NEXAVAR 200 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Nexavar 200mg film-coated tablets

sorafenib

Read all of this 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 further questions, ask your doctor or pharmacist.
• 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 experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Nexavar and what is it used for

Nexavar is used to treat liver cancer (hepatocellular carcinoma).

Nexavar is also used to treat advanced kidney cancer (advanced renal cell carcinoma) when standard treatment has not worked to slow down the disease or is considered inappropriate.

Nexavar is used to treat thyroid cancer (differentiated thyroid carcinoma).

Nexavar is a multi-kinase inhibitor. It works by slowing down the rate of growth of cancer cells and interrupting the blood supply that allows cancer cells to grow.

2. What you need to know before you take Nexavar

Do not take Nexavar

• If you are allergicto sorafenib or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or pharmacist before starting Nexavar.

Be careful with Nexavar

• If you have skin problems. Nexavar may cause skin reactions and rashes, especially on the hands and feet. Your doctor can usually treat these conditions. Otherwise, your doctor may interrupt treatment temporarily or completely.
• If you have high blood pressure. Nexavar may increase blood pressure. Your doctor will check your blood pressure and may give you a medicine to treat high blood pressure.
• If you have or have had an aneurysm(enlargement and weakening of the wall of a blood vessel) or a

tear in the wall of a blood vessel.

• If you have diabetes.Blood sugar levels in diabetic patients should be regularly checked in order to assess whether a dose adjustment of the anti-diabetic medication is necessary to minimize the risk of low blood sugar levels.
• If you have bleeding problems or are taking warfarin or phenprocoumon. Treatment with Nexavar may increase the risk of bleeding. If you are taking warfarin or phenprocoumon, medicines that thin the blood to prevent blood clots, you may have a higher risk of bleeding.
• If you have chest pain or heart problems. Your doctor will decide whether to interrupt treatment temporarily or completely.
• If you have a heart disorder,such as an abnormal electrical signal called “prolonged QT interval”.
• If you are going to have surgery or have recently had surgery. Nexavar may affect wound healing. You should usually stop taking Nexavar if you are going to have surgery. Your doctor will decide when to restart treatment with Nexavar.
• If you are taking irinotecanor docetaxel,which are also anti-cancer medicines. Nexavar may increase the effects and, in particular, the side effects of these medicines.
• If you are taking neomycin or other antibiotics. The effect of Nexavar may be reduced.
• If you have severe liver impairment. You may experience more severe side effects when taking this medicine.
• If you have kidney impairment. Your doctor will check your fluid and electrolyte balance.
• Fertility. Nexavar may reduce male and female fertility. If this applies to you, consult your doctor.
• During treatment, holes in the walls of the intestine(gastrointestinal perforation) (see section 4: Possible side effects) may occur. In this case, your doctor will interrupt treatment.
• If you have thyroid cancer.Your doctor will check your blood calcium and thyroid hormone levels.
• If you experience the following symptoms, contact your doctor immediately, as it may be a life-threatening situation:nausea, difficulty breathing, irregular heartbeats, muscle cramps, convulsions, cloudy urine, and fatigue. The cause may be a set of metabolic complications that can occur during cancer treatment as a result of the breakdown products of dying cancer cells [tumor lysis syndrome (TLS)] and may cause changes in kidney function and acute kidney failure (see also section 4: Possible side effects).

Talk to your doctor if any of these apply to you.It may be necessary to treat them or your doctor may decide to change your dose of Nexavar or stop treatment completely (see also section 4: Possible side effects).

Children and adolescents

Nexavar has not yet been tested in children and adolescents.

