Zelboraf 240 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Zelboraf 240 mg film-coated tablets

vemurafenib

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.
• This medicine has been prescribed for you only. Do not give it 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, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Zelboraf is and what it is used for

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 who have a specific change (mutation) in the gene known as "BRAF". This alteration may cause the melanoma to develop.

Zelboraf acts on the proteins produced from this altered gene and slows down or stops the progression of the cancer.

2. What you need to know before starting to take Zelboraf

Do not take Zelboraf:

• if you are allergic to vemurafenib or to any of the other ingredients of this medicine (listed in section 6). Symptoms of allergic reactions may include swelling of the face, lips, or tongue, difficulty breathing, rashes, or feeling dizzy.

Warnings and precautions

Talk to your doctor before starting to take Zelboraf.

Allergic reactions

• While taking Zelboraf, you may experience allergic reactions, which can be severe. Stop treatment with Zelboraf and seek immediate medical help if you develop any symptoms of an allergic reaction, such as swelling of the face, lips, or tongue, difficulty breathing, rashes, or feeling dizzy.

Severe skin reactions

• While taking Zelboraf, you may experience severe skin reactions. Stop treatment with Zelboraf and contact your doctor immediately if you develop a skin rash accompanied by any of the following symptoms: skin blisters, blisters or sores in the mouth, peeling skin, fever, redness or swelling of the face, hands, or soles of the feet.

Previous history of cancer

• Inform your doctor if you have previously had a type of cancer other than melanoma, as Zelboraf may cause progression of certain types of cancers.

Radiation therapy reactions

• Inform your doctor if you have received or are scheduled to receive radiation therapy, as Zelboraf may worsen the effects of radiation treatment.

Heart disorders

• Inform your doctor if you have a heart condition, such as an abnormality in the electrical activity of your heart known as “QT interval prolongation.” Your doctor will perform tests to check that your heart is functioning properly before and during treatment with Zelboraf. If necessary, your doctor may decide to temporarily or permanently discontinue your treatment with Zelboraf.

Eye problems

• Your doctor should examine your eyes while you are taking Zelboraf. Contact your doctor immediately if you experience pain, swelling, redness, blurred vision, or other changes in vision during treatment.

Musculoskeletal and connective tissue disorders

• Inform your doctor if you notice unusual thickening of the palms of your hands along with tightening of the fingers pulling inward, or unusual thickening of the soles of your feet that may be painful.

Skin examination before, during, and after treatment

• If you notice any changes in your skin while taking this medicine, please consult your doctor as soon as possible.
• During your treatment and up to 6 months afterward, your doctor will examine your skin for a type of cancer called “cutaneous squamous cell carcinoma.”
• This lesion typically appears on sun-damaged skin areas, remains localized, and can be treated surgically.
• If your doctor diagnoses this type of skin cancer, it will be treated or you will be referred to another doctor for treatment.
• In addition, your doctor will examine your head, neck, mouth, and lymph glands, and will perform regular body scans. This is a precautionary measure in case you develop squamous cell carcinoma inside your body. A genital examination (for women) and an anal examination are also recommended before and after completing treatment.
• While taking Zelboraf, you may develop new melanoma lesions. These lesions are usually surgically removed, and patients continue their treatment. Monitoring of these lesions follows the same procedure described above for cutaneous squamous cell carcinoma.

Kidney or liver problems

• Inform your doctor if you have kidney or liver problems. This may affect the activity of Zelboraf. Additionally, your doctor will perform blood tests to monitor your liver and kidney function before starting and during treatment with Zelboraf.

Sun protection

• While taking Zelboraf, you may become more sensitive to sunlight and may experience sunburns, which can be severe. During treatment, avoid exposing your skin directly to sunlight.
• If you need to be in the sun:
• wear protective clothing, including head and face coverings, long sleeves, and long pants;
• use a lip balm and a broad-spectrum sunscreen (Sun Protection Factor (SPF) of at least 30, reapplied every two to three hours).
• This will help protect you from sunburns.

