ECANSYA 150 mg Film-Coated Tablets

Зміст інструкції

1. Ecansya 150 mg film-coated tablets, 300 mg film-coated tablets, 500 mg film-coated tablets
   1. What is Ecansya and what is it used for
   2. What you need to know before taking Ecansya
   3. How to take Ecansya
   4. Possible side effects
   5. How to store Ecansya
   6. Package contents and other information

Ecansya 150 mg film-coated tablets, 300 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 they have the same symptoms as you, as it may 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 Ecansya is and what it is used for
• 2. What you need to know before you take Ecansya
• 3. How to take Ecansya
• 4. Possible side effects
• 5. How to store Ecansya
• 6. Contents of the pack and other information

1. What is Ecansya and what is it used for

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

2. What you need to know before taking Ecansya

Do not take Ecansya

• 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 know that you have no activity of the dihydropyrimidine dehydrogenase (DPD) enzyme (total absence of DPD activity).
• if you are currently being treated or have been treated in the last 4 weeks with brivudine as part of therapy for herpes zoster (shingles).

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

• if you have a partial deficiency of dihydropyridine dehydrogenase (DPD) enzyme activity,
• if you have a family member with partial deficiency or total absence of dihydropyrimidine dehydrogenase (DPD) enzyme activity
• 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 the 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 that generally does not associate with health problems, unless
you take certain medicines. If you have a DPD deficiency and take Ecansya, you are at greater
risk of developing severe side effects (listed in section 4 Possible side effects). It is recommended
to perform DPD deficiency tests before starting treatment. Do not take Ecansya if you have no
enzymatic activity. If you have reduced enzymatic activity (partial deficiency) your doctor may
prescribe a lower dose. If the results of the DPD deficiency tests are negative, severe or potentially
life-threatening side effects may still occur.

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

Other medicines and Ecansya
Before starting treatment, tell your doctor or pharmacist if you are taking, have recently
taken or might take any other medicines. This is of fundamental importance, as
taking multiple medicines at the same time can strengthen 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 Ecansya”.
In addition, special care must be taken 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 alfa,
• radiotherapy and some medicines used for the treatment of tumors (folinic acid, oxaliplatin, bevacizumab, cisplatin, irinotecan),
• medicines used to treat folic acid deficiency.

Ecansya with food and drink
You must take Ecansya 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 Ecansya if you are certainly or suspected to be pregnant.
You must not breastfeed while taking Ecansya and for 2 weeks after the last
dose.
If you are a female patient of childbearing potential, during treatment with Ecansya 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 woman of childbearing potential, during treatment with
Ecansya and for 3 months after the last dose you must use effective contraceptive methods.

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

Ecansya contains lactose
If your doctor has diagnosed you with intolerance to some sugars, contact him/her before taking
this medicine.

3. How to take Ecansya

Take this medicine following exactly the instructions of your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
Capecitabine 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 Ecansya is
established based on body surface area. This is calculated starting 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 whose weight is 64 kg and height is 1.64 m has a
body surface area of 1.7 m and must 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 m and must take 5 tablets of 500 mg twice a day.

The doctor will tell you which dose is necessary to take, when to take it and for how long.
The doctor may prescribe a combination of tablets of 150 mg, 300 mgand 500 mgfor each
dosage.

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

Ecansya tablets are generally taken for 14 days, followed by a rest period
of 7 days (during which the tablets are not taken). These 21 days correspond to a
therapy 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 Ecansya than you should
If you take more Ecansya than you should, contact your doctor as soon as possible before taking the dose
next.
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 Ecansya
Do not take the missed dose. Do not take a double dose to make up for the missed dose.
Instead, continue the normal administration of the prescribed dosage and contact your doctor.

If you stop taking Ecansya
Stopping treatment with capecitabine does not cause any side effects. Stopping the
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 doubts 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 everybody gets them.

