Tafinlar: detailed information

Package leaflet: Information for the patient

Tafinlar 50 mg hard capsules, 75 mg hard capsules

dabrafenib
Please read all of this leaflet carefully before 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. Do not pass it on to other people, even if they have the same symptoms as you, because it may be harmful to them.
If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

What Tafinlar is and what it is used for
What you need to know before taking Tafinlar
How to take Tafinlar
Possible side effects
How to store Tafinlar
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 is also used to prevent recurrence of melanoma following surgical removal.
Tafinlar in combination with trametinib is also used to treat a type of lung cancer called non-small cell lung cancer (NSCLC).
Both cancers have a specific alteration (mutation) in a gene called BRAF at position V600. This gene mutation may have caused the development of the cancer. This medicine targets the proteins produced by this mutated BRAF gene and slows down or stops the growth of the cancer.

2. What you should know before taking Tafinlar

Tafinlar should only be used to treat BRAF-mutated melanomas and NSCLC. Therefore,
before starting treatment, your doctor will check for the presence of this mutation.
If your doctor decides that you should receive combination therapy with Tafinlar and trametinib, please read
the patient information leaflet for trametinib and this leaflet carefully.
If you have further questions about using this medicine, consult your doctor, pharmacist, or
nurse.
Do not take Tafinlar:

if you are allergic to dabrafenib or any of the other ingredients of this medicine (listed in section 6). Check with your doctor if you think this applies to you.

Warnings and precautions
Talk to your doctor before taking Tafinlar. Your doctor needs to know if:

you have any liver problems.
you have or have had any kidney problems. Your doctor may take blood samples to monitor liver and kidney function while you are taking Tafinlar.
you have had types of cancer other than melanoma or NSCLC, as you may be at increased risk of developing other skin and non-skin tumours while taking Tafinlar.
you are currently undergoing or are about to receive radiotherapy treatment, as Tafinlar may worsen side effects (also see “If you have recently received radiotherapy” in section 4).

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

you have heart problems such as heart failure or irregular heartbeat.
you have eye problems, including blockage of the vein draining the eye (retinal vein occlusion) or swelling of the eye that may be caused by fluid leakage (chorioretinopathy).
you have lung or breathing problems, including difficulty breathing often accompanied by dry cough, shortness of breath, and fatigue.
you have or have had gastrointestinal problems such as diverticulitis (inflamed pouches in the colon) or metastases in the gastrointestinal tract.

Check with your doctor if you think any of these conditions may apply to you.
Conditions requiring caution
Some people taking Tafinlar develop other conditions that may be serious. You
should be aware of the important signs and symptoms to watch for while taking
this medicine. Some of these symptoms (bleeding, fever, skin changes, and eye problems) are briefly mentioned in this section, but more detailed information can be found in section 4, ‘Possible side effects’.
Bleeding
Taking Tafinlar in combination with trametinib may cause severe bleeding, including bleeding in the brain, gastrointestinal tract (such as stomach, rectum, or intestine), lungs, and other organs, which may be fatal. Symptoms may include:

headache, dizziness, or feeling weak
blood in stools or black stools
blood in urine
stomach pain
coughing or vomiting blood

