Nexavar 200 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Nexavar 200mg film-coated tablets

sorafenib

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 or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Nexavar is and what it is used for

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 effective in stopping the progression of the disease or is considered inappropriate.

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

Nexavar is a multikinase inhibitor. It works by slowing down the growth rate of cancer cells and interrupting the blood supply that supports the growth of cancer cells.

2. What you need to know before starting Nexavar

Do not take Nexavar

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

Warnings and precautions

Consult your doctor or pharmacist before starting Nexavar.

Exercise special caution with Nexavar

• If you experience skin problems. Nexavar may cause rashes and skin reactions, especially on the hands and feet. Your doctor can usually treat these conditions. Otherwise, your doctor may temporarily or permanently discontinue treatment.
• If you have hypertension. Nexavar may increase blood pressure. Your doctor will monitor your blood pressure and may prescribe medication to treat high blood pressure.
• If you have or have had an aneurysm (a bulge 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 monitored regularly to assess whether an adjustment in the dose of antidiabetic medication is needed to minimize the risk of low blood sugar levels.
• If you have bleeding disorders or are taking warfarin or fenprocoumon. Treatment with Nexavar may increase the risk of bleeding. If you are taking warfarin or fenprocoumon—medications that thin the blood to prevent blood clots—you may have an increased risk of bleeding.
• If you have chest pain or heart problems. Your doctor will decide whether to temporarily or permanently discontinue treatment.
• If you have a heart disorder, such as an abnormal electrical signal known as "QT interval prolongation."
• If you are scheduled for surgery or have recently undergone surgery. Nexavar may affect wound healing. You should normally stop taking Nexavar before undergoing surgery. Your doctor will decide when to restart treatment with Nexavar.
• If you are taking irinotecan or docetaxel, which are also anticancer medications. Nexavar may enhance the effects and, in particular, the adverse effects of these drugs.
• 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 adverse effects when taking this medication.
• If you have kidney impairment. 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, holes in the intestinal wall (gastrointestinal perforation) may occur (see section 4: Possible side effects). In such a case, your doctor will discontinue treatment.
• If you have thyroid cancer. Your doctor will monitor blood levels of calcium and thyroid hormones.
• If you experience any of the following symptoms, contact your doctor immediately, as this may be a potentially life-threatening condition: nausea, difficulty breathing, irregular heartbeat, 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 breakdown products from dying cancer cells [tumor lysis syndrome (TLS)], which may lead to changes in kidney function and acute kidney failure (see also section 4: Possible side effects).

Consult your doctor if any of these situations apply to you. Treatment may be required, or your doctor may decide to adjust your dose of Nexavar or permanently discontinue treatment (see also section 4: Possible side effects).

Children and adolescents

Nexavar has not yet been studied in children and adolescents.

Taking Nexavar with other medicines

Some medicines affect Nexavar or may be affected by it. Inform your doctor or pharmacist if you are taking, have recently taken, or might need to 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 epilepsy and other conditions
• Dexamethasone, a corticosteroid used in various conditions
• Warfarin or fenprocoumon, anticoagulants used to prevent blood clots
• Doxorubicin, capecitabine, docetaxel, paclitaxel, and irinotecan, cancer treatments
• Digoxin, a treatment for mild to moderate heart failure

Pregnancy and breastfeeding

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

You must not breastfeed during treatment with Nexavar, as this medicine may interfere with your baby's growth and development.

Driving and using machines

There is no indication 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 unit; hence, it is essentially "sodium-free."

3. How to take Nexavar

The recommended dose of Nexavar in adults is two 200 mg tablets taken twice daily.

This corresponds to a daily dose of 800 mg, or four tablets per day.

Nexavar tablets should be taken with a glass of water on an empty stomach 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 plan to eat a high-fat meal, you should take sorafenib tablets at least 1 hour before or 2 hours after the meal.

Always follow exactly the instructions given by your doctor regarding the administration of this medicine. If in doubt, consult your doctor or pharmacist again.

