Pixadil

Italy
Brand name Pixadil
Form tablets, film-coated
Active substance / Dosage
APIXABAN
Prescription type Restricted prescription – dispensable on hospital or specialist prescription
ATC code
B01AF02
Registration number 049650
Manufacturer DAY ZERO EHF

Table of Contents

Patient Information Leaflet

Pixadil 2.5 mg film-coated tablets

apixaban
Generic medicine
Please read all of this leaflet carefully before you take 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, as it may 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 Pixadil is and what it is used for
  2. What you need to know before taking Pixadil
  3. How to take Pixadil
  4. Possible side effects
  5. How to store Pixadil
  6. Contents of the pack and other information

1. What Pixadil is and what it is used for

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

  • to prevent the formation of blood clots (deep vein thrombosis [DVT]) after hip or knee replacement surgery. After surgery on the hip or knee, you may be at increased risk of developing blood clots in the veins of the 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 the 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 reach the brain, leading to stroke, or reach other organs and block 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 such blood clots from recurring in the blood vessels of the legs and/or lungs.

2. What you need to know before taking Pixadil

Do not take Pixadil 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 a body organ that leads to an increased risk of serious bleeding (such as a recent or active ulcer of the stomach or intestine, or 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 from one anticoagulant treatment to another, while you have an intravenous or arterial catheter and are 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 this medicine 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 of age;
  • if you weigh 60 kg or less;
  • severe kidney disease or are on dialysis;
  • liver problems or a history of liver problems; Pixadil should be used with caution in patients showing signs of impaired liver function;
  • you have a tube (catheter) or have received an injection into your spine (for anaesthesia or pain relief). Your doctor will advise you to take Pixadil 5 hours or more 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.

Take special care with Pixadil

  • 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 a change in therapy 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 may cause bleeding, ask your doctor.

Children and adolescents
Pixadil is not recommended for children and adolescents under 18 years of age.

Other medicines and Pixadil
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 Pixadil, while others can reduce it. Your doctor will decide whether you should be treated with Pixadil when taking these medicines and how closely you should be monitored.

The following medicines may increase the effect of Pixadil 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 of age 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 Pixadil 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, are planning to become pregnant, or are 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 Pixadil if you are pregnant. Contact your doctor immediately if you become pregnant while taking Pixadil.

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 Pixadil.

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

Pixadil contains lactose (a type of sugar) 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 Pixadil

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. Pixadil 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 Pixadil. The tablet can 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 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 or one of the other liquids (e.g., 30 mL), and swallow the rinse solution.

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

Take Pixadil as recommended:

To prevent blood clots after hip or knee replacement surgery.
The recommended dose is one 2.5 mg tablet twice daily.
For example, one in the morning and one in the evening.
You should take the first tablet 12 to 24 hours after surgery.
If you have had hip surgery, you will usually take the tablets for 32 to 38 days.
If you have had 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 and at least one additional risk factor.
The recommended dose is one 5 mg tablet twice daily.
The recommended dose is one 2.5 mg 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 value 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 5 mg 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 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 tablet twice daily, for example, one in the morning and one in the evening.
Your doctor will decide how long you should continue treatment.

Your doctor may adjust your anticoagulant treatment as follows:

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

  • Switching from an anticoagulant medicine to Pixadil
    Stop taking the anticoagulant medicine. Start taking Pixadil at the time when you would have taken your next dose of the anticoagulant, then continue as usual.

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

  • Switching from Pixadil to a vitamin K antagonist anticoagulant (e.g., warfarin)
    If your doctor tells you to start taking a vitamin K antagonist medicine, continue taking Pixadil 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 on when to stop Pixadil.

Patients undergoing cardioversion
If your abnormal heartbeat needs to be restored to normal rhythm by a procedure called cardioversion, take Pixadil exactly as directed by your doctor to prevent blood clots in blood vessels of the brain and other parts of the body.

If you take more Pixadil than you should
Contact your doctor immediately if you have taken more than the prescribed dose of Pixadil. Take the medicine pack with you, even if no tablets are left.
If you take more Pixadil than recommended, you may have an increased risk of bleeding. If bleeding occurs, surgery, blood transfusion, or other treatments to reverse the anticoagulant effect on factor Xa may be required.

If you forget to take Pixadil
Take the missed dose as soon as you remember and:

  • take your next dose of Pixadil at the usual time;
  • then continue as directed.

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 Pixadil
DO NOT stop taking Pixadil without first talking to your doctor, as the risk of developing a blood clot may be higher if you stop treatment too early.

If you have any questions about using this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Pixadil may be given for three different medical conditions. The known side effects and how frequently they occur may differ and are listed separately below. For these conditions, the most common general side effect of apixaban is bleeding, which could potentially be life-threatening and requires immediate medical attention.