Inform your doctor as soon as possible if you experience any of these symptoms.
Fever
Taking Tafinlar or the combination of Tafinlar and trametinib may cause fever, although fever is more likely when taking the combination therapy (see also section 4). In some cases, people with fever may develop low blood pressure, dizziness, or other symptoms.
Inform your doctor immediately if you develop a fever above 38°C or feel feverish while taking this medicine.
Heart problems
Tafinlar may cause heart problems or worsen existing heart conditions (see also ‘Heart conditions’ in section 4) in people taking Tafinlar in combination with trametinib.
Inform your doctor if you have a heart condition. Your doctor will perform tests to check that your heart is functioning properly before and during treatment with Tafinlar in combination with trametinib.
Inform your doctor immediately if you feel your heart beating strongly, rapidly, or irregularly, or if you experience dizziness, fatigue, vertigo, shortness of breath, or swelling in your legs. If necessary, your doctor may decide to temporarily suspend or permanently discontinue treatment.
Skin changes that may indicate a new skin cancer
Your doctor will examine your skin before starting this medicine and regularly during treatment.
Inform your doctor immediately if you notice any skin changes while taking this medicine or after treatment (see also section 4).
Eye problems
An eye examination by your doctor is required while taking this medicine.
Inform your doctor immediately if you experience redness and irritation of the eyes, blurred vision, eye pain, or other vision changes during treatment (see also section 4).
Tafinlar, when taken in combination with trametinib, may cause eye problems including blindness. Tafinlar is not recommended if you have had a blockage of the vein draining the eye (retinal vein occlusion). Inform your doctor immediately if you experience any of the following symptoms of eye problems: blurred vision, loss of vision or other vision changes, coloured spots in your vision, or halos (blurred edges around objects) during treatment. If necessary, your doctor may decide to suspend or discontinue treatment.
➔ Read the information on fever, skin changes, and eye problems in section 4 of this leaflet. Inform your doctor, pharmacist, or nurse if you experience any of the listed signs or symptoms.
Liver problems
Tafinlar in combination with trametinib may cause liver problems that can progress to serious conditions such as hepatitis and liver failure, which may be fatal. Your doctor will monitor you periodically. Signs that your liver may not be working properly include:

loss of appetite
nausea
vomiting
stomach (abdominal) pain
yellowing of the skin or whites of the eyes (jaundice)
dark-coloured urine
skin itching

Inform your doctor as soon as possible if you experience any of these symptoms.
Muscle pain
Tafinlar in combination with trametinib may cause muscle breakdown (rhabdomyolysis). Inform your doctor as soon as possible if you experience any of the following symptoms:

muscle pain
dark-coloured urine due to kidney damage

If necessary, your doctor may decide to suspend or discontinue treatment.
Hole in the stomach or intestine (perforation)
Taking the combination of Tafinlar and trametinib may increase the risk of developing holes in the intestinal wall. Inform your doctor as soon as possible if you experience severe abdominal pain.
Severe skin reactions
Severe skin reactions have been observed in people taking Tafinlar in combination with trametinib. Inform your doctor immediately if you notice skin changes (see section 4 for symptoms you should be aware of).
Inflammatory disease affecting mainly the skin, lungs, eyes, and lymph nodes
An inflammatory disease that mainly affects the skin, lungs, eyes, and lymph nodes. Common symptoms of sarcoidosis may include cough, shortness of breath, swollen lymph nodes, visual disturbances, fever, fatigue, joint pain and swelling, and painful skin nodules. Inform your doctor if you experience any of these symptoms.
Immune system disorders
Tafinlar in combination with trametinib may, in rare cases, cause a condition (haemophagocytic lymphohistiocytosis or HLH) in which the immune system produces an excessive number of infection-fighting cells called histiocytes and lymphocytes. Symptoms may include: enlargement of the liver and/or spleen, rash, swollen lymph nodes, breathing problems, easy bruising, kidney abnormalities, and heart problems. Inform your doctor immediately if you experience several symptoms at once, such as fever, swollen lymph nodes, bruising, or rash.
Tumour lysis syndrome
If you experience any of the following symptoms, inform your doctor immediately, as this may be a life-threatening condition: nausea, shortness of breath, 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 and are due to the breakdown products of dying cancer cells (tumour lysis syndrome or TLS), which may lead to changes in kidney function (see also section 4).
Children and adolescents
Tafinlar is not recommended for children and adolescents. The effects of Tafinlar in individuals under 18 years of age are unknown.
Other medicines and Tafinlar
Before starting treatment, inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines, including those without a prescription.
Some medicines may affect how Tafinlar works or may increase the likelihood of side effects. Tafinlar may also affect how other medicines work. These include:

