Bigetra

Package leaflet: Information for the patient

Bigetra, 150 mg, hard capsules
Dabigatranum etexilatum
Please read carefully the entire leaflet before taking this medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any 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 someone else, 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:

• preventing blood clots in the brain (stroke) and in other blood vessels in the body when the patient has an irregular heart rhythm known as non-valvular atrial fibrillation and at least one additional risk factor.
• treating blood clots in the veins of the legs and lungs, and preventing recurrence of blood clots in the veins of the legs and lungs.

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

• treatment of blood clots and prevention of recurrent 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 which 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. 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 by a procedure called catheter ablation in atrial fibrillation.
• if the patient has severe liver function impairment or liver disease which 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 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 had a mechanical heart valve implanted, which requires continuous use of blood-thinning medicines.

Warnings and precautions
Before starting treatment with Bigetra, patients should discuss this with their doctor. If symptoms occur during treatment with this medicine or if the patient has undergone surgery, they should consult their doctor.
The patient should inform the doctor if they currently have or have previously had any medical conditions or diseases, especially the following:

• 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 oesophagitis or gastritis.
• if the patient has gastro-oesophageal reflux (regurgitation of stomach acid into the oesophagus).
• if the patient is taking medicines which 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 of the heart (bacterial endocarditis).
• if the patient has reduced kidney function or is dehydrated (feeling thirsty and passing reduced amounts of dark (concentrated) or foamy 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 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 Bigetra 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 problems with bowel or bladder function after the anaesthetic wears off, as urgent medical care may be needed.
• if the patient falls or injures themselves during treatment, especially if they injure 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 autoimmune disorder causing increased risk of blood clots), the patient should inform their doctor, who will decide whether treatment needs to be changed.

Bigetra and other medicines
Tell your doctor or pharmacist about any medicines you are currently taking, have recently taken, or might take in the future. In particular, tell your doctor before taking Bigetra 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 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 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 should not be undertaken during treatment with Bigetra.

Driving and using machines
Bigetra has no effect or has a negligible effect on the ability to drive and use machines.

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 the doctor. In case of doubt, consult your doctor.
Take Bigetra exactly as directed below:
For the prevention of blood clots in blood vessels of the brain and body by preventing the formation of clots that occur due to irregular heart function, and for the treatment of blood clots in the veins of the legs and lungs, as well as prevention of recurrence of such clots.
The recommended dose is 300 mg taken as one 150 mg capsule twice daily.
In patients aged 80 years or above, 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 Bigetra of 220 mg taken as one 110 mg capsule twice daily due to the potential 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.
Continued use of this medicine is possible if the patient requires restoration of normal heart rhythm through a procedure called cardioversion or through a procedure called catheter ablation for atrial fibrillation. Bigetra should be taken as directed by the doctor.
In the case 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, the patient 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 of blood clots 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 be as close as possible to 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, crush, or empty the pellets from the capsule, as this may increase the risk of bleeding.

Switching anticoagulant medication
Do not switch anticoagulant medications without first obtaining 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
A missed dose may be taken if there is still at least 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 treatment with Bigetra
Bigetra should be taken exactly as prescribed by the doctor. Do not stop taking this medicine without first consulting your doctor, as the risk of blood clots may be higher if treatment is stopped prematurely. Contact your doctor if gastrointestinal discomfort occurs after taking Bigetra.

If you have any further questions regarding 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 extensive bleeding may occur, which is the most serious adverse effect. Regardless of the location, such bleeding 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), contact your doctor immediately. The doctor may decide to place the patient under close observation or change the treatment.
In case of a severe allergic reaction causing difficulty in breathing or dizziness, contact your doctor immediately.

