Zelboraf
vemurafenib
vemurafenib
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor.
This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
If you get any side effects, talk to your doctor. This includes any possible side effects not listed
in this leaflet. See section 4.
What Zelboraf is and what it is used for
What you need to know before you take Zelboraf
How to take Zelboraf
Possible side effects
How to store Zelboraf
Contents of the pack and other information
Zelboraf is an anticancer medicine that contains the active substance vemurafenib. It is used to treat adult patients with melanoma that has spread to other parts of the body or cannot be removed by surgery.
It can only be used in patients whose cancer has a change (mutation) in the “BRAF” gene. This change may have led to the development of melanoma.
Zelboraf targets proteins made from this modified gene and slows down or stops the development of your cancer.
If you are allergic to vemurafenib or any of the other ingredients of this medicine (listed in section 6 of this leaflet). Symptoms of allergic reactions may include swelling of the face, lips
or tongue, difficulty breathing, rash, or fainting sensation.
Talk to your doctor before taking Zelboraf.
Allergic reactions
such as swelling of the face, lips or tongue, difficulty breathing, rash, or fainting sensation.
Severe skin reactions
your skin, blisters or sores in your mouth, peeling of your skin, fever, redness or swelling of
your face, hands, or soles of your feet.
Previous history of cancer
Radiation therapy reactions
Heart disorder
Eye problems
changes during your treatment.
Musculoskeletal/Connective Tissue disorder
Checks of your skin before, during and after treatment
Regularly during your treatment and up to 6 months after your treatment, your doctor needs to
check your skin for a type of cancer called “cutaneous squamous cell carcinoma”.
Usually, this lesion appears on sun-damaged skin, remains local and can be cured by surgical removal.
If your doctor finds this type of skin cancer, he or she will treat it or send you to another doctor for treatment.
Additionally, your doctor needs to inspect your head, your neck, your mouth, your lymph
glands and you will undergo CT scans regularly. This is a precautionary measure in case a squamous cell carcinoma lesion would develop inside your body. Genital examinations (for women) and anal examinations are also recommended before and at the end of your treatment.
You may develop new melanoma lesions while taking Zelboraf. These lesions are usually removed by surgery and patients continue their treatment. Monitoring of these lesions occurs as
outlined above for cutaneous squamous cell carcinoma.
Kidney or liver problems
before you start taking Zelboraf and during treatment.
Sun protection
If you are taking Zelboraf, you may become more sensitive to sunlight and get sunburns that can be severe. During treatment, avoid exposing your skin to direct sunlight.
If you do plan to go into the sun:
wear clothing which protects your skin, including your head and face, arms and legs;
use a lip balm and a broad spectrum sunscreen (minimum of Sun Protection Factor (SPF) 30, re-applied every 2 to 3 hours).
This will help to protect you against sunburn.
Zelboraf is not recommended for children and adolescents. The effects of Zelboraf in people younger than 18 years old are not known.
Medicines that are known to affect the way your heart beats:
medicines for heart rhythm problems (e.g. quinidine, amiodarone)
medicines for depression (e.g. amitriptyline, imipramine)
medicines for bacterial infections (e.g. azithromycin, clarithromycin)
medicines for nausea and vomiting (e.g. ondansetron, domperidone).
Medicines that are mainly eliminated by metabolising proteins called CYP1A2 (e.g caffeine, olanzapine, theophylline), CYP3A4 (e.g. some oral contraceptives) or called CYP2C8.
Medicines that influence a protein called P-gp or BCRP (e.g. verapamil, cyclosporine, ritonavir, quinidine, itraconazole, gefitinib).
Medicines that could be influenced by a protein called P-gp (e.g. aliskiren, colchicine, digoxin, everolimus, fexofenadine) or a protein called BCRP (e.g. methotrexate, mitoxantrone, rosuvastatin).
Medicines that stimulate the metabolising proteins called CYP3A4 or a metabolising process called glucuronidation (e.g. rifampicin, rifabutin, carbamazepine, phenytoin or St John’s Wort)
Medicines that strongly inhibit the metabolising protein called CYP3A4 (e.g. ritonavir, saquinavir, telithromycin, ketoconazole, itraconazole, voriconazole, posaconazole, nefazodone,
atazanavir)
A medicine used to prevent blood clots called warfarin
A medicine called ipilimumab, another medicine for the treatment of melanoma. The combination of this medicine with Zelboraf is not recommended due to increased toxicity to the
liver.
