TAFINLAR 50 mg Hard Capsules

Зміст інструкції

1. Tafinlar 50 mg hard capsules, 75 mg hard capsules
   1. What is Tafinlar and what is it used for
   2. Cosa deve sapere prima di prendere Tafinlar
   3. How to take Tafinlar
   4. Possible side effects
   5. How to store Tafinlar
   6. Package contents and other information

Tafinlar 50 mg hard capsules, 75 mg hard capsules

dabrafenib

Read this leaflet carefully before you start taking this medicine as 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 others, even if they have the same symptoms as you, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What Tafinlar is and what it is used for
• 2. What you need to know before you take 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 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 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 with
surgery.
Tafinlar in combination with trametinib is also used to prevent the recurrence of melanoma in
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 tumors have a particular variation (mutation) in a gene called BRAF at
position V600. This gene mutation may have caused the development of the tumor. This
medicine targets the proteins produced by this mutated BRAF gene and slows down or blocks the
development of the tumor.

2. Cosa deve sapere prima di prendere Tafinlar

Tafinlar deve essere usato solo per trattare melanomi e NSCLC con mutazione BRAF. Pertanto, prima
di iniziare il trattamento, il medico verificherà la presenza di questa mutazione.
Se il medico decidesse che lei debba prendere la terapia in associazione di Tafinlar e trametinib, legga
Se ha ulteriori domande sull’uso di questo medicinale si rivolga al medico, al farmacista o
all’infermiere.

Non prenda Tafinlar:

• se è allergicoa dabrafenib o ad uno qualsiasi degli altri componenti di questo medicinale (elencati nel paragrafo 6). Controlli con il medico se pensa che ciò la riguardi.

Avvertenze e precauzioni
Si rivolga al medico prima di prendere Tafinlar. È necessario che il medico sappia se:

• ha qualsiasi problema al fegato.
• ha o ha avuto qualsiasi problema ai reni.Il medico può prelevare dei campioni di sangue per controllare la funzionalità del fegato e dei reni mentre sta prendendo Tafinlar.
• ha avuto tipi di cancro diversi dal melanoma o dal NSCLC, in quanto può essere a maggiore rischio di sviluppare altri tumori della pelle e non della pelle con l’assunzione di Tafinlar.

Prima di prendere Tafinlar in associazione con trametinibil medico deve sapere se:

• ha problemi al cuore come insufficienza cardiaca o problemi nel modo in cui il cuore batte.
• ha problemi agli occhi, inclusi un blocco della vena che drena l’occhio (occlusione venosa retinica) o gonfiore degli occhi che può essere causato da una perdita di liquidi (corioretinopatia).
• ha problemi ai polmoni o a respirare, inclusa difficoltà a respirare spesso accompagnata da tosse secca, respiro corto e stanchezza.
• ha o ha avuto problemi gastrointestinali come diverticolite (tasche infiammate nel colon) o metastasi nel tratto gastrointestinale.

Verifichi con il medicose pensa che uno di questi problemi possa riguardarla.

Condizioni per le quali può essere necessario porre attenzione
Alcune persone che assumono Tafinlar sviluppano altre condizioni che possono essere gravi. È
necessario che lei conosca i segni e i sintomi importanti a cui prestare attenzione mentre sta prendendo
questo medicinale. Alcuni di questi sintomi (sanguinamenti, febbre, modifiche della pelle e problemi
agli occhi) vengono brevemente menzionati in questo paragrafo, ma un’informazione più dettagliata si
trova nel paragrafo 4 ‘Possibili effetti indesiderati’.

Sanguinamento
L’assunzione di Tafinlar in associazione con trametinib può causare sanguinamenti gravi che
includono il sanguinamento nel cervello, nell’apparato digerente (come stomaco, retto o intestino), nei
polmoni, ed in altri organi, e può portare alla morte. I sintomi possono includere:

• mal di testa, capogiri, o sensazione di debolezza
• sangue nelle feci o feci nere
• sangue nelle urine
• dolore di stomaco
• tosse/vomito con sangue

Informi il medicoquanto prima se manifesta uno di questi sintomi.

