Package Leaflet: Information for the User

Sorafenib Stada 400 mg Film-Coated Tablets

Read this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, as 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 others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

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

2. What you need to know before you start taking Sorafenib Stada

3. How to take Sorafenib Stada

4. Possible side effects

5. Storage of Sorafenib Stada

6. Contents of the pack and additional information

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

Sorafenib is also used in the treatment of advanced kidney cancer (advanced renal cell carcinoma) when standard treatment has not slowed down the disease or is considered inappropriate.

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

Do not takeSorafenib Stada

• If you are allergicto 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 to take sorafenib.

Be especially careful with Sorafenib Stada

• If you experience the following symptoms, contact your doctor immediately, as they may be a potentially life-threatening condition: nausea, difficulty breathing, irregular heartbeats, muscle cramps, seizures, cloudy urine, and fatigue.These may be caused by a group of metabolic complications that can occur during cancer treatment, caused by the breakdown products of dying cancer cells (tumor lysis syndrome [TLS]) and may cause changes in kidney function and acute kidney injury (see also section 4: Possible side effects).
• If you experience skin problems. Sorafenib may cause rashes and skin reactions, especially on hands and feet. Your doctor may normally treat these conditions. If not, your doctor may temporarily or completely stop treatment.
• If you have hypertension. Sorafenib may increase blood pressure, and your doctor will usually control your blood pressure and may give you a medication to treat your hypertension.
• 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. Regularly check blood sugar levels in diabetic patients to evaluate if the dose of antidiabetic medication needs to be adjusted to minimize the risk of low blood sugar levels.
• If you have bleeding problems or are taking warfarin or fenprocoumon. Treatment with sorafenib may increase the risk of bleeding. If you are taking warfarin or fenprocoumon, medications that thin the blood to prevent clotting, you may have a higher risk of bleeding.
• If you have chest pain or heart problems. Your doctor may decide to temporarily or completely stop treatment.
• If you have a heart condition, such as an abnormal electrical signal called "prolonged QT interval."
• If you are about to undergo surgery, or have recently undergone an operation. Sorafenib may affect wound healing. If you are about to undergo surgery, treatment with sorafenib is usually discontinued. Your doctor will decide when to restart treatment with sorafenib.
• If you are taking irinotecan or docetaxel, which are also cancer medications. Sorafenib may increase the effects, and particularly the side effects, of these medications.
• If you are taking neomycin or other antibiotics. The effect of sorafenib may be reduced.
• If you have severe liver failure. You may experience more severe side effects when taking this medicine.
• If you have kidney failure. Your doctor will monitor your fluid and electrolyte balance.
• Fertility. Sorafenib may reduce fertility in both men and women. If this applies to you, talk to your doctor.
• During treatment, perforation of the intestinal wall(gastrointestinal perforation)may occur (see section 4: Possible side effects). In this case, your doctor will stop treatment.

Inform your doctor if any of these affect you.You may need treatment for them, or your doctor may decide to change your sorafenib dose or stop treatment completely (see also section 4: Possible side effects).

Children and adolescents

No clinical trials have been conducted with sorafenib in children and adolescents.

Other medicines and Sorafenib Stada

Some medicines may affect sorafenib, or may be affected by it. Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medicine from this list or any other medicine, including those purchased without a prescription.

• Rifampicin, neomycin, or other medicines used to treat infections(antibiotics)
• St. John's Wort, a herbal remedy for depression
• Phenobarbital, carbamazepine, or phenytoin, treatments for epilepsy and other diseases
• Dexamethasone, a corticosteroid used for various diseases
• Warfarin or fenprocoumon, anticoagulants used to prevent blood clots
• Doxorubicin, capecitabine, docetaxel, paclitaxel, and irinotecan, for cancer treatment
• Digoxin, a treatment for mild to moderate heart failure

Pregnancy and breastfeeding

Avoid becoming pregnant while being treated with sorafenib. If you can become pregnant, use an appropriate contraceptive method during treatment. If you become pregnant while being treated with sorafenib, inform your doctor immediately, who will decide whether to continue treatment.

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

Driving and operating machinery

There is no evidence that sorafenib can affect your ability to drive or operate machinery.

Sorafenib Stada contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per tablet, which is essentially "sodium-free."

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

The recommended dose of sorafenib in adults is 400 mg, taken twice a day.

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

Swallow the sorafenib tablets with a glass of water, without food or with a low- or moderate-fat meal. Do not take this medication with a high-fat meal, as this reduces the effectiveness of sorafenib. If you plan to take a high-fat meal, take the 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. In case of doubt, consult your doctor or pharmacist again..

It is essential to take this medication at the same time every day, so that there is a constant amount in the bloodstream.

The groove is only for breaking the tablet if it is difficult to swallow whole.

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

If you take more Sorafenib Stada

Inform your doctor immediatelyif you (or someone) have taken more than the prescribed dose. Taking too much sorafenib increases the likelihood of side effects or that they will be more severe, especially diarrhea and skin reactions. Your doctor may instruct you to stop taking this medication.

If you accidentally take too many sorafenib tablets (more than your usual daily dose), consult your doctor or the nearest hospital or call the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount taken.

If you forgot to take Sorafenib Stada

If you have forgotten a dose, take it as soon as you remember. If it is close to the time of the next dose, do not take the missed dose and continue normally. Do not take a double dose to compensate for the missed doses.

