Capecitabine Zentiva

Package leaflet: Information for the patient

Capecitabine Zentiva 500 mg film-coated tablets

Generic medicine
Please 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Capecitabine Zentiva is and what it is used for
2. What you need to know before taking Capecitabine Zentiva
3. How to take Capecitabine Zentiva
4. Possible side effects
5. How to store Capecitabine Zentiva
6. Contents of the pack and other information

1. What Capecitabine Zentiva is and what it is used for

Capecitabine Zentiva belongs to a group of medicines called "cytostatic agents", which block the growth of cancer cells. Capecitabine Zentiva 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 (with higher conversion in tumour tissues than in normal tissues).
Capecitabine Zentiva is used to treat cancers of the colon, rectum, stomach or breast.
Additionally, Capecitabine Zentiva is used to prevent recurrence of colon cancer after complete surgical removal of the tumour.
Capecitabine Zentiva may be used alone or in combination with other medicines.

2. What you should know before taking Capecitabina Zentiva

Do not take Capecitabina Zentiva:

• 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 an excessive reaction 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 abnormally 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 have no activity of the enzyme dihydropyrimidine dehydrogenase (DPD),
• if you are currently being treated or have been treated within the last 4 weeks with brivudine for herpes zoster (shingles or varicella).

Warnings and precautions
Talk to your doctor or pharmacist before taking Capecitabina Zentiva

• if you have a partial deficiency in the activity 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 or vice versa caused by physical exertion due to impaired blood flow to the heart),
• if you have brain disorders (e.g., a tumor that has spread to the brain) or nerve damage (neuropathy),
• if you have imbalances in calcium levels (detectable through blood tests),
• if you have diabetes,
• if you are unable to eat or drink due to severe nausea or vomiting,
• if you have diarrhea,
• if you are or may become dehydrated,
• if you have imbalances in blood ions (electrolyte imbalances, detectable through blood tests),
• if you have a history of eye problems, as you may need additional eye examinations,
• if you experience severe skin reactions.

DPD deficiency
DPD deficiency is a rare inherited condition present at birth, which generally does not cause health problems unless certain medicines are taken.
If you have an unknown DPD deficiency and take Capecitabina Zentiva, you are at increased risk of developing acute and early-onset severe adverse effects listed in section 4 “Possible side effects”.
Inform your doctor immediately if any of the side effects concern you, or if you notice any side effect not listed in this leaflet (see section 4 “Possible side effects”).

Children and adolescents
Capecitabina Zentiva is not indicated for use in children and adolescents. Do not administer Capecitabina Zentiva to children and adolescents.

Other medicines and Capecitabina Zentiva
Before starting treatment, inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This is critically important, as 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 (including during treatment breaks when no capecitabine tablets are taken).
If you have taken brivudine, you must wait at least 4 weeks after stopping brivudine before starting capecitabine therapy. See also section “Do not take Capecitabina Zentiva”.
Additionally, particular caution is required when taking the following medicines concomitantly:

• medicines for gout (allopurinol),
• blood-thinning medicines (coumarins, warfarin),
• medicines used to treat 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 Capecitabina Zentiva with food
You should take Capecitabina Zentiva no more than 30 minutes after a meal.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine. You must not take Capecitabina Zentiva if you are pregnant or think you could be. You must not breastfeed during treatment with Capecitabina Zentiva and for 2 months after the last dose.
If you are a woman who could become pregnant, you must use an effective contraceptive method during treatment with Capecitabina Zentiva and for 6 months after the last dose.
If you are a male patient whose partner could become pregnant, you must use effective contraception during treatment with Capecitabina Zentiva and for 3 months after the last dose.

Driving and using machines:
Capecitabina Zentiva may cause dizziness, nausea, or fatigue. Therefore, Capecitabina Zentiva may affect your ability to drive or operate machinery.

