CAPECITABINE ACCORD 500 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Capecitabine Accord 150 mg film-coated tablets EFG

Capecitabine Accord 300 mg film-coated tablets

Capecitabine Accord 500 mg film-coated tablets EFG

Capecitabine

Read all of this 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 further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

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

1. What Capecitabine Accord is and what it is used for

Capecitabine Accord belongs to a group of medicines called “cytostatic medicines”, which stop the growth of cancer cells. Capecitabine Accord contains capecitabine and by itself is not a cytostatic medicine. Only after being absorbed into the body does it change into an active anti-cancer medicine (more in tumor tissue than in normal tissue).

Capecitabine Accord is used for the treatment of colon, rectal, stomach, or breast cancer. Additionally, Capecitabine Accord is used to prevent the return of colon cancer after the complete removal of the tumor through surgical operation.

Capecitabine Accord can be used alone or in combination with other medicines.

2. What you need to know before taking Capecitabine Accord

Do not take Capecitabine Accord

• if you are allergic to capecitabine or any of the other ingredients of this medicine (listed in section 6). You should inform your doctor if you have any kind of allergy or overreaction to this medicine,
• if you have previously experienced severe reactions to fluoropyrimidine therapy (a group of anti-cancer medicines like fluorouracil).
• if you are pregnant or breastfeeding,
• if you have excessively low levels of white blood cells or platelets in your blood (leucopenia, neutropenia, or thrombocytopenia),
• if you have severe liver or kidney disease,
• if you know you have no activity of the enzyme dihydropyrimidine dehydrogenase (DPD) (complete DPD deficiency)
• if you are being treated or have been treated in the last 4 weeks with brivudine as part of the treatment for herpes zoster (shingles or chickenpox).

Warnings and precautions

Consult your doctor or pharmacist before starting treatment with Capecitabine Accord, if:

• you know you have a partial deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD).
• you are a relative of a person with a partial or complete deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD).
• you have liver or kidney problems
• you have or have had heart problems (e.g., irregular heartbeat) or chest pain, jaw and back pain due to circulation problems
• you have brain diseases (e.g., cancer that has spread to the brain or nerve damage (neuropathy))
• you have calcium imbalance (seen in blood tests)
• you have diabetes
• due to severe nausea and vomiting, you are unable to keep food or water in your body
• you have diarrhea
• you are or will be dehydrated
• you have an electrolyte imbalance in your blood (electrolyte imbalance, seen in tests)
• you have a history of eye problems as you may need additional eye monitoring
• you have a severe skin reaction.

DPD deficiency: DPD deficiency is a genetic condition that is not usually related to health problems unless you are being treated with certain medicines. If you have a DPD deficiency and take Capecitabine Accord, you will have a higher risk of experiencing severe side effects (indicated in section 4, Possible side effects). It is recommended that you undergo a test to detect DPD deficiency before starting treatment. If you have no enzyme activity, you should not take Capecitabine Accord. If you have reduced enzyme activity (partial deficiency), your doctor may prescribe a reduced dose. Although the test results for DPD deficiency are negative, severe and potentially fatal side effects may still occur.

Children and adolescents

Capecitabine Accord is not indicated in children and adolescents. Do not give Capecitabine Accord to children and adolescents.

Using Capecitabine Accord with other medicines

Before starting treatment, inform your doctor or pharmacist if you are using, have recently used, or might use any other medicines. This is very important because if you take more than one medicine at the same time, their effects may be increased or decreased.

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

• medicines for gout (allopurinol),
• medicines to reduce blood clotting (coumarin, warfarin),
• medicines for seizures or tremors (phenytoin)
• a medicine to treat cancer (interferon alfa)
• radiotherapy and certain medicines used to treat cancer (folinic acid, oxaliplatin, and bevacizumab, cisplatin, irinotecan).

Using Capecitabine Accord with food and drinks

You should take Capecitabine Accord within 30 minutes after finishing a meal.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

You should not take Capecitabine Accord if you are pregnant or think you may be pregnant.

You should not breastfeed while taking Capecitabine Accord and for 2 weeks after the last dose.

If you are a woman who could become pregnant, you should use effective contraception during treatment with Capecitabine Accord and for 6 months after the last dose.

