BIGETRA 110 mg HARD CAPSULES

Introduction

Package Leaflet:information for the patient

Bigetra 110 mg hard capsules EFG

dabigatran etexilate

Read the entire package leaflet carefully before starting to take this medication,as it contains important information for you.

• Keep this package leaflet, as you may need to read it again.

• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed to you only, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.
  • If you experience side effects, consult your doctor or pharmacist, even if they are side effects not listed in this package leaflet. See section 4.

Contents of the package leaflet

1. What is Bigetra and what is it used for
2. What you need to know before taking Bigetra
3. How to take Bigetra
4. Possible side effects

5 Preservation of Bigetra

1. Contents of the pack and further information

1. What is Bigetra and what is it used for

Bigetra contains the active substance dabigatran etexilate and belongs to a group of medications called anticoagulants. It works by blocking a substance in the body involved in the formation of blood clots.

Dabigatran etexilate is used in adults to:

• prevent the formation of blood clots in the veins after knee or hip replacement surgery.

• prevent the formation of blood clots in the brain (stroke) and in other blood vessels of the

body if you have a type of irregular heartbeat called non-valvular atrial fibrillation and have at least one additional risk factor.

• treat blood clots in the veins of your legs and lungs and to prevent them from forming again in the veins of your legs and lungs.

Dabigatran etexilate is used in children aged 8 years or older to:

• treat blood clots and prevent them from forming again.

2. What you need to know before taking Bigetra

Do not take Bigetra

• if you are allergic to dabigatran etexilate or any of the other ingredients of this medication (listed in section 6).
• if your kidney function is severely reduced.
• if you are currently bleeding.
• if you have any disease in an organ of the body that increases the risk of severe bleeding

(e.g., stomach ulcer, brain injury or bleeding, recent brain or eye surgery).

• if you are prone to bleeding. This tendency may be congenital, of unknown cause, or

caused by other medications.

• if you are taking medications to prevent blood clot formation (e.g., warfarin, rivaroxaban, apixaban, or heparin), except when switching to anticoagulant treatment, while having a venous or arterial catheter and being administered heparin through this catheter to keep it open, or while your normal heartbeat is being restored through a procedure called catheter ablation for atrial fibrillation.

• if your liver function is severely reduced or you have a life-threatening liver disease.
• if you are taking oral ketoconazole or itraconazole, medications used to treat fungal infections.
• if you are taking oral cyclosporine, a medication used to prevent organ rejection after a transplant.

• if you have had an artificial heart valve implanted that requires permanent anticoagulant treatment.

Warnings and precautions

Consult your doctor before starting to take this medication. During treatment with this medication, you may also need to consult your doctor if you experience any symptoms or if you need to undergo surgery.

Tell your doctorif you have or have had any disorder or disease, especially

any of the following:

• If you have an increased risk of bleeding, for example:
  • if you have recently had bleeding.
  • if you have had a surgical tissue removal (biopsy) in the last month.
  • if you have had a severe injury (e.g., a bone fracture, a head injury, or any injury that required surgical treatment).

• if you have inflammation of the esophagus or stomach.
• if you have problems with gastric juice reflux in the esophagus.
• if you are taking medications that may increase the risk of bleeding. See "Other medications and Bigetra" below.

• if you are using anti-inflammatory medications such as diclofenac, ibuprofen, or piroxicam.

• if you are over 75 years old.
• if you are an adult patient and weigh 50 kg or less.
• only if used in children: if the child has a brain infection or around the brain.

• If you have had a heart attack or have been diagnosed with diseases that increase the risk of having a heart attack.

Be careful with Bigetra

• If you need to undergo surgery:

In this case, dabigatran etexilate should be temporarily discontinued due to an increased risk of bleeding during and after surgery. It is very important that you take dabigatran etexilate before and after surgery exactly at the times indicated by your doctor.