3. How to take Capecitabine Zentiva

Always take this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Capecitabine Zentiva 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 dosage of Capecitabine
Zentiva is based on your body surface area. This is calculated from your height and weight. The usual dose for
adults is 1,250 mg/m^2 of body surface area twice daily (morning and evening). Two examples are provided: a person weighing 64 kg and 1.64 m tall has a body surface area of 1.7
m^2 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 m^2 and should take 5 tablets of
500 mg twice daily.
Capecitabine Zentiva tablets are generally taken for 14 days, followed by a 7-day rest period (during which the tablets are not taken). These 21 days constitute one treatment cycle.
When used in combination with other medicines, the usual adult dose may be less than 1,250 mg/m^2 of body surface area, and you may need to take the tablets for a different duration (for
example, every day, without any rest period).
Your doctor will inform you of the dose to take, when to take it, and for how long you need to take it.
Your doctor may prescribe you a combination of tablets 150 mg and 500 mg for each dose.

• Take the tablets in the morning and evening, as prescribed by your doctor.
• Take the tablets within 30 minutes after meals (breakfast and dinner) and swallow them whole with water. Do not crush or cut the tablets. If you are unable to swallow Capecitabine Zentiva tablets whole, tell your doctor.
• It is important to take all medicines exactly as prescribed by your doctor.

If you take more Capecitabine Zentiva than you should
If you take more Capecitabine Zentiva than prescribed, contact your doctor as soon as possible before taking the next dose.
If you take an overdose of Capecitabine Zentiva, you may experience the following side effects:
feeling unwell and malaise, diarrhoea, inflammation or ulceration of the intestine or mouth,
pain or bleeding from the intestine or stomach, or bone marrow suppression (reduction in certain types of blood cells). If you experience any of these symptoms, contact your doctor immediately.
If you forget to take Capecitabine Zentiva
Do not take the missed dose and do not double the next dose. Instead, continue with your regular dosing schedule and contact your doctor.
If you stop taking Capecitabine Zentiva
Stopping treatment with capecitabine does not cause adverse effects. However, if you are taking coumarin anticoagulants (e.g. phenprocoumon), stopping capecitabine may require your doctor to adjust the dose of the anticoagulant.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
STOP taking Capecitabine Zentiva immediately and contact your doctor if you experience any of the
following symptoms:

• Diarrhoea: if you have 4 or more additional bowel movements per day than normal, or nocturnal diarrhoea.
• Vomiting: if you vomit more than once within 24 hours.
• Nausea: if you lose your appetite and the amount of food you eat each day is much less than normal.
• Stomatitis: if you have pain, redness, swelling or ulcers in your mouth or throat.
• Hand-foot skin reaction: if you have pain, swelling and redness in your hands and/or feet.
• Fever: if your body temperature is 38°C or higher.
• Infection: if you show signs of infection caused by bacteria, viruses or other organisms.
• Chest pain: if you feel pain in the centre of your chest, especially if it occurs during physical exertion.
• Stevens-Johnson syndrome: if you develop a painful red or purple rash that spreads and blisters and/or other lesions begin to appear on mucous membranes (e.g. mouth and lips), particularly if you previously experienced light sensitivity, respiratory tract infections (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, life-threatening or fatal adverse reactions caused by Capecitabine Zentiva (e.g. stomatitis, mucosal inflammation, diarrhoea, neutropenia and neurotoxicity).

If treated early, these side effects generally improve within 2–3 days of stopping treatment. If these side effects persist, contact your doctor immediately.
Your doctor may advise you to restart the medicine at a lower dose.
Skin reactions on hands and feet may lead to loss of fingerprints, which could affect your identification via fingerprint scanning.

In addition to those listed above, other side effects have been reported with capecitabine monotherapy, which are very common and may affect more than 1 in 10 people:

• Abdominal pain.
• Rash, dry or itchy skin.
• Fatigue.
• Loss of appetite (anorexia).

These side effects can become severe. Therefore, always contact your doctor immediately if you notice any side effect. Your doctor may tell you to reduce the dose and/or temporarily stop treatment with Capecitabine Zentiva. This will help reduce the likelihood of the side effect persisting or becoming severe.

Other side effects include:
Common side effects (may affect up to 1 in 10 people) include:

• Decrease in the number of white or red blood cells in the blood (detected by blood tests).
• Dehydration, weight loss.
• Sleeplessness (insomnia), depression.
• Headache, drowsiness, dizziness, abnormal skin sensations (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 chest pain, indigestion, flatulence, dry mouth.
• Skin rash, hair loss (alopecia), skin redness, dry skin, itching.
• Skin discoloration, skin peeling, skin inflammation, nail changes.
• Joint or limb pain, chest or back pain.
• Fever, swelling of limbs, feeling unwell.
• Liver function problems (detected by blood tests) and increased bilirubin in the blood (excreted by the liver).

