Package Insert: Information for the User

Capecitabina Tarbis 150 mg Film-Coated Tablets

Capecitabina Tarbis 500 mg Film-Coated TabletsEFG

Read this package insert carefully before starting to take this medicine, as 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 section 4.

Capecitabina Tarbis belongs to the group of medications known as “cytostatic drugs”, which halt the growth of cancerous cells. This medication contains capecitabina, and by itself is not a cytostatic drug. It only becomes a cancer-fighting medication after being absorbed by the body, transforming into an active anti-cancer agent (more so in tumor tissue than in normal tissue).

Capecitabina is used for the treatment of colon cancer, rectal cancer, gastric cancer, or breast cancer. Additionally, this medication is used to prevent the reappearance of colon cancer after the complete removal of the tumor through surgery.

Capecitabina can be used alone or in combination with other medications.

Do not take Capecitabina Tarbis

• If you are allergic to capecitabina or any of the other components of this medication (listed in section 6). Inform your doctor if you have any type of allergy or exaggerated reaction to this medication,
• If you have previously experienced severe reactions to treatment with fluoropirimidina (a group of cancer medications such as fluorouracilo),
• If you are pregnant or breastfeeding,
• If you have very low levels of white blood cells or platelets in your blood (leucopenia, neutropenia, or thrombocytopenia),
• If you have severe liver diseases or kidney problems,
• If you know that you do not have any activity of the dihydropirimidina deshidrogenasa (DPD) enzyme (complete DPD deficiency),
• If you are being treated or have been treated in the last 4 weeks with brivudina as part of the treatment for herpes zoster (varicela or herpes).

Warnings and precautions

Consult your doctor or pharmacist before starting to take capecitabina

• If you know that you have a partial deficiency of the dihydropirimidina deshidrogenasa (DPD) enzyme activity,
• If you have a family member who has partial or complete deficiency of the dihydropirimidina deshidrogenasa (DPD) enzyme,

deshidrogenasa (DPD),

• If you have liver or kidney diseases,
• If you have or have had heart problems (for example, irregular heartbeat or chest and back pain caused by physical effort and due to problems with blood flow to the heart),
• If you have brain diseases (for example, cancer that has spread to the brain, or nerve damage (neuropathy)),
• If you have calcium imbalance (see blood tests),
• If you have diabetes,
• If due to nausea and vomiting you are unable to retain food or water in your body,
• If you have diarrhea,
• If you are dehydrated or become dehydrated,
• If you have blood ion imbalance (electrolyte imbalance, see blood tests),
• If you have a history of eye problems, as you will need extra eye follow-up,
• If you have a severe skin reaction.

DPD deficiency:The DPD deficiency is a genetic condition that is not usually related to health problems, unless you are being treated with certain medications. If you have a DPD deficiency and take capecitabina, you have a higher risk of severe adverse effects (listed in section 4 Possible adverse effects). It is recommended that you undergo a test to detect DPD deficiency before starting treatment. If you do not have enzyme activity, you should not take capecitabina. If you have reduced enzyme activity (partial deficiency), your doctor may prescribe a reduced dose. Although the results of the DPD deficiency test are negative, severe or potentially fatal adverse effects may occur.

Children and adolescents

Capecitabina is not indicated for children and adolescents. Do not administer capecitabina to children and adolescents.

Other medications and Capecitabina Tarbis

Inform your doctor or pharmacist if you are taking, have taken recently, or may take any other medication. This is very important, as taking multiple medications at the same time may potentiate or weaken their effects.

You also need to be very careful if you are taking any of the following medications:

• Medications for gout (alopurinol),
• Medications to reduce blood clotting (cumarina, warfarina),
• Medications for seizures or tremors (phenytoin),
• Interferon alpha,
• Radiation therapy and certain medications used to treat cancer (folic acid, oxaliplatino, bevacizumab, cisplatino, irinotecán),
• Medications used to treat folic acid deficiency.

