Zelboraf - Vemurafenib uses, dose and side effects

Zelboraf is an anti-cancer 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 with surgery.

It can only be used by patients whose cancer has a change ( mutation ) in the “BRAF” gene. This change may have resulted in the development of melanoma.

Zelboraf targets proteins from this altered gene and delays or stops the development of your cancer.

What you need to know before you take Zelboraf

Do not take Zelboraf:

if you are allergic (hypersensitive) to vemurafenib or 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, skin rash, or feeling faint.

Warnings and precautions

Talk to your doctor before taking Zelboraf.

Allergic reactions

Allergic reactions can occur while taking Zelboraf and they can be serious. Stop taking Zelboraf and get medical help immediately if you get any symptoms of an allergic reaction such as swelling of the face, lips, or tongue, difficulty breathing, skin rash, or feeling faint.

Serious skin reactions

Serious skin reactions can occur while taking Zelboraf. Stop taking Zelboraf and tell your doctor immediately if you develop a skin rash with any of the following symptoms: blisters on the skin, blisters or sores in the mouth, peeling skin, fever, redness or swelling of the face, hands, or soles of the feet.

Previously had cancer

Tell your doctor if you have had a type of cancer other than melanoma, as Zelboraf can cause some types of cancer to get worse.

Radiotherapy reactions

Tell your doctor if you have received, or will receive, radiation therapy, as Zelboraf may worsen the side effects of radiation therapy.

Heart problems

Tell your doctor if you have heart problems, such as a change in the electrical activity of the heart, the so-called “prolonged QT interval”. Your doctor will do tests to check that your heart is working properly before and during your treatment with Zelboraf. If necessary, in some cases your doctor may decide to temporarily interrupt the treatment or stop it completely.

Eye problems

Your eyes should be examined by your doctor while you are taking Zelboraf. Tell your doctor immediately if you experience eye pain, swelling, redness, blurred vision, or other vision changes during your treatment.

Musculoskeletal system and connective tissue

Tell your doctor if you notice an unusual thickening of the palms of your hands with accompanying tightening of the fingers inward, or an unusual thickening of the soles of your feet that may be painful.

Control of your skin before, during, and after treatment

If you notice any changes in your skin while taking this medicine, tell your doctor as soon as possible.
Regularly during your treatment and up to 6 months after your treatment, your doctor will need to examine your skin for a type of cancer called ‘cutaneous squamous cell carcinoma’.
Usually, this change occurs in sun-damaged skin, stays within a limited area, and can be cured by surgical removal.
If your doctor detects this type of skin cancer, he or she will treat it or see you to another doctor for treatment.
In addition, your doctor needs to examine your head, neck, mouth, your lymph nodes and you will be regularly examined with computed tomography. This is a precaution in case cutaneous squamous cell carcinoma changes develop in your body. Genital examination (for women) and anal examinations are also recommended before and at the end of your treatment.
You may develop new melanoma changes while taking Zelboraf. These changes are usually removed with surgery and patients continue their treatment. Monitoring of these changes is done in the same way as described above for cutaneous squamous cell carcinoma.

Kidney or liver problems

Tell your doctor if you have kidney or liver problems. This may affect the effect of Zelboraf. Your doctor will also take some blood tests to check your liver and kidney function before you start taking Zelboraf and during treatment.

Sun protection

Taking Zelboraf can make you more sensitive to sunlight and cause sun damage, which can be serious. Avoid exposing the skin to direct sunlight during treatment.
If you plan to stay in the sun:
- wear clothing that protects your skin, including your head and face, arms, and legs.
- use lip balm and broad-spectrum sunscreen (minimum sun protection factor (SPF) 30, reapply every two to three hours).
This will help protect you from sun damage/burn.

Children and young people

Zelboraf is not recommended for children and adolescents. The effects of Zelboraf on people younger than 18 years are not known

Other medicines and Zelboraf

Before starting treatment, tell your doctor if you are taking, have recently taken, or might take any other medicines (including those you have bought yourself at a pharmacy, grocery, or health shop). This is very important because the use of more than one drug at the same time can strengthen or weaken the effect of drugs.

You must tell your doctor if you are taking :

Medicines are known to affect how your heart beats:
- medicines for heart rhythm disorders (e.g. quinidine, amiodarone )
- medicines for depression (eg amitriptyline, imipramine)
- medicines against bacterial infections (e.g. azithromycin, clarithromycin)
- medicines for nausea and vomiting (ondansetron, domperidone)
Medicines that are mainly metabolized by a protein called CYP1A2 (eg caffeine, olanzapine, theophylline), CYP3A4 (eg some birth control pills ) or CYP2C8
Medicines that affect a protein called P-GP or BCRP (eg, verapamil, cyclosporine, ritonavir, quinidine, itraconazole, gefitinib)
Medicines that may be affected by a protein called P-GP (eg aliskiren, colchicine, digoxin, everolimus, fexofenadine) or a protein called BCRP (eg methotrexate, mitoxantrone, rosuvastatin)
Medicines that stimulate the metabolizing protein are called CYP3A4 or a metabolizing process called glucuronidation (eg rifampicin, rifabutin, carbamazepine, phenytoin, or St. John’s wort ).
Medicines that strongly inhibit the metabolizing protein called CYP3A4 (eg ritonavir, saquinavir, telithromycin, ketoconazole , itraconazole, voriconazole, posaconazole, nefazodone, atazanavir)
A medicine used to prevent blood clots called warfarin
A drug called ipilimumab, is another drug used to treat melanoma. The combination of this drug and 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), tell your doctor before taking Zelboraf.