hormonal birth control medicines (contraceptives), such as pills, injections, or patches
warfarin and acenocoumarol, medicines used to thin the blood
digoxin, used to treat heart problems
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 to lower fats (lipids) in the blood, such as gemfibrozil
some medicines used to treat certain psychiatric disorders, such as haloperidol
some antibiotics, such as clarithromycin, doxycycline, and telithromycin
some medicines for tuberculosis (TB), such as rifampicin
some medicines that reduce cholesterol levels, such as atorvastatin and simvastatin
some immunosuppressants, such as cyclosporine, tacrolimus, and sirolimus
some anti-inflammatory medicines, 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 to relieve pain, such as fentanyl and methadone
medicines to treat seizures (epilepsy), such as phenytoin, phenobarbital, primidone, valproic acid, or carbamazepine
antidepressant medicines, such as nefazodone and products containing St John’s wort (Hypericum perforatum)

➔ Inform your doctor, pharmacist, or nurse if you are taking any of these medicines (or if you are unsure). Your doctor may decide to adjust your dose.
Keep a list of the medicines you are taking so you can show it to your doctor, pharmacist, or nurse.
Pregnancy, breastfeeding, and fertility
Tafinlar is not recommended during pregnancy.

If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your doctor, pharmacist, or nurse before taking this medicine. Tafinlar is not recommended during pregnancy because it may potentially harm the unborn baby.
If you are a woman of childbearing potential, you must use a reliable method of contraception while taking Tafinlar and for at least 2 weeks after stopping it, and for 16 weeks after the last dose of trametinib taken in combination with Tafinlar.
Hormonal birth control medicines (such as pills, injections, or patches) may not work as effectively while you are taking Tafinlar or the combination treatment (Tafinlar and trametinib). You must use another effective method of contraception to avoid becoming pregnant while taking this medicine. Consult your doctor, pharmacist, or nurse.
If you become pregnant while taking this medicine, inform your doctor immediately.

Tafinlar is not recommended during breastfeeding.
It is not known whether the components of this medicine pass into breast milk.
If you are breastfeeding or planning to breastfeed, you must inform your doctor. You and your doctor will decide whether to take this medicine or breastfeed.
Fertility – men and women
Animal studies have shown that the active substance dabrafenib may permanently reduce fertility. In addition, men taking Tafinlar may experience a reduced sperm count, and sperm count may not return to normal levels after stopping the medicine.
Before starting treatment with Tafinlar, discuss with your doctor options to improve the chances of having children in the future.
Taking Tafinlar with trametinib: trametinib may impair fertility in both men and women.
If you have further questions about the effects of this medicine on sperm count, consult 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, feel tired or weak, or have low energy levels.
Descriptions of these effects can be found in sections 2 and 4.
Discuss with your doctor, pharmacist, or nurse if you are unsure about anything. Your illness, symptoms, and treatment conditions may also affect your ability to drive or operate machinery.

3. How to take Tafinlar

Take this medicine exactly as prescribed by your doctor, pharmacist, or nurse. If you have any doubts, consult your doctor, pharmacist, or nurse.

How much to take
The recommended dose of Tafinlar, either alone or in combination with trametinib, is two 75 mg capsules twice daily (corresponding to a total daily dose of 300 mg). The recommended dose of trametinib, when used in combination with Tafinlar, is 2 mg once daily.
Your doctor may decide that you should take a lower dose if you experience side effects.
Tafinlar is also available in 50 mg capsules, should a dose reduction be recommended.
Do not take more Tafinlar than your doctor has prescribed, as this may increase the risk of side effects.

How to take it
Swallow the capsules whole with water, one after the other.
Do not chew or crush the capsules, as this would cause them to 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.
You must wait at least 2 hours after eating before taking Tafinlar.

Take Tafinlar in the morning and in the evening, 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 both 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 for advice. If possible, show them the Tafinlar packaging with this leaflet.

If you forget to take Tafinlar
If you miss a dose and it is less than 6 hours until your next scheduled dose, take the missed dose as soon as you remember.
If you miss a dose and it is more than 6 hours until your next scheduled dose, skip the missed dose and take the next dose at the usual time. Then continue taking the capsules at regular intervals as usual.
Do not take a double dose to make up for a missed dose.

