Package leaflet: Information for the user

Sorafenib STADA, 400 mg, film-coated tablets
sorafenib
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for the patient.

Keep this leaflet, as you may need to read it again.
If you have any further questions, ask your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
If the patient experiences any adverse reactions, including any adverse reactions not listed in this leaflet, inform a doctor or pharmacist. See section 4.

Contents of the leaflet

What Sorafenib STADA is and what it is used for
Important information before taking Sorafenib STADA
How to take Sorafenib STADA
Possible side effects
How to store Sorafenib STADA
Contents of the pack and other information

1. What Sorafenib STADA is and what it is used for

Sorafenib STADA is used in the treatment of liver cancer (hepatocellular carcinoma).
Sorafenib STADA is also used in the treatment of advanced kidney cancer
(advanced renal cell carcinoma) in patients in whom standard therapy has failed to halt disease progression or is considered inappropriate.
Sorafenib STADA is a so-called multi-kinase inhibitor. It works by slowing down the growth of cancer cells and by cutting off the blood supply that supports the growth of cancer cells.

2. Important information before using Sorafenib STADA

When not to use Sorafenib STADA

if the patient is allergic to sorafenib or any of the other ingredients of this medicine (listed in section 6);

Warnings and precautions
Before starting treatment with Sorafenib STADA, discuss this with your doctor or pharmacist.
When to exercise special caution when using Sorafenib STADA

If the patient develops the following symptoms, contact a doctor immediately, as these may indicate a life-threatening condition: nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, cloudy urine, and fatigue. These symptoms may be caused by a group of metabolic complications that can occur during cancer treatment, resulting from products released by dying tumor cells [tumor lysis syndrome (TLS)], which may lead to impaired kidney function and acute kidney failure (see also section 4. Possible side effects).
If skin changes occur. Sorafenib STADA may cause rashes and skin reactions, especially on the palms of the hands and soles of the feet. These changes can usually be managed by the treating physician. If they do not resolve, the doctor may temporarily interrupt treatment with Sorafenib STADA or discontinue it completely.
If the person prescribed the medicine has high blood pressure. Sorafenib STADA may increase blood pressure. The treating doctor will monitor blood pressure values and, if elevated, may prescribe medications to lower it.
If the patient has or has previously had an aneurysm (a bulge and weakening of a blood vessel wall) or a tear in the wall of a blood vessel.
If the person prescribed the medicine has diabetes. In patients with diabetes, blood glucose levels should be monitored regularly to determine whether the dose of antidiabetic medication needs adjustment to minimize the risk of hypoglycemia.
If any bleeding occurs or if the patient is taking warfarin or phenprocoumon. Treatment with Sorafenib STADA may increase the risk of bleeding. A person taking warfarin or phenprocoumon, which reduce blood clotting to prevent thrombosis, may have an increased risk of bleeding.
If chest pain or heart problems occur, the doctor may decide it is necessary to interrupt or completely discontinue treatment.
If cardiac disorders occur, such as abnormal electrical activity known as "QT interval prolongation".
If surgery is planned or has recently been performed. Sorafenib STADA may affect wound healing. Usually, Sorafenib STADA is discontinued before surgery. The treating doctor will decide when to resume treatment with Sorafenib STADA.
If the person prescribed Sorafenib STADA is also taking irinotecan or receiving docetaxel, which are also anticancer medicines. Sorafenib STADA may enhance their effects, particularly their adverse effects.
If neomycin or other antibiotics are being taken, the effectiveness of Sorafenib STADA may be reduced.
If there is severe liver dysfunction, more severe adverse effects may occur during treatment.
In case of impaired kidney function, the doctor will monitor fluid and electrolyte balance.
Fertility. Sorafenib STADA may impair fertility in both men and women. Any fertility-related concerns should be discussed with the doctor.
Gastrointestinal perforation. During treatment, a break in the continuity of the gastrointestinal wall may occur (see also section 4: Possible side effects). In such a case, the doctor will recommend discontinuing treatment.

Inform your doctor if any of the above situations apply to the person prescribed Sorafenib STADA.
In these cases, appropriate treatment may be required; the doctor may decide to adjust the dose of
Sorafenib STADA or discontinue its use completely (see also section 4: Possible side effects).
Children and adolescents
Studies on the use of Sorafenib STADA in children and adolescents have not yet been conducted.
Sorafenib STADA and other medicines
Some medicines may affect the action of Sorafenib STADA, or their action may be altered by Sorafenib STADA. Inform your doctor or pharmacist about any of the medicines listed below and any other medicines currently used, recently used, or planned for use, including over-the-counter medicines:

