XELODA 150 MG FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Xeloda 150mg film-coated tablets

Xeloda 500 mg film-coated tablets

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

1. What Xeloda is and what it is used for

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

Xeloda is used for the treatment of colon, rectal, stomach, or breast cancer. Additionally, Xeloda is used to prevent the reappearance of colon cancer after the complete removal of the tumor through surgery.

Xeloda can be used alone or in combination with other medicines.

2. What you need to know before you take Xeloda

Do not take Xeloda

• 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 type of allergy or exaggerated reaction to this medicine,

• if you have previously had severe reactions to fluoropyrimidine treatment (a group of cancer medicines like fluorouracil),
• if you are pregnant or breastfeeding,
• if you have very low levels of white blood cells or platelets in your blood (leukopenia, neutropenia, or thrombocytopenia),
• if you have severe liver or kidney disease,
• if you know you have no activity of the enzyme dihydropyrimidine dehydrogenase (DPD),
• if you are being treated or have been treated in the last 4 weeks with brivudine as part of the treatment for herpes zoster (chickenpox or shingles).

Warnings and precautions

Consult your doctor or pharmacist before starting to take Xeloda

• if you know you have a partial deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD)
• if you have liver or kidney disease
• if you have heart problems, for example, an irregular heartbeat or chest and back pain caused by physical exertion 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 a 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 an electrolyte imbalance in your blood (electrolyte imbalance, see analysis)
• if you have a history of eye problems, as you will need extra monitoring of your eyes
• if you have a severe skin reaction.

DPD deficiency

DPD deficiency is a rare, congenital disorder that is not usually associated with health problems unless you take certain medicines. If you have an unrecognized DPD deficiency and take Xeloda, you have a higher risk of early and severe onset of the serious side effects mentioned in section 4. Possible side effects. Contact your doctor immediately if you are concerned about any of the side effects or if you experience any side effect not mentioned in this leaflet (see section 4. Possible side effects).

Children and adolescents

Xeloda is not indicated in children and adolescents. Do not administer Xeloda to children and adolescents.

Use of Xeloda with other medicines

Tell 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 must not take brivudine (an antiviral medicine for the treatment of shingles or chickenpox) at the same time as you are receiving treatment with capecitabine (including any rest period when you are not taking any Xeloda tablets).

If you have taken brivudine, you must wait at least 4 weeks after finishing brivudine before starting to take capecitabine. See also the section “Do not take Xeloda”.

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),
• interferon alpha,
• radiation therapy and certain medicines used for cancer treatment (folinic acid, oxaliplatin, bevacizumab, cisplatin, irinotecan),
• medicines used to treat folic acid deficiency.

Taking Xeloda with food and drinks

You must take Xeloda within 30 minutes after finishing a meal.

Pregnancy and breastfeeding

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 must not take Xeloda if you are pregnant or think you may be pregnant.

You must not breastfeed if you are taking Xeloda and for 2 weeks after the last dose.

If you are a woman who could become pregnant, you must use a reliable method of contraception during treatment with XELODA and for 6 months after the last dose.

If you are a male patient and your female partner could become pregnant, you must use a reliable method of contraception during treatment with XELODA and for 3 months after the last dose.

Driving and using machines

When taking Xeloda, you may feel dizzy, nauseous, or tired. Therefore, Xeloda may affect your ability to drive or use machines.

Xeloda contains anhydrous 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 Xeloda

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

Xeloda must be prescribed only by a doctor with experience in the use of cancer medicines.

Your doctor will prescribe a treatment schedule and the correct dose for you. The dose of Xeloda 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 night). We give you 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 2.0 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 you need 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 the morning and at night, 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 split the tablets. If you cannot swallow Xeloda tablets whole, tell your healthcare professional.
• It is important that you take all your medication as prescribed by your doctor.

Xeloda 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 to take the tablets for a different period of time (for example, every day, without a rest period).

If you take more Xeloda than you should

If you take more Xeloda 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 more capecitabine than you should: feeling unwell, diarrhea, inflammation, or ulcers in the stomach or mouth, pain or bleeding in the intestine or stomach, or bone marrow depression (decrease in certain types of blood cells). Inform your doctor immediately if you experience any of these symptoms.