The following side effects are known to occur when apixaban 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 fluids 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 breathing difficulties. Contact your doctor immediately if you experience any of these symptoms.
  • Bleeding:
  • into the muscle
  • into the eyes
  • from the gums and blood in sputum when coughing
  • from the rectum
  • Hair loss

Not known (frequency cannot be estimated from the 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 which 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

The following side effects are known to occur when apixaban 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:
  • increased gamma-glutamyl transferase (GGT) levels

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 fluids 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 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
  • into the muscle

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

  • Skin rash which 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 the 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

The following side effects are known to occur when apixaban is taken to treat or prevent recurrence of blood clots in the legs' veins 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
  • 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:
  • increased gamma-glutamyl transferase (GGT) or alanine aminotransferase (ALT) levels

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 fluids 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 breathing difficulties. 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 the available data)

  • Bleeding:
  • in the abdomen or in the space behind the abdominal cavity
  • Skin rash which 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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. 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 Pixadil

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton, bottle and blister after Exp. The expiry date refers to the last day of that month.
This medicine requires no special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Pixadil contains

  • The active substance is apixaban. Each film-coated tablet contains 2.5 mg of apixaban.
  • The other excipients are:
  • Tablet core: lactose (see section 2), microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulphate, magnesium stearate.
  • Film coating: monohydrate lactose (see section 2), hypromellose (E464), titanium dioxide (E171), macrogol 3350, triacetin, yellow iron oxide (E172), red iron oxide (E172).

Description of the appearance of Pixadil and pack sizes
Light yellow, round, film-coated tablets, marked with “TV” on one side and “G1” on the other side of the tablet. Dimensions: 5.9 – 6.5 mm in diameter, 3.0 – 3.6 mm in thickness.
Pixadil is available in

  • Blister packs of 10, 20, 60 film-coated tablets. The blisters are packaged in cardboard boxes containing a package leaflet inside.

Not all pack sizes may be marketed.
Patient Alert Card: managing information
Inside the Pixadil package, together with the package leaflet, you will find a Patient Alert Card or your doctor may provide you with a similar one.
This Patient Alert Card includes information that may be useful for you and warns other doctors that you are taking Pixadil. You must always carry this card with you.

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

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Day Zero ehf.
Reykjavíkurvegi 62
220 Hafnarfjörður
Iceland
Manufacturers
Balkanpharma Dupnitsa AD,
3 Samokovsko Shosse STSr. 2600,
Dupnitsa,
Bulgaria
Teva Pharma B.V.,
Swensweg 5,
2031 GA Haarlem,
The Netherlands
Actavis International Ltd,
4, Sqaq tal-Gidi off Valletta Road,
Luqa LQA 6000,
Malta
Actavis Group PTC ehf.,
Reykjavikurvegur 76-78,
IS-220 Hafnarfjordur,
Iceland
This medicinal product is authorised in the European Economic Area Member States under the
following names:
Germany: Pixadil
Italy: Pixadil

Patient Information Leaflet

Pixadil 5 mg film-coated tablets

apixaban
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 others, even if their symptoms are the same as yours, because it could be harmful.
  • If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Pixadil is and what it is used for

Pixadil 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 clotting. Pixadil is used in adults:

  • to prevent blood clots from forming in the heart in patients with irregular heartbeat (atrial fibrillation) who have at least one additional risk factor. Blood clots may break loose and travel to the brain, causing stroke, or travel to other organs and block normal blood flow to those organs (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.

2. What you need to know before taking Pixadil

Do not take Pixadil 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 a body organ that leads to an increased risk of serious bleeding (such as a recent or active ulcer of the stomach or intestine, 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 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 this medicine 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 of age;
  • if you weigh 60 kg or less;
  • severe kidney disease or if you are on dialysis;
  • liver problems or a history of liver problems; Pixadil will be used with caution in patients showing signs of impaired liver function;
  • 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.

Take special care with Pixadil

  • 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 therapy.

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 may cause bleeding, consult your doctor.
Children and adolescents
Pixadil is not recommended for use in children and adolescents under 18 years of age.
Other medicines and Pixadil
Inform 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 Pixadil, while others can reduce it. Your doctor will decide whether you should be treated with Pixadil when taking these medicines and how closely you should be monitored.
The following medicines may increase the effect of Pixadil 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 of age and taking acetylsalicylic acid, you may have an increased risk of bleeding;
  • 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 Pixadil 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 Pixadil if you are pregnant. Contact your doctor immediately if you become pregnant while taking Pixadil.
It is not known whether apixaban passes into breast milk. Consult your doctor, pharmacist, or nurse before taking this medicine during breastfeeding. They will advise you whether to stop breastfeeding or to stop or not start treatment with Pixadil.
Driving and using machines
Apixaban has not shown effects on the ability to drive or use machines.
Pixadil contains lactose (a type of sugar) and sodium
If your doctor has informed you that you have 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 Pixadil

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. Pixadil can 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 whole tablet, ask your doctor about other ways to take Pixadil. The tablet can be crushed and mixed with water, or 5% glucose in water, or apple juice or apple puree, immediately before taking.
Instructions for crushing the tablet:

  • Crush the tablets with a mortar and pestle.
  • Carefully transfer all 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 or one of the other liquids (e.g., 30 mL), and swallow the rinse.

