TAFINLAR 50 mg hard capsules

Introduction

Package Leaflet: Information for the Patient

Tafinlar®50mg hard capsules

Tafinlar®75mg hard capsules

dabrafenib

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Tafinlar and what is it used for

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

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

2. What you need to know before you take Tafinlar

Tafinlar can only be used to treat melanomas and NSCLC with a mutation in the BRAF gene.

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

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

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

Do not take Tafinlar

• if you are allergicto dabrafenib or any of the other ingredients of this medicine (listed in section 6).

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

Warnings and precautions

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

• you have liver problems.
• you have or have ever had kidney problems.

You may need to have blood tests while taking Tafinlar to check how well your liver and kidneys are working.

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

Before taking Tafinlar in combination with trametinib, your doctor needs to 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 veins that supply the eye (retinal vein occlusion) or swelling of the eye that may be due to a blockage of fluid (chorioretinopathy).
• If you have or have ever had breathing or lung problems, such as difficulty breathing, often accompanied by a 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.

Talk to your doctorif you think any of these conditions apply to you.

Diseases to be aware of

Some people taking Tafinlar develop other diseases that can be serious. You need to know what signs and symptoms to look out for while taking this medicine. In this section, some of these symptoms (bleeding, fever, skin changes, and eye problems) are mentioned briefly, but you will find more detailed information in section 4, “Possible side effects”.

Bleeding

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

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

Tell 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 section 4). In some cases, people with fever develop low blood pressure, dizziness, and other symptoms.

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

Heart problems

Tafinlar can cause heart problems or make existing heart problems worse (see section 4 “Heart problems”) in people taking Tafinlar with trametinib.

Tell your doctor if you have 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. Tell your doctor immediately if you feel your heart beating strongly, rapidly, or irregularly, if you feel dizzy, tired, faint, short of breath, or if your legs swell. If necessary, your doctor may decide to interrupt or stop treatment.

Skin changes that may indicate a new skin cancer

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

Consult your doctor immediatelyif you notice any changes in your skin while taking this medicine or after treatment (see also section 4).

Eye problems

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

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 a blockage in the veins that drain the eyes (retinal vein occlusion). Tell your doctor immediately if you experience any of the following symptoms related to eye problems during treatment: blurred vision, loss of vision, or other changes in vision, if you see colored dots or halos (blurred vision around objects). If necessary, your doctor may decide to interrupt or stop treatment.

• Read the information about fever, skin changes, and eye problems in section 4 of this leaflet. Tell your doctor, pharmacist, or nurse if you have any of these signs or symptoms.

Liver problems

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

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

Tell your doctor as soon as possibleif you experience these symptoms

Muscle pain

Tafinlar in combination with trametinib can cause muscle damage (rhabdomyolysis). Tell your doctor as soon as possibleif you notice any of these symptoms:

• muscle pain
• dark urine due to kidney damage

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

Perforation of the stomach or intestine

Taking the combination of Tafinlar and trametinib can increase the risk of developing a hole in the wall of the intestine. If you feel severe abdominal pain tell your doctor as soon as possible.

Severe skin reactions

Severe skin reactions have been reported in people taking Tafinlar in combination with trametinib. Tell your doctor immediatelyif you notice any changes in your skin (see section 4 for the symptoms to look out for).

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

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

Immune system disorders

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

Tumor lysis syndrome

If you experience the following symptoms, tell your doctor immediately, as it may be a life-threatening condition: nausea, difficulty breathing, irregular heartbeat, muscle cramps, seizures, 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 can cause changes in kidney function (see also section 4).

Children and adolescents

Tafinlar is not recommended in children and adolescents. The effects of Tafinlar in people under 18 years of age are not known.

Other medicines and Tafinlar

Before starting treatment, tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines. This includes medicines obtained without a prescription.

Some medicines may affect the way Tafinlar works, or make it more likely that you will have side effects. Tafinlar may also affect the way other medicines work. These include:

• birth control medicines(contraceptives) that contain hormones, such as the pill, injections, or patches
• warfarin and acenocoumarol, medicines used to make the blood more fluid
• digoxin, used to treat heart disease
• medicines to treat fungal infections, such as ketoconazole, itraconazole, voriconazole, and posaconazole
• some calcium channel blockers, used to treat high blood pressure, such as diltiazem, felodipine, nicardipine, nifedipine, or verapamil
• medicines to treat cancer, such as cabazitaxel
• some medicines that lower blood fat(lipids) levels, such as gemfibrozil
• some medicines to treat certain psychiatric disorders, such as haloperidol
• some antibiotics, such as clarithromycin, doxycycline, and telithromycin
• some medicines used to treat tuberculosis, such as rifampicin
• some medicines to lower cholesterollevels, such as atorvastatin and simvastatin
• some immunosuppressantmedicines, such as cyclosporin, tacrolimus, and sirolimus
• some anti-inflammatorymedicines, such as dexamethasone and methylprednisolone
• some medicines to treat HIV, such as ritonavir, amprenavir, indinavir, darunavir, delavirdine, efavirenz, fosamprenavir, lopinavir, nelfinavir, tipranavir, saquinavir, and atazanavir
• some medicines used for pain relief, such as fentanyl or methadone
• medicines to treat seizures(epileptic fits), such as phenytoin, phenobarbital, primidone, valproic acid, or carbamazepine
• medicines antidepressantssuch as nefazodone and St. John's Wort (Hypericum perforatum).