If you forget to take Xeloda

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 Xeloda

Stopping treatment with capecitabine does not produce side effects. In case you are taking anticoagulant medicines (e.g., acenocoumarol), stopping treatment with capecitabine may require your doctor to adjust the dose of the anticoagulant.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

STOPtaking Xeloda immediately and contact your doctor if some of these symptoms appear:

• Diarrea: if you have an increase of 4 or more bowel movements compared to your normal daily bowel movements or have nocturnal diarrhea.
• Vómito: if you vomit more than once in a 24-hour period.
• Náuseas: if you lose your appetite and the amount of food you eat each day is much less than usual.
• Estomatitis: if you have pain, redness, swelling, or sores in the mouth and/or throat.
• Skin reaction on hands and feet: if you have pain, swelling, and redness or tingling in 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 sensitivity to light, respiratory infections (e.g., bronchitis), and/or fever before.
• DPD deficiency:if you have a known DPD deficiency, you have a higher risk of early onset of toxicity and severe adverse reactions, potentially fatal or life-threatening, caused by XELODA (e.g., stomatitis, mucositis, diarrhea, neutropenia, and neurotoxicity).

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

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 Xeloda is used alone, the very frequent adverse effects that may affect more than 1 in 10 people are:

• abdominal pain
• rash, 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 Xeloda. This will help reduce the likelihood that the adverse effect will continue or become severe.

Other adverse effects are:

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

• decrease in the number of white or red blood cells (seen in blood tests)
• dehydration, weight loss
• sleeplessness (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, runny nose
• herpes labialis or infections with other herpes
• lung or respiratory tract infections (e.g., pneumonia or bronchitis)
• intestinal bleeding, constipation, pain in the upper abdomen, indigestion, gas (increased flatulence), dry mouth
• skin rashes, hair loss (alopecia), redness of the skin, dry skin, itching (pruritus), change in skin color, skin loss, skin inflammation, nail disorders
• joint pain, or pain in the limbs, chest, or back
• fever, swelling of the limbs, feeling of discomfort
• liver function problems (seen in blood tests) and increased bilirubin in the blood (excreted by the liver)

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

• blood infection, urinary tract infection, skin infection, nose and throat infection, fungal infections (including those of the mouth), flu, gastroenteritis, dental abscesses
• skin inflammation (lipomas)
• decrease in blood cells, including platelets, dilution of 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 sensation problems
• blurred or double vision
• vertigo, ear pain
• irregular heartbeats and palpitations (arrhythmias), chest pain, and heart attack (myocardial infarction)
• blood clots in deep veins, high or low blood pressure, hot flashes, cold limbs, purple spots on the skin
• blood clots in the pulmonary veins (pulmonary embolism), lung collapse, coughing up blood, asthma, exertional dyspnea
• intestinal obstruction, fluid accumulation in the abdomen, inflammation of the small or large intestine, stomach, or esophagus, pain in the lower abdomen, abdominal discomfort, acid reflux (food regurgitation from the stomach), 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, weakness, or muscle 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 frequent when capecitabine is used with other cancer medications. Other observed adverse effects are:

Frequent adverse 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
• ringing or buzzing in the ears (tinnitus), hearing loss
• vein inflammation
• 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
• bruises or reactions 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) are:

• narrowing or obstruction 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 interval 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 disease

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 Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Xeloda

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

Do not store at a temperature above 30°C.

Do not use this medicine after the expiration date shown on the packaging and on the blister after CAD. The expiration date is the last day of the month indicated.

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

6. Package Contents and Additional Information

Xeloda Composition

• The active ingredient is capecitabine.

• Xeloda 150 mg film-coated tablets

Each tablet contains 150 mg of capecitabine

• Xeloda 500 mg film-coated tablets

Each tablet contains 500 mg of capecitabine

• Other components are:

• Tablet core: anhydrous lactose, sodium croscarmellose, hypromellose (3 mPa.s), microcrystalline cellulose, magnesium stearate.
• Tablet coating: hypromellose (3 mPa.s), titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172), and talc.

Product Appearance and Package Contents

Xeloda 150 mg film-coated tablets

Light peach-colored, oblong, biconvex film-coated tablets, marked with "150" on one side and "Xeloda" on the other.

Each package contains 60 film-coated tablets (6 blisters of 10 tablets).

Xeloda 500 mg film-coated tablets

Peach-colored, oblong, biconvex film-coated tablets, marked with "500" on one side and "Xeloda" on the other.

Each package contains 120 film-coated tablets (12 blisters of 10 tablets).

Marketing Authorization Holder

CHEPLAPHARM Arzneimittel GmbH Ziegelhof 24

17489 Greifswald Germany

Manufacturer

Excella GmbH & Co. KG

Nuernberger Str. 12

90537 Feucht Germany

CHEPLAPHARM Arzneimittel GmbH

Ziegelhof 23-24

17489 Greifswald

Germany

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of the Last Revision of this Leaflet:

Other Sources of Information

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