Tafinlar 50 mg hard capsules

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Tafinlar® 50 mg hard capsules

Tafinlar® 75 mg hard capsules

dabrafenib

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Tafinlar is and what it is used for

Tafinlar is a medicine that contains the active substance dabrafenib. It is used alone or in combination with another medicine containing 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 may also be used to prevent the recurrence of melanoma after it has been surgically removed.

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 gene mutation may have caused the cancer to develop. This medicine acts on the proteins produced by the mutated BRAF gene and slows down or stops the progression of the cancer.

2. What you need to know before taking Tafinlar

Tafinlar can only be used to treat melanomas and non-small cell lung cancer (NSCLC) with a mutation in the BRAF gene.

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

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

If you have further questions about using this medicine, ask your doctor, pharmacist, or nurse.

Do not take Tafinlar

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

If you think this applies to you, consult 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.

While you are being treated with Tafinlar, your doctor may need to take blood samples to check how well your liver and kidneys are working.

• you have had or have ever had another type of cancer other than melanoma or NSCLC, as you may be at higher risk of developing other skin 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 your heartbeat.
• If you have eye problems, such as blockage of the veins supplying the eye (retinal vein occlusion) or swelling in the eye that may be due to fluid blockage (chorioretinopathy).
• If you have or have ever had breathing or lung problems, such as frequent shortness of breath often accompanied by dry cough, labored breathing, 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 doctor if you think any of the above conditions apply to you.

Conditions you need to be aware of

Some people taking Tafinlar develop other illnesses that may be serious. You need to know which signs and symptoms to watch for while taking this medicine. This section briefly mentions some of these symptoms (bleeding, fever, skin changes, and eye problems), but more detailed information can be found in section 4, “Possible side effects”.

Bleeding

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

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

Tell your doctor as soon as possible if you experience any of these symptoms.

Fever

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

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

Heart problems

Tafinlar may cause heart problems or worsen existing heart conditions (see section 4 “Heart conditions”) in people taking Tafinlar with trametinib.

Tell your doctor if you have any heart problems. Before and during treatment with Tafinlar in combination with trametinib, your doctor will perform tests to check that your heart is functioning properly. Contact your doctor immediately if you feel your heart beating strongly, your heart racing, or beating irregularly, or if you feel dizzy, tired, lightheaded, short of breath, or have swelling in your legs. If necessary, your doctor may decide to interrupt or stop treatment.

Skin changes that may indicate a new skin cancer

Your doctor will examine your skin before starting treatment with this medicine and regularly during treatment.

Contact your doctor immediately if 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.

Contact your doctor immediately if you experience redness or 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 may cause eye problems, including blindness. Trametinib is not recommended if you have ever had a blockage in the veins draining the eyes (retinal vein occlusion). Inform your doctor immediately if you experience any of the following eye-related symptoms during treatment: blurred vision, loss of vision, or other changes in vision, seeing colored spots 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 disturbances in section 4 of this leaflet. Inform your doctor, pharmacist, or nurse if you experience any of these signs or symptoms.

Liver problems

Tafinlar in combination with trametinib may cause liver problems that could lead to conditions such as hepatitis or liver failure, which may be fatal. Your doctor will monitor you periodically. Signs that your liver is not working properly include:

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

Tell your doctor as soon as possible if you experience any of these symptoms.

Muscle pain

Tafinlar in combination with trametinib may cause muscle damage (rhabdomyolysis). Tell your doctor as soon as possible if you experience any of the following symptoms:

• muscle pain
• dark urine due to kidney damage

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

Perforation of the stomach or intestine

Taking the combination of Tafinlar and trametinib may increase the risk of developing a perforation in the intestinal wall. If you experience severe abdominal pain, tell your doctor as soon as possible.

Severe skin reactions

Severe skin reactions have been reported in people taking Tafinlar in combination with trametinib. Inform your doctor immediately if you notice any changes in your skin (see section 4 for symptoms to watch for).

