and trametinib). While taking this medication, you need to use another effective method of birth control to avoid becoming pregnant. Consult your doctor, pharmacist, or nurse.
• If you become pregnant while taking this medication, consult your doctor immediately.

Tafinlar is not recommended during breastfeeding.

The components of this medication may pass into breast milk.

If you are breastfeeding, or plan to breastfeed, inform your doctor. You and your doctor will decide whether to take this medication or breastfeed.

Fertility – both men and women

Studies in animals have shown that the active substance dabrafenib can permanently reduce fertility in men. Men taking Tafinlar may also see a reduction in sperm count, and their sperm may not return to normal levels until they have stopped taking this medication.

Before starting treatment with Tafinlar, consult your doctor about options to improve your chances of having children in the future.

Taking Tafinlar with trametinib: trametinib may affect fertility in both men and women.

If you have any questions about the effects of this medication on sperm count, ask your doctor, pharmacist, or nurse.

Driving and operating machinery

Tafinlar may cause adverse effects that can affect your ability to drive or operate machinery.

Avoid driving or operating machinery if you experience vision problems or feel tired, weak, or lack energy.

The description of adverse effects can be found in sections2 and 4 of this prospectus.

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

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

How much to take

The recommended dose of Tafinlar, whether used alone or in combination with trametinib, is 2 capsules of 75 mg twice a day (which is equivalent to a daily dose of 300 mg). The recommended dose of trametinib, whether used alone or in combination with Tafinlar, is 2 mg once a day.

Your doctor will decide if you need to take a lower dose based on the side effects you have.

Tafinlar is also available in 50 mg capsules for those cases in which a dose reduction is recommended.

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

How to take it

Take the capsules whole, with water, one after the other.

Do not chew or break the capsules, as they will lose their effect.

Take Tafinlar twice a day, on an empty stomach. That is:

• Once you have taken Tafinlar, you must wait forat least 1 hourbefore eating.
• If you have eaten, you must waitfor at least 2 hoursbefore taking Tafinlar.

Take Tafinlar in the morning and at night, with a separation of about 12 hours. Take your morning and evening doses at the same time of day, every day. This will increase the likelihood that you will remember to take the capsules.

Do not take the morning and evening doses at the same time.

If you take more Tafinlar than you should

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

If you forget to take Tafinlar

If less than 6 hours have passed since the usual time when you should have taken Tafinlar, take it as soon as you remember.

If more than 6 hours have passed since the usual time when you should have taken Tafinlar, skip this dose and take the next one at your usual time. Then, continue taking the capsules at your usual times.

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

If you interrupt treatment with Tafinlar

Take Tafinlar for the time your doctor has recommended. Do not stop using it unless your doctor, pharmacist or nurse recommends it.

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

How to take Tafinlar in combination with trametinib

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

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

Severe possible side effects

Bleeding problems

Tafinlar can cause severe bleeding problems, especially in the brain when taken in combination with trametinib. Contact your doctor or nurse, and seek immediate medical attention if you experience unusual signs of bleeding, including:

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

Fever

More than 1 in 10 people who take Tafinlar may experience fever.If you have a fever while taking this medicine (a temperature of 38°C or higher) or if you have a sensation of fever, consult your doctor, pharmacist, or nurse immediately. They will perform tests to determine if there are other causes of the fever, and administer treatment.

In some cases, people who have fever may experience low blood pressure and dizziness. If the fever is severe, your doctor may recommend that you stop taking Tafinlar, or Tafinlar and trametinib, while they treat the fever with other medicines. Once the fever is controlled, your doctor will recommend that you start taking Tafinlar again.

Heart problems

Tafinlar can affect the functioning of your heartwhen taken in combination with trametinib. It is more likely to affect people with an existing heart problem. During treatment with Tafinlar in combination with trametinib, they will perform 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 they occur for the first time or if they worsen.

Skin changes

Severe skin reactions have been reported in people taking Tafinlar in combination with trametinib (frequency not known). If you notice any of the following:

• red circular or target-shaped patches on the trunk with central blisters. Skin peeling. Ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin reactions can be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome)
• generalized rash, fever, and swollen lymph nodes (DRESS or drug reaction with eosinophilia and systemic symptoms).

• Stop taking the medicine and seek medical attention immediately.