If you stop taking Tafinlar
Take Tafinlar for the entire duration recommended by your doctor. Do not stop unless your doctor, pharmacist, or nurse advises you to do so.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

How to take Tafinlar in combination with trametinib

Take Tafinlar in combination with trametinib exactly as prescribed by your doctor, pharmacist, or nurse. Do not change the dose or stop treatment with Tafinlar or trametinib unless instructed by your doctor, pharmacist, or nurse.
Take Tafinlar twice daily and trametinib once daily. It may be helpful for you to take both medicines at the same time each day. Tafinlar doses should be taken approximately 12 hours apart. Trametinib, when taken in combination with Tafinlar, should 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 or tablet 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 take a double dose to make up for a missed dose; instead, take the next dose at the scheduled time:
- If less than 6 hours remain before the next scheduled dose of Tafinlar (which is taken twice daily).
- If less than 12 hours remain before the next scheduled dose of trametinib (which is taken once daily).
If you take too many Tafinlar capsules or trametinib tablets, contact your doctor, pharmacist, or nurse immediately. If possible, bring the Tafinlar capsules and trametinib tablets with you. If possible, show them the Tafinlar and trametinib packaging, including the package leaflets.
If you experience side effects, your doctor may decide to reduce your dose of Tafinlar and/or trametinib. Always take Tafinlar and trametinib exactly as instructed by your doctor, pharmacist, or nurse.

4. Possible side effects

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

Serious possible side effects

Bleeding problems
Tafinlar may cause serious bleeding problems, especially in the brain when taken in combination with trametinib. Contact your doctor or nurse immediately for medical assistance if you experience any unusual signs of bleeding, including:
headache, dizziness, or weakness
coughing up blood or blood clots
vomiting blood or material that looks like coffee grounds
red or black, tar-like stools
Fever
Taking Tafinlar may cause fever in more than 1 in 10 people. Inform your doctor, pharmacist, or nurse immediately if you develop a fever (temperature of 38°C or higher) or feel feverish while taking this medicine. Tests will be performed to identify any other causes of fever and to manage the condition.
In some cases, people with fever may experience low blood pressure and dizziness. If the fever is severe, your doctor may recommend stopping Tafinlar or Tafinlar and trametinib temporarily while treating the fever with other medicines. Once the fever is under control, your doctor may recommend restarting Tafinlar.
Heart conditions
Tafinlar may affect how the heart pumps blood when taken in combination with trametinib. This is more likely to occur in people who already have an existing heart condition. You will be monitored for any heart problems while taking Tafinlar with trametinib. Signs and symptoms of heart problems include:
feeling your heart beat strongly, rapidly, or irregularly
dizziness
fatigue
mental confusion
shortness of breath
swelling in the legs

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

Skin changes
Severe skin reactions have been observed in people taking Tafinlar in combination with trametinib (frequency not known). If you notice any of the following reactions:
red, circular or target-shaped rashes on the trunk, with central blisters. Skin peeling. Ulcers in the mouth, throat, nose, genitals, and eyes. 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 reaction with eosinophilia and systemic symptoms). ➔ Stop taking the medicine and contact your doctor immediately.

Patients taking Tafinlar may commonly (affects up to 1 in 10 people) develop a different type of skin cancer called cutaneous squamous cell carcinoma (cuSCC). Others may develop a type of skin cancer called basal cell carcinoma (BCC). Generally, these skin changes remain localized and can be surgically removed, and treatment with Tafinlar can continue uninterrupted.
Some people taking Tafinlar may also develop new melanomas. These melanomas are usually surgically removed, and treatment with Tafinlar can continue without interruption.
Your doctor will examine your skin before you start taking Tafinlar, then again every month while you are taking this medicine, and for 6 months after you stop taking it, to check for any new skin cancers.
Your doctor will also examine your head, neck, mouth, and lymph nodes, and perform regular scans (called CT scans) of the chest and abdominal area. Blood tests may also be performed. These checks are intended to detect whether other tumours, including squamous cell carcinoma, develop inside the body. Pelvic examinations (in women) and anal examinations before and after treatment are also recommended.
Check your skin regularly while taking Tafinlar.
If you notice any of the following:

a new wart
skin lesions or red, raised bumps that bleed or do not heal
changes in the size or colour of a mole ➔ Inform your doctor, pharmacist, or nurse as soon as possible if you experience any of these symptoms, whether they are new or worsening.

