XELODA 150 mg Фильм-Coated Таблетки

Содержание инструкции

1. Xeloda 150 mg film-coated tablets, 500 mg film-coated tablets
   1. What is Xeloda and what it is used for
   2. What you need to know before taking Xeloda
   3. How to take Xeloda
   4. Possible side effects
   5. How to store Xeloda
   6. Package contents and other information

Xeloda 150 mg film-coated tablets, 500 mg film-coated tablets

capecitabine

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

• Keep this leaflet. 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 their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist (see section 4). Contents of this leaflet:
• 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. How to store Xeloda
• 6. Contents of the pack and other information

1. What is Xeloda and what it is used for

Xeloda belongs to the category of medicines called “cytostatic medicines”, which block the
growth of cancer cells. Xeloda contains capecitabine, which in itself is not a cytostatic
medicine. Only once absorbed by the body is it transformed into an active anti-cancer
medicine (to a greater extent in tumour tissues compared to normal tissues).
Xeloda is used for the treatment of colon, rectal, stomach or breast cancer.
In addition, Xeloda is used to prevent new occurrences of colon cancer following
complete surgical removal of the tumour.
Xeloda can be used alone or in combination with other medicines.

2. What you need to know before taking 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 must inform your doctor if you know you are allergic or develop excessive reactions to this medicine,
• if you have previously experienced severe reactions to fluoropyrimidine therapy (a group of anticancer medicines such as fluorouracil),
• if you are pregnant or breastfeeding,
• if you have excessively low levels of white blood cells and platelets in your blood (leukopenia, neutropenia or thrombocytopenia),
• if you have severe liver or kidney problems,
• if you have no activity of the dihydropyrimidine dehydrogenase (DPD) enzyme (total DPD deficiency),
• if you are currently being treated with or have been treated within the last 4 weeks with brivudine for herpes zoster (shingles or chickenpox).

Warnings and precautions
Talk to your doctor or pharmacist before taking Xeloda:

• if you have a partial deficiency in the activity of the dihydropyrimidine dehydrogenase (DPD) enzyme
• if you have a family member who has a partial or total deficiency in the dihydropyrimidine dehydrogenase (DPD) enzyme
• if you have kidney or liver disease,
• if you have had or have heart problems (e.g. irregular heartbeat or pain radiating from the chest to the jaw and vice versa caused by exertion and due to problems with blood flow to the heart),
• if you have brain diseases (e.g. a tumor that has spread to the brain) or nerve damage (neuropathy),
• if you have imbalances in calcium levels (detectable in blood tests),
• if you have diabetes,
• if you are unable to retain food or water in your body due to severe nausea and vomiting,
• if you suffer from diarrhea,
• if you are or may become dehydrated,
• if you have imbalances of ions in your blood (electrolyte imbalances, detectable in blood tests),
• if you have suffered from eye problems because you may need additional eye monitoring,
• if you develop a severe skin reaction.

Dihydropyrimidine dehydrogenase (DPD) deficiency
DPD deficiency is a genetic condition present at birth that generally does not associate with
health problems, unless you take certain medicines. If you have a DPD deficiency and you
take Xeloda, you are at higher risk of serious side effects (listed in section 4 “Possible
side effects”).
It is recommended to determine DPD deficiency before starting treatment. In the absence of enzymatic
activity, you should not take Xeloda. In the presence of reduced enzymatic activity (partial
deficiency), your doctor may prescribe a reduced dose. Even if the DPD deficiency test results are negative,
serious and life-threatening side effects may still occur.

Children and adolescents
Xeloda is not indicated for the treatment of children and adolescents. Do not administer Xeloda to
children and adolescents.

Other medicines and Xeloda
Before starting treatment, tell your doctor or pharmacist if you are taking, have recently
taken or may take any other medicines. This is of fundamental importance, as
taking multiple medicines at the same time can reinforce or reduce their effect.

You must not take brivudine (an antiviral medicine for the treatment of shingles
or chickenpox) at the same time as treatment with capecitabine (even
during break periods when no capecitabine tablets are taken).
If you have taken brivudine, you must wait at least 4 weeks after stopping its use
before starting therapy with capecitabine. See also section “Do not take Xeloda”.
Particular caution is also required when taking the following concomitantly:

• medicines for gout (allopurinol),
• medicines that thin the blood (coumarin, warfarin),
• medicines for the treatment of seizures or tremors (phenytoin),
• interferon alpha,
• radiotherapy and some medicines used for the treatment of tumors (folinic acid, oxaliplatin, bevacizumab, cisplatin, irinotecan),
• medicines used to treat folic acid deficiency.