• If surgery requires the placement of a catheter or injection into the spinal column (e.g., for epidural or spinal anesthesia or for pain relief):

• It is very important that you take dabigatran etexilate before and after surgery exactly at the times indicated by your doctor.
• Tell your doctor immediately if you experience numbness or weakness in your legs or bowel or bladder problems after the end of anesthesia, as this situation requires urgent attention.

• If you know you have a disease called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), inform your doctor to decide if it may be necessary to modify the treatment.

Other medications and Bigetra

Tell your doctor or pharmacist if you are taking, have recently taken, or may need to take any other medication. In particular, you must inform your doctor before taking dabigatran etexilateif you are taking any of the medications listed below:

• Medications to reduce blood clotting (e.g., warfarin, phenprocoumon, acenocoumarol, heparin, clopidogrel, prasugrel, ticagrelor, rivaroxaban, acetylsalicylic acid)

• Medications for the treatment of fungal infections (e.g., ketoconazole, itraconazole), unless they are applied only to the skin
• Medications used to treat abnormal heart rhythm (e.g., amiodarone, dronedarone, quinidine, verapamil)

If you are taking medications containing amiodarone, quinidine, or verapamil, your doctor may indicate that you should use a reduced dose of this medication according to the disease for which it was prescribed. See section 3.

• Medications for the prevention of organ rejection after a transplant (e.g., tacrolimus, cyclosporine)

• St. John's Wort, a herbal remedy for depression
• Antidepressant medications called selective serotonin reuptake inhibitors or selective serotonin and norepinephrine reuptake inhibitors
• Rifampicin or clarithromycin (two antibiotics)
• Antiviral medications for HIV (e.g., ritonavir)
• Certain medications for the treatment of epilepsy (e.g., carbamazepine, phenytoin)

Pregnancy and breastfeeding

The effects of dabigatran etexilate on pregnancy and the fetus are unknown. You should not use this medication if you are pregnant unless your doctor indicates that it is safe to do so. If you are of childbearing age, you should avoid becoming pregnant during treatment with dabigatran etexilate.

Breastfeeding is not recommended during treatment with dabigatran etexilate.

Driving and using machines

Dabigatran etexilate has no known effects on the ability to drive and use machines.

3. How to take Bigetra

Dabigatran etexilate capsules can be used in adults and children 8 years of age or older who are able to swallow the capsules whole.

Follow your doctor's instructions for administering this medication exactly. If in doubt, consult your doctor again.

TakeBigetraas recommended for the following situations:

Prevention of blood clot formation after knee or hip arthroplasty

The recommended dose is 220 mg once a day(administered in the form of 2 capsules of 110 mg).

If your renal function is decreasedby more than half or if you are 75 years of age or older, the recommended dose is 150 mg once a day(administered in the form of 2 capsules of 75 mg).

If you are taking medications containing amiodarone, quinidine, or verapamil, the recommended dose is 150 mg once a day(administered in the form of 2 capsules of 75 mg).

If you are taking medications containing verapamil and your renal function is decreasedby more than half, you should be indicated a reduced dose of dabigatran etexilate of 75 mgbecause your risk of bleeding may increase.

In both types of surgery, treatment should not be started if there is bleeding at the surgical site. If treatment cannot be started until the day after the operation, dosing should be started with 2 capsules once a day.

After knee arthroplasty

Treatment with dabigatran etexilate should be started 1-4 hours after surgery, taking a single capsule. Then, 2 capsules should be taken once a day for a total of 10 days.

After hip arthroplasty

Treatment with dabigatran etexilate should be started 1-4 hours after surgery, taking a single capsule. Then, 2 capsules should be taken once a day for a total of 28-35 days.

Preventionof cerebral or systemic vascular obstructionby blood clot formationdeveloped after abnormal heart rhythmand treatment of blood clots in the veins of your legs and lungs, including prevention of recurrence of blood clots in the veins of your legs and lungs

The recommended dose is 300 mg administeredin the form of one 150 mg capsule twice a day.

