Ecansya

Patient Information Leaflet

Ecansya 150 mg film-coated tablets, 300 mg film-coated tablets, 500 mg film-coated tablets

capecitabine
Please read this leaflet carefully before 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, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult 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 taking 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 Ecansya is and what it is used for

Ecansya belongs to a class of medicines called "cytostatic agents", which inhibit the growth of tumour cells. Ecansya contains capecitabine, which in itself is not a cytostatic medicine. Only after being absorbed by the body is it converted into an active anticancer medicine (to a greater extent in tumour tissues than in normal tissues).
Ecansya is used to treat cancers of the colon, rectum, stomach or breast.
Additionally, Ecansya is used to prevent recurrence of colon cancer following complete surgical removal of the tumour.
Ecansya may 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 to any of the other ingredients of this medicine (listed in section 6). You must inform your doctor if you know you are allergic or have had excessive reactions to this medicine,
• if you have previously experienced severe reactions to treatment with fluoropyrimidines (a group of anticancer medicines such as fluorouracil),
• 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 or kidney problems,
• if you know you have no activity of the enzyme dihydropyrimidine dehydrogenase (DPD) (complete absence of DPD activity),
• if you are currently being treated or have been treated in the last 4 weeks with brivudine for herpes zoster (shingles or chickenpox).

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

• if you have a partial deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD),
• if a family member has partial deficiency or complete absence of the enzyme dihydropyrimidine dehydrogenase (DPD),
• if you have kidney or liver disease,
• if you have had or currently have heart problems (for example, irregular heartbeat or chest pain radiating to the jaw and vice versa caused by physical exertion due to impaired blood flow to the heart),
• if you have brain disorders (for example, 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 fluids due to severe nausea and vomiting,
• if you have diarrhea,
• if you are or may become dehydrated,
• if you have imbalances in blood ions (electrolyte imbalances, detectable in blood tests),
• if you have had eye problems, as you may require additional eye monitoring,
• if you develop a severe skin reaction.

Dihydropyrimidine dehydrogenase (DPD) deficiency
DPD deficiency is a genetic condition that generally does not cause health problems unless certain medicines are taken. If you have DPD deficiency and take Ecansya, you are at increased risk of developing severe adverse effects (listed in section 4 Possible side effects). Testing for DPD deficiency is recommended before starting treatment. Do not take Ecansya if you have no enzyme activity. If you have reduced enzyme activity (partial deficiency), your doctor may prescribe you a lower dose. Even if DPD deficiency test results are negative, severe or potentially life-threatening adverse effects may still occur.
Children and adolescents
Ecansya is not indicated for use in children and adolescents. Do not administer Ecansya to children and adolescents.
Other medicines and Ecansya
Before starting treatment, inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is extremely important because taking multiple medicines together may enhance or reduce their effects.
You must not take brivudine (an antiviral medicine used to treat shingles or chickenpox) concomitantly with capecitabine treatment (even during treatment breaks when no capecitabine tablets are taken).
If you have taken brivudine, you must wait at least 4 weeks after stopping it before starting capecitabine therapy. See also section “Do not take Ecansya”.
Special caution is also required when taking the following medicines concomitantly:

• medicines for gout (allopurinol),
• blood-thinning medicines (coumarin, warfarin),
• medicines used to treat seizures or tremors (phenytoin),
• interferon alfa,
• radiotherapy and certain anticancer medicines (folic acid, oxaliplatin, bevacizumab, cisplatin, irinotecan),
• medicines used to treat folic acid deficiency.

Ecansya with food and drink
You should take Ecansya within 30 minutes after meals.
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, if you suspect you may be pregnant or are planning pregnancy, consult your doctor or pharmacist before taking this medicine. You must not take Ecansya if you are definitely or possibly pregnant.
You must not breastfeed during treatment with Ecansya and for 2 weeks after the last dose.
If you are a woman of childbearing potential, you must use effective contraception during treatment with Ecansya and for 6 months after the last dose.
If you are a male patient and your partner is a woman of childbearing potential, you must use effective contraception during treatment with Ecansya and for 3 months after the last dose.
Driving and using machines
Ecansya may cause dizziness, nausea or fatigue. Therefore, Ecansya may affect your ability to drive or operate machinery.
Ecansya contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

3. How to take Ecansya

Take this medicine exactly as prescribed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Capecitabine should only be prescribed by a doctor experienced in the use of anticancer medicines.
Your doctor will prescribe the dosage and treatment schedule appropriate for you. The dose of Ecansya is based on body surface area, which is calculated from your height and weight. The usual dose for adults is 1250 mg/m² of body surface area twice daily (in the morning and evening). Below are two examples: a person weighing 64 kg and 1.64 m tall has a body surface area of 1.7 m² and should take 4 tablets of 500 mg and 1 tablet of 150 mg twice daily. A person weighing 80 kg and 1.80 m tall has a body surface area of 2.00 m² and should take 5 tablets of 500 mg twice daily.
Your doctor will tell you which dose to take, when to take it, and for how long.
Your doctor may prescribe a combination of tablets of 150 mg, 300 mg, and 500 mg for each dose.