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

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

Immune system disorders

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

Tumor lysis syndrome

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

Children and adolescents

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

Other medicines and Tafinlar

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

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

• hormonal contraceptives, such as birth control pills, injections, or patches

• warfarin and acenocoumarol, medicines used to make the blood thinner

• digoxin, used to treat heart conditions

• 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 fats (lipids), such as gemfibrozil

• some medicines used to treat certain psychiatric disorders, such as haloperidol

• some antibiotics, such as clarithromycin, doxycycline, and telithromycin

• some medicines used for tuberculosis, such as rifampicin

• some medicines to lower cholesterol, such as atorvastatin and simvastatin

• some immunosuppressants, such as cyclosporine, tacrolimus, and sirolimus

• some anti-inflammatory medicines, such as dexamethasone and methylprednisolone

• some medicines used 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 seizures), such as phenytoin, phenobarbital, primidone, valproic acid, or carbamazepine

• antidepressants, such as nefazodone, and St. John’s wort (Hypericum perforatum)

• Talk to your doctor, pharmacist, or nurse if you are taking any of these medicines (or if you are unsure). Your doctor may consider adjusting your dose.

Keep a list of all 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 using this medicine. Tafinlar is not recommended during pregnancy, as it may harm the unborn baby.
• If you are a woman who could become pregnant, you must use a reliable method of contraception while taking Tafinlar and for 2 weeks after stopping treatment, and for 16 weeks after the last dose of trametinib when used in combination with Tafinlar.
• Hormonal contraceptives (such as birth control pills, injections, or patches) may not be as effective while taking Tafinlar or the combination treatment (Tafinlar and trametinib). Therefore, while taking this medicine, you need to use another effective method of contraception to prevent pregnancy. Consult your doctor, pharmacist, or nurse.
• If you become pregnant while taking this medicine, contact your doctor immediately.

Tafinlar is not recommended during breastfeeding

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

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

Fertility – both men and women

Animal studies have shown that the active substance dabrafenib may permanently reduce fertility in men. Also, men taking Tafinlar may experience reduced sperm count, and sperm levels may not return to normal until after stopping the medicine.

Before starting treatment with Tafinlar, consult your doctor about options to preserve fertility for future parenthood.

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

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

Driving and using machines

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

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

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

If you are unsure, talk to your doctor, pharmacist, or nurse. Your ability to drive and use machines may be affected even by the disease itself, its symptoms, or the treatment.

3. How to take Tafinlar

Follow exactly the instructions for using this medicine given by your doctor, pharmacist, or nurse. If in 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 daily (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 daily.

Your doctor will decide if you need to take a lower dose depending on any side effects you may experience.

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

Do not take more Tafinlar than your doctor has recommended, as this may 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 daily on an empty stomach. This means:

• You must wait at least 1 hour after taking Tafinlar before eating.
• If you have eaten, you must wait at least 2 hours before taking Tafinlar.

Take Tafinlar in the morning and at night, approximately 12 hours apart. Take your morning and evening doses at the same time each day. This will help you remember to take the capsules.

Do not take the morning and evening doses together.

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 time you were supposed to take Tafinlar, take it as soon as you remember.

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

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

If you stop taking Tafinlar

Take Tafinlar for as long as your doctor has recommended. Do not stop using it unless your doctor, pharmacist, or nurse advises you to do so.

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

How to take Tafinlar in combination with trametinib

• Take Tafinlar in combination with trametinib exactly as instructed by your doctor, pharmacist, or nurse. Do not change the dose or stop taking Tafinlar or trametinib unless your doctor, pharmacist, or nurse tells you to.
• Take Tafinlar twice daily and trametinib once daily. It may be helpful for you to take both medicines at the same time each day. The two Tafinlar doses should be taken approximately 12 hours apart. When trametinib is taken in combination with Tafinlar, it may be taken either with the morning dose of Tafinlar or with the evening dose of Tafinlar.
• Take Tafinlar and trametinib on an empty stomach, at least 1 hour before or 2 hours after a meal. Swallow the capsules and tablets whole with a full glass of water.
• If you miss a dose of Tafinlar or trametinib, take it as soon as you remember. Do not make up for the missed dose; take the next dose at the scheduled time:
  • If less than 6 hours remain until the next Tafinlar dose (taken twice daily).
  • If less than 12 hours remain until the next trametinib dose (taken once daily).
• If you take more Tafinlar or trametinib than you should, contact your doctor, pharmacist, or nurse immediately. Bring the Tafinlar capsules and trametinib tablets with you, if possible. If possible, show the Tafinlar and trametinib packaging with the leaflet.
• If you experience side effects, your doctor may decide to prescribe a lower dose of Tafinlar and trametinib. Take the doses of Tafinlar and trametinib exactly as instructed by your doctor, pharmacist, or nurse.