Pregnancy and breastfeeding

Use an appropriate method of contraception during your treatment and for at least 6 months after you finish your treatment. Zelboraf can reduce the effectiveness of some birth control pills. Tell your doctor if you are using an oral contraceptive.
Zelboraf is not recommended for use 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. Tell your doctor if you are pregnant or planning to become pregnant.
It is not known whether the content of Zelboraf passes into breast milk. Breastfeeding is not recommended during treatment with Zelboraf.

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor before using this medicine.

Driving ability and use of machinery

Zelboraf has side effects that may affect your ability to drive or use machines. Be aware that fatigue or eye problems may be reasons not to drive.

Important information about some ingredients in Zelboraf

This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. it is almost ‘sodium-free’.

How to take Zelboraf

Always take this medicine as directed by your doctor. Consult a doctor if you are unsure.

How many tablets to take

The recommended dose is 4 tablets twice daily (8 tablets in total).
Take 4 tablets in the morning. Then take 4 tablets in the evening.
If you experience side effects, your doctor may decide to continue the treatment but lower your dose. Always take Zelboraf as directed by your doctor.
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 tablet

If you have taken too much Zelboraf

If you take more Zelboraf than you should, contact your doctor immediately. Taking too much Zelboraf can increase the risk and severity of side effects. No cases of overdose have been observed with Zelboraf.

If you forget to take Zelboraf

If you have forgotten a dose and it is more than 4 hours until your next dose, take your dose as soon as you remember. Take the next dose at the usual time.
If it is less than 4 hours until your next dose, skip the missed dose. Take the next dose at the usual time.
Do not take a double dose to make up for a missed dose.

If you stop taking Zelboraf

You must continue to take Zelboraf for as long as your doctor prescribes it for you. If you have any further questions about how to take this medicine, ask your doctor.

Possible side effects

Like all medicines, Zelboraf can cause side effects, although not everybody gets them.

Severe allergic reactions

If you get any of these:

Swelling of the face, lips, or tongue
Difficulty breathing
Rash
Fainting feeling

Contact a doctor immediately. Do not take more Zelboraf until you have spoken to a doctor.

Worsening side effects caused by radiotherapy may occur in patients treated with radiation before, during, or after treatment with Zelboraf. This can occur in 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, scaling, or discoloration of the skin
Shortness of breath which may be accompanied by cough, fever, or chills ( pneumonitis )
Difficulty or pain in swallowing, chest pain, heartburn, or acid reflux ( oesophagitis ).

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

The side effects below are listed by frequency:

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

Skin rash, itching, dry or flaky skin
Skin problems, including warts
A type of skin cancer (cutaneous squamous cell carcinoma)
The hand-foot syndrome ( redness, peeling, or blistering of the hands and feet)
Tan, increased sensitivity to sunlight
Loss of appetite
Headache
Taste changes
Diarrhea
Constipation
Nausea, vomiting
Hair loss
Joint or muscle pain, musculoskeletal pain
Pain in arms and legs
Back pain
Fatigue
Dizziness
Fever
Swelling usually in the legs (peripheral edema )
Cough

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

Types of skin cancer ( basal cell carcinoma, new primary melanoma )
Thickening of tissue under the palm which can cause tightening of the fingers inwards; in severe cases, it can be disabling
Inflammation of the eye ( uveitis )
Bell’s palsy (a form of facial paralysis that is often reversible (transient))
Tingling or a burning sensation in the hands and feet
Arthritis
Inflammation in hair roots
Weight loss
Inflammation in the blood vessels
Problems with nerves that can cause pain, loss of sensation, and/or muscle weakness ( peripheral neuropathy )
Changes in liver test results (increase in ALT, alkaline phosphatases, bilirubin )
Changes in the electrical activity of the heart ( QT prolongation)
Inflammation of the fatty tissue under the skin.
Abnormal kidney test results (creatinine increase in the blood)
Changes in liver test results (GGT increase)
Decreased number of white blood cells ( neutropenia ).

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

The allergic reactions which may include swelling of the face and difficulty breathing
Blockage of blood flow to parts of the retina of the eye ( retinal vein occlusion)
Inflammation of the pancreas
Changes in liver test results or liver damage, including severe liver damage where the liver is damaged to such an extent that it does not function completely
A type of cancer (non-cutaneous squamous cell carcinoma )
Thickening of deep tissue under the sole can be disabling in severe cases.

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

Progression (progression) of a type of previously existing cancer with RAS mutations ( chronic myelomonocytic leukemia, pancreatic adenocarcinoma )
A type of severe skin reaction characterized by a rash along with fever and inflammation of internal organs such as the liver and kidneys.
An inflammatory disease that mainly affects the skin, lungs, and eyes ( sarcoid )
Kidney damage is characterized by inflammation ( acute interstitial nephritis) or damage to the renal tubules ( acute tubular necrosis ).

How to store Zelboraf

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

Use before the expiry date stated on the carton and blister pack after the Issue. data/EXP. The expiration date is the last day of the specified month.

Store in the original packaging. Moisture sensitive.

Medicines must not be thrown into the drain or among the household waste. Ask the pharmacist how to dispose of medicines that are no longer used. These measures will help to protect the environment.

Contents of the packaging and other information

Contents declaration

The active substance is vemurafenib. Each film-coated tablet contains 240 milligrams (mg) of vemurafenib (as a combined precipitate of vemurafenib and hypromellose acetate succinate).
Other ingredients are:
- Core: silica, colloidal, anhydrous, croscarmellose sodium, hydroxypropyl cellulose, and magnesium stearate
- Film coating: red iron oxide, macrogol 3350, polyvinyl alcohol, talc, and titanium dioxide.

Appearance and package sizes of the medicine

Zelboraf 240 mg film-coated tablets are light pink to light orange. They are oval with ‘VEM’ engraved on one side.

They are available in aluminum perforated unit dose blisters in packs of 56 x 1 tablet.

Marketing Authorisation Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG