Apixaban Zentiva

Italy
Brand name Apixaban Zentiva
Form tablets, film-coated
Active substance / Dosage
APIXABAN
Prescription type Restricted prescription – dispensable on hospital or specialist prescription
ATC code
B01AF02
Registration number 050601
Manufacturer ZENTIVA ITALIA S.R.L.

Table of Contents

Package leaflet: Information for the patient

Apixaban Zentiva 2.5 mg film-coated tablets

Equivalent medicine
Please read all of this leaflet carefully before you start 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, ask your doctor, pharmacist or nurse.
  • This medicine has been prescribed for you only. Do not give it 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, pharmacist or nurse. See section 4.

Contents of this leaflet

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

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

Apixaban Zentiva contains the active substance apixaban and belongs to a group of medicines called anticoagulants. This medicine helps prevent blood clots by inhibiting Factor Xa, an important component in the blood clotting process.
Apixaban Zentiva is used in adults:

  • to prevent the formation of blood clots (deep vein thrombosis [DVT]) after hip or knee replacement surgery. Following hip or knee surgery, you may be at increased risk of developing blood clots in the veins of your legs. This can cause swelling of the legs, with or without pain. If a blood clot travels from the leg to the lungs, it can block blood flow, causing shortness of breath, with or without chest pain. This condition (pulmonary embolism) can be life-threatening and requires immediate medical attention.
  • to prevent the formation of blood clots in the heart in patients with irregular heartbeat (atrial fibrillation) and at least one additional risk factor. Blood clots can break loose and travel to the brain, causing a stroke, or reach other organs, blocking normal blood flow to those organs (also known as systemic embolism). A stroke can be life-threatening and requires immediate medical attention.
  • to treat blood clots in the veins of the legs (deep vein thrombosis) and in the blood vessels of the lungs (pulmonary embolism), and to prevent recurrence of blood clots in the veins and/or lungs.

Apixaban Zentiva is used in children aged 28 days to less than 18 years to treat blood clots and to prevent recurrence of blood clots in the veins or blood vessels of the lungs.
For the recommended dose according to body weight, see section 3.

2. What you need to know before taking Apixaban Zentiva

Do not take Apixaban Zentiva if:

  • you are allergic to apixaban or to any of the other ingredients of this medicine (listed in section 6);
  • you have excessive bleeding;
  • you have a disease in an organ of the body that leads to a higher risk of serious bleeding (such as a recent or active ulcer of the stomach or intestine, or a recent bleeding in the brain);
  • you have a liver disease that increases the risk of bleeding (hepatic coagulopathy);
  • you are taking medicines to prevent blood clots (e.g., warfarin, rivaroxaban, dabigatran, or heparin), except when switching anticoagulant therapy, while having a venous or arterial catheter and receiving heparin through it to keep it open, or if a catheter is inserted into one of your blood vessels (transcatheter ablation) to treat an irregular heartbeat (arrhythmia).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Apixaban Zentiva if you have any of the following conditions:

  • an increased risk of bleeding, such as:
    • bleeding disorders, including conditions leading to reduced platelet function;
    • very high blood pressure not controlled by medical treatment;
    • if you are over 75 years old;
    • if you weigh 60 kg or less;
  • severe kidney disease or if you are on dialysis;
  • liver problems or a history of liver problems;
    • This medicine should be used with caution in patients showing signs of impaired liver function.
  • you have had a tube (catheter) or injection in the spinal column (for anaesthesia or pain relief). Your doctor will advise you when to start taking this medicine, usually 5 hours or more after catheter removal;
  • you have a prosthetic heart valve;
  • if your doctor finds that your blood pressure is unstable;
  • if another treatment or surgical procedure to remove a blood clot from the lungs is planned.

Take special care with Apixaban Zentiva

  • if you know you have a condition called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), inform your doctor, who will decide whether therapy adjustment is needed.

If you are scheduled for surgery or a procedure that may cause bleeding, your doctor may ask you to temporarily stop taking this medicine for a short period. If you are unsure whether a procedure might cause bleeding, consult your doctor.

Children and adolescents
Apixaban Zentiva is not recommended for children and adolescents weighing less than 35 kg.

Other medicines and Apixaban Zentiva
Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.

Some medicines can increase the effect of Apixaban Zentiva, while others may reduce it. Your doctor will decide whether you should take Apixaban Zentiva with these medicines and how closely you should be monitored.

The following medicines may increase the effect of Apixaban Zentiva and increase the risk of unwanted bleeding:

  • certain antifungal medicines (e.g., ketoconazole, etc.);
  • certain antiviral medicines for HIV/AIDS (e.g., ritonavir);
  • other medicines used to reduce blood clotting (e.g., enoxaparin, etc.);
  • anti-inflammatory drugs or painkillers (e.g., acetylsalicylic acid or naproxen). In particular, if you are over 75 years old and taking acetylsalicylic acid, your risk of bleeding may be higher;
  • medicines for high blood pressure or heart problems (e.g., diltiazem);
  • antidepressants known as selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs).

The following medicines may reduce the effect of Apixaban Zentiva in helping to prevent blood clots:

  • medicines for epilepsy or seizures (e.g., phenytoin, etc.);
  • St. John’s wort (a herbal remedy used for depression);
  • medicines for treating tuberculosis or other infections (e.g., rifampicin).

