Apinoptim

Package leaflet: Information for the patient

Apinoptim, 2.5 mg, coated tablets
Apixaban
Read the entire leaflet carefully before using this medicine, as it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm others, even if their symptoms are identical.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents

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

1. What Apinoptim is and what it is used for

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

• to prevent blood clots (deep vein thrombosis) after hip or knee replacement surgery. After hip or knee surgery, patients may have an increased risk of developing blood clots in the veins of the legs. This may lead to leg swelling, with or without pain. If a blood clot travels from the legs to the lungs, it may block blood flow through the lungs, causing breathlessness with or without chest pain. This condition (pulmonary embolism) can be life-threatening and requires immediate medical attention.
• to prevent blood clots in the heart in patients with an irregular heartbeat (atrial fibrillation) and at least one additional risk factor. Blood clots may break off and travel to the brain, causing a stroke, or to other organs, impairing blood supply to these organs (also known as systemic embolism). Stroke may be life-threatening and requires immediate medical attention.
• to treat blood clots in the deep veins of the legs (deep vein thrombosis) and in the blood vessels of the lungs (pulmonary embolism), as well as to prevent recurrence of blood clots in the blood vessels of the legs and/or lungs.

Apinoptim is used in children aged 28 days to below 18 years for the treatment of blood clots and prevention of recurrence of blood clots in veins or blood vessels of the lungs.
Information regarding body weight and recommended dosage can be found in section 3.

2. Important information before using Apinoptim

When not to use Apinoptim

• if the patient is allergic to apixaban or any of the other ingredients of this medicine (listed in section 6),
• if the patient has excessive bleeding,
• if the patient has a disease of an organ that increases the risk of serious bleeding (such as active or recently diagnosed ulcer of the stomach or intestine, recently diagnosed bleeding into the brain),
• if the patient has liver disease leading to an increased risk of bleeding (hepatic coagulopathy),
• if the patient is taking anticoagulant medicines (e.g. warfarin, rivaroxaban, dabigatran or heparin), except in situations of switching anticoagulant therapy, when an intravenous or arterial line has been inserted and heparin is administered through this line to maintain its patency, or when the patient is undergoing catheter ablation (a catheter is inserted into the vein) due to irregular heartbeat (arrhythmia).

Warnings and precautions

Before starting treatment, discuss with your doctor, pharmacist or nurse if the patient has any of the following conditions:

• increased risk of bleeding, for example:
• conditions associated with bleeding, including cases resulting in reduced platelet activity,
• very high blood pressure not controlled by medication,
• if the patient is over 75 years of age,
• if the patient weighs 60 kg or less,
• severe kidney disease or if the patient is on dialysis,
• liver disease or history of liver disorders. This medicine should be used with caution in patients showing signs of liver function abnormalities.
• a spinal catheter or spinal injection (anaesthetic or pain-relieving), in which case the doctor will advise taking this medicine 5 or more hours after removal of the catheter,
• if the patient has a heart valve prosthesis,
• if the doctor determines that the patient's blood pressure is unstable or other treatment or a surgical procedure to remove a blood clot from the lungs is planned.

When to exercise particular caution when using Apinoptim

• if the patient has a disorder called antiphospholipid syndrome (an immune system disorder causing increased risk of blood clots), the patient should inform the doctor, who will decide whether a change in treatment is necessary.

If surgery or a procedure that may cause bleeding is required, the doctor may ask the patient to temporarily stop taking this medicine for a short period. If in doubt whether a particular procedure may cause bleeding, consult the doctor.

Children and adolescents

Apinoptim is not recommended for use in children and adolescents with body weight below 35 kg.

Apinoptim and other medicines

Tell your doctor, pharmacist or nurse about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.

Some medicines may enhance the effect of Apinoptim, while others may reduce its effectiveness. The doctor will decide whether the patient should receive Apinoptim while taking other medicines and how closely monitoring should be performed.

The following medicines may enhance the effect of Apinoptim and increase the risk of unwanted bleeding:

• certain medicines used to treat fungal infections (e.g. ketoconazole and others),
• certain antiviral medicines used to treat HIV/AIDS infection (e.g. ritonavir),
• other medicines used to reduce blood clotting (e.g. enoxaparin and others),
• anti-inflammatory or pain-relieving medicines (e.g. acetylsalicylic acid or naproxen); particularly if the patient is over 75 years of age and taking acetylsalicylic acid, the risk of bleeding may be increased,
• medicines used for high blood pressure or heart problems (e.g. diltiazem),
• antidepressant medicines known as selective serotonin reuptake inhibitors or serotonin and noradrenaline reuptake inhibitors.