STOPtaking Ecansya 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 nighttime diarrhea.
• Vomiting:if you vomit more than once within 24 hours.
• Nausea:if you lose your appetite and if the amount of food you eat in a day is much less than normal.
• Stomatitis:if you experience pain, redness, swelling or ulcers in the mouth or throat.
• Hand-foot skin reaction:if you have pain, swelling and 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 experience 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, the respiratory system (e.g. bronchitis) and/or fever.
• DPD deficiency:if you have a known DPD deficiency, you are at greater risk of acute and early onset toxicity and serious, life-threatening or potentially life-threatening adverse reactions caused by Ecansya (e.g. stomatitis, mucosal inflammation, diarrhea, neutropenia and neurotoxicity).
• 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 that causes difficulty swallowing or breathing, a feeling of 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.
If severe stomatitis (ulcers in the mouth and/or throat), mucosal inflammation,
diarrhea, neutropenia (increased risk of infections), or neurotoxicity occur during the first cycle of
treatment, this may be caused by DPD deficiency (see Section 2: Warnings and precautions).
The hand-foot syndrome may 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
Ecansya as monotherapy, which may affect more than 1 in 10 people, are:

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

These side effects can become serious. Therefore, always contact your doctor immediately
when you notice the onset of a side effect. The doctor will tell you to reduce the dose and/or
temporarily stop treatment with Ecansya. 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 may affect up to 1 in 10 people) include:

• decrease in the number of white 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
• rash, hair loss (alopecia), dry skin, itching, altered skin color, skin peeling, skin inflammation, altered nails
• joint or limb (extremity) pain, chest pain or back pain
• fever, swelling of the extremities, feeling unwell
• problems with liver function (observed with blood tests) and increased bilirubin in the blood (excreted through the liver).

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

• blood infection, urinary tract infection, skin infection, nasal and throat infection, fungal infections (including those of the mouth), influenza, gastroenteritis, abscess
• soft lumps under the skin (lipoma)
• decrease in 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 disorder, 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, cold extremities (limbs), purplish spots on the skin
• blood clots in the pulmonary veins (pulmonary embolism), lung collapse, blood in cough, 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 (sign of kidney dysfunction)
• unusual vaginal bleeding
• swelling (edema), chills and stiffness.

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

• angioedema (swelling mainly in the face, lips, tongue or throat, feeling of itching and skin rashes)

Some of these side effects are more common when capecitabine is used with other
medicines for cancer treatment. Other side effects observed in this context are:
Common side effects (which may affect up to 1 in 10 people) include:

• decrease in sodium, magnesium and calcium in the blood, increased blood sugar
• 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).

Rare side effects (which 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 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 an immune system disorder.

Very rare side effects (which may 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).

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not
listed in this leaflet. You can also report side effects directly through the national reporting system
indicated in Annex V. By reporting side effects you can help provide more information on the safety
of this medicine.

5. How to store Ecansya

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack after EXP and on the blister
after EXP. The expiry date refers to the last day of that month.

For Aluminium-aluminium blisters
This medicine does not require any special storage conditions.

For PVC/PVdC-aluminium blisters
Do not store at a temperature above 30°C.
Do not dispose of any medicine in waste water 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 Ecansya contains

• The active ingredient is capecitabine. Each film-coated tablet contains 150 mg, 300 mg or 500 mg of capecitabine.
• The other ingredients are: Tablet core: Lactose, sodium croscarmellose, hypromellose (E-5), microcrystalline cellulose, magnesium stearate. Coating Ecansya 150 mg film-coated tabletsHypromellose (6cps), titanium dioxide (E171), yellow iron oxide, red iron oxide (E172), talc. Ecansya 300 mg film-coated tabletsHypromellose (6cps), titanium dioxide (E171), talc. Ecansya 500 mg film-coated tabletsHypromellose (6cps), titanium dioxide (E171), yellow iron oxide, red iron oxide (E172), talc. See section 2 “Ecansya contains lactose”.

Description of the appearance of Ecansya and package contents
Ecansya 150 mg film-coated tablets (tablets) are light peach in colour, biconvex in shape and oblong, 11.4 mm in length and 5.3 mm in width, with "150" imprinted on one side and smooth on the other side.
Ecansya 300 mg film-coated tablets (tablets) are white to off-white in colour, biconvex in shape and oblong, 14.6 mm in length and 6.7 mm in width, with "300" imprinted on one side and smooth on the other side.
Ecansya 500 mg film-coated tablets (tablets) are peach in colour, biconvex in shape and oblong, 15.9 mm in length and 8.4 mm in width, with "500" imprinted on one side and smooth on the other side.
Ecansya is available in blisters (aluminium-aluminium or PVC/PVdC-aluminium) containing 30, 60 or 120 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer:
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia.
For further information on this medicine, contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
KRKA Belgium, SA.
Tél/Tel: + 32 (0) 487 50 73 62