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor, pharmacist, or nurse before taking this medicine.

The effects of apixaban during pregnancy and on the unborn child are unknown. You must not take this medicine if you are pregnant. Contact your doctor immediately if you become pregnant while taking this medicine.

It is not known whether apixaban passes into breast milk. Consult your doctor, pharmacist, or nurse before taking this medicine while breastfeeding. They will advise you whether to stop breastfeeding or to stop or not start treatment with this medicine.

Driving and using machines
Apixaban has not shown effects on the ability to drive or operate machinery.

Apixaban Zentiva contains lactose and sodium
If your doctor has informed you of an intolerance to certain sugars, contact them before taking this medicine.

This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially ‘sodium-free’.

3. How to take Apixaban Zentiva

Take this medicine exactly as prescribed by your doctor or pharmacist. If you have any doubts, consult your doctor, pharmacist, or nurse.

Dose
Swallow the tablet with some water. Apixaban Zentiva may be taken with or without food. Try to take the tablets at the same time each day to achieve the best effect from treatment.

If you have difficulty swallowing the tablet whole, ask your doctor about other ways to take Apixaban Zentiva. The tablet may be crushed and mixed with water, 5% glucose in water, apple juice, or apple puree, immediately before administration.

Instructions for crushing the tablet:

  • Crush the tablets with a mortar and pestle.
  • Carefully transfer all of the powder into a suitable container and then mix the powder with a small amount (e.g., 30 mL [2 tablespoons]) of water or one of the other liquids listed above to prepare a mixture.
  • Swallow the mixture.
  • Rinse the mortar and pestle used to crush the tablet and the container with a small amount of water (e.g., 30 mL) or one of the other liquids, and swallow the rinse.

If necessary, your doctor may also administer the crushed Apixaban Zentiva tablet mixed with 60 mL of water or 5% glucose in water through a nasogastric tube.

Take Apixaban Zentiva as recommended:

To prevent blood clots after hip or knee replacement surgery:
The recommended dose is one 2.5 mg Apixaban Zentiva tablet twice daily, for example, one in the morning and one in the evening.
Take the first tablet 12 to 24 hours after surgery.
If you have had major hip surgery, you will usually take the tablets for 32 to 38 days. If you have had major knee surgery, you will usually take the tablets for 10 to 14 days.

To prevent blood clots in the heart in patients with irregular heartbeat (atrial fibrillation) and at least one additional risk factor:
The recommended dose is one 5 mg Apixaban Zentiva tablet twice daily.

The recommended dose is one 2.5 mg Apixaban Zentiva tablet twice daily if:

  • you have severely reduced kidney function;
  • you meet two or more of the following criteria:
    • blood test results suggest poor kidney function (serum creatinine level is 1.5 mg/dL (133 micromoles/L) or higher);
    • you are 80 years of age or older;
    • your body weight is 60 kg or less.

The recommended dose is one tablet twice daily, for example, one in the morning and one in the evening. Your doctor will decide how long you should continue treatment.

To treat blood clots in the veins of the legs and in the blood vessels of the lungs (venous thromboembolism):
The recommended dose is two 5 mg Apixaban Zentiva tablets twice daily for the first 7 days, for example, two in the morning and two in the evening.
After 7 days, the recommended dose is one 5 mg Apixaban Zentiva tablet twice daily, for example, one in the morning and one in the evening.

To prevent recurrence of blood clots after completing 6 months of treatment:
The recommended dose is one 2.5 mg Apixaban Zentiva tablet twice daily, for example, one in the morning and one in the evening.
Your doctor will decide how long you should continue treatment.

Use in children and adolescents
To treat blood clots and to prevent recurrence of blood clots in the veins or in the blood vessels of the lungs:
Take or administer this medicine exactly as prescribed by your doctor or the child’s doctor or pharmacist. If you have any doubts, consult your doctor, the child’s doctor, pharmacist, or nurse.
Try to take or administer the dose at the same time each day to achieve the best effect from treatment.

The dose of Apixaban Zentiva depends on body weight and will be calculated by the doctor.

The recommended dose for children and adolescents with body weight of at least 35 kg is four 2.5 mg Apixaban Zentiva tablets twice daily for the first 7 days, for example, four in the morning and four in the evening.
After 7 days, the recommended dose is two 2.5 mg Apixaban Zentiva tablets twice daily, for example, two in the morning and two in the evening.

For parents or caregivers: Observe the child to ensure the full dose has been taken.
It is important to attend scheduled medical appointments, as the dose may need to be adjusted as body weight changes.

Your doctor may modify your anticoagulant treatment as follows:

  • Switching from Apixaban Zentiva to another anticoagulant medicine: Stop taking Apixaban Zentiva. Start treatment with the anticoagulant medicine (e.g., heparin) at the time you would have taken your next tablet.
  • Switching from another anticoagulant medicine to Apixaban Zentiva: Stop taking the anticoagulant medicine. Start treatment with Apixaban Zentiva at the time you would have taken your next dose of the anticoagulant medicine, then continue taking it as directed.
  • Switching from a vitamin K antagonist anticoagulant (e.g., warfarin) to Apixaban Zentiva: Stop taking the vitamin K antagonist medicine. Your doctor will need to perform blood tests and advise you when to start Apixaban Zentiva.
  • Switching from Apixaban Zentiva to a vitamin K antagonist anticoagulant (e.g., warfarin): If your doctor instructs you to start taking a vitamin K antagonist medicine, continue taking Apixaban Zentiva for at least 2 days after the first dose of the vitamin K antagonist medicine. Your doctor will need to perform blood tests and advise you when to stop Apixaban Zentiva.