The following medicines may reduce the ability of Apinoptim to prevent blood clots:

• medicines used to prevent epilepsy or seizures (e.g. phenytoin and others),
• St John's wort (an herbal supplement used for depression),
• medicines used to treat tuberculosis or other infections (e.g. rifampicin).

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor, pharmacist or nurse before using this medicine.

The effect of Apinoptim on pregnancy and unborn child is unknown. This medicine should not be used during pregnancy. If the patient becomes pregnant while taking this medicine, she should contact her doctor immediately.

It is not known whether apixaban passes into human milk. The patient should consult her doctor, pharmacist or nurse before using this medicine during breastfeeding. She may be advised to discontinue breastfeeding or to discontinue/avoid starting treatment with this medicine.

Driving and operating machinery

No effects of Apinoptim on the ability to drive or operate machinery have been observed.

Apinoptim contains lactose and sodium

If the patient has previously been diagnosed with an intolerance to certain sugars, the patient should consult their doctor before taking this medicine.

This medicine contains less than 1 mmol (23 mg) of sodium per tablet; therefore, this medicine is considered "sodium-free".

3. How to take Apinoptim

This medicine should always be taken exactly as instructed by your doctor or pharmacist. If you are
unsure, please consult your doctor, pharmacist, or nurse.
Dosage
The tablet should be swallowed with water. Apinoptim may be taken regardless of meals.
To achieve the best treatment results, it is recommended to take the tablets at the same times
every day.
If you have difficulty swallowing the tablets whole, please discuss alternative ways of taking Apinoptim
with your doctor. The tablet may be crushed immediately before administration and mixed with water or
5% aqueous glucose solution, juice, or apple puree.
Instructions for crushing tablets:

• Crush the tablet with a pestle in a mortar.
• Carefully transfer the entire powder into a suitable container and mix it with a small amount, e.g., 30 mL (2 tablespoons), of water or one of the liquids listed above to prepare a mixture.
• Swallow (drink) the mixture.
• Rinse the pestle and mortar used for crushing the tablets, as well as the container, with a small amount of water or another liquid (e.g., 30 mL), and swallow (drink) the rinse liquid. If necessary, your doctor may administer crushed Apinoptim tablets mixed with 60 mL of water or 5% aqueous glucose solution via a nasogastric tube.

Apinoptim should be taken as recommended for the following indications:
Prevention of blood clots after hip or knee replacement surgery
The recommended dose is one 2.5 mg Apinoptim tablet twice daily, for example, one tablet in the morning and one in the evening.
The first tablet should be taken 12 to 24 hours after surgery.
If you underwent major hip surgery, you will usually take the tablets for 32 to 38 days.
If you underwent major knee surgery, you will usually take the tablets for 10 to 14 days.
Prevention of 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 Apinoptim tablet twice daily.
The recommended dose is one 2.5 mg Apinoptim tablet twice daily if:

• you have severe renal impairment,
• two or more of the following conditions are met:
• blood test results suggest reduced kidney function (serum creatinine concentration of 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 tablet in the morning and one in the evening. Your doctor will decide how long treatment should continue.
Treatment of blood clots in the veins of the legs and blood clots in the blood vessels of the lungs
The recommended dose is two 5 mg Apinoptim tablets twice daily for the first 7 days, for example, two tablets in the morning and two in the evening.
After 7 days, the recommended dose is one 5 mg Apinoptim tablet twice daily, for example, one tablet in the morning and one in the evening.
Prevention of recurrence of blood clots after completion of 6-month treatment
The recommended dose is one 2.5 mg Apinoptim tablet twice daily, for example, one tablet in the morning and one in the evening.
Your doctor will decide how long treatment should continue.
Use in children and adolescents
Treatment of blood clots and prevention of recurrence of blood clots in veins or pulmonary blood vessels.
This medicine should always be taken or administered exactly as directed by your doctor or pharmacist.
If you are unsure, please consult your doctor, pharmacist, or nurse.
To achieve the best treatment effect, try to take or administer the dose at the same time each day.
The Apinoptim dose depends on body weight and will be calculated by your doctor.
The recommended dose for children and adolescents weighing at least 35 kg is four 2.5 mg Apinoptim 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 Apinoptim tablets twice daily, for example, two in the morning and two in the evening.
For parents and caregivers: observe the child to ensure the full dose has been taken.
It is important to attend scheduled doctor visits, as dose adjustments may be necessary with changes in body weight.
Your doctor may change anticoagulant treatment as follows:

• Switching from Apinoptim to anticoagulant medicines Discontinue Apinoptim. Start anticoagulant treatment (e.g., heparin) at the time the next tablet was scheduled to be taken.
• Switching from anticoagulant medicines to Apinoptim Discontinue anticoagulant medicines. Begin Apinoptim treatment at the time the next anticoagulant dose was scheduled, then continue taking it regularly as prescribed.
• Switching from anticoagulant treatment including a vitamin K antagonist (e.g., warfarin) to Apinoptim Discontinue the vitamin K antagonist medicine. Your doctor must perform blood tests and will inform you when to start taking Apinoptim.
• Switching from Apinoptim to anticoagulant treatment including a vitamin K antagonist

(e.g., warfarin)
If your doctor informs you that you should start taking a vitamin K antagonist medicine, continue taking Apinoptim for at least 2 days after taking the first dose of the vitamin K antagonist medicine. Your doctor must perform blood tests and inform you when to stop taking Apinoptim.
Patients undergoing cardioversion
Patients with irregular heart rhythm who require cardioversion to restore normal heart rhythm should take this medicine at the times specified by their doctor to prevent formation of blood clots in the brain and other blood vessels of the body.
Taking more Apinoptim than recommended
If you take more than the recommended dose of this medicine, you must contact your doctor immediately.
Bring the medicine packaging with you, even if no tablets remain.
If you take more than the recommended dose of Apinoptim, your risk of bleeding may increase. If bleeding occurs, surgical treatment, blood transfusion, or other treatment to reverse the effect directed against factor Xa may be necessary.
Missing a dose of Apinoptim

• If you miss a morning dose, take it as soon as you remember, and you may take it together with your evening dose.
• A missed evening dose may only be taken that same evening. Do not take two doses the next morning instead; continue taking the medicine the next day as directed, twice daily. If you have any doubts about using the medicine or if you miss more than one dose, consult your doctor, pharmacist, or nurse.

Stopping Apinoptim
Do not stop taking this medicine without consulting your doctor, as stopping Apinoptim prematurely may increase the risk of blood clots.
If you have any further questions about using this medicine, please consult your doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Apinoptim can be used for three different medical conditions. Known adverse reactions and their frequency of occurrence may differ for each of these conditions and are listed separately below. In these conditions, the most common general adverse reaction associated with this medicine is bleeding, which may potentially be life-threatening and may require immediate medical attention.

The following adverse reactions may occur when taking Apinoptim to prevent blood clots after hip or knee surgery.

Common adverse reactions (may occur in up to 1 in 10 people)

• Anaemia, which may cause fatigue or paleness;
• Bleeding including:
  • subcutaneous haemorrhages (bruising) and swelling;
• Nausea.

Uncommon adverse reactions (may occur in up to 1 in 100 people)

• Decreased platelet count (which may affect blood clotting);
• Bleeding:
  • postoperative, including bruising and swelling, leakage of blood or other fluid from the surgical wound/incision site (wound discharge) or injection site;
  • from stomach, intestines, or bright red blood in stool;
  • blood in urine;
  • nosebleeds;
  • vaginal bleeding;
• Low blood pressure, which may lead to fainting or rapid heartbeat;
• Blood test results may indicate:
  • liver function abnormalities;
  • increased activity of certain liver enzymes;
  • increased bilirubin levels—a breakdown product of destroyed red blood cells that may cause yellowing of the skin and eyes;
• Itching.

Rare adverse reactions (may occur in up to 1 in 1000 people)

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

Frequency not known (cannot be estimated from available data)

• Bleeding:
  • into the brain or spinal canal;
  • in the lungs or throat;
  • in the mouth;
  • into the abdominal cavity or retroperitoneal space;
  • from haemorrhoids;
  • test results indicating presence of blood in stool or urine;
• Skin rash, which may form blisters and resembles small bullseyes (dark spots in the center surrounded by a lighter ring, with a dark ring around the edge) (erythema multiforme);
• Vasculitis (inflammation of blood vessels), which may cause skin rash or raised, flat, red, round spots beneath the skin surface, or bruising;
• Bleeding in the kidney, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-associated nephropathy).