• Talk to your doctor, pharmacist, or nurseif you are taking any of these medicines (or if you are not sure). Your doctor may consider adjusting your dose.

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

Pregnancy, breastfeeding, and fertility

Tafinlar is not recommended during pregnancy.

• If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor, pharmacist, or nurse before taking this medicine. Tafinlar is not recommended during pregnancy, as it may harm the unborn baby.
• If you are a woman and can become pregnant, you must use a reliable method of birth control while taking Tafinlar and for 2 weeks after finishing treatment and 16 weeks after the last dose of trametinib when given in combination with Tafinlar.
• Hormonal birth control methods (such as the pill, injections, or patches) may not be as effective when taking Tafinlar or the combination treatment (Tafinlar and trametinib). Therefore, while taking this medicine, you need to use another effective birth control method to avoid becoming pregnant. Consult your doctor, pharmacist, or nurse.
• If you become pregnant while taking this medicine, consult your doctor immediately.

Tafinlar is not recommended during breastfeeding

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

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

Fertility – both men and women

Studies in animals have shown that the active substance dabrafenib can permanently reduce fertility in men. Also, men taking Tafinlar may have reduced sperm count and it may not return to normal levels until after they have stopped taking this medicine.

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 further questions on the effects of this medicine on sperm count, ask your doctor, pharmacist, or nurse.

Driving and using machines

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

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

The description of side effects can be found in sections 2 and 4 of this leaflet.

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

3. How to take Tafinlar

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 adverse effects you have.

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

Do not take more Tafinlar than your doctor has recommended, as this may increase the risk of having adverse 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 at least 1hourbefore eating.
at least 2hoursbefore taking Tafinlar.

Take Tafinlar in the morning and at night, with a separation of about 12 hours. Take your morning and night 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 night 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 you should have taken Tafinlar, take it as soon as you remember.

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

Do not take a double dose to make up for forgotten 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 questions 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 indicates it.
• Take Tafinlar twice a dayand take trametinib once a day. It would be good for you to have the habit of taking the two medications together every day. The doses of Tafinlar should be taken with a difference of 12 hours. Trametinib, when taken in combination with Tafinlar, can be taken eitherwith the morning dose of Tafinlar orwith 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 make up for the forgotten dose and take the next dose when it is due:
• • If there are less than 6 hours left until the next dose of Tafinlar, which is taken twice a day.
  • If there are less than 12 hours left 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 and trametinib packaging with the leaflet.
• If you experience adverse 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.

4. Possible Adverse Effects

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

Possible Serious Adverse Effects

Bleeding Problems

Tafinlar may cause serious 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 your vomit looks like "coffee grounds"
• having red or black stools that look like tar

Fever

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

In some cases, people with fever may have 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 under control, your doctor will recommend that you start taking Tafinlar again.

Heart Conditions

Tafinlar may affect your heart function when taken in combination with trametinib. It is more likely to affect people with existing heart problems. During treatment with Tafinlar in combination with trametinib, you will undergo heart tests. Among the signs and symptoms related to heart problems are:

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

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

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

• Stop taking the medicine and seek immediate medical attention.

Patients taking Tafinlar may frequently develop (may affect up to 1 in 10 people) a different type of skin cancer called Squamous Cell Carcinoma (SCC). Others may develop a type of cancer called Basal Cell Carcinoma (BCC). Usually, these changes only affect the skin locally and can be removed with surgery and continue treatment with Tafinlar without needing to interrupt it.

Some people taking Tafinlar may notice that they have new melanomas. These melanomas are usually removed by surgery and treatment with Tafinlar can continue without needing to be interrupted.

Your doctor will examine your skin before starting treatment with Tafinlar. Then, your doctor will examine your skin monthly throughout 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 will regularly perform a scanner (Computed Tomography) of the chest and abdominal area. You may also have blood tests. These reviews are to detect if you have developed other cancers, including squamous cell carcinoma. It is recommended that both at the beginning and end of treatment, a pelvic exam (in women) and anal exam be performed.

Regularly Check Your Skin While Taking Tafinlar

If you notice any of the following:

• new warts
• skin ulcers or red 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 experience skin reactions (rash)while taking Tafinlar in combination with trametinib. Consult your doctorif you experience a skin rash while taking Tafinlar in combination with trametinib.

