Bigetra

Package leaflet: Information for the patient

Bigetra, 75 mg, hard capsules
Dabigatranum etexilatum
Please read carefully all the information in this leaflet before taking this medicine, because it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• 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. 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, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

1. What Bigetra is and what it is used for
2. Important information 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 responsible for blood clot formation.
Bigetra is used in adults for:

• prevention of blood clots in veins after hip or knee replacement surgery.

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

• treatment of blood clots and prevention of 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 is currently experiencing 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 hemorrhage, 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 where heparin is administered through the catheter to maintain its patency, or restoring normal heart rhythm using a 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, antifungal 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 a mechanical heart valve requiring continuous anticoagulant therapy.

Warnings and precautions
Before starting treatment with Bigetra, discuss this with your doctor. If symptoms occur or the patient undergoes surgery during treatment with this medicine, 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 (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 esophagus or stomach.
• if the patient has gastroesophageal reflux (backflow of stomach acid into the esophagus).
• if the patient is taking medicines that may increase the risk of bleeding. See below "Bigetra and other medicines".
• if the patient is taking nonsteroidal 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 and passing reduced 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 previous myocardial infarction or if the patient has been diagnosed with 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 special 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 before and after surgery.
• if surgery requires insertion of a catheter or injection into the spine (e.g. for epidural or spinal anesthesia 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 anesthesia wears off, as urgent medical care may be required.
• if the patient falls or sustains an injury during treatment, especially if the head is injured. Immediate medical attention should be sought. The doctor will assess whether there is an increased risk of bleeding.
• if the patient has a disorder called antiphospholipid syndrome (an autoimmune disorder causing increased risk of blood clots), the patient should inform the doctor, who will decide whether treatment adjustment is needed.

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, the patient should inform the doctor before taking Bigetra if they 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 medicines are used only topically on the skin.
• Medicines used to treat heart rhythm disorders (e.g. amiodarone, dronedarone, quinidine, verapamil). For 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 also 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-norepinephrine 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 the unborn child. This medicine should not be taken during pregnancy unless the doctor considers it safe. Women of childbearing potential should use effective contraception to prevent pregnancy while taking Bigetra.
Breastfeeding is not recommended during treatment with Bigetra.

Driving and operating machinery
Bigetra has no effect or 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 directed by the physician. In case of doubt, consult your doctor.
Bigetra should be taken according to the following recommendations:

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

In both types of surgery, treatment should not be initiated if there is bleeding at the surgical site. If treatment cannot be started by the day after surgery, it should be initiated at a dose of 2 capsules once daily.

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

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

Treatment and prevention of recurrence of 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 be as close as possible to 12 hours.

The recommended dose depends on body weight and age. The physician will determine the correct dose and may adjust it during treatment. All other medications should be continued unless otherwise instructed by the physician.

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

Single doses requiring the 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 help them pass into the stomach. Do not break, chew or empty the pellets from the capsule, as this may increase the risk of bleeding.

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

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

Treatment of blood clots and prevention of recurrence of blood clots in children
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, 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 according to the doctor's instructions. 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 you experience indigestion 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. 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 the blood (a substance in red blood cells)
• Abnormal liver function test results

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

• Bleeding from the nose, stomach or intestines, penis/vagina, or urinary tract (including pink or red urine due to presence of blood), from haemorrhoids, rectum, under the skin, into a joint, due to injury or after injury or surgery
• Formation of bruises or haematomas following 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 liquid stools
• Nausea
• Presence of discharge from the wound (fluid leakage from the surgical wound)
• Increased liver enzyme activity
• Yellowing of the skin or whites of the eyes caused by liver or blood disease

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

• Bleeding
• Bleeding 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-stained 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 bumps 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

Frequency unknown (cannot be estimated from available data):

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

Treatment of blood clots and prevention of recurrent 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 bumps 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 liquid 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 into the stomach or intestines, brain, rectum, penis/vagina or urinary tract (including pink or red urine due to presence of blood), or bleeding under the skin
• Decrease in haemoglobin levels in blood (a substance in red blood cells)
• Decrease in blood cell fraction
• Itching
• Coughing up blood or blood-stained 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 or blood disease

Frequency not known (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 into a joint, from a wound, surgical incision site, injection site, or site of intravenous catheter insertion
• Bleeding from haemorrhoids
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Abnormal liver function test results

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to:
Department of Monitoring Adverse Drug Reactions
Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02 222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Reporting adverse effects allows further information on the safety of the medicine to be collected.
Adverse effects may also be reported to the marketing authorisation holder.

5. How to store Bigetra medicine

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 specified 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 the sewage system. Ask your pharmacist how to dispose of medicines no longer required. Such practices help protect the environment.

6. Contents of the pack and other information

What Bigetra contains

• The active substance is dabigatran. Each hard capsule contains 75 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), purified water and hypromellose.
• The black printing ink contains shellac, iron oxide black (E 172) and potassium hydroxide.

What Bigetra looks like and contents of the pack
Bigetra 75 mg is a hard capsule with a white, opaque cap printed in black with "D75" and a white, opaque body, filled with yellowish pellets.
This medicine is available in packs containing 30 or 60 hard capsules in aluminium 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