ECANSYA 150 mg FILM-COATED TABLETS

2. What you need to know before you take 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 should inform your doctor if you have any allergies or hypersensitivity reactions to this medicine,
• if you have previously experienced 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) (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 (chickenpox or shingles).

Warnings and precautions

Talk to your doctor or pharmacist before taking Ecansya

• if you know you have a partial deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD)
• if you are a relative of a person with a partial or complete 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 (e.g., cancer that has spread to the brain or nerve damage (neuropathy))
• if you have a calcium imbalance (seen 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 have diarrhea
• if you are dehydrated or become dehydrated
• if you have an electrolyte imbalance in your blood (electrolyte imbalance, see blood tests)
• 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 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 Ecansya, 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 Ecansya. 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

Ecansya is not indicated in children and adolescents. Do not give Ecansya to children and adolescents.

Using Ecansya with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take 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),
• interferon alfa,
• radiotherapy and certain medicines used to treat cancer (folinic acid, oxaliplatin, bevacizumab, cisplatin, irinotecan),
• medicines used to treat folic acid deficiency.

Taking Ecansya with food and drinks

You should take Ecansya 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 Ecansya if you are pregnant or think you may be pregnant.

You must not breastfeed your baby while taking Ecansya and for 2 weeks after the last dose. If you are a woman who could become pregnant, you must use an effective method of birth control during treatment with Ecansya and for 6 months after the last dose.

If you are a male patient and your female partner could become pregnant, you must use an effective method of birth control during treatment with Ecansya and for 3 months after the last dose.

Driving and using machines

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

Ecansya 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 Ecansya

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

Capecitabine should only be prescribed 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 Ecansya 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 daily (morning and evening). We provide two examples: a person weighing 64 kg and measuring 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 daily. A person weighing 80 kg and measuring 1.80 m has a body surface area of 2.0 m2, so they should take 5 tablets of 500 mg, twice daily.

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, 300 mg, and 500 mg tablets 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 finishing a meal and swallow them whole with water. Do not crush or split the tablets. If you cannot swallow Ecansya tablets whole, inform your healthcare professional.
• It is important that you take all your medication as prescribed by your doctor.

Ecansya 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 you may need to take the tablets for a different period (e.g., every day, without a 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 and 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 gut or mouth, pain, and bleeding in the intestine or stomach, or bone marrow depression (reduction of certain types of blood cells).

Tell your doctor immediately if you experience any of these symptoms.

If you forget to take Ecansya

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 Ecansya

Stopping treatment with capecitabine does not produce side effects.

In case you are taking anticoagulant medicines (e.g., containing acenocoumarol), stopping treatment with capecitabine may require your doctor to adjust the dose 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, this medicine can cause adverse effects, although not all people suffer from them.

STOPtaking Ecansya 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 nocturnal 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 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, 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 life-threatening or fatal, caused by Ecansya (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 rashes. It could be a sign of angioedema.

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.

If severe stomatitis (sores in the mouth and/or throat), mucositis, diarrhea, neutropenia (increased risk of infections), or neurotoxicity occur during the first treatment cycle, there may be 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 Ecansya is used alone, very frequent adverse effects that may affect more than 1 in 10 people are:

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

These adverse effects can be serious; therefore, always contact your doctor immediatelywhen you start to feel an adverse effect. Your doctor may advise you to decrease the dose and/or temporarily stop treatment with Ecansya. This will help reduce the likelihood of the adverse effect continuing or becoming severe.

Other adverse effects are:

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

• decrease in white or red blood cell count (seen in blood tests),
• dehydration, weight loss,
• 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,
• cold sores or infections with other herpes viruses,
• 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), skin color change, skin loss, skin inflammation, nail disorders,
• pain in the joints or limbs, chest or back,
• fever, swelling of the limbs, feeling unwell,
• 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 (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 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, sun-induced skin reaction, redness of the palms, swelling, or pain in the face,
• joint or muscle swelling or stiffness, bone pain, weakness, or muscle stiffness,
• fluid accumulation in the kidneys, increased urination frequency 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 adverse effects (may affect up to 1 in 1,000 people) include:

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

Some of these adverse effects are more frequent when capecitabine is used with other medicines for cancer treatment. Other observed adverse effects are as follows:

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,
• inflammation of the veins,
• 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 medicines administered by injection at the same time).

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

• 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 arrhythmia (including ventricular fibrillation, torsades de pointes, and bradycardia),
• Eye inflammation that causes eye pain and potential vision problems,
• Skin inflammation that causes red scaly patches due to an immune system disorder.

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

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

Reporting 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 does not appear in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Ecansya

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

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

For aluminum/aluminum blister

No special storage conditions are required.

PVC/PVdC/aluminum blister

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 medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Ecansya

• The active ingredient is capecitabine. Each film-coated tablet contains 150 mg, 300 mg, or 500 mg of capecitabine.
• The other ingredients (excipients) are:

Core of the tablet

Lactose, sodium croscarmellose, hypromellose (E-5), microcrystalline cellulose, magnesium stearate.

Film coating

Ecansya 150 mg film-coated tablets

Hypromellose (6cps), titanium dioxide (E171), yellow and 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 and red iron oxide (E172), talc.

See section 2 "Ecansya contains lactose".

Appearance of the Product and Package Contents

Ecansya 150 mg film-coated tablets (tablets) are light peach-colored, oblong, biconvex, 11.4 mm long, and 5.3 mm wide, with the mark "150" on one side and smooth on the other.

Ecansya 300 mg film-coated tablets (tablets) are white to bone-colored, oblong, biconvex, 14.6 mm long, and 6.7 mm wide, with the mark "300" on one side and smooth on the other.

Ecansya 500 mg film-coated tablets (tablets) are peach-colored, oblong, biconvex, 15.9 mm long, and 8.4 mm wide, with the mark "500" on one side and smooth on the other.

Ecansya is available in blisters (aluminum/aluminum or PVC/PVdC/aluminum) containing 30, 60, or 120 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer

Pharmacare Premium Limited, HHF 003, Hal Far Industrial Estate Birzebbugia, BBG 3000, Malta KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

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

Date of Last Revision of this Leaflet

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