Taking Nexavar with other medicines

Some medicines affect Nexavar or may be affected by it. Tell your doctor or pharmacist if you are taking, have recently taken, or might take any of the medicines listed below or any other medicine, including those obtained without a prescription:

• Rifampicin, neomycin, or other medicines used to treat infections (antibiotics)
• St. John's Wort, a herbal remedy for depression
• Phenytoin, carbamazepine, or phenobarbital, treatments for epilepsyand other conditions
• Dexamethasone, a corticosteroidused in various conditions
• Warfarin or phenprocoumon, anticoagulants used to prevent blood clot formation
• Doxorubicin, capecitabine, docetaxel, paclitaxel, and irinotecan, which are anti-cancer treatments
• Digoxin, a treatment for mild to moderate heart failure

Pregnancy and breastfeeding

Avoid becoming pregnant during treatment with Nexavar.If you can become pregnant, use adequate contraceptive methods during treatment. If you become pregnant during treatment with Nexavar, inform your doctor immediately, who will decide whether you should continue treatment.

Do not breastfeed during treatment with Nexavaras this medicine may interfere with the growth and development of your baby.

Driving and using machines

There are no indications that Nexavar affects the ability to drive or use machines.

Nexavar contains sodium

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

3. How to take Nexavar

The recommended dose of Nexavar in adults is 2 tablets of 200mg, twice a day.

This is equivalent to a daily dose of 800 mg or 4 tablets per day.

Nexavar tablets should be taken with a glass of wateroutside of meals or with a low- or moderate-fat meal. Do not take this medicine with a high-fat meal, as this reduces the effectiveness of Nexavar. If you intend to take a high-fat meal, you should take the sorafenib tablets at least 1 hour before or 2 hours after the meal.

Follow the instructions for administration of this medicine exactly as indicated by your doctor. If you are in doubt, consult your doctor or pharmacist again.

It is important to take this medicine at the same time each day to maintain a steady amount in the bloodstream.

Normally, you will continue to take this medicine as long as it provides clinical benefits and you do not experience unacceptable side effects.

If you take more Nexavar than you should

Consult your doctor immediatelyif you (or anyone else) have taken a higher dose than prescribed. Taking too much Nexavar increases the likelihood of side effects or makes them more severe, especially diarrhea or skin problems. Your doctor may instruct you to stop taking this medicine.

If you forget to take Nexavar

If you have missed a dose, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and continue with your regular schedule. Do not take a double dose to make up for the missed dose.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. This medicine can also affect some laboratory test results.

Very common:

may affect more than 1 in 10 people

• diarrhea
• nausea
• feeling weak or tired (fatigue)
• pain (including mouth pain, abdominal pain, headache, bone pain, tumor pain)
• hair loss (alopecia)
• redness or pain on the palms of the hands and soles of the feet (hand-foot skin reaction)
• itching or rash
• vomiting
• bleeding (including bleeding in the brain, intestinal wall, and respiratory tract)
• high blood pressure or increased blood pressure (hypertension)
• infections
• loss of appetite (anorexia)
• constipation
• joint pain (arthralgia)
• fever
• weight loss
• dry skin

Common:

may affect up to 1 in 10 people

• flu-like illness
• indigestion (dyspepsia)
• difficulty swallowing (dysphagia)
• inflamed mouth or dry mouth, pain in the tongue (stomatitis and mucosal inflammation)
• low calcium levels in the blood (hypocalcemia)
• low potassium levels in the blood (hypokalemia)
• low blood sugar levels (hypoglycemia)
• muscle pain (myalgia)
• nerve damage (including numbness or tingling in fingers and toes) (peripheral sensory neuropathy)
• depression
• erectile dysfunction (impotence)
• voice changes (dysphonia)
• acne
• inflamed, dry, or scaly skin that peels (dermatitis, skin peeling)
• heart failure
• heart attack (myocardial infarction)or chest pain
• ringing in the ears (tinnitus)
• kidney failure
• high levels of protein in the urine (proteinuria)
• general weakness or loss of strength (asthenia)
• low white blood cell count (leukopenia and neutropenia)
• low red blood cell count (anemia)
• low platelet count in the blood (thrombocytopenia)
• inflammation of the hair follicles (folliculitis)
• underactive thyroid gland (hypothyroidism)
• low sodium levels in the blood (hyponatremia)
• distortion of the sense of taste (dysgeusia)
• redness of the face and often other areas of the skin (flushing)
• runny nose (rhinorrhea)
• heartburn (gastroesophageal reflux disease)
• skin cancer (keratoacanthoma/squamous cell skin cancer)
• thickening of the outer layer of the skin (hyperkeratosis)
• sudden, involuntary muscle contractions (muscle spasms)