Children and adolescents

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

Other medicines and Zelboraf

Before starting treatment, inform your doctor if you are taking, have recently taken, or might need to take any other medicines. This is very important, as taking more than one medicine at the same time may increase or decrease their pharmacological effects.

Please make sure to inform your doctor if you are taking:

• Medicines known to affect the way your heart beats:
• medicines for heart rhythm disorders (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 primarily eliminated by metabolic proteins called CYP1A2 (e.g., caffeine, olanzapine, theophylline) or CYP3A4 (e.g., some oral contraceptives) or CYP2C8.
• Medicines that interfere with 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 by a protein called BCRP (e.g., methotrexate, mitoxantrone, rosuvastatin).
• Medicines that stimulate metabolic proteins called CYP3A4 or the metabolic process called glucuronidation (e.g., rifampicin, rifabutin, carbamazepine, phenytoin, or St. John's wort).
• Medicines that strongly inhibit the metabolizing protein 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 used to treat melanoma. The combination of this medicine with Zelboraf is not recommended due to increased liver toxicity.

If you are taking any of these medicines (or if you are unsure), please inform your doctor before taking Zelboraf.

Pregnancy and breastfeeding

• Use an appropriate contraceptive method during treatment and for at least 6 months after completing treatment. Zelboraf may reduce the effectiveness of some oral contraceptives. Inform your doctor if you are taking an oral contraceptive.
• Zelboraf is not recommended during pregnancy unless your doctor considers that the benefit to the mother outweighs the risk to the baby. There is no information on the safety of Zelboraf in pregnant women. Inform your doctor if you are pregnant or planning to become pregnant.
• It is unknown whether any components of Zelboraf pass into breast milk. Breastfeeding is not recommended during treatment with Zelboraf.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Driving and using machines

Zelboraf has side effects that may affect your ability to drive or operate machinery. Feelings of fatigue or eye problems may impair your ability to drive.

Important information about some ingredients of Zelboraf

This medicine contains less than 23 mg of sodium (1 mmol) per tablet, which is essentially “sodium-free.”

3. How to take Zelboraf

Follow exactly your doctor's instructions on how to take this medicine. If in doubt, consult your doctor again.

How many tablets to take

• The recommended dose is 4 tablets twice daily (a total of 8 tablets).
• Take 4 tablets in the morning and then 4 tablets in the evening.
• If you experience any adverse effects, your doctor may reduce your dose to allow you to continue treatment. Always take Zelboraf exactly as your doctor has instructed.
• If you vomit, continue taking Zelboraf as usual and do not take an additional dose.

How to take your tablets

• 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

If you take more Zelboraf than you should, inform your doctor immediately. Taking more Zelboraf than prescribed may increase the likelihood and severity of adverse effects. Cases of overdose with Zelboraf have not been observed.

If you forget to take Zelboraf

• If you forget to take a dose and there are more than 4 hours until your next dose, take the missed dose as soon as you remember. Then take your next dose at the usual time.
• If less than 4 hours remain before your next dose, skip the missed dose and continue taking Zelboraf according to your regular schedule.
• Do not take a double dose to make up for a missed dose.

If you stop taking Zelboraf

It is important to take Zelboraf for the entire duration of treatment prescribed by your doctor.

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

4. Possible adverse effects

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

Severe allergic reactions

If you experience:

• Swelling of the face, lips, or tongue
• Difficulty breathing
• Rash
• Feeling faint

Inform your doctor immediately. Do not take any more Zelboraf tablets until you have spoken to your doctor.

Worsening of adverse effects due to radiation may occur in patients who have received radiotherapy before, during, or after treatment with Zelboraf. This may occur in areas previously treated with radiation, such as the skin, esophagus, gallbladder, liver, rectum, and lungs.

Inform your doctor immediately if you notice any of the following symptoms:

• Skin rash, blistering, peeling, or discoloration of the skin
• Difficulty breathing, possibly accompanied by cough, fever, or chills (pneumonitis)
• Difficulty or pain when swallowing, chest pain, burning sensation, or acid reflux (esophagitis)

Please inform your doctor as soon as possible if you notice any changes in your skin.