Patients undergoing cardioversion
If your abnormal heart rhythm needs to be restored to normal by a procedure called cardioversion, take this medicine at the times your doctor tells you to, to prevent blood clots in the blood vessels of the brain and other parts of your body.

If you take more Apixaban Zentiva than you should
Inform your doctor immediately if you have taken more than the prescribed dose of this medicine. Bring the medicine pack with you, even if no tablets are left.
If you take more Apixaban Zentiva than recommended, you may have an increased risk of bleeding. If bleeding occurs, you may require surgery, a blood transfusion, or other treatments that can reverse the anticoagulant activity against factor Xa.

If you forget to take Apixaban Zentiva

  • If you forget to take your morning dose, take it as soon as you remember; you may take it together with your evening dose.
  • A forgotten evening dose may only be taken on the same evening. Do not take two doses the next morning; instead, continue with your regular twice-daily dosing schedule the following day.

If you have any doubts about what to do or if you have missed more than one dose, consult your doctor, pharmacist, or nurse.

If you stop taking Apixaban Zentiva
Do not stop taking this medicine without first talking to your doctor, as stopping treatment too early may increase your risk of developing a blood clot.
If you have any questions about how to use this medicine, speak to your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Apixaban Zentiva may be prescribed for three different medical conditions. The known side effects and their frequency may differ for each of these conditions and are listed separately below. For these conditions, the most common general side effect of this medicine is bleeding, which can potentially be life-threatening and requires immediate medical attention.

The following side effects are known to occur when Apixaban Zentiva is taken to prevent blood clots after hip or knee replacement surgery.

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

  • Anaemia, which may cause tiredness or pale skin;
  • Bleeding, including:
    • bruising and swelling;
  • Nausea (feeling unwell).

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

  • Reduction in the number of platelets in the blood (which may affect blood clotting);
  • Bleeding:
    • occurring after surgery, including bruising and swelling, leakage of blood or fluid from the surgical wound/incision (wound discharge) or from the injection site;
    • from the stomach, intestine, or clear/red blood in the stools;
    • blood in the urine;
    • from the nose;
    • from the vagina;
  • Low blood pressure, which may cause weakness or a rapid heartbeat;
  • Blood tests may show:
    • abnormalities in liver function;
    • increased levels of certain liver enzymes;
    • increased bilirubin, a product of red blood cell breakdown, which may cause yellowing of the skin and eyes;
  • Itching.

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

  • Allergic reactions (hypersensitivity) which may cause: swelling of the face, lips, mouth, tongue and/or throat, and difficulty breathing. Contact your doctor immediately if you experience any of these symptoms.
  • Bleeding:
    • into the muscle;
    • in the eyes;
    • from the gums and blood in sputum when coughing;
    • from the rectum;
  • Hair loss.

Not known (frequency cannot be estimated from available data)

  • Bleeding:
    • in the brain or spinal cord;
    • in the lungs or throat;
    • in the mouth;
    • in the abdomen or in the space behind the abdominal cavity;
    • from haemorrhoids;
    • blood tests showing blood in the stools or urine;
    • Skin rash that may form blisters and appears as small targets (dark central spots surrounded by a lighter area, with a dark ring around the edge) (erythema multiforme);
    • Inflammation of blood vessels (vasculitis), which may present as skin rashes or sharp, flat, red, round spots under the skin surface or bruising.
    • Bleeding in the kidney, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-related nephropathy).

The following side effects are known to occur when Apixaban Zentiva is taken to prevent blood clots in the heart in patients with irregular heartbeat and at least one additional risk factor.

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

  • Bleeding, including:
    • in the eyes;
    • in the stomach or intestine;
    • from the rectum;
    • blood in the urine;
    • from the nose;
    • from the gums;
    • bruising and swelling;
  • Anaemia, which may cause tiredness or pale skin;
  • Low blood pressure, which may cause weakness or a rapid heartbeat;
  • Nausea (feeling unwell);
  • Blood tests may show:
    • an increase in gamma-glutamyltransferase (GGT).

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

  • Bleeding:
    • in the brain or spinal cord;
    • in the mouth or blood in sputum when coughing;
    • in the abdomen or from the vagina;
    • clear/red blood in the stools;
    • bleeding occurring after surgery, including bruising and swelling, leakage of blood or fluid from the surgical wound/incision (wound discharge) or from the injection site;
    • from haemorrhoids;
    • blood tests showing blood in the stools or urine;
  • Reduction in the number of platelets in the blood (which may affect blood clotting);
  • Blood tests may show:
    • abnormalities in liver function;
    • increased levels of certain liver enzymes;
    • increased bilirubin, a product of red blood cell breakdown, which may cause yellowing of the skin and eyes;
  • Skin rash;
  • Itching;
  • Hair loss;
  • Allergic reactions (hypersensitivity) which may cause: swelling of the face, lips, mouth, tongue and/or throat, and difficulty breathing. Contact your doctor immediately if you experience any of these symptoms.

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

  • Bleeding:
    • in the lungs or throat;
    • in the space behind the abdominal cavity;
    • into the muscle.