If you are a male patient and your female partner could become pregnant, you should use effective contraception during treatment with Capecitabine Accord and for 3 months after the last dose.

Driving and using machines

While taking Capecitabine Accord, you may feel dizzy, nauseous, or tired. Therefore, Capecitabine Accord may affect your ability to drive or use machines. Do not drive if you feel dizzy, nauseous, or tired after taking this medicine.

Capecitabine Accord contains lactose

If your doctor has told you that you have an intolerance to some sugars, consult your doctor before taking this medicine.

3. How to take Capecitabine Accord

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

Capecitabine Accord should only be prescribed by a doctor with experience in the use of anti-cancer medicines.

Your doctor will prescribe a treatment schedule and the correct dose for you. The dose of Capecitabine Accord depends on your body surface area. This is calculated by measuring your height and weight. The usual dose for adults is 1,250 mg/m2 of body surface area twice a day (morning and evening). We give two examples: a person whose weight is 64 kg and height is 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 whose weight is 80 kg and height is 1.80 m has a body surface area of 2.00 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 you should 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 the morning and evening, as prescribed by your doctor.
• Take the tablets within 30 minutes after finishing a meal, and swallow them whole with water. Do not crush or cut the tablets. If you cannot swallow the Capecitabine Accord tablets whole, talk to your doctor or pharmacist.
• It is important that you take all your medication as prescribed by your doctor.

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

In combination with other medicines, the usual dose in adults may be less than 1,250 mg/m2 of body surface area, and it may be necessary for you to take the tablets for a different period (e.g., every day, without a rest period).

If you take more Capecitabine Accord than you should:

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

You may experience the following side effects if you take much more capecitabine than you should: feeling dizzy or vomiting, diarrhea, inflammation or ulcers in the intestine or mouth, pain or bleeding in the intestine or stomach, or bone marrow depression (reduction of certain types of blood cells). Inform your doctor immediately if you experience any of these symptoms.

If you forget to take Capecitabine Accord:

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

If you stop taking Capecitabine Accord:

Stopping treatment with capecitabine does not produce side effects.

In case you are taking anticoagulant coumarins (e.g., phenprocoumon), stopping treatment with capecitabine may require your doctor to adjust the doses of the anticoagulant.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, Capecitabina Accord can cause adverse effects, although not all people suffer from them.

STOPtaking Capecitabina Accord immediately and contact your doctor if any of these symptoms appear:

• Diarrhea: if you have an increase of 4 or more bowel movements compared to your normal daily bowel movements or have nighttime 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 much less than usual.
• Stomatitis: if you have pain, redness, swelling, or ulcers in the mouth and/or throat.
• Skin Reaction on Hands and Feet: if you have pain, swelling, and redness or tingling of 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 or viruses, or other organisms.
• Chest Pain:if you have localized pain in the center of the chest, especially if it occurs while exercising.
• Steven-Johnson Syndrome:if you have painful red or purple rashes that spread and blisters and other lesions that start to appear on the mucous membrane (e.g., mouth and lips), particularly if you have had previous sensitivity to light, respiratory infections (e.g., bronchitis), and/or fever.
• DPD Deficiency:if you have a known DPD deficiency, you have a higher risk of early onset of toxicity and severe adverse reactions, potentially life-threatening or fatal, caused by Capecitabina Accord (e.g., stomatitis, mucositis, diarrhea, neutropenia, and neurotoxicity).
• 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 rash. This could be a sign of angioedema.

Detected in time, these adverse effects usually improve within 2 or 3 days of stopping the medication. However, if these adverse effects continue, contact your doctor immediately. Your doctor may advise you to resume treatment with a lower dose.

If severe stomatitis (ulcers in the mouth and/or throat), mucositis, diarrhea, neutropenia (increased risk of infections), or neurotoxicity occur during the first treatment cycle, it is possible that there is a DPD deficiency (see section 2: Warnings and Precautions).

The skin reaction on hands and feet can lead to the loss of fingerprints, which can affect your identification through fingerprint analysis.

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

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

These adverse effects can be severe; therefore, always contact your doctor immediatelywhen you start to feel an adverse effect. Your doctor may advise you to reduce the dose and/or temporarily stop treatment with Capecitabina Accord. This will help reduce the likelihood that the adverse effect will continue or become severe.