Febbre
L’assunzione di Tafinlar o dell’associazione di Tafinlar e trametinib può causare febbre, anche se
questa è più probabile se sta assumendo il trattamento in associazione (vedere anche paragrafo 4). In
alcuni casi, le persone con febbre possono sviluppare pressione del sangue bassa, capogiri o altri
sintomi.

Informi immediatamente il medicose le viene la febbre superiore a 38 °C o sente salire la febbre
mentre sta assumendo questo medicinale.

Disturbi del cuore
Tafinlar può causare problemi al cuore, o peggiorare problemi al cuore già esistenti (vedere anche
‘Condizioni del cuore’ nel paragrafo 4), nelle persone che assumono Tafinlar in associazione con
trametinib.

Informi il medico se ha un disturbo del cuore.Il medico eseguirà esami per verificare che il cuore
funzioni correttamente prima e durante il trattamento con Tafinlar in associazione con trametinib.
Informi immediatamente il medico se sente il cuore che batte forte, accelerato o che batte in modo
irregolare, o se avverte capogiri, stanchezza, vertigini, respiro corto, o gonfiore alle gambe. Se
necessario, il medico può decidere di sospendere il trattamento o di interromperlo del tutto.

Modifiche della pelle che possono indicare un novo cancro della pelle
Il medico controllerà la sua pelle prima di iniziare a prendere questo medicinale e regolarmente
durante il trattamento.

Informi immediatamente il medicose nota qualsiasi modifica della pelle mentre sta prendendo
questo medicinale o dopo il trattamento (vedere anche paragrafo 4).

Problemi agli occhi
Deve essere effettuato un controllo degli occhi da parte del medico mentre sta prendendo questo
medicinale.
Informi immediatamente il medicose presenta rossore e irritazione agli occhi, visione offuscata,
dolore agli occhi e altri cambiamenti nella visione durante il trattamento (vedere anche paragrafo 4).
Tafinlar, quando assunto in associazione con trametinib, può causare problemi agli occhi inclusa
cecità. Tafinlar non è raccomandato se ha avuto un blocco della vena che drena l’occhio (occlusione
della vena della retina). Informi immediatamente il medico se presenta i seguenti sintomi di problemi
agli occhi: visione offuscata, perdita della vista o altri cambiamenti della vista, punti colorati nella
visione o aloni (visione del bordo degli oggetti offuscato) durante il trattamento. Se necessario, il
medico può decidere di sospendere il trattamento o di interromperlo del tutto.
➔ Legga le informazioni sulla febbre, le modifiche della pelle e i problemi agli occhi nel
paragrafo 4 di questo foglio. Informi il medico, il farmacista o l’infermiere se presenta uno
qualsiasi dei segni e sintomi elencati.
Problemi al fegato
Tafinlar in associazione con trametinib può causare problemi al fegato che possono progredire in
condizioni gravi come epatite e insufficienza epatica, che possono essere fatali. Il medico la
monitorerà periodicamente. Segni che il suo fegato può non lavorare correttamente includono:

• perdita di appetito
• sensazione di malessere (nausea)
• provare malessere (vomito)
• dolore allo stomaco (addome)
• ingiallimento della pelle o del bianco degli occhi (ittero)
• urine di colore scuro
• prurito della pelle

Informi il medicoquanto prima se manifesta uno di questi sintomi.

Dolore ai muscoli
Tafinlar in associazione con trametinib può causare rottura dei muscoli (rabdomiolisi). Informi il
medicoquanto prima se manifesta uno di questi sintomi:

• dolore ai muscoli
• urine scure dovute ad un danno ai reni

Se necessario, il medico può decidere di sospendere il trattamento o di interromperlo del tutto.