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

  • Skin rash that may form blisters and appears as small targets (dark central spots surrounded by a lighter area, with a dark ring around the edge) (erythema multiforme).

Not known (frequency cannot be estimated from available data)

  • Inflammation of blood vessels (vasculitis), which may present as skin rashes or sharp, flat, red, round spots under the skin surface or bruising.
  • Bleeding in the kidney, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-related nephropathy).

The following side effects are known to occur when Apixaban Zentiva is taken to treat or prevent recurrence of blood clots in the leg veins and lung blood vessels.

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

  • Bleeding, including:
    • from the nose;
    • from the gums;
    • blood in the urine;
    • bruising and swelling;
    • in the stomach, intestine, or from the rectum;
    • in the mouth;
    • from the vagina;
  • Anaemia, which may cause tiredness or pale skin;
  • Reduction in the number of platelets in the blood (which may affect blood clotting);
  • Nausea (feeling unwell);
  • Skin rash;
  • Blood tests may show:
    • an increase in gamma-glutamyltransferase (GGT) or alanine aminotransferase (ALT).

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

  • Low blood pressure, which may cause weakness or a rapid heartbeat;
  • Bleeding:
    • in the eyes;
    • in the mouth or blood in sputum when coughing;
    • clear/red blood in the stools;
    • blood tests showing blood in the stools or urine;
    • bleeding occurring after surgery, including bruising and swelling, leakage of blood or fluid from the surgical wound/incision (wound discharge) or from the injection site;
    • from haemorrhoids;
    • into the muscle;
  • Itching;
  • Hair loss;
  • Allergic reactions (hypersensitivity) which may cause: swelling of the face, lips, mouth, tongue and/or throat, and difficulty breathing. Contact your doctor immediately if you experience any of these symptoms.
  • Blood tests may show:
    • abnormalities in liver function;
    • increased levels of certain liver enzymes;
    • increased bilirubin, a product of red blood cell breakdown, which may cause yellowing of the skin and eyes.

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

  • Bleeding:
    • in the brain or spinal cord;
    • in the lungs.

Not known (frequency cannot be estimated from available data)

  • Bleeding:
    • in the abdomen or in the space behind the abdominal cavity;
  • Skin rash that may form blisters and appears as small targets (dark central spots surrounded by a lighter area, with a dark ring around the edge) (erythema multiforme);
  • Inflammation of blood vessels (vasculitis), which may present as skin rashes or sharp, flat, red, round spots under the skin surface or bruising.

Other side effects in children and adolescents
Tell the child’s doctor immediately if you notice any of these symptoms:

  • Allergic reactions (hypersensitivity) which may cause: swelling of the face, lips, mouth, tongue and/or throat, and difficulty breathing. The frequency of these side effects is common (may affect up to 1 in 10 people).

In general, the side effects observed in children and adolescents treated with Apixaban Zentiva have been similar to those seen in adults and have mainly been mild to moderate in severity. The side effects observed more frequently in children and adolescents were nosebleeds and abnormal vaginal bleeding.

Very common side effects (may affect more than 1 in 10 people)

  • Bleeding, including:
    • from the vagina;
    • from the nose.

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

  • Bleeding, including:
    • from the gums;
    • blood in the urine;
    • bruising and swelling;
    • from the intestine or rectum;
    • clear/red blood in the stools;
    • bleeding occurring after any surgery, including bruising and swelling, leakage of blood or fluid from the surgical wound/incision (wound discharge) or from the injection site;
  • Hair loss;
  • Anaemia, which may cause tiredness or pale skin;
  • Reduction in the number of platelets in the child’s blood (which may affect blood clotting);
  • Nausea (feeling unwell);
  • Skin rash;
  • Itching;
  • Low blood pressure, which may cause the child to feel weak or have a rapid heartbeat;
  • Blood tests may show:
    • abnormalities in liver function;
    • increased levels of certain liver enzymes;
    • increased alanine aminotransferase (ALT).

Not known (frequency cannot be determined from available data)

  • Bleeding:
    • in the abdomen or in the space behind the abdominal cavity;
    • in the stomach;
    • in the eyes;
    • in the mouth;
    • from haemorrhoids;
    • in the mouth or blood in sputum when coughing;
    • in the brain or spinal cord;
    • in the lungs;
    • into the muscle;
  • Skin rash that may form blisters and appears as small targets (dark central spots surrounded by a lighter area, with a dark ring around the edge) (erythema multiforme);
  • Inflammation of blood vessels (vasculitis), which may present as skin rashes or sharp, flat, red, round spots under the skin surface or bruising;
  • Blood tests may show:
    • an increase in gamma-glutamyltransferase (GGT);
    • blood tests showing blood in the stools or urine.
  • Bleeding in the kidney, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-related nephropathy).