People taking Tafinlar may develop a type of skin cancer calledcutaneous squamous cell carcinoma (cuCCE)in up to 1 in 10 people. Others may develop a type of cancer calledbasal cell carcinoma (CBC). These changes usually only affect the skin locally and can be removed with surgery and continue treatment with Tafinlar without interruption.

Some people taking Tafinlar may notice that they have new melanomas. These melanomas are usually removed with surgery and treatment with Tafinlar can continue without interruption.

Your doctor will examine your skin before starting treatment with Tafinlar. Subsequently, your doctor will examine your skin monthly during treatment and for 6 months after treatment ends. The reason for these reviews is to look for new cancerous lesions.

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

Regularly review your skin while taking Tafinlar

If you notice any of the following:

• new warts
• skin lesions or red, swollen bumps that bleed or do not heal
• changes in the size or color of moles

• Consult your doctor, pharmacist, or nurse as soon as possiblewhether the symptoms appear for the first time or if they worsen.

You may experienceskin reactions (rash)while taking Tafinlar in combination with trametinib.Consult your doctorif you experience a skin rash while taking Tafinlar in combination with trametinib.

Eye problems

People taking Tafinlar alone may develop a rare eye condition called uveitis, which can damage your vision if left untreated. This can occur frequently (up to 1 in 10 people) in people taking Tafinlar in combination with trametinib.

The uveitis can develop rapidly, and symptoms include:

• redness and irritation of the eyes
• blurred vision
• eye pain
• increased sensitivity to light
• floaters

• Consult your doctor, pharmacist, or nurse immediatelyif you experience any of these symptoms.

Tafinlar can cause eye problems when taken in combination with trametinib. Trametinib is not recommended 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 Tafinlar in combination with trametinib and during treatment. Your doctor may ask you to stop taking trametinib or refer you to a specialist if you experience vision symptoms, including:

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

• Consult your doctor, pharmacist, or nurse immediately if you experience these symptoms.

It is very important to contact your doctor, pharmacist, or nurse immediately if you develop these symptoms,especially if you have eye pain and redness that do not improve quickly. In this case, you should see an eye specialist (ophthalmologist) for a complete eye examination.

Immune system disorders

If you experience several symptoms, such as fever, swollen lymph nodes, bruises, or skin rash at the same time, inform your doctor immediately. This 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 section2 (rare frequency).

Tumor lysis syndrome

Inform your doctor immediately if you experience the following symptoms: nausea, difficulty breathing, irregular heartbeats, muscle cramps, seizures, cloudy urine, decreased urine production, and fatigue. These may be signs of a condition resulting from rapid cell breakdown in some people, which can be fatal (tumor lysis syndrome or TLS), see section2 (unknown frequency).

Severe possible side effects in patients taking Tafinlar alone

Side effects that can be observed while taking Tafinlar alone:

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

• papilloma (a type of skin tumor that is usually harmless)

• decreased appetite
• headache
• cough
• nausea, feeling of dizziness (vomiting)
• diarrhea
• thickening of the outer layers of the skin
• unusual hair loss or fine hair
• skin rash
• redness and inflammation of the palms of the hands, fingers, and soles of the feet (see "Skin changes" in section4)
• joint pain, muscle pain, or pain in the hands or feet
• fever (see "Fever" in section4)
• lack of energy
• chills
• feeling weak

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

• skin effects, including skin cancer (squamous cell carcinoma), growths similar to warts, skin marks, lesions, or uncontrolled growths (basal cell carcinoma), dry skin, itching, or redness of the skin, patches of thickened skin, with scales or hardness (actinic keratosis), skin with lesions or redness, increased skin sensitivity to the sun
• constipation
• flu-like symptoms
• nerve problems that can cause pain, loss of sensation, or numbness in the hands and feet and/or muscle weakness (peripheral neuropathy)

Common side effects that can appear in blood tests

• low levels of phosphate in the blood (hypophosphatemia)
• high levels of sugar in the blood (hyperglycemia)

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

• new melanoma
• allergic reaction (hypersensitivity)
• inflammation of the eyes (uveitis, see "Eye problems" in section4)
• pancreatitis (inflammation of the pancreas that causes severe abdominal pain)
• panniculitis (inflammation of the fatty layer under the skin)
• kidney problems, kidney failure
• inflammation of the kidneys
• skin lesions that are painful, red, or purple, or sores that appear mainly on arms, legs, face, and neck, with fever (signs of acute febrile neutrophilic dermatosis)

Side effects when Tafinlar is taken with trametinib

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

You may also experiencenew side effects due to taking trametinib at the same time as Tafinlar, which are listed below.