Foro nello stomaco o nell'intestino (perforazione)
L’assunzione dell’associazione di Tafinlar e trametinib può aumentare il rischio di sviluppare fori
nella parete intestinale. Informi il medicoil più presto possibile se avverte forte dolore all’addome.

Reazioni cutanee gravi
Sono state osservate reazioni cutanee gravi in persone che assumevano Tafinlar in associazione con
trametinib. Informi immediatamente il medico se nota cambiamenti alla pelle (vedere il paragrafo°4
per i sintomi di cui è necessario lei sia informato).

Malattia infiammatoria che colpisce soprattutto la pelle, i polmoni, gli occhi e i linfonodi
Una malattia infiammatoria che colpisce soprattutto la pelle, i polmoni, gli occhi e i linfonodi. Sintomi
comuni della sarcoidosi possono includere tosse, respiro corto, ingrossamento dei linfonodi, disturbi
visivi, febbre, stanchezza, dolore e gonfiore delle articolazioni e rigonfiamenti dolorosi sulla pelle.
Informi il medico se presenta uno di questi sintomi.

Disturbi del sistema immunitario
Tafinlar in associazione con trametinib può, in rari casi, causare una condizione (linfoistiocitosi
emofagocitica o HLH) in cui il sistema immunitario produce una quantità eccessiva rispetto al normale
di cellule che combattono le infezioni, chiamate istiociti e linfociti. I sintomi possono includere:
ingrossamento del fegato e/o della milza, eruzione cutanea, ingrossamento dei linfonodi, problemi
respiratori, facilità di comparsa dei lividi, anomalie ai reni e problemi al cuore. Informi
immediatamente il medico se manifesta contemporaneamente più sintomi quali febbre, gonfiore delle
ghiandole linfatiche, lividi o eruzione cutanea.

Sindrome da lisi tumorale
Se manifesta i seguenti sintomi, informi immediatamente il medico poiché questa può essere una
condizione pericolosa per la vita: nausea, respiro affannoso, battito cardiaco irregolare, crampi
muscolari, crisi convulsive, intorbidimento dell’urina, diminuzione della produzione di urina e
stanchezza. Queste possono essere causate da un gruppo di complicazioni metaboliche che possono
verificarsi durante il trattamento del cancro e sono causate dai prodotti di degradazione delle cellule
cancerose morenti (sindrome da lisi tumorale o TLS) e possono portare a cambiamenti nella
funzionalità renale (vedere anche paragrafo 4).

Bambini e adolescenti
Tafinlar non è raccomandato nei bambini e negli adolescenti. Gli effetti di Tafinlar nelle persone di età
inferiore ai 18 anni non sono noti.

Altri medicinali e Tafinlar
Prima di iniziare il trattamento, informi il medico, il farmacista o l’infermiere se sta assumendo, ha
recentemente assunto, o potrebbe assumere qualsiasi altro medicinale, compresi quelli senza
prescrizione medica.
Alcuni medicinali possono avere effetto sul funzionamento di Tafinlar o possono aumentare la
probabilità che lei abbia effetti indesiderati. Tafinlar può anche avere effetto sul funzionamento di altri
medicinali. Questi includono:

• medicinali per il controllo delle nascite( contraccettivi) contenenti ormoni, come pillole, iniezioni o cerotti
• warfarin e acenocumarolo, medicinali usati per fluidificare il sangue
• digossina, usata per trattare i disturbi del cuore
• medicinali per trattare le infezioni fungine, come chetoconazolo, itraconazolo, voriconazolo e posaconazolo
• alcuni calcio-antagonisti, usati per trattare la pressione alta del sangue, come diltiazem, felodipina, nicardipina, nifedipina o verapamil
• medicinali per trattare il cancro, come cabazitaxel
• alcuni medicinali per abbassare i grassi (lipidi)nel sangue, come gemfibrozil
• alcuni medicinali usati per trattare alcuni disturbi psichiatrici,come aloperidolo
• alcuni antibiotici, come claritromicina, doxiciclina e telitromicina
• alcuni medicinali per la tubercolosi(TB), come rifampicina
• alcuni medicinali che riducono i livelli di colesterolo, come atorvastatina e simvastatina
• alcuni immunosoppressori, come ciclosporina, tacrolimus e sirolimus
• alcuni medicinali anti- infiammatori, come desametasone e metilprednisolone
• alcuni medicinali per trattare l’ HIV, come ritonavir, amprenavir, indinavir, darunavir, delavirdina, efavirenz, fosamprenavir, lopinavir, nelfinavir, tipranavir, saquinavir e atazanavir
• alcuni medicinali usati per alleviare il dolore, come fentanyl e metadone
• medicinali per trattare le convulsioni ( epilessia), come fenitoina, fenobarbital, primidone, acido valproico o carbamazepina
• medicinali anti- depressivi,come nefazodone e medicinali contenenti l’erba di San Giovanni ( Hypericum perforatum)

➔ Informi il medico, il farmacista o l’infermierese sta assumendo uno di questi medicinali (o se
non è sicuro). Il medico può decidere di modificare la dose.
Tenga una lista dei medicinali che prende, in modo da poterla mostrare al medico, al farmacista o
all’infermiere.

Gravidanza, allattamento e fertilità
Tafinlar non è raccomandato durante la gravidanza.

• Se è in corso una gravidanza, se sospetta o sta pianificando una gravidanza, chieda consiglio al medico, al farmacista o all’infermiere prima di prendere questo medicinale. Tafinlar non è raccomandato durante la gravidanza perché può potenzialmente provocare danno al feto.
• Se è una donna in età fertile, deve usare un metodo per il controllo delle nascite affidabile mentre sta prendendo Tafinlar e per almeno 2 settimane dopo che ha smesso di prenderlo e per 16 settimane dopo aver preso ultima dose di trametinib assunto in associazione con Tafinlar.
• I medicinali per il controllo delle nascite contenenti ormoni (come pillole, iniezioni o cerotti) possono non funzionare così bene mentre sta prendendo Tafinlar o il trattamento in associazione (Tafinlar come pure trametinib). È necessario utilizzare un altro efficace metodo per il controllo delle nascite in modo da non iniziare una gravidanza mentre sta assumendo questo medicinale. Chieda consiglio al medico, al farmacista o all’infermiere.
• Se inizia una gravidanza mentre sta assumendo questo medicinale, informi immediatamente il medico.

Tafinlar non è raccomandato durante l’allattamento con latte materno.
Non è noto se i componenti di questo medicinale possano passare nel latte materno.
Se sta allattando con latte materno, o sta pianificando di farlo, deve informare il medico. Lei e il
medico deciderete se prendere questo medicinale o allattare.

Fertility – men and women
Studies in animals have shown that the active substance dabrafenib may permanently reduce fertility. Furthermore, men taking Tafinlar may experience a reduction in sperm count, and the sperm count may not return to normal levels after stopping this medicine.
Before starting treatment with Tafinlar, talk to your doctor about options to improve the chances of having children in the future.

Taking Tafinlar with trametinib:trametinib may impair fertility in 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 have 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 or weak or if your energy levels are low.
Descriptions of these effects can be found in paragraphs 2 and 4.
Discuss with your doctor, pharmacist or nurse if you are unsure about anything. Also, the disease, symptoms and treatment conditions can have effects on the ability to drive or use machines.

3. How to take Tafinlar

Take this medicine following exactly the instructions of your doctor, pharmacist or
nurse. If you have any doubts, ask your doctor, pharmacist or nurse.