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

Very common:

may affect more than 1 in 10 people

• diarrhea
• feeling of dizziness (nausea)
• feeling weak or tired (fatigue)
• pain (including mouth pain, abdominal pain, headache, bone pain, tumor pain)
• hair loss (alopecia)
• red or painful palms and soles of the feet (hand-foot reaction)
• itching or rash
• vomiting
• bleeding (including bleeding in the brain, intestinal wall, and respiratory tract,bleeding)
• 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 (dispepsia)
• difficulty swallowing (dysphagia)
• dry or inflamed mouth, tongue pain (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)
• alterations in sensitivity in the fingers of the hand and feet, including tingling or numbness (peripheral sensory neuropathy)
• depression
• erectile dysfunction (impotence)
• voice alteration (hoarseness)
• acne
• inflamed, dry, or scaly skin that peels (dermatitis, skin peeling)
• heart failure
• heart attack (myocardial infarction) and chest pain
• tinnitus (ringing in the ear)
• kidney insufficiency
• abnormally high levels of protein in the urine (proteinuria)
• general weakness or loss of strength (asthenia)
• decrease in the number of white blood cells (leukopenia and neutropenia)
• decrease in the number of red blood cells (anemia)
• low platelet count in the blood (thrombocytopenia)
• inflammation of the hair follicles (folliculitis)
• low activity of the thyroid gland (hypothyroidism)
• low sodium levels in the blood (hyponatremia)
• alteration of the sense of taste (ageusia)
• flushing of the face and often other parts of the skin (flushing)
• nasal secretion (rhinorrhea)
• acid reflux (gastroesophageal reflux disease)
• skin cancer (squamous cell carcinoma)
• thickening of the outer layer of the skin (hyperkeratosis)
• sudden and involuntary muscle contraction (muscle spasms)

Uncommon:

may affect up to 1 in 100 people

• inflammation of the stomach wall (gastritis)
• abdominal pain caused by pancreatitis, inflammation of the gallbladder and/or bile ducts
• yellowing of the skin or eyes (jaundice) caused by high levels of bile pigments (hyperbilirubinemia)
• allergic reactions (including skin reactions and urticaria)
• dehydration
• breast enlargement (gynecomastia)
• difficulty breathing (pulmonary disease)
• eczema
• hyperactivity of the thyroid gland (hyperthyroidism)
• multiple skin eruptions (erythema multiforme)
• abnormally high blood pressure
• gastrointestinal perforation (gastrointestinal perforation)
• reversible inflammation in the back of the brain that may be associated with headache, altered consciousness, seizures, and visual symptoms including loss of vision (posterior reversible encephalopathy syndrome)
• severe and sudden allergic reactions (anaphylactic reaction)

Rare:

may affect up to 1 in 1,000 people

• allergic reaction with swelling of the skin (e.g. face, tongue) that may cause difficulty breathing or swallowing (angioedema)
• abnormal heart rhythm (prolonged QT interval)
• inflammation of the liver, which may cause nausea, vomiting, abdominal pain, and yellowing of the skin (drug-induced hepatitis)
• a rash-like sunburn on the skin that has been previously exposed to radiation and may be severe (radiation recall dermatitis)
• severe skin and/or mucous membrane reactions that may include painful blisters and fever, including extensive skin peeling (Stevens-Johnson syndrome and toxic epidermal necrolysis)
• abnormal muscle degradation that may lead to kidney problems (rhabdomyolysis)
• kidney damage that causes the loss of large amounts of protein (nephrotic syndrome)
• inflammation of the blood vessels in the skin 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).
• difficulty breathing, irregular heartbeats, muscle cramps, seizures, cloudy urine, and fatigue (tumor lysis syndrome [TLS]) (see section 2).

Reporting of adverse reactions:

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. 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 packaging and on the blister pack after CAD. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medications should not be disposed of through drains or in the trash. Dispose of the packaging and medications you no longer need at the SIGRE point of your pharmacy.In case of doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition ofSorafenib Stada

• The active ingredient is sorafenib. Each film-coated tablet contains 400 mg of sorafenib (as tosilate).
• The other ingredients are:

Core of the tablet:hypromellose 2910 (E464), croscarmellose sodium, microcrystalline cellulose (E460), magnesium stearate (E470b), sodium lauryl sulfate.

Coating of the tablet: hypromellose 2910 (E464), titanium dioxide (E171), macrogol 3350 (E1521).

Appearance of the product and contents of the package

Sorafenib Stada 400 mg are film-coated tablets, white to off-white in color, oval in shape, with a notch on one side and smooth on the other, with dimensions of 20.1 mm x 10.1 mm ± 5%.

Sorafenib Stada 400 mg is available in:

Packages with aluminum-OPA/Alu/PVC blisters containing 28, 30, 56, 60, multiple pack of 84 (3 packs of 28), multiple pack of 112 (4 packs of 28), multiple pack of 120 (4 packs of 30) film-coated tablets.

Packages with perforated single-dose aluminum-OPA/Alu/PVC blisters containing 28x1, 30x1, 56x1, 60x1, multiple pack of 84x1 (3 packs of 28x1), multiple pack of 112x1 (4 packs of 28x1), multiple pack of 120x1 (4 packs of 30x1) film-coated tablets.

Only some package sizes may be commercially marketed.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder

STADA, S.L.

Frederic Mompou, 5

08960 Sant Just Desvern (Barcelona)

Spain

[email protected]

Responsible manufacturer

Remedica Ltd

Aharnon Street, Limassol Industrial Estate

Limassol 3056

Cyprus

or

PharOS MT Ltd

HF62X, Hal Far Industrial Estate

Birzebbugia BBG3000

Malta

or

Stada Arzneimittel AG

Stadastrasse 2-18

61118 Bad Vilbel

Germany

Last review date of this leaflet:July 2022

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es