Capecitabine Medac: detailed information

Package leaflet: Information for the patient

Capecitabina medac 150 mg film-coated tablets, 500 mg film-coated tablets

capecitabine
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 pass it on to other people, even if they have the same symptoms as yours, 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

What Capecitabina medac is and what it is used for
What you need to know before taking Capecitabina medac
How to take Capecitabina medac
Possible side effects
How to store Capecitabina medac
Contents of the pack and other information

1. What Capecitabina medac is and what it is used for

Capecitabina medac belongs to a class of medicines called "cytostatic agents", which block the growth of tumour cells. Capecitabina medac contains capecitabine, which is not itself 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).
Capecitabina medac is used for the treatment of cancers of the colon, rectum, stomach, or breast.
Additionally, Capecitabina medac is used to prevent recurrence of colon cancer following complete surgical removal of the tumour.
Capecitabina medac may be used alone or in combination with other medicines.

2. What you should know before taking Capecitabine medac

Do not take Capecitabine medac:

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 excessive reactions to this medicine,
if you have previously had severe reactions to treatment with fluoropyrimidines (a group of anticancer medicines such as fluorouracil),
if you are pregnant or breastfeeding,
if you have severely low levels of white blood cells or platelets in the 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 Capecitabine medac:

if you know you have a partial deficiency in the activity of the enzyme dihydropyrimidine dehydrogenase (DPD)
if you have a family member with partial deficiency or complete absence of the enzyme dihydropyrimidine dehydrogenase (DPD)
if you have liver or kidney disease
if you have or have had heart problems (e.g. irregular heartbeat or chest, jaw, and back pain caused by physical exertion due to reduced blood flow to the heart)
if you have brain disorders (e.g. cancer that has spread to the brain) or nerve damage (neuropathy)
if you have calcium imbalances (detected by 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 become dehydrated
if you have electrolyte imbalances in the blood (electrolyte imbalance, detected by blood tests)
if you have experienced eye problems, as you may require additional eye monitoring
if you experience 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 Capecitabine medac, 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 Capecitabine medac if you have no
enzyme activity. If you have reduced enzyme activity (partial deficiency), your doctor may prescribe a
lower dose. Even if DPD deficiency test results are negative, severe or potentially life-threatening
adverse effects may still occur.
Children and adolescents
Capecitabine medac is not indicated for the treatment of children and adolescents. Do not administer
Capecitabine medac to children and adolescents.
Other medicines and Capecitabine medac
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
increase or reduce their effects.
You must not take brivudine (an antiviral medicine used to treat shingles or chickenpox) at the same
time as capecitabine treatment (including during treatment breaks when no capecitabine tablets are
being taken).
If you have taken brivudine, you must wait at least 4 weeks after stopping it before starting
capecitabine treatment. See also section “Do not take Capecitabine medac”.
Particular caution is also required when taking the following medicines concomitantly:

medicines for gout (allopurinol)
medicines that thin the blood (coumarin, warfarin)
medicines for seizures or tremors (phenytoin)
interferon alfa
radiotherapy and certain anticancer medicines (folinic acid, oxaliplatin, bevacizumab, cisplatin, irinotecan)
medicines used to treat folic acid deficiency

Capecitabine medac with food and drink
You should take Capecitabine medac within 30 minutes after finishing a meal.
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, suspect you may be pregnant, or are planning pregnancy, consult your doctor or pharmacist before taking this medicine. You must not take Capecitabine medac if you are pregnant or suspect you are pregnant.
You must not breastfeed during treatment with Capecitabine medac and for 2 weeks after the last dose.
If you are a woman of childbearing potential, you must use effective contraception during treatment with Capecitabine medac 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 Capecitabine medac and for 3 months after the last dose.
Driving and using machines
Capecitabine medac may cause dizziness, nausea, or fatigue. Therefore, it may affect your ability to drive or operate machinery.
Capecitabine medac contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact your doctor before taking this medicine.
Capecitabine medac contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per film-coated tablet, i.e. essentially ‘sodium-free’.

3. How to take Capecitabina medac

Take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Capecitabina medac must be prescribed only by a doctor experienced in the use of anticancer medicines.
Your doctor will prescribe the dose and treatment schedule appropriate for you. The dose of Capecitabina medac is determined based on body surface area, which is calculated according to your height and weight. The usual dose for adults is 1,250 mg/m² of body surface area twice daily (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 150 mg and 500 mg tablets for each dose.

Take the tablets in the morning and in the evening, strictly following your doctor's instructions.
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 the Capecitabina medac tablets whole, inform your healthcare provider.
It is important to take all your medicines exactly as instructed by your doctor.

Capecitabina medac 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 lower than 1,250 mg/m² of body surface area, and the tablets may need to be taken for a different duration (for example, every day without any rest period).

If you take more Capecitabina medac than you should
If you take more Capecitabina medac than prescribed, contact your doctor as soon as possible before taking the next dose.
If you take a much higher dose than you should, you may experience the following side effects: nausea or vomiting, 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). Inform your doctor immediately if you experience any of these symptoms.

If you forget to take Capecitabina medac
Do not take the missed dose. Do not take a double dose to make up for the forgotten dose. Instead, continue taking the medicine at your usual prescribed dose and consult your doctor for advice.

If you stop taking Capecitabina medac
Stopping treatment with capecitabine does not cause side effects. However, if you are taking coumarin anticoagulants (e.g. containing fenprocoumon), stopping capecitabine treatment may require your doctor to adjust your anticoagulant dose.

