Package leaflet: Information for the user

Capecitabine PharOS 150 mg film-coated tablets

Capecitabine PharOS 500 mg film-coated tablets

capecitabine

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 further questions, ask your doctor or pharmacist.

- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

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

2. What you need to know before you take Capecitabine PharOS

3. How to take Capecitabine PharOS

4. Possible side effects

5. How to store Capecitabine PharOS

6. Contents of the pack and other information

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

Capecitabine PharOS belongs to the group of medicines called "cytostatic medicines", which stop the growth of cancer cells. Capecitabine PharOS contains 150 mg capecitabine, which itself is not a cytostatic medicine. Only after being absorbed by the body is it changed into an active anti‑cancer medicines (more in tumour tissue than in normal tissue).

Capecitabine PharOS belongs to the group of medicines called "cytostatic medicine", which stop the growth of cancer cells. Capecitabine PharOS contains 500 mg capecitabine, which itself is not a cytostatic medicine. Only after being absorbed by the body is it changed into an active anti‑cancer medicine (more in tumour tissue than in normal tissue).

Capecitabine PharOS is prescribed by doctors for the treatment of colon, rectal, gastric, or breast cancers. Furthermore, Capecitabine PharOS is prescribed by doctors to prevent new occurrence of colon cancer after complete removal of the tumour by surgery.

Capecitabine PharOS may be used either alone or in combination with other medicines.

2. What you need to know before you take Capecitabine PharOS

Do not take Capecitabine PharOS:

- 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 that you have an allergy or over‑reaction to this medicine.

- ifyoupreviouslyhavehadseverereactionstofluoropyrimidinetherapy(agroupofanticancer medicinessuchasfluorouracil),

- if you are pregnant or nursing

- if you have severely low levels of white cells or platelets in the blood (leukopenia, neutropenia or thrombocytopenia),

- if you have severe liver or kidney problems,

- if you have a known deficiency for the enzyme dihydropyrimidine dehydrogenase (DPD) involved in the metabolism of uracil and thymine, or

- if you are being treated now or have been treated in the last 4 weeks with brivudine, sorivudine or similar classes of substance as part of herpes zoster (chickenpox or shingles) therapy.

Warnings and precautions

Talk to your doctor or pharmacist before taking Capecitabine PharOS if you:

- have liver or kidney diseases

- have or had heart problems (for example an irregular heartbeat or pains to the chest, jaw and back brought on by physical effort and due to problems with the blood flow to the heart)

- have brain diseases (for example cancer that has spread to the brain, or nerve damage (neuropathy)

- have calcium imbalances (seen in blood tests)

- have diabetes

- have diarrhoea

- are or become dehydrated

- have imbalances of ions in your blood (electrolyte imbalances, seen in tests)

- have a history of eye problems as you may need extra monitoring of your eyes

- have a severe skin reaction.

DPD deficiency:DPD deficiency is a rare condition present at birth that is not usually associated with health problems unless you receive certain medicines. If you have an unrecognised DPD deficiency and take Capecitabine PharOS, you may experience severe forms of the side effects listed under section 4 Possible side effects. Contact your doctor immediately if you are concerned about any of the side effects or if you notice any additional side effects not listed in the leaflet (see section 4 Possible side effects).

Children and adolescents

Capecitabine PharOS is not indicated in children and adolescents. Do not give Capecitabine PharOS to children and adolescents.

Other medicines and Capecitabine PharOS

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.This is extremely important, as taking more than one medicine at the same time can strengthen or weaken the effect of the medicines. You need to be particularly careful if you are taking any of the following:

- gout medicines (allopurinol),

- blood-thinning medicines (coumarin, warfarin),

- certain anti-viral medicines (sorivudine and brivudine),

- medicines for seizures or tremors (phenytoin),

- interferon alpha,

- radiotherapy and certain medicines used to treat cancer (folinic acid, oxaliplatin, bevacizumab, cisplatin, irinotecan),

Capecitabine PharOS with food and drink

You should take Capecitabine PharOS no later than 30 minutes after meals.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast‑feeding, 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 Capecitabine PharOS if you are pregnant or think you might be. You must not breast‑feed if you are taking Capecitabine PharOS. Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Capecitabine PharOS may make you feel dizzy, nauseous or tired. It is therefore possible that Capecitabine PharOS could affect your ability to drive a car or operate machinery.

3. How to takeCapecitabine PharOS

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Capecitabine PharOS should only be prescribed by a doctor experienced in the use of anticancer medicines.

Capecitabine PharOS tablets should be swallowed with waterand within 30 minutes of a meal.