4. Possible adverse effects

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

Serious possible 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 vomit that looks like “coffee grounds”
• red stools or black, tarry-looking stools.

Fever

More than 1 in 10 people taking Tafinlar may develop fever. If you develop a fever while taking this medicine (temperature of 38°C or higher) or feel feverish, contact your doctor, pharmacist or nurse immediately. You will be tested to determine whether there are other possible causes of the fever, and you will be given treatment.

In some cases, people with fever may experience low blood pressure and dizziness. If the fever is severe, your doctor may recommend that you stop taking Tafinlar, or both Tafinlar and trametinib, while you are treated for the fever with other medicines. Once the fever is under control, your doctor will advise you to restart Tafinlar.

Heart conditions

Tafinlar may affect heart function when taken in combination with trametinib. This is more likely in people who already have an existing heart condition. During treatment with Tafinlar in combination with trametinib, you will undergo heart tests. Signs and symptoms related to heart problems include:

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

If you experience any of these symptoms, inform your doctor as soon as possible, whether you are experiencing them for the first time or if you think they are worsening.

Skin changes

Severe skin reactions have been reported in people taking Tafinlar in combination with trametinib (frequency unknown). If you notice any of the following:

• red spots on the trunk that are circular or target-shaped, with central blisters. Skin peeling. Mouth, throat, nose, genital, or eye ulcers. These severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome)

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

• Stop taking the medicine and seek immediate medical attention.

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

Some people taking Tafinlar may develop new melanomas. These melanomas are usually removed surgically, and treatment with Tafinlar can continue without interruption.

Your doctor will examine your skin before starting treatment with Tafinlar. Afterwards, your doctor will examine your skin monthly throughout treatment and for 6 months after treatment ends. These examinations are performed to detect new cancerous lesions.

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

Check your skin regularly while taking Tafinlar

If you notice any of the following:

• new warts

• skin sores or red, raised bumps that bleed or do not heal

• changes in the size or color of moles

• Contact your doctor, pharmacist, or nurse as soon as possible, whether symptoms are new or worsening.

You may develop skin reactions (rash) while taking Tafinlar in combination with trametinib. Contact your doctor if you develop a skin rash while taking Tafinlar with trametinib.

Eye problems

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

Uveitis can develop rapidly, and symptoms include:

• redness and irritation of the eyes

• blurred vision

• eye pain

• increased sensitivity to light

• floating spots

• Contact your doctor, pharmacist, or nurse immediately if you experience any of these symptoms.

Tafinlar may cause eye problems when taken in combination with trametinib. Trametinib is not recommended if you have ever had a blockage in the veins draining the eyes (retinal vein occlusion). Your doctor will advise you to have an eye 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 or symptoms affecting vision, including:

• loss of vision

• redness and irritation in the eyes

• seeing colored spots

• seeing halos (blurred vision around objects)

• blurred vision

• Contact your doctor, pharmacist, or nurse immediately if these symptoms occur.

It is very important that you 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 such cases, you should see a specialist (ophthalmologist) for a complete eye examination.

Immune system disorders

If you experience several symptoms at once, such as fever, swollen lymph nodes, bruising, or skin rash, 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 section 2 (rare frequency).

Tumour lysis syndrome

Inform your doctor immediately if you experience the following symptoms: nausea, difficulty breathing, irregular heartbeat, muscle cramps, seizures, cloudy urine, reduced urine output, and fatigue. These may be signs of a condition caused by the rapid breakdown of cancer cells, which can be fatal in some people (tumour lysis syndrome or TLS); see section 2 (frequency not known).