How much to take
The recommended dose of Tafinlar, both alone and in combination with trametinib, is two 75 mg capsules
twice daily (corresponding to a 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 need to 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 recommended,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 may otherwise affect their efficacy.
Take Tafinlar twice daily, on an empty stomach. This means that

• after taking Tafinlar, you must wait at least 1 hourbefore eating.
• after eating, you must wait at least 2 hoursbefore taking Tafinlar.

Take Tafinlar in the morning and evening, approximately 12 hours apart. Take the morning and evening doses of
Tafinlar at the same time each day. This will increase the likelihood of remembering to
take the capsules.
Do not take the morning and evening doses of Tafinlar at the same time.

If you take more Tafinlar than you should
If you take too many Tafinlar capsules, contact your doctor, pharmacistor nurse for
advice. If possible, show them the Tafinlar packaging with this leaflet.

If you forget to take Tafinlar
If you forget a dose and less than 6 hours have passed, take it as soon as you remember.
If you forget a dose and more than 6 hours have passed, skip that 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 time recommended by your doctor. Do not stop taking it unless your doctor,
pharmacist or nurse tells 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 following exactly the instructions of your doctor, pharmacist or nurse. Do not change the dose or stop treatment with Tafinlar or trametinib without your doctor, pharmacist or nurse telling you to do so.
• Take Tafinlar twice dailyand take trametinib once daily.It may be best for you to get into the habit of taking 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 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. Swallow the capsules or tablet whole with a full glass of water.
• If you forget a dose of Tafinlar or trametinib, take it as soon as you remember. Do not compensate for the missed dose and take the next dose directly when it is due: o If less than 6 hours remain until the next dose of Tafinlar, which must be taken twice daily. o If less than 12 hours remain until the next dose of trametinib, which must be 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 with the leaflets.
• If you experience side effects, your doctor may decide to reduce your dose of Tafinlar and/or trametinib. Take the doses of Tafinlar and trametinib following exactly the instructions of your doctor, pharmacist or nurse.

4. Possible side effects

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

Possible serious side effects

Bleeding problems
Tafinlar can cause serious bleeding problems, especially in the brain when taken in
combination with trametinib. Contact your doctor or nurse for immediate
medical assistance if you experience any unusual signs of bleeding, including:

• headache, dizziness, or weakness
• coughing up blood or blood clots
• vomiting blood or looking like coffee grounds
• red or black stools that look like tar

Fever
Taking Tafinlar can cause fever in more than 1 in 10 people. Tell your doctor, pharmacist or nurse immediately if you get a fever (temperature of 38ºC or higher) or feel
your temperature rising while taking this medicine.Tests will be done to
find out if there are other causes for the fever and to treat the problem.
In some cases, people with a fever may experience a drop in blood pressure and
dizziness. If the fever is severe, your doctor may recommend stopping Tafinlar or
Tafinlar and trametinib, during the treatment of the fever with other medicines. Once the fever is
under control, your doctor may recommend starting Tafinlar again.

Heart conditions
Tafinlar can affect how the heart pumps blood when taken in combination with
trametinib. This is more likely to affect people who already have a heart problem.
You will be monitored for any heart problems while taking Tafinlar in combination
with trametinib. Signs and symptoms of heart problems include:

• feeling your heartbeat is strong, fast, or irregular
• dizziness
• fatigue
• feeling confused
• shortness of breath
• swelling in your legs

Tell your doctoras soon as possible if you have any of these symptoms, whether they occur for the
first time or get worse.

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:

• reddish patches on the trunk that are circular or target-shaped, with blisters in the center. Peeling of the skin. 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-syndromeor drug reaction with eosinophilia and systemic symptoms). ➔ stop taking the medicine and contact your doctor immediately.

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

• new wart
• skin lesions or reddish bump that bleeds or does not heal
• change in the size or color of a mole. ➔ Tell your doctor, pharmacist or nurse as soon as possibleif you have any of these symptoms, whether they occur for the first time or get worse.