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 at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Apixaban Zentiva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date 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.
Crushed tablets
Apixaban Zentiva tablets crushed are stable in water, 5% glucose in water, apple juice and apple puree for up to 4 hours.
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 Apixaban Zentiva contains
The active substance is apixaban. Each tablet contains 2.5 mg of apixaban.
The other ingredients are: microcrystalline cellulose (type 101), lactose, sodium lauryl sulfate,
sodium croscarmellose (E468), magnesium stearate (E572) in the tablet core; hypromellose
2910 (E464), monohydrate lactose, titanium dioxide (E171), triacetin (E1518), red iron oxide
(E172) as the tablet coating.
Description of the appearance of Apixaban Zentiva and package contents
Film-coated tablets (tablets), yellow, round, convex, with a diameter of 6.2 mm ± 0.2 mm.
Packaged in PVC/PVDC/Al blisters.
Pack sizes: 10, 14, 20, 28, 30, 56, 60, 90, 100, 120, 168, 200 film-coated tablets.
Not all pack sizes may be marketed.
Patient Card: managing information
Inside the package, together with the package leaflet, you will find a Patient Card or your
doctor may provide you with a similar one.
This Patient Card includes information that may be useful to you and alerts other
doctors that you are taking Apixaban Zentiva. The card should always remain with the patient or the
caregiver.

  1. Take the card.
  2. Complete the following sections or ask your doctor to do so:
    • Name:
    • Date of birth:
    • Indication:
    • Weight:
    • Dose: ......... mg twice daily
    • Doctor's name:
    • Doctor's telephone number:
  3. Always keep the card with you.

Marketing Authorization Holder
Zentiva Italia S.r.l.
Via P. Paleocapa, 7
20121 Milan
Italy
Manufacturer
Pharmadox Healthcare Limited
KW20A Kordin Industrial Park
Paola, PLA 3000
Malta
This medicinal product is authorized in the Member States of the European Economic Area under the
following names:
Austria, Czech Republic, Denmark, Estonia, France, Germany, Iceland, Italy, Latvia, Lithuania,
Norway, Netherlands, Spain, Sweden: Apixaban Zentiva
Portugal: Apixabano Zentiva

Patient information leaflet

Apixaban Zentiva 5 mg film-coated tablets

Generic medicine
Please read this leaflet carefully before 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, pharmacist or nurse.
  • This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
  • If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

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

Apixaban Zentiva contains the active substance apixaban and belongs to a group of medicines called anticoagulants. This medicine helps prevent the formation of blood clots by blocking Factor Xa, an important component in blood coagulation.
Apixaban Zentiva is used in adults:

  • to prevent the formation of blood clots in the heart in patients with irregular heartbeat (atrial fibrillation) and with at least one additional risk factor. Blood clots can break loose and travel to the brain, causing stroke, or travel to other organs, blocking normal blood flow to those organs (also known as systemic embolism). A stroke can be life-threatening and requires immediate medical attention.
  • to treat blood clots in the veins of the legs (deep vein thrombosis) and in the blood vessels of the lungs (pulmonary embolism), and to prevent blood clots from re-forming in the blood vessels of the legs and/or lungs.

Apixaban Zentiva is used in children aged 28 days up to but less than 18 years to treat blood clots and to prevent blood clots from re-forming in the veins or blood vessels of the lungs.
For the recommended dose according to body weight, see section 3.

2. What you need to know before taking Apixaban Zentiva

Do not take Apixaban Zentiva if:

  • you are allergic to apixaban or to any of the other ingredients of this medicine (listed in section 6);
  • you have excessive bleeding;
  • you have a disease in an organ of the body that leads to a higher risk of serious bleeding (such as a recent or active ulcer of the stomach or intestine, or a recent bleeding in the brain);
  • you have a liver disease that leads to an increased risk of bleeding (hepatic coagulopathy);
  • you are taking medicines to prevent blood clots (e.g., warfarin, rivaroxaban, dabigatran, or heparin), except when switching anticoagulant therapy, while you have a venous or arterial catheter and are receiving heparin through that catheter to keep it open, or if a catheter is inserted into one of your blood vessels (transcatheter ablation) to treat an irregular heartbeat (arrhythmia).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Apixaban Zentiva if you have any of the following conditions:

  • an increased risk of bleeding, such as:
    • bleeding disorders, including conditions leading to reduced platelet function;
    • very high blood pressure not controlled by medical treatment;
    • if you are over 75 years old;
    • if you weigh 60 kg or less;
  • severe kidney disease or if you are on dialysis;
  • liver problems or a history of liver problems;
    • This medicine will be used with caution in patients showing signs of impaired liver function.
  • you have had a tube (catheter) or an injection in the spine (for anaesthesia or pain relief). Your doctor will tell you when to start taking this medicine, usually at least 5 hours after removal of the catheter;
  • you have a prosthetic heart valve;
  • if your doctor finds that your blood pressure is unstable, or if another treatment or surgical procedure to remove a blood clot from the lungs is planned.

Exercise particular caution with Apixaban Zentiva

  • if you know you have a condition called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), inform your doctor, who will decide whether you need to change your treatment.

If you are scheduled for surgery or a procedure that may cause bleeding, your doctor may ask you to temporarily stop taking this medicine for a short period. If you are unsure whether a procedure might cause bleeding, consult your doctor.

Children and adolescents
This medicine is not recommended for children and adolescents weighing less than 35 kg.

Other medicines and Apixaban Zentiva
Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
Some medicines can increase the effect of Apixaban Zentiva, while others can reduce it. Your doctor will decide whether you should be treated with Apixaban Zentiva when taking these medicines and how closely you should be monitored.