Xeloda with food and drink
You must take Xeloda within 30 minutes of finishing meals.

Pregnancy and breastfeeding
If you are pregnant or breastfeeding, if you suspect or are planning a
pregnancy ask your doctor or pharmacist for advice before taking this medicine. You must not
take Xeloda if you are certainly or suspected to be pregnant.
You must not breastfeed during therapy with XELODA and for 2 weeks after the last
dose.
If you are a female patient of childbearing potential, during treatment with XELODA and for 6 months after the last dose
you must use effective contraceptive methods.
If you are a male patient and your partner is a female patient of childbearing potential, during treatment with
XELODA and for 3 months after the last dose you must use effective contraceptive methods.

Driving and using machines
Xeloda can cause dizziness, nausea or fatigue. It is therefore possible that Xeloda may affect
your ability to drive vehicles or use machines.

Xeloda contains anhydrous lactoseIf your doctor has diagnosed you with intolerance to some sugars,
contact him before taking this medicine.

Xeloda contains sodium
Xeloda contains less than 1 mmol (23 mg) of sodium per tablet, which is essentially ‘sodium-free’.

3. How to take Xeloda

Take this medicine following exactly the instructions of your doctor or pharmacist. If you
have any doubts, ask your doctor or pharmacist.
Xeloda must only be prescribed by a doctor specialized in the use of anticancer medicines.
The doctor will prescribe the dosage and treatment regimen indicated for you. The dosage of Xeloda is
established based on body surface area. This is calculated from height and weight. The usual dose
for adults is 1250 mg/m of body surface area twice a day (morning and evening). Below are two
examples: a person weighing 64 kg and height 1.64 m has a body surface area of 1.7 m and must take 4
500 mg tablets and 1 150 mg tablet twice a day. A person weighing 80 kg and height 1.80 m has a
body surface area of 2.00 m and must take 5 500 mg tablets twice a day.

Your doctor will tell you which dose you need to take, when to take it, and for how long.
The doctor may prescribe a combination of 150 mgand 500 mgtablets for each dose.

• Take the tablets in the morning and evening, as prescribed by your doctor.
• Take the tablets within 30 minutes of finishing a meal(breakfast and dinner) and swallow themwhole with water. Do not crush or cut the tablets. If you cannot swallow theXeloda tablets whole, inform your healthcare provider.
• It is important to take all medicines as prescribed by your doctor.

Xeloda tablets are usually taken for 14 days, followed by a 7-day rest period
(during which the tablets are not taken). These 21 days correspond to a treatment cycle.
In combination with other medicines, the usual dose for adults may be less than 1250 mg/m of
body surface area and you may need to take the tablets for a different period of time
(for example every day, without any 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.
If you take much more capecitabine than you should, you may experience the following side effects:
nausea or vomiting, diarrhea, inflammation or ulceration of the intestine or mouth, pain or
bleeding from the intestine or stomach, or bone marrow suppression (reduction of
certain types of blood cells). If you experience any of these symptoms, seek immediate
medical attention.

If you forget to take Xeloda:
Do not take the missed dose. Do not take a double dose to make up for the missed dose.
Instead, continue with the normal schedule of the prescribed dosage and contact your doctor.

If you stop taking Xeloda:
Stopping treatment with capecitabine does not cause any side effects. Stopping
treatment with capecitabine, if you are taking coumarin anticoagulants (containing
for example phenprocoumon), may require your doctor to adjust the dose of the anticoagulant.
If you have any questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

STOPtaking Xeloda immediately and contact your doctor if you experience any of the following symptoms:

• Diarrhea:if you experience an increase of 4 or more bowel movements per day compared to your normal bowel habits, or nocturnal diarrhea.
• Vomiting:if you vomit more than once within 24 hours.
• Nausea:if you lose your appetite and the amount of food you eat in a day is much less than usual.
• Stomatitis:if you experience pain, redness, swelling, or ulcers in the mouth or throat.
• Hand-foot reaction:if you experience pain, swelling, redness, or tingling in your hands and/or feet.
• Fever:if you have a body temperature equal to or greater than 38 °C.
• Infection:if you experience signs of infection caused by bacteria or viruses, or other organisms.
• Chest pain: if you feel pain localized in the center of the chest, especially if it occurs during exercise.
• Stevens-Johnson syndrome:if you experience a painful red or purplish rash that spreads and forms blisters and/or other lesions that begin to appear on the mucous membranes (e.g., mouth and lips), especially if you have previously experienced sensitivity to light, respiratory infections (e.g., bronchitis) and/or fever.
• Angioedema:If you notice any of the following symptoms, seek immediate medical attention as urgent medical treatment may be needed: swelling, mainly in the face, lips, tongue or throat, causing difficulty swallowing or breathing, itching and skin rashes. This could be a sign of angioedema.

If detected early, these side effects generally improve within 2-3 days after stopping the medicine. However, if the side effects should persist, contact your doctor immediately. The latter may advise you to resume taking the medicine at a lower dose.
In case of severe stomatitis (sores in the mouth and/or throat), inflammation of the mucous membranes, diarrhea, neutropenia (increased risk of infections) or neurotoxicity that occur during the first cycle of treatment, there may be a DPD deficiency (see section 2: Warnings and precautions).
The hand-foot syndrome can lead to loss of fingerprints, which may affect your identification using a fingerprint reader.
In addition to those listed above, other very common side effects reported with the use of Xeloda in monotherapy, which may affect more than 1 in 10 people, are:

• abdominal pain
• skin rash, dry skin or itchy skin
• fatigue
• loss of appetite (anorexia).

These side effects can become serious. Therefore, always contact your doctor immediatelywhen you notice the onset of a side effect. The doctor will tell you to reduce the dose and/or temporarily suspend treatment with Xeloda. This will help to reduce the likelihood of persistence of the side effect or its transformation into a serious side effect.
Other side effects are:
Common side effects (which can affect up to 1 in 10 people) include:

• decreased number of white blood cells or red blood cells in the blood (observed in tests)
• dehydration, weight loss
• insomnia, depression
• headache, drowsiness, dizziness, abnormal skin sensation (numbness or tingling), altered taste
• eye irritation, increased tearing, redness of the eye (conjunctivitis)
• inflammation of the veins (thrombophlebitis)
• shortness of breath, nosebleeds, cough, runny nose
• cold sores or other herpes infections
• lung or respiratory infections (e.g., pneumonia or bronchitis)
• intestinal bleeding, constipation, pain in the upper abdomen, indigestion, flatulence, dry mouth
• skin rash, hair loss (alopecia), dry skin, itching, altered skin color, skin peeling, skin inflammation, changes in nails
• joint or limb pain (extremities), chest pain or back pain
• fever, swelling of the limbs, feeling unwell
• problems with liver function (observed with blood tests) and increased bilirubin in the blood (excreted through the liver) Uncommon side effects (which can affect up to 1 in 100 people) include:
• blood infection, urinary tract infection, skin infection, infections of the nose and throat, fungal infections (including those of the mouth), influenza, gastroenteritis, abscess
• soft lumps under the skin (lipoma)
• decreased blood cells including platelets, blood thinning (observed in tests)
• allergy
• diabetes, decreased potassium in the blood, malnutrition, increased triglycerides in the blood
• confusion, panic attacks, depressed mood, decreased libido
• difficulty speaking, memory impairment, loss of coordination of movements, balance disturbance, fainting, nerve damage (neuropathy) and sensory perception problems
• blurred or double vision
• vertigo, ear pain
• irregular heartbeat and palpitations (arrhythmia), chest pain and heart attack (infarction)
• blood clots in the deep veins, high or low blood pressure, hot flashes, coldness in the extremities (limbs), purplish spots on the skin
• blood clots in the pulmonary veins (pulmonary embolism), lung collapse, blood in sputum, asthma, shortness of breath during exertion
• intestinal obstruction, fluid collection in the abdomen, inflammation of the small or large intestine, stomach or esophagus, pain in the lower abdomen, abdominal discomfort, heartburn (reflux of food from the stomach), blood in the stool
• jaundice (yellowing of the skin and eyes)
• skin ulcer and blisters, skin reaction to sunlight, redness of the palms, swelling or pain in the face
• swelling or stiffness of the joints, bone pain, muscle weakness or stiffness
• fluid collection in the kidneys, increased frequency of urination at night, incontinence, blood in the urine, increased creatinine in the blood (a sign of kidney dysfunction)
• unusual vaginal bleeding
• swelling (edema), chills and stiffness. Rare side effects (which can 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 blockage of bile secretion (cholestatic hepatitis)
• specific changes in the electrocardiogram (prolongation of the QT interval)
• certain types of arrhythmias (including ventricular fibrillation, torsade de pointes, and bradycardia)
• eye inflammation causing eye pain and potential vision problems
• skin inflammation leading to the formation of red patches and scaling due to a disease of the immune system.
• swelling, mainly in the face, lips, tongue or throat, itching and skin rashes (angioedema) Very rare side effects (which can affect up to 1 in 10,000 people) include:
• severe skin reactions, such as rash, ulceration and blistering, which may involve ulcers in the mouth, nose, genitals, hands, feet and eyes (redness and swelling of the eyes) Some of these side effects are more common when capecitabine is used with other medicines for the treatment of tumors. Other side effects observed in this context are:

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

• decreased sodium, magnesium and calcium in the blood, increased sugar in the blood
• nerve pain
• ringing in the ears (tinnitus), hearing loss
• inflammation of the veins
• hiccups, altered voice
• pain or altered/abnormal sensation in the mouth, jaw pain
• sweating, night sweats
• muscle spasm
• difficulty urinating, blood or protein in the urine
• bruising or reactions at the injection site (caused by medicines administered simultaneously by injection). Reporting of side effectsIf you get any side effects, talk to your doctor, pharmacist or nurse. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Xeloda

Keep out of sight and reach of children.
Do not store at a temperature above 30 °C, store in the original package to protect
the medicine from humidity.
Do not use this medicine after the expiry date which is reported on the outer packaging and on the
blister after Scad./EXP. The expiry date refers to the last day of that month.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Xeloda contains

• 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
• The other ingredients are:
• Tablet core: anhydrous lactose, sodium croscarmellose, hypromellose (3 mPa.s), microcrystalline cellulose, magnesium stearate (see section 2 “Xeloda contains anhydrous lactose and sodium”).
• Tablet coating: hypromellose, titanium dioxide, yellow iron oxide, red iron oxide and talc. Description of the appearance of Xeloda and package contentsXeloda 150 mg film-coated tablets Light peach-colored film-coated tablet, biconvex and oblong in shape, with “150” imprinted on one side and “Xeloda” on the other side.

Each pack contains 60 film-coated tablets (6 blisters of 10 tablets).
Xeloda 500 mg film-coated tablets
Peach-colored film-coated tablet, biconvex and oblong in shape, with “500” imprinted on
one side and “Xeloda” on the other side.
Each pack 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

Other sources of information
More detailed information on this medicine is available on the website of the European
Medicines Agency (EMA): http://www.ema.europa.eu/.

ANNEX IV
SCIENTIFIC CONCLUSIONS AND JUSTIFICATIONS FOR VARIATIONS TO THE
MARKETING AUTHORISATIONS
Scientific conclusions
Taking into account the assessment of the Pharmacovigilance and Risk Assessment Committee
(Pharmacovigilance and Risk Assessment Committee, PRAC) of the Periodic Safety Update Reports (Periodic Safety Update Report, PSUR) for capecitabine, the scientific conclusions
are as follows:
In light of the data available from the literature demonstrating that impaired renal function is associated with increased levels of uracil in the blood, which could lead to a false
diagnosis of dihydropyrimidine dehydrogenase (DPD) deficiency and subsequently to an underdosage of
capecitabine, the PRAC concluded that the medicine information of medicines containing
capecitabine must be amended accordingly.
Having examined the PRAC recommendation, the Committee for Medicinal Products for Human Use
(Committee for Medicinal Products for Human Use,CHMP) agrees with the related overall conclusions and with the justifications for the recommendation.

Justifications for variations to the marketing authorisations
Based on the scientific conclusions on capecitabine, the CHMP considers that the benefit/risk
ratio of the medicines containing capecitabine as listed in the EURD list remains
unchanged, save for the proposed changes to the product information.
The CHMP recommends the variation of the marketing authorisations.