Rifampicin, neomycin, or other medicines used to treat infections (antibiotics)
St. John’s wort, used in the treatment of depression
Phenytoin, carbamazepine, or phenobarbital, medicines used in epilepsy and other disorders
Dexamethasone, a corticosteroid used in various diseases
Warfarin or phenprocoumon, anticoagulant medicines used to prevent thrombosis
Doxorubicin, capecitabine, docetaxel, paclitaxel, and irinotecan – anticancer medicines
Digoxin, used in the treatment of mild to moderate heart failure

Pregnancy and breastfeeding
Avoid becoming pregnant while taking Sorafenib STADA. If there is any possibility that the patient could become pregnant, an effective method of contraception should be used during treatment. If pregnancy occurs during treatment, the patient should contact the doctor immediately, who will decide whether treatment may be continued.
Breastfeeding must not be performed during treatment with Sorafenib STADA, as sorafenib may affect the growth and development of the infant.
Driving and operating machinery
There are no data indicating that Sorafenib STADA may impair the ability to drive or operate machinery.
Sorafenib STADA contains sodium.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning it is considered "sodium-free".

3. How to use Sorafenib STADA

This medicine should always be taken as prescribed by the doctor. If in doubt, consult the doctor or pharmacist.
The recommended dose of Sorafenib STADA for adults is 400 mg twice daily.
This corresponds to a daily dose of 800 mg or two tablets.
Sorafenib STADA should be swallowed with a glass of water, on an empty stomach or with a low- or
moderately fat meal. Do not take the medicine with high-fat meals, as this may reduce the effectiveness of Sorafenib STADA.
If a high-fat meal is planned, the tablets should be taken at least 1 hour before or 2 hours after the meal.
This medicine should always be taken as prescribed by the doctor. If in doubt, consult the doctor or pharmacist.
It is important to take this medicine at approximately the same time each day to ensure a consistent level of medicine in the bloodstream.
The tablet break line is only intended to assist in splitting the tablet if difficulty is experienced in swallowing the tablet whole.
This medicine is usually taken as long as it provides clinical benefit and the patient does not experience unacceptable adverse reactions.
Taking more Sorafenib STADA than prescribed
Immediately inform the doctor if the person prescribed Sorafenib STADA (or anyone else) has taken more than the prescribed dose.
Taking Sorafenib STADA in excess may increase the risk of adverse reactions or make them more severe, especially diarrhea and skin reactions.
The doctor may advise discontinuing treatment with this medicine.
Missing a dose of Sorafenib STADA
If a patient misses a dose, it should be taken as soon as remembered. If the next dose is due soon, the missed dose should be skipped and treatment should continue as before. Do not take a double dose to make up for a missed dose.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
This medicine may also affect the results of certain blood tests.

Very common:
May affect more than 1 in 10 people

Diarrhoea
Nausea (feeling sick)
Feeling weak or tired (fatigue)
Pain (including mouth pain, abdominal pain, bone pain, headache, tumour-related pain)
Hair loss (alopecia)
Redness or pain in the palms of the hands or soles of the feet (hand-foot syndrome)
Itching or rash
Vomiting
Bleeding (including brain haemorrhage, intestinal wall bleeding, respiratory tract bleeding, haemorrhage)
High blood pressure or periodic 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 people

Flu-like symptoms
Indigestion (dyspepsia)
Difficulty swallowing (dysphagia)
Inflammation or dryness in the mouth, tongue pain (stomatitis and mucosal inflammation)
Low blood calcium levels (hypocalcaemia)
Low blood potassium levels (hypokalaemia)
Low blood sugar levels (hypoglycaemia)
Muscle pain (myalgia)
Sensory disturbances in fingers and toes, including tingling or numbness (peripheral sensory neuropathy)
Depression
Erectile dysfunction (impotence)
Voice changes (dysphonia)
Acne
Inflammatory skin reactions, dry and flaky skin (dermatitis, skin desquamation)
Heart failure
Heart attack (myocardial infarction) or chest pain
Tinnitus (ringing in the ear)
Kidney failure
Exceptionally high protein levels in urine (proteinuria)
General weakness or loss of strength (asthenia)
Decreased white blood cell count (leucopenia and neutropenia)
Decreased red blood cell count (anaemia)
Low platelet count (thrombocytopenia)
Inflammation of hair follicles (folliculitis)
Reduced thyroid activity (hypothyroidism)
Low blood sodium levels (hyponatraemia)
Taste disturbances (dysgeusia)
Flushing of the face and often other skin areas (flushing)
Watery nasal discharge (watery rhinitis)
Heartburn (gastro-oesophageal reflux disease)
Skin cancer (squamous cell carcinoma/skin squamous cell carcinoma)
Thickening of the outer skin layer (hyperkeratosis)
Sudden, involuntary muscle spasms (muscle spasms)