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

Eye problems
Patients taking Tafinlar alone may uncommonly (affects up to 1 in 100 people) develop an eye condition called uveitis, which can damage vision if untreated. This may occur commonly (affects 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 eye
blurred vision
eye pain
increased sensitivity to light
floating spots in front of the eyes ➔ Contact your doctor, pharmacist, or nurse immediately if you experience these symptoms.

Tafinlar may cause eye problems when taken in combination with trametinib. Trametinib is not recommended if you have previously had blockage of the vein draining the eye (retinal vein occlusion). Your doctor may recommend an eye examination before starting Tafinlar with trametinib and during treatment. Your doctor may ask you to stop taking trametinib or refer you to a specialist if you develop signs and symptoms affecting vision, including:

loss of vision
redness and irritation of the eye
coloured spots in vision
halos (blurred edges around objects)
blurred vision ➔ Inform your doctor, pharmacist, or nurse as soon as possible if you experience any of these symptoms.

It is very important to inform your doctor, pharmacist, or nurse immediately if you develop these symptoms, especially if you have eye pain and redness that do not resolve quickly. They may arrange for you to see an ophthalmologist for a complete eye examination.

Immune system disorders
Inform your doctor immediately if you experience several symptoms at once, such as fever, swollen lymph nodes, bruising, or skin rash. These may be signs of a condition (hemophagocytic lymphohistiocytosis) in which the immune system produces an excessive number of infection-fighting cells called histiocytes and lymphocytes, which can cause various symptoms; see section 2 (rare frequency).
Tumour lysis syndrome
Inform your doctor immediately if you experience the following symptoms: nausea, shortness of breath, 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).
If you have recently received radiotherapy
In patients who have received radiotherapy before, during, or after treatment with Tafinlar, worsening of radiation-related side effects may occur (common frequency). This may affect the area treated with radiation, such as the skin or spine. If any of the following symptoms occur after radiation treatment, including but not limited to:
skin rash, blisters, peeling, or skin colour changes
back pain ➔ Inform your doctor or nurse immediately

Possible side effects in patients taking Tafinlar alone
Side effects you may experience when taking Tafinlar alone include:

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

Papilloma (a type of skin tumour that is usually not dangerous)
Decreased appetite
Headache
Cough
Nausea, vomiting
Diarrhoea
Thickening of the outer skin layers
Unusual hair loss or thinning
Skin rash
Redness and swelling of the palms of the hands, fingers, and soles of the feet (see ‘Skin changes’ at the beginning of section 4)
Joint pain, muscle pain, or pain in hands or feet
Fever (see ‘Fever’ at the beginning of section 4)
Lack of energy
Chills
Weakness

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

Skin effects including cutaneous squamous cell carcinoma (a type of skin cancer), wart-like growths, skin tags (acrochordons), uncontrolled skin growths or lesions (basal cell carcinoma), dry skin, itchy or red skin, thickened scaly skin areas, or rough skin (actinic keratosis), skin lesions, red skin, increased skin sensitivity to sunlight
Constipation
Flu-like illness
Nerve condition that may cause pain, numbness, or tingling in hands and feet and/or muscle weakness (peripheral neuropathy)

Common side effects that may be detected in blood tests

Low blood phosphate levels (hypophosphataemia)
Increased blood sugar levels (hyperglycaemia)

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

New melanoma
Allergic reactions (hypersensitivity)
Eye inflammation (uveitis, see ‘Eye problems’ at the beginning of section 4)
Pancreatitis (causing severe abdominal pain)
Inflammation of the fat layer under the skin (panniculitis)
Kidney problems, kidney failure
Kidney inflammation
Raised, painful red to dark red skin spots or ulcers mainly on arms, legs, face, and neck, accompanied by fever (signs of acute febrile neutrophilic dermatosis)