The following medicines may increase the effect of Apixaban Zentiva and increase the risk of unwanted bleeding:

  • certain medicines for fungal infections (e.g., ketoconazole, etc.);
  • certain antiviral medicines for HIV/AIDS (e.g., ritonavir);
  • other medicines used to reduce blood clotting (e.g., enoxaparin, etc.);
  • anti-inflammatory drugs or painkillers (e.g., acetylsalicylic acid or naproxen). Particularly if you are over 75 years old and taking acetylsalicylic acid, your risk of bleeding may be higher;
  • medicines for high blood pressure or heart problems (e.g., diltiazem);
  • antidepressants known as selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors.

The following medicines may reduce the effect of Apixaban Zentiva in helping to prevent blood clots:

  • medicines for epilepsy or seizures (e.g., phenytoin, etc.);
  • St. John’s wort (a herbal remedy used for depression);
  • medicines to treat tuberculosis or other infections (e.g., rifampicin).

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, ask your doctor, pharmacist, or nurse for advice before taking this medicine.

The effects of apixaban during pregnancy and on the unborn child are unknown. You must not take this medicine if you are pregnant. Contact your doctor immediately if you become pregnant while taking this medicine.
It is not known whether apixaban passes into breast milk. Consult your doctor, pharmacist, or nurse before taking this medicine while breastfeeding. They will advise you whether to stop breastfeeding or to stop or not start treatment with this medicine.

Driving and using machines
Apixaban has not shown effects on the ability to drive or use machinery.

Apixaban Zentiva contains lactose and sodium
If your doctor has informed you of an intolerance to certain sugars, contact them before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially ‘sodium-free’.

3. How to take Apixaban Zentiva

Take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor, pharmacist, or nurse.

Dose
Swallow the tablet with some water. Apixaban Zentiva may be taken with or without food. Try to take the tablets at the same time each day to achieve the best effect from treatment.
If you have difficulty swallowing the tablet whole, ask your doctor about other ways to take Apixaban Zentiva. The tablet may be crushed and mixed with water, 5% glucose in water, apple juice, or apple puree, immediately before administration.

Instructions for crushing the tablet:

  • Crush the tablets with a mortar and pestle.
  • Carefully transfer all of the powder into a suitable container and then mix the powder with a small amount, e.g., 30 mL (2 tablespoons), of water or one of the other liquids mentioned above to prepare a mixture.
  • Swallow the mixture.
  • Rinse the mortar and pestle used to crush the tablet and the container with a small amount of water (e.g., 30 mL) or one of the other liquids, and swallow the rinse.

If necessary, your doctor may also administer the crushed Apixaban Zentiva tablet mixed with 60 mL of water or 5% glucose in water through a nasogastric tube.

Take Apixaban Zentiva as recommended:
To prevent blood clots from forming in the heart in patients with irregular heartbeat and at least one additional risk factor.
The recommended dose is one tablet of Apixaban Zentiva 5 mg twice daily.
The recommended dose is one tablet of Apixaban Zentiva 2.5 mg twice daily if:

  • you have severely reduced kidney function;
  • you meet two or more of the following conditions:
    • blood test results suggest poor kidney function (serum creatinine level is 1.5 mg/dL (133 micromoles/L) or higher);
    • you are 80 years of age or older;
    • your body weight is 60 kg or less.

The recommended dose is one tablet twice daily, for example, one in the morning and one in the evening.
Your doctor will decide how long you should continue treatment.

To treat blood clots in the veins of the legs and in the blood vessels of the lungs
The recommended dose is two tablets of Apixaban Zentiva 5 mg twice daily for the first 7 days, for example, two in the morning and two in the evening.
After 7 days, the recommended dose is one tablet of Apixaban Zentiva 5 mg twice daily, for example, one in the morning and one in the evening.

To prevent recurrence of blood clots after completion of 6 months of treatment
The recommended dose is one tablet of Apixaban Zentiva 2.5 mg twice daily, for example, one in the morning and one in the evening.
Your doctor will decide how long you should continue treatment.

Use in children and adolescents
To treat blood clots and to prevent recurrence of blood clots in the veins or in the blood vessels of the lungs.
Take or administer this medicine exactly as instructed by your doctor, the child’s doctor, or pharmacist. If you have any doubts, consult your doctor, the child’s doctor, pharmacist, or nurse.
Try to take or administer the dose at the same time each day to achieve the best effect from treatment.
The dose of Apixaban Zentiva depends on body weight and will be calculated by the doctor.
The recommended dose for children and adolescents with a body weight of at least 35 kg is two tablets of Apixaban Zentiva 5 mg twice daily for the first 7 days, for example, two in the morning and two in the evening.
After 7 days, the recommended dose is one tablet of Apixaban Zentiva 5 mg twice daily, for example, one in the morning and one in the evening.
For parents or caregivers: observe the child to ensure the entire dose has been taken.
It is important to keep scheduled medical appointments, as the dose may need to be adjusted as body weight changes.

Your doctor may change your anticoagulant treatment as follows:

  • Switching from Apixaban Zentiva to another anticoagulant medicine
    Stop taking Apixaban Zentiva. Start treatment with the anticoagulant medicine (e.g., heparin) at the time you would have taken your next tablet.

  • Switching from another anticoagulant medicine to Apixaban Zentiva
    Stop taking the anticoagulant medicine. Start treatment with Apixaban Zentiva at the time you would have taken your next dose of the anticoagulant medicine, then continue taking it as usual.

  • Switching from a vitamin K antagonist anticoagulant (e.g., warfarin) to Apixaban Zentiva
    Stop taking the vitamin K antagonist medicine. Your doctor will need to perform blood tests and advise you when to start treatment with Apixaban Zentiva.