Lietuva
UAB KRKA Lietuva
Tel: + 370 5 236 27 40

България
КРКА България ЕООД
Teл.: + 359 (02) 962 34 50

Luxembourg/Luxemburg
KRKA Belgium, SA.
Tél/Tel: + 32 (0) 487 50 73 62 (BE)

Česká republika
KRKA ČR, s.r.o.
Tel: + 420 (0) 221 115 150

Magyarország
KRKA Magyarország Kereskedelmi Kft.
Tel.: + 36 (1) 355 8490

Danmark
KRKA Sverige AB
Tlf: + 46 (0)8 643 67 66 (SE)

Malta

• E. J. Busuttil Ltd. Tel: + 356 21 445 885

Deutschland
TAD Pharma GmbH
Tel: + 49 (0) 4721 606-0

Nederland
KRKA Belgium, SA.
Tel: + 32 (0) 487 50 73 62 (BE)

Eesti
KRKA, d.d., Novo mesto Eesti filiaal
Tel: + 372 (0) 6 671 658

Norge
KRKA Sverige AB
Tlf: + 46 (0)8 643 67 66 (SE)

Ελλάδα
KRKA ΕΛΛΑΣ ΕΠΕ
Τηλ: + 30 2100101613

Österreich
KRKA Pharma GmbH, Wien
Tel: + 43 (0)1 66 24 300

España
KRKA Farmacéutica, S.L.
Tel: + 34 911 61 03 80

Polska
KRKA-POLSKA Sp. z o.o.
Tel.: + 48 (0)22 573 7500

France
KRKA France Eurl
Tél: + 33 (0)1 57 40 82 25

Portugal
KRKA Farmacêutica, Sociedade Unipessoal Lda.
Tel: + 351 (0)21 46 43 650

Hrvatska
KRKA - FARMA d.o.o.
Tel: + 385 1 6312 100

România
KRKA Romania S.R.L., Bucharest
Tel: + 4 021 310 66 05

Ireland
KRKA Pharma Dublin, Ltd.
Tel: + 353 1 413 3710

Slovenija
KRKA, d.d., Novo mesto
Tel: + 386 (0) 1 47 51 100

Ísland
LYFIS ehf.
Sími: + 354 534 3500

Slovenská republika
KRKA Slovensko, s.r.o.
Tel: + 421 (0) 2 571 04 501

Italia
KRKA Farmaceutici Milano S.r.l.
Tel: + 39 02 3300 8841

Suomi/Finland
KRKA Finland Oy
Puh/Tel: + 358 20 754 5330

ΚύπροςSverige
KRKA Sverige AB
KI.PA. (PHARMACAL) LIMITED Tel: + 46 (0)8 643 67 66 (SE)
Τηλ: + 357 24 651 882

Latvija
KRKA Latvija SIA
Tel: + 371 6 733 86 10

United Kingdom (Northern Ireland)
KRKA Pharma Dublin, Ltd.
Tel: + 353 1 413 3710
More detailed information on this medicine is available on the website of the European Medicines Agency http://www.ema.europa.eu/

ANNEX IV
SCIENTIFIC CONCLUSIONS AND MOTIVATIONS FOR VARIATION OF THE TERMS
OF THE MARKETING AUTHORISATIONS
Scientific conclusions
Taking into account the evaluation by the Pharmacovigilance and Risk Assessment Committee (PRAC) of the Periodic Safety Update Reports (PSURs) for capecitabine, the scientific conclusions are as follows:
In light of the available literature data demonstrating that impaired renal function is associated with increased blood uracil levels, which could lead to a false diagnosis of dihydropyrimidine dehydrogenase (DPD) deficiency and subsequently to underdosing of capecitabine, the PRAC concluded that the medicine’s information for medicines containing capecitabine must be amended accordingly.
Having examined the PRAC recommendation, the Committee for Medicinal Products for Human Use (CHMP) agrees with the related overall conclusions and with the motivations of the recommendation.

Motivations for variation of the terms of 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 terms of the marketing authorisations.