Possible side effects when Tafinlar and trametinib are taken together
When taking Tafinlar and trametinib together, you may experience one of the side effects listed above, although the frequency may change (increase or decrease).
You may also experience additional side effects due to taking trametinib together with Tafinlar.
Inform your doctor as soon as possible if you experience any of these side effects, whether they are new or worsening.
Also read the trametinib package leaflet for details on side effects you may experience with trametinib.
The side effects you may experience while taking Tafinlar in combination with trametinib are:

Very common side 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 can range from mild to severe (haemorrhage)
Cough
Stomach pain
Constipation
Diarrhoea
Nausea, vomiting
Skin rash, dry skin, itching, red skin
Joint pain, muscle pain, or pain in hands or feet
Muscle spasms
Lack of energy, feeling weak
Chills
Swelling of hands or feet (peripheral oedema)
Fever
Flu-like illness

Very common side effects that may be detected in blood tests

Abnormal liver laboratory test results

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

Urinary tract infection
Skin effects including skin infection (cellulitis), inflammation of hair follicles, nail disorders such as changes in the nail bed, nail pain, nail infections and swelling of the cuticles, blistering skin rash with pus, cutaneous squamous cell carcinoma (a type of skin cancer), papilloma (a type of skin tumour that is usually not dangerous), wart-like growths, increased skin sensitivity to sunlight (see also “Skin changes” at the beginning of section 4)
Dehydration (low levels of water or fluids)
Blurred vision, vision problems, eye inflammation (uveitis)
Reduced heart pumping efficiency
Low blood pressure (hypotension)
Localised tissue swelling
Shortness of breath
Dry mouth
Mouth pain or mouth ulcers, inflammation of mucous membranes
Acne-like problems
Thickening of the outer skin layer (hyperkeratosis), thickened or scaly, crusted skin areas (actinic keratosis), cracked or damaged skin
Increased sweating, night sweats
Unusual hair loss or thinning
Red, painful hands and feet
Inflammation of the fat layer under the skin (panniculitis)
Mucosal inflammation
Facial swelling
Nerve condition that may cause pain, numbness, or tingling in hands and feet and/or muscle weakness (peripheral neuropathy)
Irregular heartbeat (atrioventricular block)

Common side effects that may be detected in blood tests

Low white blood cell counts
Decreased number of red blood cells (anaemia), platelets (cells that help blood to clot), and a type of white blood cells (leucopenia)
Low levels of sodium (hyponatraemia) or phosphate (hypophosphataemia) in the blood
Increased blood sugar levels
Increased creatine phosphokinase, an enzyme mainly found in the heart, brain, and skeletal muscles
Increased levels of certain substances (enzymes) produced by the liver

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

Development of a new skin cancer (melanoma)
Skin fibromas (skin tags)
Allergic reactions (hypersensitivity)
Eye changes including eye swelling due to fluid leakage (chorioretinopathy), separation of the light-sensitive membrane at the back of the eye (the retina) from its supporting layer (retinal detachment), and swelling around the eyes
Slower than normal heart rate and/or reduced heart rate
Lung inflammation (pneumonitis)
Pancreatitis
Intestinal inflammation (colitis)
Kidney failure
Kidney inflammation
Inflammatory disease affecting mainly the skin, lungs, eyes, and lymph nodes (sarcoidosis)
Raised, painful red to dark red skin spots or ulcers mainly on arms, legs, face, and neck, accompanied by fever (signs of acute febrile neutrophilic dermatosis)

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

A hole (perforation) in the stomach or intestine

Not known (frequency cannot be estimated from available data):

Inflammation of the heart muscle (myocarditis), which may cause shortness of breath, fever, palpitations, and chest pain
Inflamed, scaly skin (exfoliative dermatitis)
Localised skin reactions at tattoo sites

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Tafinlar

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label of the bottle and on the
packaging after Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Tafinlar contains

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, red iron oxide (E172), titanium dioxide (E171), and hypromellose (E464). Additionally, the capsules are printed with black ink containing black iron oxide (E172), shellac, and propylene glycol.

