Package Insert: Information for the User

Nexavar 200Film-Coated Tablets

sorafenib

Read this package insert carefully before you start taking this medicine, because it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section4.

Nexavar is used in the treatment of liver cancer (hepatocellular carcinoma).

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

Nexavar is used in the treatment of thyroid cancer (differentiated thyroid carcinoma).

Nexavar is amulti-tyrosine kinase inhibitor. It acts by slowing down the growth rate of cancer cells and disrupting the blood supply that allows cancer cells to grow.

Do not take Nexavar

• If you are allergicto sorafenib or any of the other components of this medication (listed in section6).

Warnings and precautions

Consult your doctor or pharmacist before starting to take Nexavar.

Be especially careful with Nexavar

• If you experience skin problems. Nexavar may cause rashes and skin reactions, especially on hands and feet. Your doctor can usually treat these conditions. Otherwise, your doctor may temporarily or completely stop treatment.
• If you have hypertension. Nexavar may increase blood pressure. Your doctor will monitor your blood pressure and may prescribe medication to treat hypertension.
• If you have or have had an aneurysm(an enlargement and weakening of a blood vessel wall)or a

tear in the wall of a blood vessel.

• If you have diabetes.Blood sugar levels in diabetic patients should be regularly monitored to assess whether a dose adjustment of antidiabetic medication is necessary to minimize the risk of low blood sugar levels.
• If you have bleeding problems or are taking warfarin or fenprocumona. Treatment with Nexavar may increase the risk of bleeding. If you are taking warfarinor fenprocumona, medications that thin the blood to prevent blood clots, you may be at higher risk of bleeding.
• If you have chest pain or heart problems. Your doctor will decide whether to temporarily or completely stop treatment.
• If you have a heart condition,such as an abnormal electrical signal called “prolongation of the QT interval”.
• If you are about to undergo surgery or have recently undergone surgery. Nexavar may affect wound healing. Normally, you should stop taking Nexavar before surgery. Your doctor will decide when to restart treatment with Nexavar.
• If you are taking irinotecanor docetaxel,which are also anticancer medications. Nexavar may increase the effects and, in particular, the adverse effects of these medications.
• If you are taking neomicina or other antibiotics. The effect of Nexavar may be reduced.
• If you have severe liver failure. You may experience more severe side effects when taking this medication.
• If you have kidney failure. Your doctor will monitor your fluid and electrolyte balance.
• Fertility. Nexavar may reduce male and female fertility. If this applies to you, consult your doctor.
• During treatment, perforation of the intestinal walls(gastrointestinal perforation)(see section4: Possible side effects) may occur. In this case, your doctor will stop treatment.
• If you have thyroid cancer.Your doctor will monitor your blood calcium and thyroid hormone levels.
• If you experience the following symptoms, contact your doctor immediately, as they may be life-threatening:nausea, difficulty breathing, irregular heartbeats, muscle cramps, seizures, 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).

Consult your doctor if any of these aspects affect you.You may need to undergo treatment for them or your doctor may decide to adjust your Nexavar dose or completely stop treatment (see also section4: Possible side effects).

Children and adolescents

No studies have been conducted with Nexavar in children and adolescents.

Taking Nexavar with other medications

Some medications affect Nexavar or may be affected by it. Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any of the medications listed below or any other medication, including those purchased without a prescription:

• Rifampicin, neomicina, or other medications used to treat infections (antibiotics)
• St. John's Wort, a herbal remedy fordepression
• Phenobarbital, carbamazepine, or phenytoin, treatments forepilepsyand other conditions
• Dexamethasone, acorticosteroidused in various conditions
• Warfarin or fenprocumona, anticoagulants used toprevent blood clots
• Doxorubicin, capecitabine, docetaxel, paclitaxel, and irinotecan, which areanticancer medications
• Digoxin, a treatment formild to moderate heart failure

Pregnancy and breastfeeding

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

Do not breastfeed your baby during treatment with Nexavaras this medication may interfere with your baby's growth and development.

Driving and operating machinery

No evidence suggests that Nexavar affects your ability to drive or operate machinery.

Nexavar contains sodium

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

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

This is equivalent to a daily dose of 800mg or four tablets a 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 medication with a high-fat meal, as this reduces the effectiveness of Nexavar. If you plan to take a high-fat meal, take the Nexavar tablets at least 1 hour before or 2 hours after the meal.

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

It is essential to take this medication at the same time every day to maintain a stable amount in the bloodstream.