  • Switching from Apixaban Zentiva to a vitamin K antagonist anticoagulant (e.g., warfarin)
    If your doctor tells you to start taking a vitamin K antagonist medicine, continue taking Apixaban Zentiva for at least 2 days after the first dose of the vitamin K antagonist medicine. Your doctor will need to perform blood tests and advise you when to stop treatment with Apixaban Zentiva.

Patients undergoing cardioversion
If your abnormal heartbeat needs to be restored to normal through a procedure called cardioversion, take this medicine at the times your doctor instructs you to, to prevent blood clots in the blood vessels of the brain and other blood vessels in your body.

If you take more Apixaban Zentiva than you should
Contact your doctor immediately if you have taken more than the prescribed dose of this medicine. Bring the medicine pack with you, even if no tablets remain.
If you take more Apixaban Zentiva than recommended, you may have an increased risk of bleeding. If bleeding occurs, surgery, a blood transfusion, or other treatments that can reverse the anti-factor Xa activity may be needed.

If you forget to take Apixaban Zentiva

  • If you forget to take a morning dose, take it as soon as you remember. You may take it together with your evening dose.
  • A forgotten evening dose may be taken only on the same evening. Do not take two doses the next morning; instead, continue with your usual twice-daily dosing schedule the next day.

If you are unsure what to do or if you have missed more than one dose, consult your doctor, pharmacist, or nurse.

If you stop taking Apixaban Zentiva
Do not stop taking this medicine without first talking to your doctor, as your risk of developing a blood clot may be higher if you stop treatment too early.
If you have any questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them. The most common serious side effect with this medicine is bleeding, which may potentially be life-threatening and requires immediate medical attention.

The following side effects are known to occur when Apixaban Zentiva is taken to prevent blood clots forming in the heart in patients with irregular heartbeat and at least one additional risk factor.

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

  • Bleeding, including:
    • in the eyes;
    • in the stomach or intestine;
    • from the rectum;
    • blood in the urine;
    • from the nose;
    • from the gums;
    • bruising and swelling;
  • Anaemia, which may cause tiredness or pale skin;
  • Low blood pressure, which may cause weakness or a fast heartbeat;
  • Nausea (feeling unwell);
  • Blood tests may show:
    • an increase in gamma-glutamyltransferase (GGT).

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

  • Bleeding:
    • in the brain or spinal cord;
    • in the mouth or blood in coughed-up mucus when coughing;
    • in the abdomen or from the vagina;
    • bright red blood in the stools;
    • bleeding occurring after surgery, including bruising and swelling, leakage of blood or fluid from the surgical wound/incision (wound discharge) or from the injection site;
    • from haemorrhoids;
    • tests showing blood in the stools or urine;
  • Decrease in the number of platelets in the blood (which may affect blood clotting);
  • Blood tests may show:
    • abnormalities in liver function;
    • increase in some liver enzymes;
    • increase in bilirubin, a product of the breakdown of red blood cells, which may cause yellowing of the skin and eyes.
  • Skin rash;
  • Itching;
  • Hair loss;
  • Allergic reactions (hypersensitivity) which may cause: swelling of the face, lips, mouth, tongue and/or throat, and breathing difficulties. Contact your doctor immediately if you experience any of these symptoms.

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

  • Bleeding:
    • in the lungs or throat;
    • in the space behind the abdominal cavity;
    • in the muscle.

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

  • Skin rash which may blister and appear as small target-like spots (dark central spots surrounded by a paler area, with a dark ring around the edge) (erythema multiforme).

Not known (frequency cannot be estimated from available data)

  • Inflammation of blood vessels (vasculitis), which may present as skin rashes or small, flat, red, round spots or bruises under the skin surface.
  • Bleeding in the kidney, sometimes with blood in the urine, leading to the kidneys being unable to function properly (anticoagulant-related nephropathy).

The following side effects are known to occur when Apixaban Zentiva is taken to treat or prevent recurrence of blood clots in the veins of the legs and in the blood vessels of the lungs.

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

  • Bleeding, including:
    • from the nose;
    • from the gums;
    • blood in the urine;
    • bruising and swelling;
    • in the stomach, intestine, or from the rectum;
    • from the mouth;
    • from the vagina;
  • Anaemia, which may cause tiredness or pale skin;
  • Decrease in the number of platelets in the blood (which may affect blood clotting);
  • Nausea (feeling unwell);
  • Skin rash;
  • Blood tests may show:
    • an increase in gamma-glutamyltransferase (GGT) or alanine aminotransferase (ALT).

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

  • Low blood pressure, which may cause weakness or a fast heartbeat;
  • Bleeding:
    • in the eyes;
    • in the mouth or blood in coughed-up mucus when coughing;
    • bright red blood in the stools;
    • tests showing blood in the stools or urine;
    • bleeding occurring after any surgery, including bruising and swelling, leakage of blood or fluid from the surgical wound/incision (wound discharge) or from the injection site;
    • from haemorrhoids;
    • in the muscle;
  • Itching;
  • Hair loss;
  • Allergic reactions (hypersensitivity) which may cause: swelling of the face, lips, mouth, tongue and/or throat, and breathing difficulties. Contact your doctor immediately if you experience any of these symptoms;
  • Blood tests may show:
    • abnormalities in liver function;
    • increase in some liver enzymes;
    • increase in bilirubin, a product of the breakdown of red blood cells, which may cause yellowing of the skin and eyes.