Skin reactions (rash)can occur while taking Tafinlar in
combination with trametinib. Tell your doctorif you develop a rash while
taking Tafinlar in combination with trametinib.

Eye problems
Patients taking Tafinlar alone may uncommonly (may affect up to 1 in 100) develop an eye problem called uveitis, which can damage your vision if it is not
treated. This can occur commonly (may affect up to 1 in 10) in patients who
are taking Tafinlar in combination with trametinib.
Uveitis can develop quickly and symptoms include:

• redness and irritation of the eye
• blurred vision
• eye pain
• increased sensitivity to light
• floaters in your vision ➔ Contact your doctor, pharmacist or nurse immediatelyif you have these symptoms.

Tafinlar can cause eye problems when taken in combination with trametinib. Trametinib
is not recommended if you have had a blockage of the vein that drains the eye (retinal vein
occlusion). Your doctor may recommend an eye exam before taking Tafinlar in
combination with trametinib and while you are being treated. Your doctor may ask you to stop
taking trametinib or send you to a specialist if you develop signs and symptoms in your vision that
include:

• loss of vision
• redness and irritation of the eye
• colored spots in your vision
• halo (blurred vision of the edge of objects)
• blurred vision ➔ Tell your doctor, pharmacist or nurse as soon as possible if you experience any ofthese symptoms.

It is very important to tell your doctor, pharmacist or nurse immediatelyif you develop
these symptoms, especially if you have eye pain and redness that does not resolve quickly.
They may arrange a visit to the ophthalmologist for a comprehensive eye exam.

Immune system disorders
Tell your doctor immediately if you experience more than one symptom at the same time such as fever,
swollen lymph glands, bruising or rash. These may be signs of a condition (hemophagocytic lymphohistiocytosis) in which the immune system produces an amount
excessive compared to normal of cells that fight infections, called histiocytes and lymphocytes, and which
can cause various symptoms, see paragraph 2 (rare frequency).

Tumor lysis syndrome
Tell your doctor immediately if you experience the following symptoms: nausea, shortness of breath, irregular heartbeat, 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 can be fatal in some people (tumor lysis
syndrome or TLS), see paragraph 2 (frequency not known).

Possible side effects in patients taking only Tafinlar
The side effects you may experience when taking Tafinlar alone are as follows:

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

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

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

• Effects on the skin including squamous cell carcinoma of the skin (a type of skin cancer), wart-like growths, skin tags, uncontrolled skin growths or lesions (basal cell carcinoma), dry skin, itchy skin or redness of the skin, areas of scaly thickened skin, or rough skin (actinic keratosis), skin lesions, redness of the skin, increased sensitivity of the skin to the sun
• Constipation
• Flu-like illness
• Condition affecting the nerves that can cause pain, loss of sensation or tingling in the hands and feet and/or muscle weakness (peripheral neuropathy)

Common side effects that may become apparent from blood tests

• Low level of phosphorus (hypophosphatemia) in the blood
• Increased blood sugar levels (hyperglycemia)

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

• New melanoma
• Allergic reactions (hypersensitivity)
• Inflammation of the eye (uveitis, see ‘Eye problems’ at the beginning of paragraph 4)
• Inflammation of the pancreas (causing severe abdominal pain)
• Inflammation of the fat layer under the skin (panniculitis)
• Kidney problems, kidney failure
• Inflammation of the kidneys
• Bumpy or ulcerated skin lesions, painful, reddish to dark red located 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
While 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 trametinibtogether with
Tafinlar.
Tell your doctor as soon as possible if you experience any of these side effects, whether for the first time or
if they worsen.
experience with trametinib.
The side effects that you may experience while taking Tafinlar in combination with
trametinib are as follows:

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 may be mild to severe (hemorrhage)
• Cough
• Stomach pain
• Constipation
• Diarrhea
• Nausea, vomiting
• Skin rash, dry skin, itching, skin redness
• Joint pain, muscle pain, or pain in the hands and feet
• Muscle spasms
• Lack of energy, feeling weak
• Chills
• Swelling of hands or feet (peripheral edema)
• Fever
• Flu-like illness

Very common side effects that may become apparent from blood tests

• Abnormal laboratory test results related to the liver

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

• Urinary tract infection
• Effects on the skin including skin infection (cellulitis), inflammation of hair follicles, nail disorders such as changes in the nail bed, nail pain, infection and swelling of the cuticles, skin rash with pus-filled blisters, squamous cell carcinoma (a type of skin cancer), papilloma (a type of skin tumor that is usually not dangerous), wart-like growths, increased sensitivity of the skin to the sun (see also “Skin changes” at the beginning of paragraph 4)
• Dehydration (low levels of water or fluids)
• Blurred vision, vision problems, eye inflammation (uveitis)
• Heart pumping less efficiently
• Low blood pressure (hypotension)
• Localized tissue swelling
• Shortness of breath
• Dry mouth
• Mouth pain or mouth sores, inflammation of the mucous membranes
• Acne-like problems
• Thickening of the outer layer of skin (hyperkeratosis), areas of thickened skin or scaly and crusty skin (actinic keratosis), cracks or lesions on the skin
• Increased sweating, night sweats
• Unusual hair loss or thinning
• Red and painful hands and feet
• Inflammation of the fat layer under the skin (panniculitis)
• Inflammation of the mucous membrane
• Facial swelling
• A condition affecting the nerves that can cause pain, loss of sensation or tingling in the hands and feet and/or muscle weakness (peripheral neuropathy)
• Irregular heartbeat (atrioventricular block)

Common side effects that may become apparent from blood tests

• Low levels of white blood cells in the blood
• Decreased number of red blood cells (anemia), platelets (cells that help the blood to clot), and a type of white blood cells (leukopenia)
• Low levels of sodium (hyponatremia) or phosphate (hypophosphatemia) 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 tumor (melanoma)
• Skin fibromas (porri)
• Allergic reactions (hypersensitivity)
• Changes in the eyes including eye swelling caused by fluid leakage (chorioretinopathy), separation of the posterior membrane of the eye sensitive to light (the retina) from its supporting layer (retinal detachment) and swelling around the eyes.
• Heart rate slower than normal and/or decreased heart rate
• Lung inflammation (pneumonia)
• Inflammation of the pancreas
• Inflammation of the intestine (colitis)
• Kidney failure
• Kidney inflammation
• Inflammatory disease that mainly affects the skin, lungs, eyes and lymph nodes (sarcoidosis)
• Raised or ulcerated skin spots, painful, ranging in color from red to dark red located mainly on the 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 can cause shortness of breath, fever, palpitations and chest pain.
• Inflamed and scaly skin (exfoliative dermatitis)

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed in this leaflet. 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
pack after Exp. The expiry date refers to the last day of that month.
This medicine does not require any particular storage conditions.
Do not dispose of any medicine in waste water 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 ingredients are: microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide, red iron oxide (E172), titanium dioxide (E171), and hypromellose (E464). In addition, the capsules are printed with black ink containing black iron oxide (E172), shellac and propylene glycol.

Description of Tafinlar and package contents
Tafinlar 50 mg hard capsules are opaque, dark red in colour and imprinted with ‘GS TEW’ and
’50 mg’.
Tafinlar 75 mg hard capsules are opaque, dark pink in colour and imprinted with ‘GS LHF’ and
’75 mg’.
The bottles are opaque, white-coloured plastic bottles with a plastic screw cap.
The bottles also include a silica gel desiccant in a small cylinder-shaped container.
The desiccant must be kept inside the bottle and must not be 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 Pharma GmbH
Roonstraße 25
D-90429 Nuremberg
Germany
Glaxo Wellcome, S.A.
Avda. Extremadura, 3
09400 Aranda De Duero
Burgos
Spain
Novartis Farmacéutica S.A.
Gran Via de les Corts Catalanes 764
08013 Barcelona
Spain
Novartis Pharma GmbH
Sophie-Germain-Strasse 10
90443 Norimberga
Germany
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder

België/Belgique/Belgien
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11

Lietuva
SIA Novartis Baltics Lietuvos filialas
Tel: +370 5 269 16 50

България
Novartis Bulgaria EOOD
Тел: +359 2 489 98 28

Luxembourg/Luxemburg
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11

Česká republika
Novartis s.r.o.
Tel: +420 225 775 111

Magyarország
Novartis Hungária Kft.
Tel.: +36 1 457 65 00

Danmark
Novartis Healthcare A/S
Tlf.: +45 39 16 84 00

Malta
Novartis Pharma Services Inc.
Tel: +356 2122 2872

Deutschland
Novartis Pharma GmbH
Tel: +49 911 273 0

Nederland
Novartis Pharma B.V.
Tel: +31 88 04 52 555

Eesti
SIA Novartis Baltics Eesti filiaal
Tel: +372 66 30 810

Norge
Novartis Norge AS
Tlf: +47 23 05 20 00

Ελλάδα
Novartis (Hellas) A.E.B.E.
Τηλ: +30 210 281 17 12

Österreich
Novartis Pharma GmbH
Tel: +43 1 86 6570

España
Novartis Farmacéutica, S.A.
Tel: +34 93 306 42 00

Polska
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

Hrvatska
Novartis Hrvatska d.o.o.
Tel. +385 1 6274 220

România
Novartis Pharma Services Romania SRL
Tel: +40 21 31299 01

Ireland
Novartis Ireland Limited
Tel: +353 1 260 12 55

Slovenija
Novartis Pharma Services Inc.
Tel: +386 1 300 75 50

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Novartis Slovakia s.r.o.
Tel: +421 2 5542 5439

Italia
Novartis Farma S.p.A.
Tel: +39 02 96 54 1

Suomi/Finland
Novartis Finland Oy
Puh/Tel: +358 (0)10 6133 200

Κύπρος
Novartis Pharma Services Inc.
Τηλ: +357 22 690 690

Sverige
Novartis Sverige AB
Tel: +46 8 732 32 00

Latvija
SIA Novartis Baltics
Tel: +371 67 887 070

Other sources of information
More detailed information on this medicinal product is available on the website of the European
Medicines Agency, https://www.ema.europa.eu .
This leaflet is available in all official languages of the European Union/European Economic Area on the
website of the European Medicines Agency.

ANNEX IV
SCIENTIFIC CONCLUSIONS AND JUSTIFICATION FOR THE VARIATION OF THE
MARKETING AUTHORISATION
Scientific conclusions
In light of the assessment by the Pharmacovigilance and Risk Assessment Committee
(PRAC) of the Periodic Safety Update Report (PSUR) for dabrafenib, the PRAC’s scientific
conclusions are as follows:
In light of available risk data from the literature and spontaneous reports, including in some cases a
close temporal association, a positive de-challenge and/or re-challenge, and in view of a plausible
mechanism of action, the PRAC considers that a causal relationship between dabrafenib and probable
uveitis resembling Vogt-Koyanagi-Harada (VKH) syndrome is at least a reasonable
possibility. The PRAC concluded that the product information for products containing dabrafenib
should be amended accordingly.
Having examined the PRAC’s recommendation, the Committee for Human Medicinal Products
(CHMP) agrees with the overall conclusions and the justification for the recommendation.

Justification for the variation of the marketing authorisation
Based on the scientific conclusions on dabrafenib, the CHMP considers that the benefit/risk
balance of the medicinal product(s) containing dabrafenib is unchanged, save for the proposed changes
to the product information.
The CHMP recommends the variation of the marketing authorisation.