Your doctor will prescribe a dose and treatment regimen that is right for you. The dose of Capecitabine PharOS is based on your body surface area. This is calculated from your height and weight. The recommended dose for adults is 1250 mg/m²of body surface area taken two times daily (morning and evening). Two examples are provided here: A person whose body weight is 64 kg and height is 1.64 m has a body surface area of 1.7 m²and should take 4 tablets of 500 mg and 1 tablet of 150 mg two times daily. A person whose body weight is 80 kg and height is 1.80 m has a body surface area of 2.00 m²and should take 5 tablets of 500 mg two times daily.

Capecitabine PharOS tablets are usually taken for 14 days followed by a 7 day rest period (when no tablets are taken). This 21 day period is one treatment cycle.

In combination with other medicines the recommended dose for adults may be less than 1250 mg/m²of body surface area, and you may need to take the tablets over a different time period (e.g. every day, with no rest period).

Your doctor will tell you what dose you need to take, when to take it and for how long you need to take it.

Your doctor may want you to take a combination of 150 mgand 500 mgtablets for each dose.

- Take the tablets morning and eveningas prescribed by your doctor.

- Take the tablets within 30 minutes after the end of a meal(breakfast and dinner).

- It is important that you take all your medicine as prescribed by your doctor.

If you take more Capecitabine PharOS than you should

If you take more Capecitabine PharOS than you should, contact your doctor as soon as possible before taking the next dose.

You might get the following side effects if you take a lot more capecitabine than you should: feeling or being sick, diarrhoea, inflammation or ulceration of the gut or mouth, pain or bleeding from the intestine or stomach, or bone marrow depression (reduction in certain kinds of blood cells). Tell your doctor immediately if you experience any of these symptoms.

If you forget to take Capecitabine PharOS:

Do not take the missed dose at all and do not double the next one. Instead, continue your regular dosing schedule and check with your doctor.

If you stop taking Capecitabine PharOS

There are no side‑effects caused by stopping treatment with Capecitabine PharOS. In case you are using coumarin anticoagulants (containing e.g. phenprocoumon), stopping Capecitabine PharOS might require that your doctor adjusts your anticoagulant dose.

If you have any further questions on 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 Capecitabine PharOS immediately and contact your doctor if any of these symptoms occur:

- Diarrhoea:if you have an increase of 4 or more bowel movements compared to your normal bowel movements each day or any diarrhoea at night.

- Vomiting:if you vomit more than once in a 24‑hour time 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 your mouth and/or throat.

- Hand-and-foot skin-reaction: if you have pain, swelling, redness or tingling of hands and/or feet.

- Fever:if you have a temperature of 38 °C or greater.

- Infection:if you experience signs of infection caused by bacteria or virus, or other organisms.

- Chest pain: if you experience pain localised to the centre of the chest, especially if it occurs during exercise.

- Steven-Johnson syndrome: if you experience painful red or purplish rash that spreads and blisters and/or other lesions begin to appear in the mucous membrane (e.g. mouth and lips), in particular if you had before light sensitivity, infections of the respiratory system (e.g. bronchitis) and/or fever.

If caught early, these side effects usually improve within 2 to 3 days after treatment discontinuation. If these side effects continue, however, contact your doctor immediately. Your doctor may instruct you to restart treatment at a lower dose.

In addition to the above, when Capecitabine PharOS is used alone, very common side effects, which may affect more than 1 person in 10 are:

• abdominal pain

• tiredness

• loss of appetite (anorexia)

These side effects can become severe; therefore, it is important that you always contact your doctor immediately when you start to experience a side effect. Your doctor may instruct you to decrease the dose and/or temporarily discontinue treatment with Capecitabine PharOS. This will help reduce the likelihood that the side effect continues or becomes severe.

Other side effects are:

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

• decreases in the number of white blood cells or red blood cells (seen in tests)

• dehydration, weight loss

• sleeplessness (insomnia), depression

• headache, sleepiness, dizziness, abnormal sensation in the skin (numbness or tingling sensation), taste changes

• eye irritation, increased tears, eye redness (conjunctivitis)

• inflammation of the veins (thrombophlebitis)

• shortness of breath, nose bleeds, cough, runny nose

• cold sores or other herpes infections

• infections of the lungs or respiratory system (e.g. pneumonia or bronchitis)

• bleeding from the gut, constipation, pain in upper abdomen, indigestion, excess wind, dry mouth

• skin rash, hair loss (alopecia), skin reddening, dry skin, itching (pruritus), skin discolouration, skin loss, skin inflammation, nail disorder

• pain in the joints, or in the limbs (extremities), chest or back

• fever, swelling in the limbs, feeling ill

• problems with liver function (seen in blood tests) and increased blood bilirubin (excreted by the liver).