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

  • in the brain or spinal cord;
  • in the lungs.

Not known (frequency cannot be estimated from available data)

  • Bleeding:
    • in the abdomen or in the space behind the abdominal cavity.
  • Skin rash which may blister and appear as small target-like spots (dark central spots surrounded by a paler area, with a dark ring around the edge) (erythema multiforme);
  • Inflammation of blood vessels (vasculitis), which may present as skin rashes or small, flat, red, round spots or bruises under the skin surface;
  • Bleeding in the kidney, sometimes with blood in the urine, leading to the kidneys being unable to function properly (anticoagulant-related nephropathy).

Other side effects in children and adolescents
Contact the child’s doctor immediately if you notice any of these symptoms:

  • Allergic reactions (hypersensitivity) which may cause: swelling of the face, lips, mouth, tongue and/or throat, and breathing difficulties. The frequency of these side effects is common (may affect up to 1 in 10 people).

In general, the side effects observed in children and adolescents treated with Apixaban Zentiva have been of a similar type to those seen in adults and have mainly been mild to moderate in severity. The side effects observed more frequently in children and adolescents were nosebleeds and abnormal vaginal bleeding.

Very common side effects (may affect more than 1 in 10 people)

  • Bleeding, including: from the vagina; from the nose.

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

  • Bleeding, including: from the gums; blood in the urine; bruising and swelling; from the intestine or rectum; bright red blood in the stools; bleeding occurring after any surgery, including bruising and swelling, leakage of blood or fluid from the surgical wound/incision (wound discharge) or from the injection site;
  • Hair loss;
  • Anaemia, which may cause tiredness or pale skin;
  • Decrease in the number of platelets in the child’s blood (which may affect blood clotting);
  • Nausea (feeling unwell);
  • Skin rash;
  • Itching;
  • Low blood pressure, which may cause the child to feel weak or have a fast heartbeat;
  • Blood tests may show:
    • abnormalities in liver function;
    • increase in some liver enzymes;
    • increase in alanine aminotransferase (ALT).

Not known (frequency cannot be estimated from available data)

  • Bleeding:
    • in the abdomen or in the space behind the abdominal cavity;
    • in the stomach;
    • in the eyes;
    • in the mouth;
    • from haemorrhoids;
    • in the mouth or blood in coughed-up mucus when coughing;
    • in the brain or spinal cord;
    • in the lungs;
    • in the muscle;
  • Skin rash which may blister and appear as small target-like spots (dark central spots surrounded by a paler area, with a dark ring around the edge) (erythema multiforme);
  • Inflammation of blood vessels (vasculitis), which may present as skin rashes or small, flat, red, round spots or bruises under the skin surface;
  • Blood tests may show:
    • an increase in gamma-glutamyltransferase (GGT);
    • tests showing blood in the stools or urine. Bleeding in the kidney, sometimes with blood in the urine, leading to the kidneys being unable to function properly (anticoagulant-related nephropathy).

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Apixaban Zentiva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after "Exp".
The expiry date refers to the last day of that month.
This medicine requires no special storage conditions.
Crushed tablets
Crushed tablets of Apixaban Zentiva are stable in water, 5% glucose solution, apple juice, and apple puree for up to 4 hours.
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 Apixaban Zentiva contains

  • The active substance is apixaban. Each tablet contains 5 mg of apixaban.
  • The other components are: microcrystalline cellulose (type 101), lactose, sodium lauryl sulfate, sodium croscarmellose (E468), magnesium stearate (E572) in the tablet core; hypromellose 2910 (E464), monohydrate lactose, titanium dioxide (E171), triacetin (E1518), red iron oxide (E172) as the tablet coating.

Description of the appearance of Apixaban Zentiva and package contents
Pink, oval-shaped, film-coated tablets (tablets) with dimensions 10.2 x 5.2 mm ± 0.2 mm.
Packaged in PVC/PVDC/Al blisters.
Pack sizes: 10, 14, 20, 28, 30, 56, 60, 90, 100, 120, 168, 200 film-coated tablets.
Not all pack sizes may be marketed.

Patient Card: information management
Inside the package, together with the package leaflet, you will find a Patient Card or your doctor may provide you with a similar one.
This Patient Card includes information that may be useful to you and alerts other doctors that you are taking Apixaban Zentiva.
The card should always be kept by the patient or caregiver.

  1. Take the card.
  2. Complete the following sections or ask your doctor to do so:
    • Name:
    • Date of birth:
    • Indication:
    • Weight:
    • Dose: .............. mg twice daily
    • Doctor’s name:
    • Doctor’s telephone number:
  3. Always keep the card with you.

Marketing Authorization Holder
Zentiva Italia S.r.l.
Via P. Paleocapa, 7
20121 Milan
Italy

Manufacturer
Pharmadox Healthcare Limited
KW20A Kordin Industrial Park
Paola, PLA 3000
Malta

This medicinal product is authorized in the European Economic Area Member States under the following names:
Austria, Czech Republic, Denmark, Estonia, France, Germany, Iceland, Italy, Latvia, Lithuania, Norway, Netherlands, Spain, Sweden: Apixaban Zentiva
Portugal: Apixabano Zentiva