If you are taking any of these medicines (or if you are not sure), please talk to your doctor before taking Zelboraf.
6 months after the end of your treatment. Zelboraf may decrease the efficacy of some oral contraceptives. Please tell your doctor if you are taking an oral contraceptive.
Zelboraf is not recommended for use during pregnancy unless your doctor considers that the benefit for the mother outweighs the risk for the baby. There is no information about the safety
of Zelboraf in pregnant women. Tell your doctor if you are pregnant or planning to become pregnant.
It is not known whether the ingredients in Zelboraf pass into human milk. Breast-feeding is not
recommended during treatment with Zelboraf.
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.
Zelboraf has side effects that can affect your ability to drive or to operate machines. Beware of fatigue
or eye problems that could be a reason for not driving.
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-
free’.
Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.
The recommended dose is 4 tablets twice a day (a total of 8 tablets).
Take 4 tablets in the morning. Then take 4 tablets in the evening.
If you experience side effects, your doctor may decide to carry on your treatment but lower your dose. Always take Zelboraf exactly as your doctor has told you.
In case of vomiting, continue to take Zelboraf as usual and do not take an additional dose.
Do not take Zelboraf regularly on an empty stomach.
Swallow the tablets whole with a glass of water. Do not chew or crush the tablets.
If you take more Zelboraf than you should, talk to your doctor immediately. Taking too much Zelboraf
may increase the likelihood and severity of side effects. No cases of overdose have been observed with Zelboraf.
If you forget a dose and it is more than 4 hours before your next dose, just take your dose as
soon as you remember it. Take the next dose at the usual time.
If it is less than 4 hours before your next dose, skip the missed dose. Then take the next dose at the usual time.
Do not take a double dose to make up for a forgotten dose.
It is important to keep taking Zelboraf for as long as your doctor prescribes it for you. If you have any
further questions on the use of this medicine, ask your doctor.
Like all medicines, Zelboraf can cause side effects, although not everybody gets them. Serious allergic reactions
If you get any of these:
Swelling of the face, lips or tongue
Difficulty breathing
Rash
Fainting sensation.
Call a doctor immediately. Do not use any more Zelboraf until you have spoken to a doctor.
Worsening of radiation treatment side effects can occur in patients who are treated with radiation before, during, or after Zelboraf treatment. This can occur on the area that was treated with radiation, such as the skin, esophagus, bladder, liver, rectum, and lungs.
Tell your doctor immediately if you experience any of the following symptoms:
Skin rash, blistering, peeling or discoloration of the skin
Shortness of breath, which may be accompanied by a cough, fever or chills (pneumonitis)
Difficulty or pain when swallowing, chest pain, heartburn or acid reflux (esophagitis).
Side effects are listed below by frequency:
Very common (may affect more than 1 in 10 people):
Rash, itching, dry or scaly skin
Skin problems including warts
A type of skin cancer (cutaneous squamous cell carcinoma)
Palmar plantar syndrome (i.e. redness, skin peeling or blisters on hands and feet)
Sunburn, being more sensitive to sunlight
Loss of appetite
Headache
Changes in the way things taste
Diarrhoea
Constipation
Feeling sick (nausea), vomiting
Hair loss
Joint or muscle pain, musculoskeletal pain
Pain in the extremities
Back pain
Feeling tired (fatigue)
Dizziness
Fever
Swelling usually in the legs (peripheral oedema)
Cough.
Common (may affect up to 1 in 10 people):
Types of skin cancers (basal cell carcinoma, new primary melanoma)
Thickening of tissues underneath the palm of the hand which may cause tightening of the fingers inward; it can be disabling if severe
Inflammation of the eye (uveitis)
Bell's palsy (a form of facial paralysis that is often reversible)
Tingling or burning feelings in hands and feet
Inflammation of joints
Inflammation of hair’s roots
Weight loss
Inflammation of blood vessels
Problem with the nerves that can produce pain, loss of sensation and/or muscle weakness (neuropathy peripheral)
Change in liver tests results (ALT, alkaline phosphatase and bilirubin increase)
Changes in electrical activity of the heart (QT prolongation)
Inflammation of the fatty tissue under the skin
Abnormal kidney blood test results (creatinine increased).