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

Ecansya tablets are generally taken for 14 days, followed by a 7-day rest period (during which no tablets are taken). These 21 days constitute one treatment cycle.
When used in combination with other medicines, the usual adult dose may be lower than 1250 mg/m² of body surface area, and it may be necessary to take the tablets for a different duration (e.g., every day, without any rest period).

If you take more Ecansya than you should
If you take more Ecansya than prescribed, contact your doctor as soon as possible before taking the next dose.
If you take a much higher dose of capecitabine than recommended, you may experience the following adverse effects: nausea or vomiting, diarrhoea, inflammation or ulceration of the intestine or mouth, abdominal pain or gastrointestinal bleeding, or bone marrow suppression (reduction in certain types of blood cells). If you experience any of these symptoms, seek immediate medical advice.

If you forget to take Ecansya
Do not take the missed dose. Do not take a double dose to make up for the forgotten dose. Instead, continue with your regular dosing schedule and contact your doctor.

If you stop taking Ecansya
Stopping treatment with capecitabine does not cause adverse effects. However, if you are taking anticoagulant coumarins (e.g., phenprocoumon), stopping capecitabine may require your doctor to adjust the dose of your anticoagulant.
If you have any questions about using this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
IMMEDIATELY STOP taking Ecansya and contact your doctor if you experience any of the following symptoms:

• Diarrhea: if you have 4 or more bowel movements per day than usual, or experience nocturnal diarrhea.
• Vomiting: if you vomit more than once within 24 hours.
• Nausea: if you lose your appetite and the amount of food consumed in a day is much lower 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, redness, or tingling in the hands and/or feet.
• Fever: if your body temperature is equal to or higher than 38°C.
• Infection: if you show signs of infection caused by bacteria, viruses, or other organisms.
• Chest pain: if you feel pain located in the center of the chest, especially if it occurs during physical exertion.
• Stevens-Johnson syndrome: if you develop a painful red or purplish rash that spreads and forms blisters and/or other lesions starting in the mucous membranes (e.g., mouth and lips), particularly if you previously experienced light sensitivity, respiratory symptoms (e.g., bronchitis), and/or fever.
• DPD deficiency: if you have a known DPD deficiency, you are at higher risk of developing acute, early-onset toxicity and severe, potentially fatal or life-threatening adverse reactions due to Ecansya (e.g., stomatitis, mucosal inflammation, diarrhea, neutropenia, and neurotoxicity).
• Angioedema: if you notice any of the following symptoms, seek immediate medical help as urgent treatment may be required: swelling mainly affecting the face, lips, tongue, or throat causing difficulty in swallowing or breathing, itching sensation, and skin rashes. These could be signs of angioedema.

If detected early, these adverse reactions generally improve within 2–3 days after stopping the medicine. However, if adverse reactions persist, contact your doctor immediately. Your doctor 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 treatment cycle, this may be due to DPD deficiency (see Section 2: Warnings and precautions).
The hand-foot syndrome may lead to loss of fingerprints, which could affect your identification using fingerprint readers.

In addition to those listed above, other very common adverse reactions reported with Ecansya monotherapy, affecting more than 1 in 10 people, are:

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

These adverse reactions can become severe. Therefore, always contact your doctor immediately if you notice any adverse reaction. Your doctor may instruct you to reduce the dose and/or temporarily discontinue treatment with Ecansya. This will help reduce the likelihood of the adverse reaction persisting or becoming severe.

Other adverse reactions are:
Common adverse reactions (may affect up to 1 in 10 people) include:

• decrease in the number of white or red blood cells in the blood (observed in laboratory tests)
• dehydration, weight loss
• sleep disturbance (insomnia), depression
• headache, drowsiness, dizziness, abnormal skin sensation (numbness or tingling), altered taste
• eye irritation, increased tearing, eye redness (conjunctivitis)
• inflammation of veins (thrombophlebitis)
• shortness of breath, nosebleeds, cough, runny nose
• cold sores or other herpes infections
• lung or respiratory tract infections (e.g., pneumonia or bronchitis)
• intestinal bleeding, constipation, upper abdominal pain, indigestion, flatulence, dry mouth
• skin rash, hair loss (alopecia), skin redness, dry skin, itching, skin color changes, skin peeling, skin inflammation, nail changes
• joint or limb (extremities) pain, chest pain, back pain
• fever, limb swelling, feeling unwell
• liver function abnormalities (detected in blood tests) and increased bilirubin in the blood (excreted via the liver).