Eyelid Problems

Patients taking Tafinlar alone may infrequently develop (may affect up to 1 in 100 people) an eye disorder called uveitis, which if left untreated can damage your vision. This can occur frequently (may affect up to 1 in 10 people) in patients taking Tafinlar in combination with trametinib.

Uveitis can develop quickly, 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 have any of these symptoms.

Tafinlar may cause eye problems when taken in combination with trametinib. It is not recommended to take trametinib 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 signs and symptoms in your vision, including:

• vision loss
• redness and irritation in the eyes
• seeing colored dots
• seeing a halo (blurred vision around objects)
• blurred vision

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

especially if you have eye pain and redness that do not improve quickly. In this case, you should see a specialist (ophthalmologist) for a complete eye exam.

Immune System Disorders

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

Tumor Lysis Syndrome

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

Possible Adverse Effects in Patients Taking Tafinlar Alone

Adverse Effects That May Be Observed While Taking Tafinlar Alone:

Very Common Adverse Effects (May Affect More Than 1 in 10 People)

• papilloma (a type of non-cancerous skin tumor)

• decreased appetite
• headache
• cough
• feeling of nausea (nausea), discomfort (vomiting)
• diarrhea
• thickening of the outer layers of the skin
• unusual hair loss or thinning hair
• rash
• redness and inflammation of the palms of the hands, fingers, and soles of the feet (see "Skin Changes" in section 4)
• joint pain, muscle pain, or pain in the hands or feet
• fever (see "Fever" in section 4)
• lack of energy
• chills
• feeling of weakness

Common Adverse Effects (May Affect Up to 1 in 10 People)

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

Common Adverse Effects That May Appear in Blood Tests

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

Uncommon Adverse Effects (May Affect Up to 1 in 100 People)

• new melanoma
• allergic reaction (hypersensitivity)
• eye inflammation (uveitis, see "Eye Disorders" in section 4)
• pancreatitis (which causes severe abdominal pain)
• inflammation of the fatty layer under the skin (panniculitis)
• kidney problems, kidney failure
• kidney inflammation
• red, purple, or painful skin patches, or ulcers that appear mainly on the arms, legs, face, and neck, with fever (signs of acute febrile neutrophilic dermatosis)

Adverse Effects When Tafinlar is Taken with Trametinib

When Tafinlar is taken with trametinib, you may experience any of the adverse effects mentioned earlier, although their frequency may change (increase or decrease)

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

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

Read the trametinib package insert for more details on adverse effects that may appear while taking trametinib.

The adverse effects that may be seen while taking Tafinlar in combination with trametinib are:

Very Common Adverse Effects (May Affect More Than 1 in 10 People)

• inflammation of the nose and throat
• decreased appetite
• headache
• dizziness
• high blood pressure (hypertension)
• bleeding, in different parts of the body, which can be mild or severe (hemorrhage)
• cough
• stomach pain
• constipation
• diarrhea
• feeling of nausea (nausea), discomfort (vomiting)
• rash, dry skin, itching, or 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 Adverse Effects That May Appear in Blood Tests

• abnormal liver blood test results

Common Adverse Effects (May Affect Up to 1 in 10 People)

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

Common Adverse Effects That May Appear in Blood Tests

• low white blood cell count
• decreased red blood cells (anemia), blood platelets (cells that help blood clot), and a type of white blood cell (leukopenia)
• low sodium (hyponatremia) or phosphate (hypophosphatemia) levels in the blood
• high 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)

• new skin cancer (melanoma)
• skin marks
• allergic reactions (hypersensitivity)
• eye changes, such as swelling due to fluid accumulation (chorioretinopathy), separation of the light-sensitive membrane in the back of the eye (retina) from its supporting layers (retinal detachment), and swelling around the eyes
• abnormally slow heart rate and/or decreased heart rate
• lung inflammation (pneumonitis)
• pancreatitis
• inflammation of the intestines (colitis)
• kidney failure
• kidney inflammation
• inflammatory disease that mainly affects the skin, lungs, eyes, and lymph nodes (sarcoidosis)
• red, purple, or painful skin patches, or ulcers that appear mainly on the arms, legs, face, and neck, with fever (signs of acute febrile neutrophilic dermatosis)

Rare Adverse Effects (May Affect Up to 1 in 1,000 People):

• a hole (perforation) in the stomach or intestine 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 (exfoliative dermatitis)

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this package insert. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Tafinlar

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

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

This medicine does not require special storage conditions.

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

6. Package Contents and Additional Information

Tafinlar Composition

• The active ingredient is dabrafenib. Each hard capsule contains dabrafenib mesylate, equivalent to 50 mg or 75 mg 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.

Product Appearance and Package Contents

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

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

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

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

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

Marketing Authorization Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Manufacturer

Lek Pharmaceuticals d.d.

Verovskova ulica 57

1526, Ljubljana

Slovenia

Novartis Pharmaceutical Manufacturing LLC

Verovskova ulica 57

1000, Ljubljana

Slovenia

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

Date of Last Revision of this Leaflet:

Other Sources of Information

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

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