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

• Blood infection, urinary tract infection, skin infection, nose and throat infection, fungal infections (including in the mouth), influenza, gastroenteritis, dental abscess.
• Lumps under the skin (lipoma).
• Decreased blood cells including platelets, blood thinning (detected in blood tests).
• Allergic reaction.
• Diabetes, low potassium in the blood, malnutrition, increased triglycerides in the blood.
• Confusion, panic attacks, mood depression, reduced libido.
• Difficulty speaking, memory impairment, loss of coordination, balance problems, fainting, nerve damage (neuropathy) and sensory problems.
• Blurred or double vision.
• Dizziness, ear pain.
• Irregular heartbeat and palpitations (arrhythmia), chest pain and heart attack (infarction).
• Blood clots in deep veins, high or low blood pressure, hot flushes, coldness in limbs (extremities), purple spots on the skin.
• Blood clots in the 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 oesophagus, lower abdominal pain, abdominal discomfort, heartburn (food reflux from the stomach), blood in stools.
• Jaundice (yellowing of the skin and eyes).
• Skin ulceration and blistering, skin reactions 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 creatinine in blood (a sign of kidney dysfunction).
• Unusual vaginal bleeding.
• Swelling (oedema), chills and stiffness.

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

• Decreased sodium, magnesium and calcium in the blood, increased blood sugar.
• Nerve pain.
• Ringing or noise in the ears (tinnitus), hearing loss.
• Inflammation of veins.
• Hiccups, voice changes.
• Pain or altered/abnormal sensations in the mouth, jaw pain.
• Sweating, night sweats.
• Muscle spasm.
• Difficulty urinating, blood or protein in urine.
• Bruising or reactions at injection site (caused by medicines administered simultaneously by injection).

Rare side effects (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 the electrocardiogram (ECG) (prolongation of the QT interval).
• Certain types of arrhythmias (including ventricular fibrillation, torsade de pointes, and bradycardia).
• Eye inflammation causing eye pain and, possibly, vision problems.
• Skin inflammation causing red, scaly patches due to an immune system disorder.
• Acute kidney failure secondary to dehydration.

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

• Severe skin reaction, such as rashes, ulcers and blisters, which may involve ulcers in the mouth, nose, genitals, hands, feet and eyes (red and swollen eyes).
• Toxic damage to the white matter of the brain (toxic leukoencephalopathy).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. Side effects can also be reported directly via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse. Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Capecitabine Zentiva

Keep out of sight and reach of children.
Do not store above 30°C.
Do not use this medicine after the expiry date stated on the packaging after "Exp". The expiry date refers to the last day of that month.
Medicines should not be disposed of 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 Capecitabina Zentiva contains

• The active substance is capecitabine. Each film-coated tablet contains 500 mg of capecitabine.
• The other components are:
• Tablet core: croscarmellose sodium, microcrystalline cellulose, hypromellose, anhydrous colloidal silica, magnesium stearate.
• Tablet coating: hypromellose, titanium dioxide (E171), talc, macrogol 400, red iron oxide (E172), yellow iron oxide (E172).

Description of the appearance of Capecitabina Zentiva and package contents
Capecitabina Zentiva 500 mg film-coated tablets
Film-coated, peach-coloured, oblong capsule-shaped tablets, embossed with "500" on one side. Approximately 17.1 mm x 8.1 mm in size.
The package of Capecitabina Zentiva 500 mg film-coated tablets contains 120 film-coated tablets.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
Zentiva Italia S.r.l.
Viale Bodio 37/B
20158 Milano, Italy

Manufacturer:
Remedica Ltd
Aharnon Street, Limassol Industrial Estate, 3056 Limassol
Cyprus

This medicinal product is authorized in the European Economic Area countries under the following names:
Capecitabine Zentiva in Estonia, France, Lithuania, Latvia, Poland, and the United Kingdom; Capecitabine/Zentiva in Cyprus and Greece; Capecitabin Zentiva in Germany; Capecitabin-Zentiva in Hungary; Capecitabina Zentiva in Italy.