The following adverse reactions may occur when taking Apinoptim to prevent blood clots in the heart in patients with irregular heartbeat and at least one additional risk factor.

Common adverse reactions (may occur in up to 1 in 10 people)

• Bleeding, including:
  • into the eyes;
  • into the stomach or intestines;
  • from rectum;
  • blood in urine;
  • nosebleeds;
  • from gums;
  • subcutaneous haemorrhage (bruising) and swelling;
• Anaemia, which may cause fatigue or paleness;
• Low blood pressure, which may lead to fainting or rapid heartbeat;
• Nausea;
• Blood test results may indicate:
  • increased gamma-glutamyl transferase (GGT) activity.

Uncommon adverse reactions (may occur in up to 1 in 100 people)

• Bleeding:
  • into the brain or spinal canal;
  • in the mouth or blood in sputum when coughing;
  • into the abdominal cavity or from vagina;
  • bright red blood in stool;
  • postoperative bleeding, including bruising and swelling, leakage of blood or fluid from surgical wound/incision site (wound discharge) or injection site;
  • from haemorrhoids;
  • presence of blood in stool or urine detected in laboratory tests;
• Decreased platelet count (which may affect blood clotting);
• Blood test results may indicate:
  • abnormal liver function;
  • increased activity of certain liver enzymes;
  • increased bilirubin levels—breakdown product of red blood cells, which may cause yellowing of the skin and eyes;
• Skin rash;
• Itching;
• Hair loss;
• Allergic (hypersensitivity) reactions, which may cause: swelling of the face, lips, mouth, tongue and (or) throat, and breathing difficulties. If any of these symptoms are observed, contact your doctor immediately.

Rare adverse reactions (may occur in up to 1 in 1000 people)

• Bleeding:
  • in the lungs or throat;
  • into retroperitoneal space;
  • into muscle tissue.

Very rare adverse reactions (may occur in up to 1 in 10,000 people)

• Skin rash, which may form blisters and resembles small bullseyes (dark spots in the center surrounded by a lighter ring, with a dark ring around the edge) (erythema multiforme).

Frequency not known (cannot be estimated from available data)

• Vasculitis (inflammation of blood vessels), which may cause skin rash or raised, flat, red, round spots beneath the skin surface, or bruising;
• Bleeding in the kidney, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-associated nephropathy).

The following adverse reactions may occur when taking Apinoptim to treat or prevent recurrence of blood clots in the veins of the lower limbs and in blood vessels of the lungs.

Common adverse reactions (may occur in up to 1 in 10 people)

• Bleeding, including:
  • nosebleeds;
  • from gums;
  • blood in urine;
  • subcutaneous haemorrhage (bruising) and swelling;
  • in stomach, intestines, or from rectum;
  • in mouth;
  • vaginal bleeding;
• Anaemia, which may cause fatigue or paleness;
• Decreased platelet count (which may affect clotting);
• Nausea;
• Skin rash;
• Blood test results may indicate:
  • increased gamma-glutamyl transferase (GGT) or alanine aminotransferase (AlAT) activity.

Uncommon adverse reactions (may occur in up to 1 in 100 people)

• Low blood pressure, which may lead to fainting or rapid heartbeat;
• Bleeding:
  • into the eyes;
  • in the mouth or blood in sputum when coughing;
  • bright red blood in stool;
  • test results indicating blood in stool or urine;
  • postoperative bleeding, including bruising and swelling, leakage of blood or fluid from surgical wound/incision site (wound discharge) or injection site;
  • from haemorrhoids;
  • into muscle tissue;
• Itching;
• Hair loss;
• Allergic (hypersensitivity) reactions, which may cause: swelling of the face, lips, mouth, tongue and (or) throat, and breathing difficulties. If any of these symptoms are observed, contact your doctor immediately;
• Blood test results may indicate:
  • abnormal liver function;
  • increased activity of certain liver enzymes;
  • increased bilirubin levels—breakdown product of red blood cells, which may cause yellowing of the skin and eyes.

Rare adverse reactions (may occur in up to 1 in 1000 people)

• Bleeding:
  • into the brain or spinal canal;
  • in the lungs.

Frequency not known (cannot be estimated from available data)

• Bleeding:
  • into the abdominal cavity or retroperitoneal space;
• Skin rash, which may form blisters and resembles small bullseyes (dark spots in the center surrounded by a lighter ring, with a dark ring around the edge) (erythema multiforme);
• Vasculitis (inflammation of blood vessels), which may cause skin rash or raised, flat, red, round spots beneath the skin surface, or bruising;
• Bleeding in the kidney, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-associated nephropathy).