If you are 80 years of age or older, the recommended dose is 220 mg administeredin the form of one 110 mg capsule twice a day.

If you are using medications containing verapamil, you should be indicated a reduced dose of dabigatran etexilate of 220 mg takenin the form of one 110 mg capsule twice a day, since your risk of bleeding may increase.

If you have a potentially higher risk of bleeding, your doctor may decide to prescribe a dose of 220 mg administeredin the form of one 110 mg capsule twice a day.

You can continue taking this medication if it is necessary to restore your normal heart rhythm through a procedure called cardioversion. Take dabigatran etexilate as your doctor has indicated.

If you have been fitted with a medical device (vascular endoprosthesis) in a blood vessel to keep it open in a procedure called percutaneous coronary intervention with endoprosthesis placement, you may receive treatment with dabigatran etexilate once your doctor has decided that normal blood coagulation control has been achieved. Take dabigatran etexilate as your doctor has indicated.

Treatment of blood clots and prevention of recurrence of blood clots in children

Dabigatran etexilateshould be taken twice a day, one dose in the morning and one dose in the evening, approximately at the same time every day. The administration interval should be as close as possible to 12 hours.

The recommended dose depends on weight and age. Your doctor will determine the correct dose. It is possible that your doctor will adjust the dose during treatment. Continue using all other medications unless your doctor indicates that you should stop using one.

Table 1 shows the single and total daily doses of dabigatran etexilate in milligrams (mg). The doses depend on the patient's weight in kilograms (kg) and age in years.

Table 1: Dosing table for dabigatran etexilate capsules

Doses requiring combinations of more than one capsule:

300 mg: two 150 mg capsules or four 75 mg capsules

260 mg: one 110 mg capsule plus one 150 mg capsule or one 110 mg capsule plus two 75 mg capsules

220 mg: two 110 mg capsules

185 mg: one 75 mg capsule plus one 110 mg capsule

150 mg: one 150 mg capsule or two 75 mg capsules

How to take Bigetra

Dabigatran etexilate can be taken with or without food. The capsule should be swallowed whole with a glass of water to ensure release in the stomach. Do not break, chew, or open the capsule to take only its contents, as this may increase the risk of bleeding.

Changing anticoagulant treatment

Do not change your anticoagulant treatment without specific instructions from your doctor.

If you take more Bigetra than you should

Taking too much of this medication increases the risk of bleeding. Contact your doctor immediately if you have taken too many capsules. There are specific treatment options available.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Bigetra

Prevention of blood clot formation after knee or hip arthroplasty

Take the remaining daily doses of dabigatran etexilate at the same time the next day.

Do not take a double dose to make up for forgotten doses.

Adult use: Prevention of cerebral or systemic vascular obstruction by blood clot formation developed after abnormal heart rhythm and treatment of blood clots in the veins of your legs and lungs, including prevention of recurrence of blood clots in the veins of your legs and lungs

Child use: Treatment of blood clots and prevention of recurrence of blood clots

A forgotten dose can be taken up to 6 hours before the next dose.

A forgotten dose should be omitted if the time remaining before the next dose is less than 6 hours.

Do not take a double dose to make up for forgotten doses.

If you interrupt treatment with Bigetra

Take dabigatran etexilate exactly as prescribed. Do not interrupt your treatment with this medication without consulting your doctor first, as the risk of developing a blood clot may be higher if you interrupt treatment too soon.

Contact your doctor if you experience indigestion after taking dabigatran etexilate.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Dabigatran etexilate acts on blood coagulation; therefore, most adverse effects are related to signs such as bruising or bleeding.

Episodes of major or severe bleeding may occur, which are the most serious adverse effects and, regardless of their location, can cause disability, be potentially life-threatening, or even cause death. In some cases, these bleedings may not be apparent.