Description of the appearance of Tafinlar and contents of the pack
Tafinlar 50 mg hard capsules are opaque, dark red in colour, and marked with ‘GS TEW’ and ‘50 mg’.
Tafinlar 75 mg hard capsules are opaque, dark pink in colour, and marked with ‘GS LHF’ and ‘75 mg’.
The bottles are opaque, white plastic, with a plastic screw cap.
The bottles also contain a silica desiccant gel in a small cylindrical container.
The desiccant should be kept 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. It is possible that not all pack sizes are 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 about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Novartis Pharma N.V. SIA Novartis Baltics Lietuvos filialas
Tél/Tel: +32 2 246 16 11 Tel: +370 5 269 16 50

България Luxembourg/Luxemburg
Novartis Bulgaria EOOD Novartis Pharma N.V.
Тел: +359 2 489 98 28 Tél/Tel: +32 2 246 16 11

Česká republika Magyarország
Novartis s.r.o. Novartis Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 457 65 00

Danmark Malta
Novartis Healthcare A/S Novartis Pharma Services Inc.
Tlf.: +45 39 16 84 00 Tel: +356 2122 2872

Deutschland Nederland
Novartis Pharma GmbH Novartis Pharma B.V.
Tel: +49 911 273 0 Tel: +31 88 04 52 555

Eesti Norge
SIA Novartis Baltics Eesti filiaal Novartis Norge AS
Tel: +372 66 30 810 Tlf: +47 23 05 20 00

Ελλάδα Österreich
Novartis (Hellas) A.E.B.E. Novartis Pharma GmbH
Τηλ: +30 210 281 17 12 Tel: +43 1 86 6570

España Polska
Novartis Farmacéutica, S.A. Novartis Poland Sp. z o.o.
Tel: +34 93 306 42 00 Tel.: +48 22 375 4888

France Portugal
Novartis Pharma S.A.S. Novartis Farma - Produtos Farmacêuticos, S.A.
Tél: +33 1 55 47 66 00 Tel: +351 21 000 8600

Hrvatska România
Novartis Hrvatska d.o.o. Novartis Pharma Services Romania SRL
Tel. +385 1 6274 220 Tel: +40 21 31299 01

Ireland Slovenija
Novartis Ireland Limited Novartis Pharma Services Inc.
Tel: +353 1 260 12 55 Tel: +386 1 300 75 50

Ísland Slovenská republika
Vistor hf. Novartis Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 5542 5439

Italia Suomi/Finland
Novartis Farma S.p.A. Novartis Finland Oy
Tel: +39 02 96 54 1 Puh/Tel: +358 (0)10 6133 200

Κύπρος Sverige
Novartis Pharma Services Inc. Novartis Sverige AB
Τηλ: +357 22 690 690 Tel: +46 8 732 32 00

Latvija
SIA Novartis Baltics
Tel: +371 67 887 070

Other sources of information
More 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.

ANNEX IV
SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS OF THE
MARKETING AUTHORISATION

Scientific conclusions
Taking into account the evaluation by the Pharmacovigilance Risk Assessment Committee (PRAC) of the Periodic Safety Update Report (PSUR) for dabrafenib, the scientific conclusions of the PRAC are as follows:
Considering the available data on radiation recall reactions and photosensitisation from clinical studies, the literature, and spontaneous reports—some of which show a close temporal relationship and event localisation within the irradiated area—and in view of a plausible mechanism of action, the PRAC considers that a causal relationship between dabrafenib and enhanced radiation toxicity is at least a reasonable possibility. The PRAC concluded that the product information for medicinal products containing dabrafenib should therefore be amended accordingly.

Having reviewed the PRAC's recommendation, the Committee for Medicinal Products for Human Use (CHMP) agrees with the general conclusions and the rationale behind the recommendation.

Grounds for the variation to the terms of the marketing authorisation
Based on the scientific conclusions regarding dabrafenib, the CHMP considers that the benefit-risk balance of medicinal products containing dabrafenib remains favourable, subject to the proposed changes to the product information.
The CHMP recommends a variation to the terms of the marketing authorisation.