Additional adverse reactions in children and adolescents
If any of the following symptoms occur, contact your doctor immediately:

• Allergic (hypersensitivity) reactions, which may cause: swelling of the face, lips, mouth, tongue and (or) throat, and breathing difficulties. The frequency of these adverse reactions is classified as "common" (may occur in up to 1 in 10 people).

In general, adverse reactions observed in children and adolescents treated with Apinoptim were similar to those seen in adults and were mostly mild or moderate in severity. Adverse reactions occurring more frequently in children and adolescents include nosebleeds and abnormal vaginal bleeding.

Very common adverse reactions (may occur in more than 1 in 10 people)

• Bleeding, including:
  • vaginal bleeding;
  • nosebleeds.

Common adverse reactions (may occur in up to 1 in 10 people)

• Bleeding, including:
  • from gums;
  • blood in urine;
  • subcutaneous haemorrhages (bruising) and swelling;
  • from intestine or rectum;
  • bright red blood in stool;
  • postoperative bleeding, including subcutaneous haemorrhages (bruising) and swelling, leakage of blood or fluid (discharge) from surgical wound or injection site;
• Hair loss;
• Anaemia, which may cause fatigue or paleness;
• Decreased platelet count (which may affect coagulation);
• Nausea;
• Skin rash;
• Itching;
• Low blood pressure, which may cause fainting or rapid heartbeat;
• Blood test results may indicate:
  • abnormal liver function;
  • increased activity of certain liver enzymes;
  • increased alanine aminotransferase (ALT).

Frequency not known (cannot be estimated from available data)

• Bleeding:
  • into the abdominal cavity or retroperitoneal space;
  • in stomach;
  • in eyes;
  • in mouth;
  • from haemorrhoids;
  • in mouth or blood in sputum during coughing;
  • into brain or spine;
  • in lungs;
  • into muscle;
• Skin rash, which may form blisters and resembles small bullseyes (dark spots in the center surrounded by a lighter ring, with a dark ring around the edge) (erythema multiforme);
• Vasculitis, which may cause skin rash or raised, flat, red, round spots beneath the skin surface or bruising;
• Blood test results may indicate:
  • increased gamma-glutamyl transferase (GGT) activity;
  • presence of blood in stool or urine;
• Bleeding in the kidney, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-associated nephropathy).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49 21 301, fax: 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder. Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Apinoptim

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the outer carton and blister pack after: EXP. The expiry date refers to the last day of the stated month.
No special storage instructions apply for this medicine.
Crushed tablets
Crushed Apinoptim tablets are stable in water, 5% glucose solution in water, apple juice, and apple puree for up to 4 hours.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the packaging and other information

What Apinoptim contains

• The active substance is apixaban. Each coated tablet contains 2.5 mg of apixaban.
• The other ingredients are:
  • Tablet core: microcrystalline cellulose (type 101), anhydrous lactose, sodium lauryl sulfate, sodium croscarmellose, magnesium stearate,
  • Coating: hypromellose 2910, monohydrate lactose, titanium dioxide (E171), triacetin, yellow iron oxide (E172). What Apinoptim looks like and contents of the pack The coated tablets are yellow, round, with a diameter of 6.2 mm ± 0.2 mm. Blister made of PVC/PVDC/Aluminium, packed in a cardboard box. Pack sizes: 20, 60 coated tablets. Not all pack sizes may be marketed.

Patient Warning Card: information for use
A Patient Warning Card is included in the packaging, or your doctor may provide you with a similar card.
The Patient Warning Card contains helpful information for the patient and warns other physicians that the patient is taking Apinoptim. You should always carry this card with you.

1. Take the card.
2. Fill in the following details or ask your doctor to complete them:
   • Name and surname:
   • Date of birth:
   • Indication:
   • Dose: ......... mg twice daily
   • Doctor's name:
   • Doctor's telephone number:
3. Fold the card and always carry it with you.

Marketing Authorisation Holder
Synoptis Pharma Sp. z o.o.
Krakowiaków Street 65
02-255 Warsaw
Phone: +48 22 32 160 240
Manufacturer
PHARMADOX Healthcare Limited
KW20A Kordin Industrial Park
Paola, PLA 3000
Malta
January 2026