Capecitabina Tarbis with food and drinks

You should take this medication before or 30 minutes after eating.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication. You should not take this medication if you are pregnant or think you may be.

You should not breastfeed your baby if you are taking capecitabina and for up to 2 weeks after the last dose.

If you are a woman who may become pregnant, you should use an effective contraceptive method during treatment with capecitabina and for up to 6 months after the last dose.

If you are a male patient and your female partner may become pregnant, you should use an effective contraceptive method during treatment with capecitabina and for up to 3 months after the last dose.

Driving and operating machines

When taking capecitabina, you may feel dizzy, nauseous, or tired. Therefore, capecitabina may affect your ability to drive vehicles or operate machines.

Capecitabina Tarbis contains lactose

If your doctor has indicated that you have an intolerance to certain sugars, consult with him before taking this medication.

Capecitabina Tarbis contains sodium

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

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

Capecitabina should only be prescribed by a doctor experienced in the use of cancer medications.

Your doctor will prescribe a treatment schedule and correct dose for you. The dose of capecitabina depends on your body surface area. This is calculated by measuring your height and weight. The usual dose for adults is 1,250 mg/m2of body surface area twice a day (morning and night). Here are two examples: a person weighing 64 kg and measuring 1.64 m has a body surface area of 1.7 m2, so they should take 4 tablets of 500 mg and 1 tablet of 150 mg twice a day. A person weighing 80 kg and measuring 1.80 m has a body surface area of 2.0 m2, so they should take 5 tablets of 500 mg twice a day.

Your doctor will tell you what dose you need to take, when to take it, and for how long you need to take it.

Your doctor may instruct you to take a combination of 150 mg and 500 mg tablets for each dose.

• Take the tablets in themorning and at night, as prescribed by your doctor.
• Take the tabletswithin 30 minutes of finishing breakfast or dinner and swallow them whole with water.Do not crush or divide the tablets. If you cannot swallow the capecitabina tablets whole, tell your healthcare professional.
• It is essential to take all your medication as prescribed by your doctor.

Capecitabina tablets are usually taken for 14 consecutive days followed by a 7-day break (during which no tablets are taken). This 21-day period is a treatment cycle.

In combination with other medications, the usual dose in adults may be less than 1,250 mg/m2of body surface area, and it may be necessary to take the tablets for a different period of time (for example, every day, without a break).

If you take more Capecitabina Tarbis than you should

If you take more capecitabina than you should, contact your doctor as soon as possible before taking the next dose.

You may experience the following adverse effects if you take more capecitabina than you should: feeling unwell, diarrhea, inflammation or ulcers in the stomach or mouth, abdominal or stomach pain, or bleeding, or bone marrow depression (decrease in certain types of blood cells). Inform your doctor immediately if you experience any of these symptoms.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20 indicating the medication and the amount ingested.

If you forgot to take Capecitabina Tarbis

Do not take the missed dose. Do not take a double dose to make up for the missed dose. Instead, continue your usual dosing schedule and consult your doctor.

If you interrupt treatment with Capecitabina Tarbis

Stopping treatment with capecitabina does not produce adverse effects. If you are taking anticoagulant medications (such as acenocoumarol), stopping treatment with capecitabina may require your doctor to adjust the dose of the anticoagulant.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

STOP taking capecitabine immediately and contact your doctor if you experience any of the following symptoms:

• Diarrhea:if you have an increase of 4 or more bowel movements compared to your normal bowel movements per day or have nocturnal diarrhea.
• Vomiting:if you vomit more than once in a 24-hour period.
• Nausea:if you lose your appetite and the amount of food you eat each day is significantly less than usual.
• Stomatitis:if you have pain, redness, swelling, or sores in your mouth and/or throat.
• Hand and foot reaction:if you have pain, swelling, redness, or tingling in your hands and/or feet.
• Fever:if you have a temperature of 38°C or higher.
• Infection:if you have signs of infection caused by bacteria, viruses, or other organisms.
• Chest pain:if you have localized pain in the center of your chest, especially if it occurs while exercising.
• Steven-Johnson syndrome:if you have painful, red, or purple rashes that spread and blisters and/or other lesions that appear on mucous membranes (e.g., mouth and lips), particularly if you have had sensitivity to light, respiratory infections (e.g., bronchitis), and/or fever.
• Angioedema:seek immediate medical attention if you notice any of the following symptoms; you may need urgent medical treatment: swelling mainly of the face, lips, tongue, or throat that makes it difficult to swallow or breathe, itching, and rashes. It could be a sign of angioedema.