Possible adverse effects in patients taking Tafinlar alone

Adverse effects that may occur while taking Tafinlar alone:

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

• papilloma (a type of skin tumour that is usually not harmful)
• decreased appetite
• headache
• cough
• feeling sick (nausea), discomfort (vomiting)
• diarrhoea
• 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 weak

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

• skin effects including skin squamous cell carcinoma (a type of skin cancer), wart-like growths, skin marks, uncontrolled skin lesions or growths (basal cell carcinoma), dry skin, itchy or red skin, thickened, scaly, or hardened skin patches (actinic keratosis), skin lesions or redness, increased skin sensitivity to sunlight
• constipation
• flu-like symptoms
• nerve problems that may cause pain, loss of sensation, or tingling in the hands and feet and/or muscle weakness (peripheral neuropathy)

Common adverse effects that may appear in blood tests

• low levels of phosphate in the blood (hypophosphataemia)
• increased blood sugar levels (hyperglycaemia)

Uncommon adverse effects (may affect up to 1 in 100 people)

• new melanoma
• allergic reaction (hypersensitivity)
• eye inflammation (uveitis, see “Eye changes” in section 4)
• inflammation of the pancreas (causing severe abdominal pain)
• inflammation of the fat layer under the skin (panniculitis)
• kidney problems, kidney failure
• kidney inflammation
• raised, painful, red to dark purple skin spots or sores, mainly appearing on 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 previously listed adverse effects, although their frequency may change (increase or decrease).

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

Inform your doctor as soon as possible if you notice symptoms, whether they are new or worsening.

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

The adverse effects that may occur 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 various parts of the body, which may be mild or severe (haemorrhage)
• cough
• stomach pain
• constipation
• diarrhoea
• feeling sick (nausea), discomfort (vomiting)
• 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 oedema)
• fever
• flu-like symptoms

Very common adverse effects that may appear in blood tests

• abnormal liver function test results in blood

Common (may affect up to 1 in 10 people)

• urinary tract infection
• skin effects including skin infection (cellulitis), inflammation of hair follicles in the skin, nail disorders such as changes in the nail bed, nail pain, infection and inflammation of the cuticles, blistering skin rashes with pus, skin squamous cell carcinoma (a type of skin cancer), papilloma (a type of tumour usually not harmful), wart growth, increased skin sensitivity to sunlight (see also “Skin changes” in section 4)
• dehydration (low levels of water or fluids)
• blurred vision, vision problems, eye inflammation (uveitis)
• less efficient heart pumping
• low blood pressure (hypotension)
• localized swelling of tissues
• shortness of breath
• dry mouth
• mouth ulcers or pain, mucosal inflammation
• acne-like problems
• thickening of the outer layer of skin (hyperkeratosis), thickened, scaly, or hardened skin patches (actinic keratosis), cracked or fissured skin
• increased sweating, night sweats
• unusual hair loss or thinning
• redness, pain in hands and feet
• inflammation of the fat layer under the skin (panniculitis)
• mucosal inflammation
• facial swelling
• nerve problems that may cause pain, loss of sensation, or tingling in the hands and feet and/or muscle weakness (peripheral neuropathy)
• irregular heartbeat (atrioventricular block)

Common adverse effects that may appear in blood tests

• low levels of white blood cells
• decreased red blood cells (anaemia), platelets in blood (cells that help blood to clot), and a type of white blood cells (leucopenia)
• low levels of sodium (hyponatraemia) or phosphate (hypophosphataemia) in blood
• increased blood sugar levels
• increased creatine phosphokinase, an enzyme mainly found in the heart, brain, and skeletal muscle
• increased levels of certain substances (enzymes) produced by the liver

Uncommon adverse effects (may affect up to 1 in 100 people)

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

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

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

Frequency not known (cannot be estimated from available data)

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

Reporting of adverse effects

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

5. Storage of Tafinlar

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

Do not use this medicine after the expiry date stated on the label of the bottle and on the outer packaging, following the abbreviation EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

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

6. Contents of the pack and other information

Composition of Tafinlar

• The active substance 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, iron oxide red (E-172), titanium dioxide (E-171), and hypromellose (E-464). In addition, the capsules are printed with black ink containing black iron oxide (E-172), shellac, and propylene glycol.

Nature of the product and pack contents

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

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

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

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

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

Marketing Authorisation 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 Nuremberg
Germany

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

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

Date of the most recent review of this leaflet:

Other sources of information

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

This leaflet can be found on the European Medicines Agency website in all languages of the European Union/European Economic Area.