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

• blood infection, urinary tract infection, infection of the skin, infections in the nose and throat, fungal infections (including those of the mouth), influenza, gastroenteritis, tooth abscess

• lumps under the skin (lipoma)

• decreases in blood cells including platelets, thinning of blood (seen in tests)

• allergy

• diabetes, decrease in blood potassium, malnutrition, increased blood triglycerides

• confusional state, panic attacks, depressed mood, decreased libido

• difficulty speaking, impaired memory, loss of movement coordination, balance disorder, fainting, nerve damage (neuropathy) and problems with sensation

• blurred or double vision

• vertigo, ear pain

• irregular heartbeat and palpitations (arrhythmias), chest pain and heart attack (infarction)

• blood clots in the deep veins, high or low blood pressure, hot flushes, cold limbs (extremities), purple spots on the skin

• blood clots in the veins in the lung (pulmonary embolism), collapsed lung, coughing up blood, asthma, shortness of breath on exertion

• bowel obstruction, collection of fluid in the abdomen, inflammation of the small or large intestine, the stomach or the oesophagus, pain in the lower abdomen, abdominal discomfort, heartburn (reflux of food from the stomach), blood in the stool

• jaundice (yellowing of skin and eyes)

• skin ulcer and blister, hives, reaction of the skin with sunlight, reddening of palms, swelling or pain of the face

• joint swelling or stiffness, bone pain, facial pain, muscle weakness or stiffness

• fluid collection in the kidneys, increased frequency of urination during the night, incontinence, blood in the urine, increase in blood creatinine (sign of kidney dysfunction)

• unusual bleeding from the vagina

• swelling (oedema), chills and rigors

Some of these side effects are more common when capecitabine is used with other medicines for the treatment of cancer. Other side-effects seen in this setting are the following:

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

• decrease in blood sodium, magnesium or calcium, increase in blood sugar,

• nerve pain,

• ringing or buzzing in the ears (tinnitus), loss of hearing,

• vein inflammation,

• hiccups, change in voice,

• pain or altered/abnormal sensation in the mouth, pain in the jaw,

• sweating, night sweats,

• muscle spasm,

• difficulty in urination, blood or protein in the urine,

• bruising or reaction at the injection site (caused by medicines given by injection at the same time)

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

• narrowing or blockage of tear duct (lacrimal duct stenosis)

• liver failure

• inflammation leading to dysfunction or obstruction in bile secretion (cholestatic hepatitis)

• specific changes in the electrocardiogram (QT prolongation)

• certain types of arrhythmia (including ventricular fibrillation, torsade de pointes, and bradycardia)

• eye inflammation causing eye pain and possibly eyesight problems

• inflammation of the skin causing red scaly patches due to an immune system illness

• kidney failure due to dehydration.

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

• severe skin reaction such as skin rash, ulceration and blistering which may involve ulcers of the mouth, nose, genitalia, hands, feet and eyes (red and swollen eyes).

Reporting of side effects

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

5. How to store Capecitabine PharOS

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

Do not store above 30°C.

Do not use this medicine after the expiry date which is stated on the carton after EXP.

The expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Capecitabine PharOS contains

Capecitabine PharOS 150 mg film-coated tablets:

- The active substance is capecitabine. Each film-coated tablet contains 150 mg capecitabine.

Capecitabine PharOS 500 mg film-coated tablets:

- The active substance is capecitabine. Each film-coated tablet contains 500 mg capecitabine.

- The other ingredients are:

- Tablet core: Croscarmellose Sodium, Microcrystalline Cellulose, Hypromellose, Silica colloidal anhydrous, Magnesium Stearate,

- Tablet coating: Hypromellose, Titanium Dioxide (E171), Talc, Macrogol 400, Red Iron Oxide (E172), Yellow Iron Oxide (E172)

What Capecitabine PharOS looks like and contents of the pack

Capecitabine PharOS 150 mg film-coated tablets:

Light-peach oval film-coated tablets embossed with “150” on one side. Of approximate dimensions 11.4 mm x 5.9 mm.

Capecitabine PharOS 150 mg film-coated tablet pack contains 60 film-coated tablets.

Capecitabine PharOS 500 mg film-coated tablets:

Peach, oblong capsule-shaped, film-coated tablets embossed with “500” on one side. Of approximate dimensions 17.1 mm x 8.1 mm.

Capecitabine PharOS 500 mg film-coated tablet pack contains 120 film-coated tablets.

Marketing Authorisation Holder and Manufacturer:

Marketing Authorisation Holder

PharOS – Pharmaceutical Oriented Services Ltd

Lesvou Str. (end), Thesi Loggos, Industrial Zone

14452, Metamorfossi Attikis

Greece

Manufacturer

Remedica LTD

Aharnon Street, Limassol Industrial Estate,

3056 Limassol

Cyprus

This medicinal product is authorised in the Member States of the EEA under the following names:

This leaflet was last revised in

<To be completed nationally>

2015-08-28