If detected in time, these side effects usually improve within 2 to 3 days after stopping treatment. However, if these side effects continue, contact your doctor immediately. Your doctor may instruct you to restart treatment with a lower dose.

If you experience severe stomatitis (mouth and/or throat irritation), mucosal inflammation, diarrhea, neutropenia (increased risk of infections), or neurotoxicity during the first cycle of treatment, it is possible that you have a DPD deficiency (see Section 2: Warnings and Precautions).

The hand and foot reaction can lead to loss of fingerprints, which can affect your identification through fingerprint analysis.

In addition to the above, when capecitabine is used alone, the very common side effects that may affect more than 1 in 10 people are:

• abdominal pain
• hives, dry skin, or itching
• fatigue
• loss of appetite (anorexia)

These side effects can be severe; therefore,contact your doctor immediatelywhen you start to feel a side effect.Your doctor may advise you to reduce the dose and/or temporarily stop treatment with this medicine. This will help reduce the likelihood of the side effect continuing or becoming severe.

Other side effects are:

Common side effects(may affect up to 1 in 10 people) include:

• decrease in white blood cells or red blood cells (see blood tests)
• dehydration, weight loss
• insomnia, depression
• headache, drowsiness, dizziness, strange sensation in the skin (tingling or numbness), taste disturbances
• eye irritation, increased tearing, redness of the eyes (conjunctivitis)
• inflammation of the veins (thrombophlebitis)
• difficulty breathing, nasal bleeding, cough, nasal discharge
• herpes labialis or infections by other herpes
• respiratory or airway infections (e.g., pneumonia or bronchitis)
• intestinal bleeding, constipation, upper abdominal pain, indigestion, gas (flatulence), dry mouth
• hives on the skin, hair loss (alopecia), redness of the skin, dry skin, itching (pruritus), skin color change, skin loss, skin inflammation, nail disorders
• joint pain, or pain in the extremities, chest, or back
• fever, swelling of the extremities, feeling unwell
• liver function problems (seen in blood tests) and increased bilirubin in the blood (excreted by the liver)

Uncommon side effects(may affect up to 1 in 100 people) include:

• blood infection, urinary tract infection, skin infection, nasal and throat infection, fungal infections (including those in the mouth), flu, gastroenteritis, dental abscesses
• skin inflammation (lipomas)
• decrease in blood cells, including platelets, dilution of the blood (seen in blood tests)
• allergies
• diabetes, decrease in potassium in the blood, malnutrition, increase in triglycerides in the blood
• confusion, panic attacks, depression, decreased libido
• difficulty speaking, memory problems, loss of motor coordination, balance disorder, fainting, nerve damage (neuropathy), and sensory problems
• blurred or double vision
• vertigo, ear pain
• irregular heartbeat and palpitations (arrhythmias), chest pain, and heart attack (myocardial infarction)
• formation of blood clots in deep veins, high or low blood pressure, hot flashes, cold extremities, purple spots on the skin
• formation of blood clots in pulmonary veins (pulmonary embolism), pulmonary collapse, coughing up blood, asthma, shortness of breath
• intestinal obstruction, accumulation of fluid in the abdomen, inflammation of the small or large intestine, stomach, or esophagus, lower abdominal pain, abdominal discomfort, acid reflux (regurgitation of food), blood in the stool
• jaundice (yellowing of the skin and eyes)
• skin ulcers and blisters, skin reaction to sunlight, redness of the palms, swelling or pain in the face
• swelling of the joints or stiffness, bone pain, muscle weakness or stiffness
• fluid accumulation in the kidneys, increased frequency of urination at night, incontinence, blood in the urine, increased creatinine in the blood (sign of kidney dysfunction)
• unusual vaginal bleeding
• swelling (edema), chills, and stiffness