Other adverse effects are:

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

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

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

• blood infection, urinary tract infection, skin infection, nose and throat infections, mycosis (including oral), flu, gastroenteritis, dental abscess
• subcutaneous lumps (lipoma)
• decrease in blood cells, including platelets, anemia (seen in blood tests)
• allergy
• diabetes, decreased potassium in the blood, malnutrition, increased triglycerides in the blood
• confusion, panic attacks, depression, reduced libido
• difficulty speaking, altered memory, loss of movement coordination, balance disorders, fainting, nerve damage (neuropathy), and sensitivity problems
• blurred or double vision
• vertigo, ear pain
• irregular heartbeat and palpitations (arrhythmias), chest pain, and heart attack (infarction)
• blood clots in deep veins, high or low blood pressure, hot flashes, cold limbs, purple spots on the skin
• blood clots in the lungs (pulmonary embolism), lung atelectasis, coughing up blood, asthma, breathing difficulties during exercise
• intestinal obstruction, fluid accumulation in the abdomen, inflammation of the small or large intestine, stomach, or esophagus, lower abdominal pain, abdominal discomfort, acid reflux, 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 or numbness of the joints, 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

Some of these adverse effects are more common when capecitabine is used with other cancer medications. Other adverse effects observed in this setting are the following:

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

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

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

• narrowing or blockage of the tear duct (stenosis of the tear duct)
• liver failure
• inflammation leading to dysfunction or obstruction of bile secretion (cholestatic hepatitis)
• specific changes in the electrocardiogram (QT prolongation)
• certain types of arrhythmias (including ventricular fibrillation, torsades de pointes, and bradycardia)
• eye inflammation that causes eye pain and possible vision problems
• skin inflammation that causes red scaly patches due to an immune system disorder
• angioedema (swelling mainly of the face, lip, tongue, or throat, itching, and rash)

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

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

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the national reporting system included in Annex V. By reporting adverse effects, you can help provide more information on the safety of this medication.

5. Storage of Capecitabina Accord

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date indicated on the packaging after CAD.

For aluminum/aluminum blister

This medication does not require any special storage conditions.

PVC/PVDC/aluminum blister (perforated monodoses)

Do not store above 30°C

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Capecitabina Accord

• The active ingredient is capecitabine

Each film-coated tablet contains 150 mg of capecitabine.

Each film-coated tablet contains 300 mg of capecitabine.

Each film-coated tablet contains 500 mg of capecitabine.

• The other ingredients are:

Tablet core: anhydrous lactose, sodium croscarmellose, hypromellose, microcrystalline cellulose, magnesium stearate.

Tablet coating (for 150 mg): hypromellose, titanium dioxide (E171), yellow iron oxide, and red iron oxide (E172), talc.

Tablet coating (for 300 mg): hypromellose, titanium dioxide (E171), talc. Tablet coating (for 500 mg): hypromellose, titanium dioxide (E171), yellow iron oxide, red iron oxide (E172), talc.

Appearance of the Product and Package Contents

Capecitabina Accord 150 mg are film-coated tablets of light peach color, oblong, biconvex, 11.4 mm in length, and 5.3 mm in width, with the mark "150" on one side and smooth on the other.

Capecitabina Accord 300 mg are film-coated tablets of white to beige color, oblong, biconvex, 14.6 mm in length, and 6.7 mm in width, with the mark "300" on one side and smooth on the other.

Capecitabina Accord 500 mg are film-coated tablets of peach color, oblong, biconvex, 15.9 mm in length, and 8.4 mm in width, with the mark "500" on one side and smooth on the other.

Capecitabina Accord is available in blister packs containing 30, 60, or 120 film-coated tablets or in perforated monodose blisters containing 30 x 1, 60 x 1, or 120 x 1 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona, s/n,

Edifici Est 6ª planta,

08039 Barcelona,

Spain

Manufacturer

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50, 95-200 Pabianice, Poland

Accord Healthcare B.V.,

Winthontlaan 200,

3526 KV Utrecht,

Netherlands

Date of the Last Revision of this Leaflet

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