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

You will usually continue taking this medicine for as long as you are obtaining clinical benefit and do not experience unacceptable adverse effects.

If you take more Nexavar than you should

Contact your doctor immediately if you (or anyone else) have taken more than the prescribed dose. Taking too much Nexavar increases the likelihood of adverse effects occurring or of them being more severe, particularly diarrhea or skin problems. Your doctor may instruct you to stop taking this medicine.

If you forget to take Nexavar

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse 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 tiredness (fatigue)
• pain (including mouth sores, abdominal pain, headache, bone pain, tumor pain)
• hair loss (alopecia)
• red or painful palms and soles (hand–foot skin reaction)
• pruritus or rash
• vomiting
• bleeding (including bleeding in the brain, intestinal wall, and respiratory tract)
• hypertension or increases in 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 patients

• flu-like illness
• indigestion (dyspepsia)
• difficulty swallowing (dysphagia)
• inflamed or dry mouth, tongue pain (stomatitis and mucosal inflammation)
• low blood calcium levels (hypocalcemia)
• low blood potassium levels (hypokalemia)
• low blood sugar levels (hypoglycemia)
• muscle pain (myalgia)
• altered sensation in fingers and toes, including tingling or numbness (peripheral sensory neuropathy)
• depression
• erection problems (impotence)
• voice changes (dysphonia)
• acne
• inflamed, dry, or scaly skin, with peeling (dermatitis, skin desquamation)
• heart failure
• heart attack (myocardial infarction) or chest pain
• tinnitus (ringing in the ears)
• kidney failure
• abnormally high levels of protein in the urine (proteinuria)
• general weakness or loss of strength (asthenia)
• decreased number of white blood cells (leukopenia and neutropenia)
• decreased number of red blood cells (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 taste sensation (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 patients

• inflammation of the stomach lining (gastritis)
• abdominal pain due to pancreatitis, inflammation of the gallbladder and/or bile ducts
• yellowing of the skin or eyes (jaundice) caused by elevated levels of bile pigments (hyperbilirubinemia)
• allergic-type reactions (including skin rashes and hives)
• dehydration
• breast enlargement (gynecomastia)
• difficulty breathing (lung 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 posterior part of the brain, which may be associated with headache, altered consciousness, seizures, and visual symptoms including vision loss (reversible posterior leukoencephalopathy syndrome)
• sudden severe allergic reaction (anaphylactic reaction)

Rare:

may affect up to 1 in 1,000 patients

• allergic reaction with swelling of the skin (e.g., face, tongue) that may cause difficulty breathing or swallowing (angioedema)
• abnormal heart rhythm (QT prolongation)
• liver inflammation that may lead to nausea, vomiting, abdominal pain, and yellowing of the skin (drug-induced hepatitis)
• a sunburn-like rash, which may occur in skin previously exposed to radiotherapy and may be severe (radiation recall 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 causing loss of large amounts of protein (nephrotic syndrome)
• inflammation of blood vessels in the skin that may cause a rash (leukocytoclastic vasculitis)

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

• impaired brain function that may be associated with, for example, drowsiness, behavioral changes, or confusion (encephalopathy)
• enlargement and weakening of a blood vessel wall or tearing of a blood vessel wall (aneurysms and arterial dissections)
• nausea, difficulty breathing, irregular heartbeat, muscle cramps, seizures, cloudy urine, and fatigue (tumor lysis syndrome [TLS]) (see section 2)

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may 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 Nexavar

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

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

Do not store this medicine above 25°C.

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

6. Contents of the pack and other information

Composition of Nexavar

• The active ingredient is sorafenib. Each film-coated tablet contains 200 mg of sorafenib (as tosylate).
• The other components are:

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

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

Appearance of the product and contents of the pack

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

Marketing Authorization Holder

Bayer AG
51368 Leverkusen
Germany

Manufacturer

Bayer AG
Kaiser-Wilhelm-Allee
51368 Leverkusen
Germany

Further information on this medicinal product is available upon request to the local representative of the Marketing Authorization Holder.

Date of the most recent review of this leaflet:

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