If necessary, your doctor may also administer the crushed Pixadil tablet mixed with 60 mL of water or 5% glucose in water through a nasogastric tube.
Take Pixadil as recommended:
To prevent blood clots in the heart in patients with irregular heartbeat and at least one additional risk factor.
The recommended dose is one 5 mg tablet twice daily.
The recommended dose is one 2.5 mg tablet 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 value 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 leg veins and blood vessels of the lungs
The recommended dose is two 5 mg 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 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 tablet twice daily, for example, one in the morning and one in the evening.
Your doctor will decide how long you should continue treatment.
Your doctor may modify your anticoagulant treatment as follows:

  • Switching from Pixadil to an anticoagulant medicine

Stop taking Pixadil. Start treatment with the anticoagulant medicine (e.g., heparin) at the time you would have taken your next tablet.

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

Patients undergoing cardioversion
If your abnormal heartbeat needs to be restored to normal using a procedure called cardioversion, take Pixadil at the times your doctor instructs you to, to prevent blood clots in blood vessels in the brain and other blood vessels in your body.
If you take more Pixadil than you should
Contact your doctor immediately if you have taken more than the prescribed dose of Pixadil. Bring the medicine pack with you, even if no tablets remain.
If you take more Pixadil 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 Pixadil
Take the missed dose as soon as you remember and:

  • take your next dose of Pixadil at the usual time
  • then continue as directed.

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 Pixadil
DO NOT stop taking Pixadil without first talking to your doctor, because the risk of developing a blood clot may be higher if you stop treatment too early.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

The following side effects are known to occur when apixaban is taken to prevent the formation of 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 intestines;
  • 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-glutamyl transferase (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 phlegm;
  • in the abdomen or from the vagina;
  • bright red blood in the stools;
  • bleeding occurring after surgery, including bruising and swelling, bleeding or fluid leakage 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 clotting);
  • Blood tests may show:
  • abnormalities in liver function;
  • increase in some liver enzymes;
  • increase in bilirubin, a product of red blood cell breakdown, which may cause yellowing of the skin and eyes;
  • 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;
  • in the muscle.

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

  • Rash which may blister 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 the 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.

The following side effects are known to occur when apixaban is taken to treat or prevent the recurrence of blood clots in the veins of the legs and 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, intestines, or from the rectum;
  • in 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 clotting);
  • Nausea (feeling unwell);
  • Rash;
  • Blood tests may show:
  • an increase in gamma-glutamyl transferase (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 coughed-up phlegm;
  • bright red blood in the stools;
  • tests showing blood in the stools or urine;
  • bleeding occurring after surgery, including bruising and swelling, bleeding or fluid leakage 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 difficulty breathing. 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 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 the available data)

  • Bleeding:
  • in the abdomen or in the space behind the abdominal cavity.
  • Rash which may blister 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.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. 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 Pixadil

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton, bottle, 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 you no longer use. This will help protect the environment.

6. Package contents and other information

What Pixadil contains

  • The active substance is apixaban. Each film-coated tablet contains 5 mg of apixaban.
  • The other excipients are:
  • Tablet core: lactose (see section 2), microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, magnesium stearate.
  • Film coating: monohydrate lactose (see section 2), hypromellose (E464), titanium dioxide (E171), macrogol 3350, triacetin, red iron oxide (E172).

Description of the appearance of Pixadil and package contents
Pink, modified oval-shaped, film-coated tablets, marked with “TV” on one side and “G2” on the other side. Dimensions: 9.9 – 10.5 mm in length, 5.0 – 5.6 mm in width, 4.2 – 4.8 mm in thickness.
Pixadil is available in

  • Blister packs containing 28 or 60 film-coated tablets. The blisters are packaged in cardboard boxes with a package leaflet inside the box.

Not all pack sizes may be marketed.
Patient Alert Card: managing information
Inside the Pixadil package, together with the package leaflet, you will find a Patient Alert Card or your doctor may provide you with a similar one.
This Patient Alert Card includes information that may be useful for you and alerts other physicians that you are taking Pixadil. You must always carry this card with you.

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

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Day Zero ehf.
Reykjavíkurvegi 62
220 Hafnarfjörður
Iceland
Manufacturers
Balkanpharma Dupnitsa AD,
3 Samokovsko Shosse STSr. 2600,
Dupnitsa,
Bulgaria
Teva Pharma B.V.,
Swensweg 5,
2031 GA Haarlem,
The Netherlands
Actavis International Ltd,
4, Sqaq tal-Gidi off Valletta Road,
Luqa LQA 6000,
Malta
Actavis Group PTC ehf.,
Reykjavikurvegur 76-78,
IS-220 Hafnarfjordur,
Iceland
This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Germany: Pixadil
Italy: Pixadil