Change in liver tests results (GGT increase)
Decreased white blood cells (neutropenia).
Uncommon (may affect up to 1 in 100 people):
Allergic reactions that may include swelling of the face and difficulty breathing
Blockage of blood flow to part of the eye (retinal vein occlusion)
Inflammation of the pancreas
Change in liver laboratory tests results or liver injury, including severe liver injury where liver is injured to the extent that it is not able to fully perform its function
A type of cancer (non-cutaneous squamous cell carcinoma)
Thickening of deep tissues underneath the sole of the feet that may be disabling if severe
Rare (may affect up to 1 in 1,000 people)
Progression of a type of pre-existing cancers with RAS mutations (Chronic Myelomonocytic Leukaemia, Pancreatic adenocarcinoma)
A type of severe skin reaction characterised by rash accompanied by fever and inflammation of internal organs such as liver and kidney
Inflammatory disease mainly affecting the skin, lung and eye (sarcoidosis)
Types of kidney injury characterized by inflammation (acute interstitial nephritis) or damage to the tubules of the kidney (acute tubular necrosis).
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.
Keep this medicine out of the sight and reach of children.
Do not use Zelboraf after the expiry date which is stated on the carton and the blister after EXP. The expiry date refers to the last day of that month.
Store in the original package in order to protect from moisture.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.
The active substance is vemurafenib. Each film-coated tablet contains 240 milligrams (mg) of
vemurafenib (as a co-precipitate of vemurafenib and hypromellose acetate succinate).
The other ingredients are:
Tablet core: colloidal anhydrous silica, croscarmellose sodium, hydroxypropyl cellulose and magnesium stearate
Film-coating: iron oxide red, macrogol 3350, polyvinyl alcohol, talc and titanium dioxide.
Zelboraf 240 mg film-coated tablets are pinkish white to orange white. They are oval with “VEM”
engraved on one side.
They are available in aluminium perforated unit dose blisters in packs of 56 x 1 tablets.
Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen Germany
Grenzach-Wyhlen Germany
For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
N.V. Roche S.A.
Tél/Tel: +32 (0) 2 525 82 11
UAB “Roche Lietuva”
Tel: +370 5 2546799
Рош България ЕООД Тел: +359 2 818 44 44
(Voir/siehe Belgique/Belgien)
Roche s. r. o.
Tel: +420 - 2 20382111
Roche (Magyarország) Kft.
Tel: +36 - 1 279 4500
Roche a/s
Tlf: +45 - 36 39 99 99
(See Ireland)
Roche Pharma AG Tel: +49 (0) 7624 140
Roche Nederland B.V. Tel: +31 (0) 348 438050
Roche Eesti OÜ
Tel: + 372 - 6 177 380
Roche Norge AS
Tlf: +47 - 22 78 90 00
Roche (Hellas) A.E.
Τηλ: +30 210 61 66 100
Roche Austria GmbH
Tel: +43 (0) 1 27739
Roche Farma S.A.
Tel: +34 - 91 324 81 00
Roche Polska Sp.z o.o. Tel: +48 - 22 345 18 88
Roche
Tél: +33 (0) 1 47 61 40 00
Roche Farmacêutica Química, Lda
Tel: +351 - 21 425 70 00
Roche d.o.o.
Tel: +385 1 4722 333
Roche România S.R.L. Tel: +40 21 206 47 01
Roche Products (Ireland) Ltd.
Tel: +353 (0) 1 469 0700
Roche farmacevtska družba d.o.o.
Tel: +386 - 1 360 26 00
Roche a/s
c/o Icepharma hf Sími: +354 540 8000
Roche S.p.A.
Tel: +39 - 039 2471
Roche Oy
Puh/Tel: +358 (0) 10 554 500
Γ.Α.Σταμάτης & Σια Λτδ. Τηλ: +357 - 22 76 62 76
Roche AB
Tel: +46 (0) 8 726 1200
Roche Latvija SIA Tel: +371 - 6 7039831
Roche Products (Ireland) Ltd. Tel: +44 (0) 1707 366000