Uncommon:

may affect up to 1 in 100 people

• inflammation of the stomach lining (gastritis)

• abdominal pain caused by pancreatitis, inflammation of the gallbladder, and/or the bile ducts.
• yellowing of the skin and eyes (jaundice)caused by high levels of bile pigments (hyperbilirubinemia)
• allergic reactions (including skin reactions and hives)
• dehydration
• breast enlargement (gynecomastia)
• difficulty breathing (lung disease)
• eczema
• overactive thyroid gland (hyperthyroidism)
• multiple skin rashes (erythema multiforme)
• abnormally high blood pressure
• holes in the walls of the intestine (gastrointestinal perforation)
• reversible inflammation of the back of the brain, which may be associated with headache, altered consciousness, seizures, and visual symptoms including loss of vision (reversible posterior leukoencephalopathy syndrome)
• severe allergic reaction (anaphylactic reaction)

Rare:

may affect up to 1 in 1,000 people

• allergic reaction with swelling of the skin (e.g., face, tongue) that can cause difficulty breathing or swallowing (angioedema)
• abnormal heart rhythm (QT prolongation)
• inflammation of the liver that can lead to nausea, vomiting, abdominal pain, and yellowing of the skin (drug-induced hepatitis)
• a rash that looks like a sunburn, which can occur on skin that has been exposed to radiation before and can be severe (radiation-induced dermatitis)
• severe skin and/or mucous membrane reactions that can include painful blisters or fever, including widespread skin peeling (Stevens-Johnson syndrome and toxic epidermal necrolysis)
• abnormal muscle breakdown that can lead to kidney problems (rhabdomyolysis)
• kidney damage that causes large amounts of protein to be lost (nephrotic syndrome)
• inflammation of the blood vessels in the skin that can cause a rash (leukocytoclastic vasculitis)

Frequency not known:the frequency cannot be estimated from the available data.

• brain damage that can be associated with, for example, drowsiness, changes in behavior, or confusion (encephalopathy)
• enlargement and weakening of the wall of a blood vessel or tear in the wall of a blood vessel (aneurysms and arterial dissections).
• nausea, difficulty breathing, irregular heartbeats, muscle cramps, convulsions, cloudy urine, and fatigue (tumor lysis syndrome [TLS]) (see section 2).

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. 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.

5. Storing Nexavar

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

Do not use this medicine after the expiry datestated on the carton and on each blister after EXP. The expiry date is the last day of the month stated.

Do not store this medicine at a temperature above 25°C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Packaging Contents and Additional Information

Nexavar Composition

• The activeingredient is sorafenib. Each film-coated tablet contains 200 mg of sorafenib (as tosylate)
• The othercomponents are:

Tablet core: sodium croscarmellose, microcrystalline cellulose, hypromellose, sodium laurilsulfate, magnesium stearate.

Tablet coating: hypromellose, macrogol, titanium dioxide (E 171), red iron oxide (E 172).

Product Appearance and Packaging Contents

The film-coated tablets with Nexavar 200 mg have a red color and are round with the Bayer cross on one side and "200" on the other. They are available in calendar packs of 112 tablets: four transparent blisters with 28 tablets each.

Marketing Authorization Holder

Bayer AG

51368 Leverkusen

Germany

Manufacturer

Bayer AG

Kaiser-Wilhelm-Allee

51368 Leverkusen

Germany

You can request more information about this medication by contacting the local representative of the marketing authorization holder.

Date of the Last Revision of this Leaflet:

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