Prabixan

Package leaflet: Information for the patient

PRABIXAN, 110 mg, hard capsules
dabigatran etexilate
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Prabixan is and what it is used for

Prabixan contains dabigatran etexilate as the active substance and belongs to a group of medicines called anticoagulants. It works by blocking a substance in the body responsible for blood clot formation.
Prabixan is used in adults for:

• preventing the formation of blood clots in veins after hip or knee replacement surgery.
• preventing the formation of blood clots in the brain (stroke) and in other blood vessels in the body in patients who have a type of irregular heartbeat called non-valvular atrial fibrillation and at least one additional risk factor.
• treating blood clots in the veins of the legs and lungs and preventing the recurrence of blood clots in the veins of the legs and lungs.

Prabixan is used in children for:

• treating blood clots and preventing recurrence of blood clots.

2. Important information before taking Prabixan

When not to take Prabixan

• if the patient is allergic to dabigatran etexilate or any of the other ingredients of this medicine (listed in section 6).
• if the patient has severe kidney function impairment.
• if the patient is currently experiencing bleeding.
• if the patient has a disease of any internal organ which increases the risk of major bleeding (e.g. peptic ulcer of the stomach, brain injury or intracranial haemorrhage, recent brain or eye surgery).
• if the patient has an increased tendency to bleed. This may be congenital, of unknown cause, or caused by taking other medicines.
• if the patient is taking anticoagulant medicines (e.g. warfarin, rivaroxaban, apixaban, or heparin), except when switching anticoagulant therapy, inserting a venous or arterial catheter, when heparin is administered through the catheter to maintain its patency, or during a catheter ablation procedure for atrial fibrillation to restore normal heart rhythm.
• if the patient has severe liver function impairment or liver disease that may lead to death.
• if the patient is taking oral ketokonazole or itraconazole, medicines used to treat fungal infections.
• if the patient is taking oral cyclosporine, a medicine used to prevent rejection of transplanted organs.
• if the patient is taking dronedarone, a medicine used to treat heart rhythm disorders.
• if the patient is taking a combination medicine containing glecaprevir and pibrentasvir, an antiviral medicine used to treat hepatitis C virus infection.
• if the patient has an artificial heart valve that requires lifelong anticoagulant therapy.

Warnings and precautions
Before starting treatment with Prabixan, discuss this with your doctor. If you have experienced any symptoms or undergone any surgical procedure while being treated with this medicine, you should consult your doctor.
The patient should inform the doctor if they currently have or have previously had any medical conditions or diseases, especially those listed below:

• if the patient has an increased risk of bleeding, such as:
• if the patient has recently experienced bleeding.
• if the patient has undergone a surgical tissue biopsy within the last month.
• if the patient has sustained a serious injury (e.g. bone fracture, head injury, or any injury requiring surgical treatment).
• if the patient has inflammation of the oesophagus or stomach.
• if the patient has gastro-oesophageal reflux (regurgitation of stomach acid into the oesophagus).
• if the patient is taking medicines that may increase the risk of bleeding. See below "Prabixan with other medicines".
• if the patient is taking non-steroidal anti-inflammatory drugs such as diclofenac, ibuprofen, piroxicam.
• if the patient has an infection in or around the heart (bacterial endocarditis).
• if the patient has reduced kidney function or is dehydrated (feeling thirsty and passing reduced amounts of dark (concentrated) and/or frothy urine).
• if the patient is over 75 years of age.
• if the patient is an adult weighing 50 kg or less.
• only when used in children: if the child has an infection around or within the brain.
• if the patient has had a heart attack or has been diagnosed with conditions increasing the risk of heart attack.
• if the patient has liver disease affecting blood test results. In such cases, use of this medicine is not recommended.

When to exercise special caution when taking Prabixan

• if the patient needs to undergo surgery: In such cases, temporary discontinuation of Prabixan is necessary due to the increased risk of bleeding during and immediately after surgery. It is very important to take Prabixan exactly as directed by the doctor both before and after surgery.
• if surgery requires insertion of a catheter or administration of an injection into the spine (e.g. for epidural or spinal anaesthesia or for pain relief):
• It is very important to take Prabixan exactly as directed by the doctor both before and after surgery.
• The patient should immediately inform the doctor if they experience numbness or weakness in the lower limbs, or bowel or bladder dysfunction after the anaesthetic wears off, as urgent medical care is required.
• if the patient has fallen or injured themselves during treatment, especially if they injured their head. Immediate medical attention is required. The doctor will assess whether there is an increased risk of bleeding.
• if the patient has a condition called antiphospholipid syndrome (an immune system disorder causing increased risk of blood clots), the patient should inform their doctor, who will decide whether a change in treatment is necessary.

Prabixan with other medicines
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take. In particular, tell your doctor before taking Prabixan if you are taking any of the following medicines:

• Medicines that reduce blood clotting (e.g. warfarin, phenprocoumon, acenocoumarol, heparin, clopidogrel, prasugrel, ticagrelor, rivaroxaban, acetylsalicylic acid).
• Medicines used to treat fungal infections (e.g. ketoconazole, itraconazole), unless these are applied only to the skin.
• Medicines used to treat heart rhythm disorders (e.g. amiodarone, dronedarone, quinidine, verapamil). In patients taking medicines containing amiodarone, quinidine, or verapamil, the doctor may recommend a lower dose of Prabixan depending on the condition for which the medicine was prescribed. See section 3.
• Medicines used to prevent rejection of transplanted organs (e.g. tacrolimus, cyclosporine).
• A combination medicine containing glecaprevir and pibrentasvir (an antiviral medicine used to treat hepatitis C virus infection).
• Anti-inflammatory and pain-relieving medicines (e.g. acetylsalicylic acid, ibuprofen, diclofenac).
• St. John's wort, a herbal medicine used to treat depression.
• Antidepressant medicines known as selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors.
• Rifampicin or clarithromycin (both antibiotics).
• Antiviral medicines used to treat AIDS (e.g. ritonavir).
• Some medicines used to treat epilepsy (e.g. carbamazepine, phenytoin).

Pregnancy and breastfeeding
It is not known what effect Prabixan has on pregnancy or the unborn child. This medicine should not be taken during pregnancy unless the doctor determines it is safe. Women of childbearing potential should avoid becoming pregnant while taking Prabixan.
Breastfeeding should not be undertaken during treatment with Prabixan.

Driving and operating machinery
Prabixan has no effect or a negligible effect on the ability to drive and operate machinery.

3. How to take Prabixan

Prabixan capsules can be used in adults and children aged 8 years or older who are able to swallow capsules whole. Other age-appropriate pharmaceutical forms are available for treating children under 8 years of age.
This medicine should always be taken as prescribed by your doctor. If in doubt, consult your doctor.
Take Prabixan exactly as directed below:

Prevention of blood clots after hip or knee replacement surgery
The recommended dose is 220 mg once daily (taken as two 110 mg capsules).
In patients with renal function reduced by more than half or in patients aged 75 years or older, the recommended dose is 150 mg once daily (taken as two 75 mg capsules).
In patients taking medicines containing amiodarone, quinidine, or verapamil, the recommended dose of Prabixan is 150 mg once daily (taken as two 75 mg capsules).
Patients taking medicines containing verapamil who also have renal function reduced by more than half should take a reduced dose of Prabixan 75 mg due to an increased risk of bleeding.

Treatment should not be initiated if there is bleeding at the surgical site. If treatment cannot be started within the day following surgery, it should be initiated with a dose of two capsules once daily.

After knee replacement surgery
Begin treatment with one capsule taken 1 to 4 hours after completion of surgery. Then take two capsules once daily for a total of 10 days.

After hip replacement surgery
Begin treatment with one capsule taken 1 to 4 hours after completion of surgery. Then take two capsules once daily for a total of 28 to 35 days.

Prevention of thromboembolic events in the brain and body by preventing clot formation due to abnormal heart function, and treatment and prevention of recurrent venous thromboembolism (blood clots in the legs and lungs)
The recommended dose is 300 mg taken as one 150 mg capsule twice daily.
In patients aged 80 years or older, the recommended dose is 220 mg taken as one 110 mg capsule twice daily.
Patients taking medicines containing verapamil should receive a reduced dose of Prabixan of 220 mg taken as one 110 mg capsule twice daily due to a possible increased risk of bleeding.
In patients with potentially increased risk of bleeding, the doctor may recommend treatment with a dose of 220 mg taken as one 110 mg capsule twice daily.
Treatment with this medicine may be continued if the patient requires restoration of normal heart rhythm via a procedure called cardioversion. Prabixan should be taken as directed by your doctor.

In patients undergoing implantation of a medical device (stent) into a blood vessel to maintain its patency using a procedure known as percutaneous coronary intervention with stent implantation, treatment with Prabixan may be initiated once the doctor has confirmed adequate control of blood coagulation. Prabixan should be taken as directed by your doctor.

Treatment and prevention of recurrent venous thromboembolism in children
Prabixan should be taken twice daily, one dose in the morning and one in the evening, approximately at the same time each day. The interval between doses should ideally be 12 hours.

The recommended dose depends on body weight and age. The doctor will determine the correct dose and may adjust it during treatment. Continue taking all other prescribed medicines unless your doctor advises otherwise.

Table 1 shows the single and total daily doses of Prabixan in milligrams (mg).
Doses are based on the patient's body weight in kilograms (kg) and age in years.
Table 1: Dosing table for Prabixan capsules

Single doses requiring combination of more than one capsule:
300 mg: two 150 mg capsules or
four 75 mg capsules
260 mg: one 110 mg capsule and one 150 mg capsule or
one 110 mg capsule and two 75 mg capsules
220 mg: two 110 mg capsules
185 mg: one 75 mg capsule and one 110 mg capsule
150 mg: one 150 mg capsule or
two 75 mg capsules

How to take Prabixan
Prabixan may be taken with or without food. The capsules should be swallowed whole,
with a glass of water, to facilitate passage into the stomach. Do not break, chew or empty the pellets from the capsule, as this may increase the risk of bleeding.

Instructions for opening blisters
The pictogram below shows how to remove Prabixan capsules from the blister pack.

Detach the single dose along the perforated line.

Peel back the protective foil from the blister and remove the capsule.

• Do not push capsules through the blister foil.
• Do not remove the foil until the capsule is needed.

Switching anticoagulant therapy
Do not switch anticoagulant medication without receiving specific instructions from your doctor.

Taking more Prabixan than recommended
Taking too high a dose of this medicine increases the risk of bleeding. If a patient has taken too many capsules, contact a doctor immediately. Specific treatment methods are available.

Missed dose of Prabixan
Prevention of blood clots after surgery (joint replacement of hip or knee joint)
Continue taking the missed daily dose of Prabixan at the usual time on the following day.
Do not take a double dose to make up for a missed dose.

Use in adults: Prevention of blood clots in blood vessels of the brain and body by preventing formation of clots caused by irregular heart rhythm, and treatment and prevention of recurrence of blood clots in the veins of the legs and lungs
Use in children: Treatment of blood clots and prevention of recurrence of blood clots

A missed dose may be taken up to 6 hours before the next scheduled dose.
If less than 6 hours remain before the next scheduled dose, the missed dose should not be taken.
Do not take a double dose to make up for a missed dose.

Stopping Prabixan
Prabixan should be taken as directed by the doctor. Do not stop taking this medicine without first consulting your doctor, as the risk of developing a blood clot may be greater if treatment is stopped prematurely. Contact your doctor if you experience gastrointestinal discomfort after taking Prabixan.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Prabixan affects the blood clotting system, therefore most adverse reactions involve symptoms such as bruising or bleeding. Severe or extensive bleeding may occur, which is the most serious adverse reaction, and regardless of location, it may lead to disability, be life-threatening, or even result in death. In some cases, these bleedings may not be visible.
If bleeding occurs that does not stop spontaneously, or symptoms of excessive bleeding (unusual weakness, fatigue, paleness, dizziness, headache, or unexplained swelling) appear, contact your doctor immediately. The doctor may decide to place the patient under close observation or change the medication.
In case of a serious allergic reaction, which may cause difficulty breathing or dizziness, contact your doctor immediately.

Possible adverse reactions listed below are grouped according to their frequency of occurrence:

Prevention of blood clots after hip or knee replacement surgery
Common (may occur in up to 1 in 10 people):

• Decreased haemoglobin levels in blood (the substance in red blood cells)
• Abnormal liver function test results in laboratory tests.

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

• Bleeding may occur from the nose, into the stomach or intestines, from the penis/vagina or urinary tract (including pink or red urine due to presence of blood), from haemorrhoids, from the rectum, under the skin, into a joint, following injury or after a surgical procedure
• Development of bruises or haematomas after surgery
• Blood in stool detected in laboratory tests
• Decreased number of red blood cells in blood
• Decreased blood cell count
• Allergic reaction
• Vomiting
• Frequent passage of loose or watery stools
• Nausea
• Discharge from wound (fluid leakage from surgical wound)
• Increased liver enzyme activity
• Yellowing of the skin or whites of the eyes due to liver or blood disease.

Rare (may occur in up to 1 in 1,000 people):

• Bleeding
• Bleeding may occur into the brain, from the surgical incision site, injection site, or site of intravenous catheter insertion
• Blood-tinged discharge from the site of intravenous catheter insertion
• Coughing up blood or blood-tinged sputum
• Decreased platelet count in blood
• Decreased number of red blood cells in blood after surgery
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Skin rash with dark red, raised, itchy bumps due to allergic reaction
• Sudden change in skin colour and appearance
• Itching
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Inflammation of the oesophagus and stomach
• Regurgitation of stomach contents into the oesophagus (reflux)
• Abdominal pain or stomach pain
• Indigestion
• Difficulty swallowing
• Discharge of fluid from wound
• Discharge of fluid from surgical wound.

Frequency not known (frequency cannot be estimated from available data):

• Difficulty breathing or wheezing
• Decreased number or even absence of white blood cells (which help fight infections)
• Hair loss.

Prevention of blood clots in blood vessels of the brain and body by preventing clots caused by irregular heart function
Common (may occur in up to 1 in 10 people):

• Bleeding may occur from the nose, into the stomach or intestines, from the penis/vagina or urinary tract (including pink or red urine due to presence of blood), or under the skin
• Decreased number of red blood cells in blood
• Abdominal pain or stomach pain
• Indigestion
• Frequent passage of loose or watery stools
• Nausea.

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

• Bleeding
• Bleeding may occur from haemorrhoids, from the rectum, or into the brain
• Development of haematomas
• Coughing up blood or blood-tinged sputum
• Decreased platelet count in blood
• Decreased haemoglobin levels in blood (the substance in red blood cells)
• Allergic reaction
• Sudden change in skin colour and appearance
• Itching
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Inflammation of the oesophagus and stomach
• Regurgitation of stomach contents into the oesophagus (reflux)
• Vomiting
• Difficulty swallowing
• Abnormal liver function test results in laboratory tests.

Rare (may occur in up to 1 in 1,000 people):

• Bleeding may occur into a joint, from the surgical incision site, from a wound, injection site, or site of intravenous catheter insertion
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Skin rash with dark red, raised, itchy bumps due to allergic reaction
• Decreased blood cell count
• Increased liver enzyme activity
• Yellowing of the skin or whites of the eyes due to liver or blood disease.

Frequency not known (frequency cannot be estimated from available data):

• Difficulty breathing or wheezing
• Decreased number or even absence of white blood cells (which help fight infections)
• Hair loss.

In clinical trials, the number of heart attacks with Prabixan was numerically higher than with warfarin. The overall number of events was low.

Treatment of blood clots in the legs and lungs, and prevention of recurrence of blood clots in the legs and lungs
Common (may occur in up to 1 in 10 people):

• Bleeding may occur from the nose, into the stomach or intestines, from the anus, from the penis/vagina or urinary tract (including pink or red urine due to presence of blood), or under the skin
• Indigestion.

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

• Bleeding
• Bleeding may occur into a joint or following injury
• Bleeding may occur from haemorrhoids
• Decreased number of red blood cells in blood
• Development of haematomas
• Coughing up blood or blood-tinged sputum
• Allergic reaction
• Sudden change in skin colour and appearance
• Itching
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Inflammation of the oesophagus and stomach
• Regurgitation of stomach contents into the oesophagus (reflux)
• Nausea
• Vomiting
• Abdominal pain or stomach pain
• Frequent passage of loose or watery stools
• Abnormal liver function test results in laboratory tests
• Increased liver enzyme activity.

Rare (may occur in up to 1 in 1,000 people):

• Bleeding may occur from the surgical incision site, injection site, site of intravenous catheter insertion, or into the brain
• Decreased platelet count in blood
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Skin rash with dark red, raised, itchy bumps due to allergic reaction
• Difficulty swallowing.

Frequency not known (frequency cannot be estimated from available data):

• Difficulty breathing or wheezing
• Decreased haemoglobin levels in blood (the substance in red blood cells)
• Decreased blood cell count
• Decreased number or even absence of white blood cells (which help fight infections)
• Yellowing of the skin or whites of the eyes due to liver or blood disease
• Hair loss.

In clinical trials, the number of heart attacks with dabigatran etexilate was higher than with warfarin. The overall number of events was low. No difference in the number of heart attacks was observed in patients treated with dabigatran compared to patients receiving placebo.

Treatment of blood clots and prevention of recurrent blood clots in children
Common (may occur in up to 1 in 10 people):

• Decreased number of red blood cells in blood
• Decreased platelet count in blood
• Skin rash with dark red, raised, itchy bumps due to allergic reaction
• Sudden change in skin colour and appearance
• Development of haematomas
• Nosebleeds
• Regurgitation of stomach contents into the oesophagus (reflux)
• Vomiting
• Nausea
• Frequent passage of loose or watery stools
• Indigestion
• Hair loss
• Increased liver enzyme activity.

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

• Decreased number of white blood cells (which help fight infections)
• Bleeding may occur into the stomach or intestines, into the brain, from the anus, from the penis/vagina or urinary tract (including pink or red urine due to presence of blood), or under the skin
• Decreased haemoglobin levels in blood (the substance in red blood cells)
• Decreased blood cell count
• Itching
• Coughing up blood or blood-tinged sputum
• Abdominal pain or stomach pain
• Inflammation of the oesophagus and stomach
• Allergic reaction
• Difficulty swallowing
• Yellowing of the skin or whites of the eyes due to liver or blood disease.

Frequency not known (frequency cannot be estimated from available data):

• Absence of white blood cells (which help fight infections)
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Difficulty breathing or wheezing
• Bleeding
• Bleeding may occur into a joint, from a wound, surgical incision site, injection site, or site of intravenous catheter insertion
• Bleeding may occur from haemorrhoids
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Abnormal liver function test results in laboratory tests.

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 Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store the medicine Prabixan

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister pack following EXP.
The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Prabixan contains

• The active substance is dabigatran. Each hard capsule contains 110 mg of dabigatran etexilate (as mesilate).
• The other ingredients are: tartaric acid, arabic gum, hypromellose 2910, dimethicone 350, talc and hydroxypropylcellulose.
• The capsule shell contains carrageenan, potassium chloride, titanium dioxide (E 171), indigo carmine (E 132), hypromellose 2910 and purified water.
• The black printing ink contains shellac, iron oxide black (E172) and potassium hydroxide.

What Prabixan looks like and contents of the pack
Prabixan 110 mg is a hard capsule (approximately 19 x 7 mm) with an opaque light blue cap and an opaque light blue body. The imprint "110" is printed on the body of the hard capsule.
The medicine is available in packs containing 10, 30, 60, 100 or 180 hard capsules, in a multipack containing 3 packs of 60 hard capsules (180 hard capsules) or in a multipack containing 2 packs of 50 hard capsules (100 hard capsules), in blisters made of OPA/Aluminium/PVC//Aluminium foil, packed in a cardboard box.
Single-dose blisters
This medicine is available in packs containing 10 × 1, 30 × 1, 60 × 1, 100 × 1 or 180 × 1 hard capsules, in a multipack containing 3 packs of 60 × 1 hard capsules (180 hard capsules) or in a multipack containing 2 packs of 50 × 1 hard capsules (100 hard capsules), in perforated single-dose blisters made of OPA/Aluminium/PVC//Aluminium foil of the "peel off" type, packed in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. +48 22 364 61 01

Importer
Laboratori Fundacio Dau
Poligono Industrial Zona - De La Zona Franca De Barcelona
Carrer Lletra C De La Zona Franca 12-14
08040 Barcelona
Spain
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park
Paola PLA 3000
Malta

This medicinal product is authorised in the European Economic Area countries under the following names:
Germany: PRABIXAN 110mg capsules