Uncommon:
May affect up to 1 in 100 people

Inflammation of the mucous membrane (lining) of the stomach
Abdominal pain caused by inflammation of the pancreas, inflammation of the gallbladder and/or bile ducts
Yellowing of the skin or eyes (jaundice) due to high levels of bile pigments (hyperbilirubinaemia)
Allergic reactions (including skin reactions and hay fever)
Dehydration
Breast enlargement (gynaecomastia)
Breathing difficulties (lung disease)
Skin rash (eczema)
Increased thyroid activity (hyperthyroidism)
Various skin eruptions (erythema multiforme)
Exceptionally high blood pressure
Perforation of the intestinal wall (gastrointestinal perforation)
Reversible swelling of the posterior part of the brain, which may be associated with headache, altered consciousness, seizures, and visual disturbances including loss of vision (reversible posterior leukoencephalopathy syndrome)
Sudden, severe allergic reaction (anaphylactic reaction)

Rare:
May affect up to 1 in 1000 people

Allergic reaction with skin swelling (e.g. face, tongue), which may cause breathing or swallowing difficulties (angioedema)
Irregular heart rhythm (QT interval prolongation)
Inflammation of the liver, which may cause nausea, vomiting, abdominal pain and jaundice (drug-induced hepatitis)
Sunburn-like rash, which may occur on skin previously exposed to radiotherapy, and may be severe (radiation-induced dermatitis)
Severe skin and/or mucosal reactions, including painful blisters and fever, including extensive skin detachment (Stevens-Johnson syndrome and toxic epidermal necrolysis)
Abnormal breakdown of skeletal muscle tissue, which may lead to kidney dysfunction (rhabdomyolysis)
Kidney damage causing loss of large amounts of protein (nephrotic syndrome)
Inflammation of blood vessels in the skin, which may cause a rash (leucocytoclastic vasculitis)

Not known (frequency cannot be estimated from available data)

Brain function disorders, which may include drowsiness, behavioural changes or disorientation (encephalopathy)
Enlargement and weakening of a blood vessel wall or tearing of a blood vessel wall (aneurysm and arterial dissection)
Nausea, shortness of breath, irregular heartbeat, muscle spasms, seizures, cloudy urine and fatigue [tumour lysis syndrome (TLS)] (see section 2).

Reporting of adverse reactions
If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
PL-02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Sorafenib STADA

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister pack and the cardboard box
after: EXP. The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. Such measures help protect the environment.

6. Package contents and other information

What Sorafenib STADA contains

The active substance is sorafenib. Each tablet contains 400 mg of sorafenib (as tosylate).
Other ingredients are:
Tablet core: hypromellose 2910 (E464), sodium croscarmellose, microcrystalline cellulose (E460), magnesium stearate (E470b), sodium lauryl sulfate
Coating: hypromellose 2910 (E464), titanium dioxide (E171), macrogol 3350 (E1521)

What Sorafenib STADA looks like and contents of the pack
White to off-white, oval, film-coated tablets with a breakline on one side and plain on the other, measuring 20.1 mm x 10.1 mm ± 5%.
Aluminum-OPA/Alu/PVC blisters containing: 28, 30, 56, 60 tablets; multipack 84 (3 packs of 28), multipack 112 (4 packs of 28), multipack 120 (4 packs of 30) film-coated tablets.
Aluminum-OPA/Alu/PVC blister packs divided into single doses containing: 28 x 1, 30 x 1, 56 x 1, 60 x 1, multipack 84 x 1 (3 packs of 28 x 1), multipack 112 x 1 (4 packs of 28 x 1), multipack 120 x 1 (4 packs of 30 x 1) film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:
STADA Arzneimittel AG
Stadastrasse 2-18
61118 Bad Vilbel
Germany

Manufacturers:

Remedica Ltd Aharnon Street, Limassol Industrial Estate Limassol, 3056, Cyprus
PharOS MT Ltd HF62X, Hal Far Industrial Estate Birzebbugia
BBG3000, Malta
STADA Arzneimittel AG Stadastrasse 2-18 61118 Bad Vilbel Germany
Laboratori Fundació Dau Calle Lletra C de la Zona Franca 12-14, Polígono Industrial de la Zona Franca de Barcelona, 08040, Barcelona Spain

This medicinal product is authorised in the European Economic Area under the following names:
Netherlands: Sorafenib STADA Arzneimittel 400 mg, filmomhulde tabletten
Czech Republic, Poland: Sorafenib STADA
Germany: Sorafenib STADA 400 mg Filmtabletten
Spain: Sorafenib STADA 400 mg comprimidos recubiertos con película
Croatia: Sorafenib STADA 400 mg filmom obložene tablete
Hungary: SORAFENIB STADA 400 mg filmtabletta
Romania: SORAFENIB STADA 400 mg comprimate filmate
Belgium, Luxembourg: Sorafenib EG 400 mg