The adverse effects listed below are arranged by frequency:

Very common (may affect more than 1 in 10 patients):

• Rash or skin eruption, itching, dry or scaly skin
• Skin disorders including warts
• A type of skin cancer (cutaneous squamous cell carcinoma)
• Palmoplantar syndrome (i.e., redness, peeling, or blistering of the skin on hands and feet)
• Sunburn, increased sensitivity to sunlight
• Loss of appetite
• Headache
• Changes in taste perception
• Diarrhea
• Constipation
• Feeling unwell (nausea), vomiting
• Hair loss
• Pain in muscles or joints, musculoskeletal pain
• Pain in the limbs
• Back pain
• Feeling tired (fatigue)
• Dizziness
• Fever
• Swelling, usually in the legs (peripheral edema)
• Cough

Common (may affect up to 1 in 10 patients):

• Types of skin cancers (basal cell carcinoma, new primary melanoma)
• Thickening of tissues beneath the palm of the hand, which may cause fingers to bend inward; if severe, it may be disabling
• Inflammation of the eye (uveitis)
• Bell’s palsy (a form of facial paralysis, often reversible)
• Tingling or burning sensation in hands or feet
• Joint inflammation
• Inflammation at the base of hair follicles
• Weight loss
• Inflammation of blood vessels
• Nerve problems that may cause pain, loss of sensation, and/or muscle weakness (peripheral neuropathy)
• Changes in liver function tests (increased ALT, alkaline phosphatase, and bilirubin)
• Changes in the heart's electrical activity (prolongation of QT interval)
• Inflammation of fatty tissue beneath the skin
• Abnormal blood test results in kidney function (increased creatinine)
• Changes in liver function tests (increased GGT)
• Decrease in white blood cells (neutropenia)
• Low platelet count (thrombocytopenia)
• Mouth pain or mouth ulcers, inflammation of mucous membranes (stomatitis)

Uncommon (may affect up to 1 in 100 patients):

• 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
• Changes in liver laboratory tests or liver damage, including severe liver damage to the point where the liver cannot function properly
• A type of cancer (non-cutaneous squamous cell carcinoma)
• Thickening of deep tissues beneath the sole of the foot, which could be
• disabling if severe

Rare (may affect more than 1 in 1,000 patients):

• Progression of certain pre-existing cancers with RAS mutations (Chronic Myelomonocytic Leukemia, Pancreatic Adenocarcinoma)
• A severe type of skin reaction characterized by rash accompanied by fever and inflammation of internal organs such as the liver and kidneys
• Inflammatory diseases affecting mainly the skin, lungs, and eyes (sarcoidosis)
• Types of kidney damage characterized by inflammation (acute interstitial nephritis) or damage to the kidney tubules (acute tubular necrosis)

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V.

By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Zelboraf

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

Do not use this medicine after the expiry date stated on the packaging and blister after EXP. The expiry date refers to the last day of the month indicated.

Store in the original packaging to protect from moisture.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of any unused medicine and its packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Zelboraf

• The active substance is vemurafenib. Each film-coated tablet contains 240 milligrams (mg) of vemurafenib (in the form of a co-precipitate of vemurafenib and succinic acid acetate of hypromellose).
• The other components are:
• Tablet core: colloidal anhydrous silica, sodium croscarmellose, hydroxypropyl cellulose, and magnesium stearate
• Film coating: red iron oxide (E172), macrogol 3350, polyvinyl alcohol, talc, and titanium dioxide (E171).

Appearance of the product and contents of the pack

Zelboraf 240 mg film-coated tablets are white-pink to slightly orange in colour. They are oval-shaped with the imprint “VEM” engraved on one side.

It is supplied in single-dose aluminum blister packs in packages containing 56 × 1 tablets.

Marketing Authorization Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer responsible

Roche Pharma AG

Emil-Barell-Strasse 1

D-79639

Grenzach-Wyhlen

Germany

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

Date of the most recent review of this summary:

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