Normally, you will continue to take this medication 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 dose higher than prescribed. Taking too much Nexavar increases the likelihood of side effects or more severe side effects, especially diarrhea or skin problems. Your doctor may instruct you to stop taking this medication.

If you forgot 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 as usual. Do not take a double dose to make up for the missed dose.

Like all medicines, this medicine can cause side effects, although not everyone will experience them. This medicine may also affect some laboratory test results.

Very common:

may affect more than 1 in 10 patients

• diarrhea
• nausea
• feeling of weakness or fatigue(fatigue)
• pain (including mouth pain, abdominal pain, headache, bone pain, tumor pain)
• hair loss(alopecia)
• redness or pain on palms and soles of the feet(hand-foot syndrome)
• pruritus or exanthema
• vomiting
• bleeding (including cerebral hemorrhage, intestinal wall hemorrhage, and respiratory tract hemorrhage)
• high blood pressure or increased blood pressure(hypertension)
• infections
• loss of appetite(anorexia)
• constipation
• joint pain(arthralgias)
• fever
• weight loss
• dry skin

Common:

may affect up to 1 in 10 patients

• influenza-like illness
• indigestion(dyspepsia)
• difficulty swallowing(dysphagia)
• inflamed or dry mouth, tongue pain(stomatitis and mucosal inflammation)
• low calcium levels in the blood(hypocalcemia)
• low potassium levels in the blood(hypokalemia)
• low blood sugar(hypoglycemia)
• muscle pain(myalgias)
• alterations in sensitivity in fingers and toes, including numbness or tingling(peripheral sensory neuropathy)
• depression
• erectile dysfunction(impotence)
• voice alteration(dysphonia)
• acne
• inflamed, dry, or scaly skin that peels(dermatitis, skin peeling)
• heart failure
• heart attack(myocardial infarction)or chest pain
• tinnitus (ringing in the ears)
• kidney insufficiency
• abnormally high protein levels in the urine(proteinuria)
• general weakness or loss of strength(asthenia)
• decreased white blood cell count(leukopenia and neutropenia)
• decreased red blood cell count(anemia)
• low platelet count in the blood(thrombocytopenia)
• inflammation of 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)
• nasal secretion(rhinorrhea)
• pyrosis(gastroesophageal reflux disease)
• skin cancer(squamous cell carcinoma)
• thickening of the outer layer of the skin(hyperkeratosis)
• sudden, involuntary muscle contractions(muscle spasms)

Uncommon:

may affect up to 1 in 100 patients

• inflammation of the stomach lining(gastritis)

• abdominal pain caused by pancreatitis, inflammation of the gallbladder and/or bile ducts.
• yellow skin or eyes(jaundice)caused by elevated levels of bile pigments(hyperbilirubinemia)
• allergic reactions (including skin reactions and rashes)
• dehydration
• breast enlargement(gynecomastia)
• difficulty breathing(pulmonary disease)
• eczema
• overactive thyroid gland(hyperthyroidism)
• multiple skin eruptions(erythema multiforme)
• abnormally high blood pressure
• perforation of the intestinal wall(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, sudden allergic reaction(anaphylactic reaction)

Rare:

may affect up to 1 in 1,000 patients

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

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

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

Reporting of adverse reactions

If you experienceany type of adverse reaction, consult your doctor or pharmacist, even if it is apossibleadverse reaction that does not appear in this leaflet.You can also report themdirectlythrough the national reporting system included in theAppendixV.By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration datethat appears on the box and on each blister after CAD and EXP. The expiration date is the last day of the month indicated.

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

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Nexavar

• The active principle is sorafenib. Each film-coated tablet contains 200 mg of sorafenib (in the form of tosilate)
• The other components are:

Core of the tablet:sodium croscarmellose, microcrystalline cellulose, hypromellose, sodium lauryl sulfate, magnesium stearate.

Coating of the tablet:hypromellose, macrogol, titanium dioxide (E 171), iron oxide red (E 172).

Appearance of the product and contents of the package

The film-coated tablets with faces of Nexavar 200 mg are red, round, with the cross of Bayer on one face and "200" on the other. They are presented in a calendar pack of 112 tablets: four transparent blisters with 28 tablets each.

Holder of the marketing authorization

Bayer AG

51368 Leverkusen

Germany

Responsible for manufacturing

Bayer AG

Kaiser-Wilhelm-Allee

51368 Leverkusen

Germany

For more information about this medication, please contact the local representative of the marketing authorization holder.

Date of the last review of this leaflet:

The detailed information about this medication is available on the website of the European Medicines Agency:http://www.ema.europa.eu.