If you have any questions about using this medicine, speak to 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 medac 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 if you have 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 in a day is much lower than normal.
Stomatitis: if you experience pain, redness, swelling or ulcers in the mouth.
Hand-foot 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 in the centre 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 sensitivity to light, respiratory tract infections (e.g. bronchitis) and/or fever.
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. This could be a sign of angioedema.

If detected early, these side effects usually improve within 2–3 days after stopping treatment. However, if side effects persist, contact your doctor immediately. Your doctor may advise you to restart treatment at a lower dose.
If severe stomatitis (ulcers in the mouth and/or throat), mucosal inflammation, diarrhoea, neutropenia (increased risk of infections), or neurotoxicity occur during the first treatment cycle, this may be caused by DPD deficiency (see section 2: Warnings and precautions).
The hand-foot syndrome may lead to loss of fingerprints, which could affect your identification using a fingerprint reader.

In addition to those listed above, when Capecitabine medac is used alone, very common side effects that may affect more than 1 in 10 people are:

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

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

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

decrease in the number of white or red blood cells (detected by blood tests)
dehydration, weight loss
insomnia, depression
headache, drowsiness, dizziness, abnormal sensation in the skin (numbness or tingling), taste disturbances
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, excess intestinal gas, flatulence, dry mouth
skin rash, hair loss (alopecia), skin redness, dry skin, itching, skin colour changes, skin peeling, skin inflammation, nail disorders
joint or limb (extremity) pain, chest pain, back pain
fever, swelling of limbs, feeling unwell
liver function problems (detected by blood tests) and increased blood bilirubin (excreted by the liver)

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

blood infection, urinary tract infection, skin infection, nose and throat infections, fungal infections (including in the mouth), influenza, gastroenteritis, dental abscess
fatty lumps under the skin (lipoma)
reduction in blood cells, including platelets, blood thinning (detected by blood tests)
allergy
diabetes, low blood potassium, malnutrition, increased blood triglycerides
confusion, panic attacks, depressed mood, reduced libido
difficulty speaking, memory disturbances, loss of motor coordination, balance disorders, fainting, nerve damage (neuropathy) and sensory perception problems
blurred or double vision
vertigo, ear pain
irregular heartbeat and palpitations (arrhythmias), chest pain and heart attack (myocardial infarction)
blood clots in deep veins, high or low blood pressure, hot flushes, cold extremities, purple spots on the skin
blood clots in the lung veins (pulmonary embolism), collapsed lung, blood in sputum, asthma, shortness of breath on exertion
intestinal obstruction, fluid accumulation in the abdomen, inflammation of the small intestine or colon, stomach or oesophagus, lower abdominal pain, abdominal discomfort, gastric burning (food reflux from the stomach), blood in stools
jaundice (yellowing of the skin and eyes)
skin ulcers and blisters, skin reaction to sunlight, redness of the palms of the hands, 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 (oedema), chills and stiffness

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

decreased sodium, magnesium or calcium in the blood, increased blood sugar
nerve pain
ringing or buzzing 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 (may affect up to 1 in 1,000 people):

angioedema (swelling mainly affecting face, lips, tongue or throat, itching sensation and skin rashes)
narrowing or blockage of tear ducts (lacrimal duct stenosis)
liver failure
inflammation leading to impaired or blocked bile secretion (cholestatic hepatitis)
specific changes in the electrocardiogram (QT prolongation)
certain types of arrhythmias (including ventricular fibrillation, torsade de pointes and bradycardia)
inflammatory eye condition causing eye pain and potential vision problems
skin inflammation leading to red patches and peeling due to an immune system disorder

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

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

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

5. How to store Capecitabine medac

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.
This medicine does not require any special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Capecitabina medac contains

The active substance is capecitabine.

Each film-coated tablet contains 150 mg of capecitabine
Each film-coated tablet contains 500 mg of capecitabine

The other components are: Tablet core: anhydrous lactose, sodium croscarmellose (E 468), hypromellose (E 464), microcrystalline cellulose (E 460), magnesium stearate (E 572); see section 2 “Capecitabina medac contains lactose”.

Tablet coating:
Capecitabina medac 150 mg film-coated tablets
Hypromellose (E 464), titanium dioxide (E 171), yellow iron oxide (E 172), red iron oxide (E 172), talc
Capecitabina medac 500 mg film-coated tablets
Hypromellose (E 464), titanium dioxide (E 171), yellow iron oxide (E 172), red iron oxide (E 172), talc

Description of the appearance of Capecitabina medac and contents of the pack
Capecitabina medac 150 mg film-coated tablets
Light peach-coloured, biconvex, elongated film-coated tablet, printed with “150” on one side and smooth on the other side.
Capecitabina medac 500 mg film-coated tablets
Peach-coloured, biconvex, elongated film-coated tablet, printed with “500” on one side and smooth on the other side.
Capecitabina medac is available in blister packs (aluminium-aluminium). Each pack contains 28, 30, 56, 60, 84, 112 or 120 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
medac
Gesellschaft für klinische Spezialpräparate mbH
Theaterstr. 6
22880 Wedel
Germany
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 AUTHORISATION

Scientific conclusions
Taking into account the assessment by the Pharmacovigilance Risk Assessment Committee (PRAC) of the Periodic Safety Update Reports (PSURs) for capecitabine, the following scientific conclusions were reached:
In view of available data from the literature demonstrating that impaired renal function is associated with increased levels of uracil in the 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 on 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 the variation of the terms of the marketing authorisations.