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

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

The side effects that can be seen while taking Tafinlar in combination with trametinib are as follows:

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

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

Very common side effects that can appear in blood tests

• abnormal results in blood tests for liver function

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

• urinary tract infection
• skin effects, including skin infection (cellulitis), inflammation of hair follicles in the skin, changes in nails, such as changes in the nail bed, nail pain, skin infection, and inflammation of cuticles, skin eruptions with pus-filled blisters, skin cancer (squamous cell carcinoma), papilloma (a type of tumor that is usually harmless), warts, increased skin sensitivity to the sun (see also "Skin changes" in section4)
• dehydration (low water or fluid levels)
• blurred vision, eye problems, inflammation of the eye (uveitis)
• inefficient heart pumping
• low blood pressure (hypotension)
• localized swelling of tissues
• labored breathing
• dry mouth
• mouth ulcers or pain, inflammation of the mucosa
• acne-like symptoms
• thickening of the outer layer of the skin (hyperkeratosis), patches of thickened skin, with scales or hardness (actinic keratosis), dry skin, or skin cracks
• increased sweating, night sweats
• unusual hair loss or volume loss
• redness, pain in hands and feet
• panniculitis (inflammation of the fatty layer under the skin)
• inflammation of the mucosa
• swelling of the face
• nerve problems that can cause pain, loss of sensation, or numbness in the hands and feet and/or muscle weakness (peripheral neuropathy)
• irregular heartbeats (atrioventricular block)

Common side effects that can appear in blood tests

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

Rare side effects (can 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 (choroidopathy), 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
• slow heart rate and/or decreased heart rate
• inflammation of the lungs (pneumonitis)
• pancreatitis (inflammation of the pancreas)
• inflammation of the intestines (colitis)
• kidney failure
• inflammation of the kidneys
• sarcoidosis (inflammatory disease that mainly affects the skin, lungs, eyes, and lymph nodes)
• skin lesions that are painful, red, or purple, or sores that appear mainly on arms, legs, face, and neck, with fever (signs of acute febrile neutrophilic dermatosis)

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

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

Unknown frequency (cannot be estimated from available data)

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

Reporting side effects

If you experienceany type of side effect, consult your doctor, pharmacist, or nurse, even if it is apossibleside effect that does not appear in this prospectus.You can also report them directly throughthenational notification system included in theAppendixV.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

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

This medication does not require special storage conditions.

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

Composition of Tafinlar

• The active ingredient is dabrafenib. Each hard capsule containsmesylate ofdabrafenib, equivalent to 50mg or 75mg of dabrafenib.
• The other components are: microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide, red iron oxide (E-172), titanium dioxide (E-171), and hypromellose (E-464). Additionally, the capsules are printed with black ink containing black iron oxide (E-172), shellac, and propylene glycol.

Appearance of the product and contents of the pack

Tafinlar 50mg hard capsules are dark red opaque and are printed with “GS TEW” and “50mg”.

Tafinlar 75mg hard capsules are dark pink opaque and are printed with “GS LHF” and “75mg”.

The bottles are made of plastic, white opaque with plastic screw-top caps.

The bottles include a desiccant with silica gel in a small cylindrical container. This desiccant must be left inside the bottle and not ingested.

Tafinlar 50mg and 75mg hard capsules are available in packs containing 28 or 120capsules. Not all packs may be marketed in your country.

Marketing Authorization Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Responsible for manufacturing

Lek Pharmaceuticals d.d.

Verovskova ulica 57

1526, Ljubljana

Slovenia

Novartis Pharmaceutical Manufacturing LLC

Verovskova ulica 57

1000, Ljubljana

Slovenia

Novartis Pharma GmbH

Roonstraße 25

D-90429 Nuremberg

Germany

Glaxo Wellcome, S.A.

Avda.Extremadura, 3

09400 Aranda de Duero

Burgos

Spain

Novartis Farmacéutica S.A.

Gran Via de les Corts Catalanes 764

08013 Barcelona

Spain

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

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

Last revision date of this leaflet:

Other sources of information

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

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