The possible adverse effects listed below are categorized according to their frequency of occurrence:

Prevention of thromboembolic events in the brain and throughout the body by preventing the formation of blood clots that occur due to 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 from the urinary tract (including pink or red discoloration of urine due to presence of blood), or bleeding under the skin
• Decrease in the number of red blood cells in the 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 hemorrhoidal nodules, from the rectum, or into the brain
• Formation of bruises (hematomas)
• Coughing up blood or blood-stained sputum
• Decrease in the number of platelets in the blood
• Decrease in hemoglobin content in the blood (a substance in red blood cells)
• Allergic reaction
• Sudden change in skin color and appearance
• Itching
• Stomach or intestinal ulcer (including esophageal ulceration)
• Inflammation of the esophagus and stomach
• Regurgitation of stomach contents into the esophagus (reflux)
• Vomiting
• Difficulty swallowing
• Abnormal liver function test results in laboratory analyses

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

• Bleeding into a joint, from a surgical incision site, from a wound, from an injection site, or from the 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 bumps due to an allergic reaction
• Decrease in the number of blood cells
• Increase in liver enzyme activity
• Yellowing of the skin or whites of the eyes due to liver or blood disease

Unknown frequency (frequency cannot be estimated from available data):

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

In clinical trials, the number of myocardial infarctions observed with the use of Bigetra was numerically higher than with warfarin. The overall number of events was small.

Treatment of venous thromboembolism in the legs and lungs, and prevention of recurrent venous thromboembolism 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 discoloration of urine due to presence of blood), or bleeding under the skin
• Indigestion

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

• Bleeding
• Bleeding may occur into a joint or following trauma
• Bleeding from hemorrhoidal nodules may occur
• Decrease in the number of red blood cells in the blood
• Formation of bruises (hematomas)
• Coughing up blood or blood-stained sputum
• Allergic reaction
• Sudden change in skin color and appearance
• Itching
• Stomach or intestinal ulcer (including esophageal ulceration)
• Inflammation of the esophagus and stomach
• Regurgitation of stomach contents into the esophagus (reflux)
• Nausea
• Vomiting
• Abdominal pain or stomach pain
• Frequent passage of loose or watery stools
• Abnormal liver function test results in laboratory analyses
• Increase in liver enzyme activity

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

• Bleeding from a surgical incision site, from an injection site, from the site of intravenous catheter insertion, or bleeding into the brain
• Decrease in the number of platelets in the 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 bumps due to an allergic reaction
• Difficulty swallowing

Unknown frequency (frequency cannot be estimated from available data):

• Difficulty breathing or wheezing
• Decrease in hemoglobin content in the blood (a substance in red blood cells)
• Decrease in the number of blood cells
• Decrease in the number of, 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 myocardial infarctions observed with the use of dabigatran was numerically higher 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 and prevention of recurrence of blood clots in children

Common (may occur in up to 1 in 10 people):

• Decrease in the number of red blood cells in the blood
• Decrease in the number of platelets in the blood
• Skin rash consisting of dark red, raised, itchy bumps due to an allergic reaction
• Sudden change in skin color and appearance
• Formation of bruises (hematomas)
• Nosebleeds
• Regurgitation of stomach contents into the esophagus (reflux)
• Vomiting
• Nausea
• Frequent passage of loose or watery stools
• Indigestion
• Hair loss
• Increase in liver enzyme activity

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

• Decrease in the number of white blood cells (which help fight infections)
• Bleeding may occur into the stomach or intestines, into the brain, from the rectum, from the penis/vagina or urinary tract (including pink or red discoloration of urine due to presence of blood), or bleeding under the skin
• Decrease in hemoglobin content in the blood (a substance in red blood cells)
• Decrease in the number of blood cells
• Itching
• Coughing up blood or blood-stained sputum
• Abdominal pain or stomach pain
• Inflammation of the esophagus and stomach
• Allergic reaction
• Difficulty swallowing
• Yellowing of the skin or whites of the eyes due to liver or blood disease

Unknown frequency (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 a surgical incision site, from an injection site, or from the site of intravenous catheter insertion
• Bleeding from hemorrhoidal nodules may occur
• Stomach or intestinal ulcer (including esophageal ulceration)
• Abnormal liver function test results in laboratory analyses

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
Reporting adverse effects helps provide more information on the safety of the medicine.
Adverse effects can also be reported to the marketing authorization holder.

5. How to store Bigetra medicine

Keep this medicine out of the 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 in use. 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 150 mg of dabigatran etexilate (as mesilate).
• The other ingredients are: tartaric acid, acacia gum, 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, iron oxide black (E 172) and potassium hydroxide.

What Bigetra looks like and contents of the pack
Bigetra 150 mg is a hard capsule with a blue, opaque cap printed in black with "D150" and a white, opaque body, filled with yellowish pellets.
This medicine is available in packs containing 30, 60, 100 or 180 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