Rare side effects(may affect up to 1 in 1,000 people) include:

• nasolacrimal duct narrowing or obstruction
• liver failure
• inflammation leading to dysfunction or obstruction in bile secretion (hepatitis colestásica)
• specific changes in the electrocardiogram (prolongation of the QT interval)
• specific types of arrhythmias (including ventricular fibrillation, torsade de pointes, and bradycardia)
• inflammation of the eyes causing eye pain and potential vision problems
• inflammation of the skin causing red, scaly patches due to an autoimmune disease
• swelling mainly of the face, lips, tongue, or throat, itching, and rashes (angioedema)

Very rare side effects(may affect up to 1 in 10,000 people) include:

• severe skin reactions such as skin rashes, ulcers, and blisters that may involve ulcers in the mouth, nose, genitals, hands, feet, and eyes (red, swollen eyes)

Some of these side effects are more frequent when capecitabine is used with other cancer treatments. Other side effects observed are as follows:

Common side effects(may affect up to 1 in 10 people) include:

• decrease in sodium, magnesium, or calcium in the blood, increase in blood sugar
• neuropathic pain
• tinnitus or ringing in the ears, hearing loss
• inflammation of the veins
• hoarseness, voice change
• pain or altered sensation in the mouth, jaw pain
• sweating, night sweats
• muscle spasms
• difficulty urinating, blood or protein in the urine
• bruising or reactions at the injection site (caused by medications administered by injection at the same time)

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicinal Products for Human Use:https://www.notificaram.es.

By reporting side effects, 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 date that appears on the box 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.

Medicines should not be disposed ofthrough drains or in the trash. Dispose of the packaging and unused medicines at the SIGRE collection pointat the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and unused medicines. By doing so, you will help protect the environment.

Composition of Capecitabina Tarbis

The active ingredient is capecitabina.

Each film-coated tablet contains 150 mg of capecitabina.

Each film-coated tablet contains 500 mg of capecitabina.

The other components (excipients) are:

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

Coating material: Hypromellose (E464), titanium dioxide (E171), talc (E553b), iron oxide red (E172), iron oxide yellow (E172).

Appearance of the product and contents of the package

Capecitabina Tarbis 150 mg film-coated tablets EFG:

Film-coated tablets, biconvex, light orange in color, 11.4 mm x 5.4 mm, oval shape, engraved with a "6" on one side and an "H" on the other side.

Capecitabina Tarbis 500 mg film-coated tablets EFG:

Film-coated tablets, biconvex, orange in color, 15.9 mm x 8.4 mm, oval shape, engraved with "3" on one side and "H" on the other side.

Each package contains 60, 100, and 120 film-coated tablets.

The pre-cut single-dose blister pack contains 60 x 1, 100 x 1, and 120 x 1 film-coated tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder

Tarbis Farma S.L.

Gran Vía Carlos III, 94

08028 Barcelona

Spain

Responsible for manufacturing

Amarox Pharma B.V.

Rouboslaan 32

Voorschoten, 2252TR

Netherlands

This medicine is authorized in the member states of the European Economic Area with the following names:

Germany:Capecitabin Amarox 150 mg Filmtabletten

Capecitabin Amarox 500 mg Filmtabletten

Netherlands:Capecitabine Amarox 150 mg, filmomhulde tabletten

Capecitabine Amarox 500 mg, filmomhulde tabletten

Spain:Capecitabina Tarbis 150 mg film-coated tablets EFG

Capecitabina Tarbis 500 mg film-coated tablets EFG

Last review date of this leaflet: June 2023

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