Bigetra

Package leaflet: Information for the patient

Bigetra, 110 mg, hard capsules
Dabigatranum etexilatum
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

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

Leaflet contents

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

1. What Bigetra is and what it is used for

Bigetra 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 that is responsible for blood clot formation.
Bigetra is used in adults for:

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

Bigetra is used in children aged 8 years and older for:

• treating blood clots and preventing recurrence of blood clots.

2. Important information before taking Bigetra

When not to take Bigetra

• 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 currently has active bleeding.
• if the patient has a disease of any internal organ that increases the risk of major bleeding (e.g. gastric ulcer, brain injury or intracranial haemorrhage, recent brain or eye surgery).
• if the patient has an increased tendency to bleed, which may be congenital, of unknown cause, or caused by 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 heart rhythm restoration procedure called catheter ablation for atrial fibrillation.
• if the patient has severe liver function impairment or liver disease that may lead to death.
• if the patient is taking oral ketoconazole or itraconazole, medicines used to treat fungal infections.
• if the patient is taking oral cyclosporine, a medicine used to prevent organ transplant rejection.
• 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 a mechanical heart valve requiring lifelong anticoagulant therapy.

Warnings and precautions
Before starting treatment with Bigetra, discuss it with your doctor. If symptoms occur during treatment
with this medicine or if the patient has undergone surgery, consult a 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 suffered 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 (stomach acid flowing back into the oesophagus).
• if the patient is taking medicines that may increase the risk of bleeding. See below “Bigetra and other medicines”.
• if the patient is taking non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac, ibuprofen, piroxicam.
• if the patient has an infection in the heart (bacterial endocarditis).
• if the patient has reduced kidney function or is dehydrated (feeling thirsty, passing small amounts of dark (concentrated) 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 myocardial infarction or has a condition increasing the risk of myocardial infarction.
• if the patient has liver disease affecting blood test results. In such cases, use of this medicine is not recommended.

When to exercise particular caution when taking Bigetra

• if the patient needs to undergo surgery: In such cases, temporary discontinuation of Bigetra is necessary due to the increased risk of bleeding during and immediately after surgery. It is very important to take Bigetra exactly as directed by the doctor both before and after surgery.
• if surgery involves insertion of a catheter or injection into the spine (e.g. for epidural or spinal anaesthesia or for pain relief):
• It is very important to take Bigetra exactly as directed by the doctor before and after surgery.
• The patient should immediately inform the doctor if numbness or weakness in the lower limbs or problems with bowel or bladder function occur after the anaesthesia wears off, as urgent medical care is required.
• if the patient falls or sustains an injury during treatment, especially if the head is injured. Immediate medical attention is required. The doctor will assess whether there may be an increased risk of bleeding.
• if the patient has a condition called antiphospholipid syndrome (an autoimmune disorder causing increased risk of blood clots), the patient should inform their doctor, who will decide whether treatment needs to be adjusted.

Bigetra and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take. In particular,
inform the doctor before taking Bigetra if the patient is 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 Bigetra depending on the condition for which the medicine was prescribed. See section 3.
• Medicines used to prevent organ transplant rejection (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).
• Certain medicines used to treat epilepsy (e.g. carbamazepine, phenytoin).

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

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

3. How to take Bigetra

Bigetra capsules can be used in adults and children aged 8 years or older who are able to swallow capsules whole.
This medicine should always be taken as prescribed by your doctor. If in doubt, consult your doctor.
Take Bigetra exactly as directed below:

Prevention of blood clots after hip or knee replacement surgery (arthroplasty)
The recommended dose is 220 mg once daily (taken as 2 capsules of 110 mg).
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 2 capsules of 75 mg).
In patients taking medicines containing amiodarone, quinidine, or verapamil, the recommended dose of Bigetra is 150 mg once daily (taken as 2 capsules of 75 mg).
Patients taking medicines containing verapamil who also have renal function reduced by more than half should take a reduced dose of Bigetra 75 mg due to 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 2 capsules once daily.

After knee joint replacement surgery
Treatment with Bigetra should be initiated by taking one capsule within 1 to 4 hours after surgery. Then, take two capsules once daily for a total of 10 days.

After hip joint replacement surgery
Treatment with Bigetra should be initiated by taking one capsule within 1 to 4 hours after surgery. Then, take two capsules once daily for a total of 28 to 35 days.

Prevention of thromboembolic events in blood vessels of the brain and body by preventing clot formation due to abnormal heart rhythm, treatment of blood clots in the legs and lungs, and prevention of recurrent 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 Bigetra at a reduced dose of 220 mg, taken as one 110 mg capsule twice daily, due to possible increased risk of bleeding.
In patients with potentially increased risk of bleeding, the doctor may recommend treatment with Bigetra at a dose of 220 mg, taken as one 110 mg capsule twice daily.

This medicine may be continued if the patient requires restoration of normal heart rhythm via a procedure called cardioversion. Bigetra should be taken as directed by the doctor.

In cases of 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, patients may receive treatment with Bigetra after the doctor has confirmed adequate control of blood coagulation. Bigetra should be taken as directed by the doctor.

Treatment and prevention of recurrent blood clots in children
Bigetra 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 medications unless your doctor advises otherwise.

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

Single doses requiring the simultaneous administration 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 Bigetra
Bigetra 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.

Switching anticoagulant therapy
Do not switch anticoagulant therapy without first obtaining detailed instructions from your doctor.

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

Adult use: Prevention of blood clots in blood vessels of the brain and body by preventing formation of clots due to abnormal heart function, and treatment of blood clots in the veins of the legs and lungs, as well as prevention of recurrence of such clots
Pediatric use: Treatment of blood clots and prevention of recurrent blood clots

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

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

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Bigetra affects the blood clotting system; therefore, most adverse effects are related to symptoms such as bruising or bleeding. Severe or major bleeding may occur, which is the most serious adverse effect, 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 that does not stop spontaneously occurs, or symptoms of excessive bleeding (unusual weakness, fatigue, paleness, dizziness, headache, or unexplained swelling), contact your doctor immediately. The doctor may decide to place the patient under close observation or change the treatment.
In case of a serious allergic reaction, which may cause difficulty breathing or dizziness, contact your doctor immediately.

The possible adverse effects 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):

• Decrease in haemoglobin levels in blood (the substance in red blood cells)
• Abnormal liver function test results

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 haemorrhoidal nodules, from the rectum, under the skin, into a joint, due to trauma or following trauma or surgical procedure
• Formation of haematomas or bruising occurring after surgery
• Blood in stool detected in laboratory tests
• Decrease in number of red blood cells in blood
• Decrease in number of blood cells
• 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 caused by liver disease or blood disorders

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
• Decrease in number of platelets in blood
• Decrease in 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 consisting of dark red, raised, itchy nodules due to an 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
• Fluid discharge from wound
• Fluid discharge from surgical wound

Not known (frequency cannot be estimated from available data):

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

Prevention of thromboembolic events in the brain and body by preventing formation of clots caused by abnormal 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
• Decrease in 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 haemorrhoidal nodules, rectum, or into the brain
• Formation of haematomas
• Coughing up blood or blood-tinged sputum
• Decrease in number of platelets in blood
• Decrease in 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

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

• Bleeding may occur into a joint, from the surgical incision site, 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 consisting of dark red, raised, itchy nodules due to an allergic reaction
• Decrease in number of blood cells
• Increased liver enzyme activity
• Yellowing of the skin or whites of the eyes caused by liver disease or blood disorders

Not known (frequency cannot be estimated from available data):

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

In clinical trials, the number of myocardial infarctions was numerically higher with dabigatran 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 due to trauma
• Bleeding may occur from haemorrhoidal nodules
• Decrease in number of red blood cells in blood
• Formation 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
• 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
• Decrease in number of platelets in blood
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Skin rash consisting of dark red, raised, itchy nodules due to an allergic reaction
• Difficulty swallowing

Not known (frequency cannot be estimated from available data):

• Difficulty breathing or wheezing
• Decrease in haemoglobin levels in blood (the substance in red blood cells)
• Decrease in number of blood cells
• Decrease in number or even absence of white blood cells (which help fight infections)
• Yellowing of the skin or whites of the eyes caused by liver disease or blood disorders
• Hair loss

In clinical trials, the number of myocardial infarctions was numerically higher with dabigatran than with warfarin. The overall number of events was low. No difference in the number of myocardial infarctions was observed between patients treated with dabigatran and those receiving placebo.

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

• Decrease in number of red blood cells in blood
• Decrease in number of platelets in blood
• Skin rash consisting of dark red, raised, itchy nodules due to an allergic reaction
• Sudden change in skin colour and appearance
• Formation 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):

• Decrease in 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
• Decrease in haemoglobin levels in blood (the substance in red blood cells)
• Decrease in number of blood cells
• 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 caused by liver disease or blood disorders

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, from the surgical incision site, injection site, or site of intravenous catheter insertion
• Bleeding may occur from haemorrhoidal nodules
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Abnormal liver function test results

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to:
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.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
By reporting adverse effects, additional information on the safety of the medicine can be collected.
Adverse effects can also be reported to the marketing authorisation holder.

5. How to store the medicine Bigetra

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton or blister pack following:
"Expiry date (EXP)" or "EXP". The expiry date refers to the last day of the stated month.
Do not store above 30°C. Store in the original packaging to protect from light and moisture.
Medicines must not be disposed of via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the packaging and other information

What Bigetra contains

• The active substance is dabigatran. Each hard capsule contains 110 mg of dabigatran etexilate (as mesilate).
• The other ingredients are: tartaric acid, dried dispersion, hypromellose 15 cP, dimethicone, talc, and hydroxypropylcellulose.
• The capsule shell contains carrageenan, potassium chloride, titanium dioxide (E 171), indigo carmine (E 132), purified water, and hypromellose.
• The black printing ink contains shellac, black iron oxide (E 172), and potassium hydroxide.

What Bigetra looks like and contents of the pack
Bigetra 110 mg is a hard capsule with a blue, opaque cap printed with "D110" in black ink and a blue, opaque body, filled with yellowish pellets.
This medicine is available in packs containing 10, 30, 60, 100, or 180 hard capsules in aluminum blisters.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
tel. 22 732 77 00

Manufacturer
Adamed Pharma S.A.
ul. Marszałka Józefa Piłsudskiego 5
95-200 Pabianice