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

• blood infection, urinary tract infection, skin infection, nose and throat infection, fungal infections (including oral), influenza, gastroenteritis, abscess
• soft lumps under the skin (lipoma)
• decrease in blood cells including platelets, blood thinning (observed in laboratory tests)
• allergy
• diabetes, low blood potassium, malnutrition, increased blood triglycerides
• confusion, panic attacks, mood depression, reduced libido
• difficulty speaking, memory impairment, loss of motor coordination, balance problems, fainting, nerve damage (neuropathy), and sensory perception issues
• blurred or double vision
• dizziness, ear pain
• irregular heartbeat and palpitations (arrhythmia), chest pain, heart attack (myocardial infarction)
• blood clots in deep veins, high or low blood pressure, hot flushes, cold extremities, purplish spots on the skin
• blood clots in lung veins (pulmonary embolism), lung collapse, coughing up blood, asthma, shortness of breath on exertion
• intestinal obstruction, fluid accumulation in the abdomen, inflammation of the small or large intestine, stomach, or esophagus, lower abdominal pain, abdominal discomfort, heartburn (stomach contents reflux), blood in stools
• jaundice (yellowing of the skin and eyes)
• skin ulcers and blisters, skin reaction to sunlight, redness of palms, facial swelling or pain
• joint swelling or stiffness, bone pain, muscle weakness or stiffness
• fluid accumulation in the kidneys, increased frequency of urination at night, incontinence, blood in urine, increased blood creatinine (a sign of kidney dysfunction)
• unusual vaginal bleeding
• swelling (edema), chills, and stiffness.

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

• angioedema (swelling mainly affecting face, lips, tongue, or throat, itching sensation, and skin rashes)

Some of these adverse reactions are more common when capecitabine is used in combination with other anticancer medicines. Other adverse reactions observed in this context are:
Common adverse reactions (may affect up to 1 in 10 people) include:

• decreased sodium, magnesium, and calcium levels in blood, increased blood sugar
• nerve pain
• ringing in the ears (tinnitus), hearing loss
• inflammation of veins
• hiccups, voice changes
• pain or altered/abnormal sensation in the mouth, jaw pain
• sweating, night sweats
• muscle spasms
• difficulty urinating, blood or protein in urine
• bruising or injection site reactions (caused by concomitantly administered injectable medicines).

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

• narrowing or blockage of the tear duct (lacrimal duct stenosis)
• liver failure
• inflammation leading to impaired or blocked bile secretion (cholestatic hepatitis)
• specific changes in electrocardiogram (ECG) (prolongation of 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 red patches and skin peeling due to an immune system disorder.

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

• severe skin reactions such as rash, ulceration, and blister formation, which may lead to ulcers in the mouth, nose, genitals, hands, feet, and eyes (eye redness and swelling).

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report adverse reactions directly via the national reporting system listed in Annex V. By reporting adverse reactions, you 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 carton and 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 above 30°C.
Do not dispose of any medicine via 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 Ecansya contains

• The active substance is capecitabine. Each film-coated tablet contains 150 mg, 300 mg, or 500 mg of capecitabine.
• The other components are:
  Tablet core: Lactose, sodium croscarmellose, hypromellose (E-5), microcrystalline cellulose, magnesium stearate.
  Film coating:
  Ecansya 150 mg film-coated tablets: Hypromellose (6cps), titanium dioxide (E171), yellow iron oxide, red iron oxide (E172), talc.
  Ecansya 300 mg film-coated tablets: Hypromellose (6cps), titanium dioxide (E171), talc.
  Ecansya 500 mg film-coated tablets: Hypromellose (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 contents of the pack
Ecansya 150 mg film-coated tablets are light peach-coloured, biconvex, oblong tablets, 11.4 mm in length and 5.3 mm in width, with "150" engraved on one side and smooth on the other.
Ecansya 300 mg film-coated tablets are white to off-white, biconvex, oblong tablets, 14.6 mm in length and 6.7 mm in width, with "300" engraved on one side and smooth on the other.
Ecansya 500 mg film-coated tablets are peach-coloured, biconvex, oblong tablets, 15.9 mm in length and 8.4 mm in width, with "500" engraved on one side and smooth on the other.
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 Authorization Holder and Manufacturer:
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia.
For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

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

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

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

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

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

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

Ελλάδα
KRKA ΕΛΛΑΣ ΕΠΕ
Τηλ: + 30 2100101613

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

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

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

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

Ísland
LYFIS ehf.
Sími: + 354 534 3500

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

Κύπρος
KI.PA. (PHARMACAL) LIMITED
Τηλ: + 357 24 651 882

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

United Kingdom (Northern Ireland)
KRKA Pharma Dublin, Ltd.
Tel: + 353 1 413 3710

More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/

ANNEX IV
SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE 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 available literature data demonstrating that impaired renal function is associated with increased levels of uracil in blood, which could lead to a false diagnosis of dihydropyrimidine dehydrogenase (DPD) deficiency and subsequently to underdosing of capecitabine, the PRAC concluded that the product information for medicinal products containing capecitabine should be amended accordingly.
Having reviewed the PRAC recommendation, the Committee for Medicinal Products for Human Use (CHMP) agrees with the general conclusions and the rationale of the recommendation.

Grounds for the variation of the terms of the marketing authorisations
Based on the scientific conclusions for capecitabine, the CHMP considers that the benefit-risk balance of medicinal products containing capecitabine, as listed in the EURD list, remains unchanged, subject to the proposed amendments to the product information.
The CHMP recommends a variation to the terms of the marketing authorisations.