If you experience any episode of bleeding that does not stop by itself or if you experience signs of excessive bleeding (exceptional weakness, fatigue, pallor, dizziness, headache, or unexplained swelling), consult your doctor immediately. Your doctor may decide to keep you under close observation or change your medication.

Inform your doctor immediately if you experience a severe allergic reaction that causes

difficulty breathing or dizziness.

Possible adverse effects are listed below, grouped according to their frequency of occurrence.

Prevention of blood clot formation after knee or hip arthroplasty

Frequent (may affect up to 1 in 10 people):

• Decrease in the amount of hemoglobin in the blood (the substance present in red blood cells)
• Anomalies in liver function tests

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

• Bleeding may occur from the nose, stomach, or intestine, from the penis/vagina or urinary tract (including blood in the urine that turns the urine pink or red), from hemorrhoids, rectum, under the skin, from a joint, or after an injury or surgery
• Formation of hematomas or bruising after surgery
• Detection of blood in stool in a laboratory test
• Decrease in the number of red blood cells in the blood
• Decrease in the proportion of blood cells
• Allergic reaction
• Vomiting
• Frequent loose or liquid stools
• Feeling of nausea
• Pus discharge from a wound (discharge of liquid from a surgical wound)
• Increased liver enzymes
• Yellowish discoloration of the skin or whites of the eyes, caused by liver or blood problems

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

• Bleeding
• Bleeding may occur in the brain, at the site of a surgical incision, at the site of an injection, or at the site of a catheter in a vein
• Bloody discharge from the site of a catheter in a vein
• Coughing up blood or sputum with blood spots
• Decrease in the number of platelets in the blood
• Decrease in the number of red blood cells in the blood after surgery
• Severe allergic reaction that causes difficulty breathing or dizziness
• Severe allergic reaction that causes swelling of the face or throat
• Skin rash with dark red, prominent, and itchy bumps, caused by an allergic reaction
• Sudden change in skin color and physical appearance
• Itching
• Ulcer in the stomach or intestine (including ulcer in the esophagus)
• Inflammation of the esophagus and stomach
• Reflux of gastric juice into the esophagus
• Abdominal pain or stomach pain
• Indigestion
• Difficulty swallowing
• Fluid leaking from a wound
• Fluid leaking from a wound after surgery

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

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

Prevention of cerebral or systemic vascular obstruction by blood clot formation

developed after abnormal heart rhythm

Frequent (may affect up to 1 in 10 people):

• Bleeding may occur from the nose, stomach, or intestine, from the penis/vagina or urinary tract (including blood in the urine that turns the urine pink or red), or under the skin
• Decrease in the number of red blood cells in the blood
• Abdominal pain or stomach pain
• Indigestion
• Frequent loose or liquid stools
• Feeling of nausea

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

• Bleeding
• Bleeding may occur from hemorrhoids, rectum, or brain
• Formation of hematomas
• Coughing up blood or sputum with blood spots
• Decrease in the number of platelets in the blood
• Decrease in the amount of hemoglobin in the blood (the substance present in red blood cells)

• Allergic reaction
• Sudden change in skin color and physical appearance
• Itching
• Ulcer in the stomach or intestine (including ulcer in the esophagus)
• Inflammation of the esophagus and stomach
• Reflux of gastric juice into the esophagus
• Vomiting
• Difficulty swallowing
• Anomalies in liver function tests

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

• Bleeding may occur in a joint, at the site of a surgical incision, in a wound, at the site of an injection, or at the site of a catheter in a vein

• Severe allergic reaction that causes difficulty breathing or dizziness
• Severe allergic reaction that causes swelling of the face or throat
• Skin rash with dark red, prominent, and itchy bumps, caused by an allergic reaction
• Decrease in the proportion of blood cells
• Increased liver enzymes
• Yellowish discoloration of the skin or whites of the eyes, caused by liver or blood problems

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

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

• Hair loss

In a clinical trial, the rate of heart attacks with dabigatran etexilate was numerically higher than with warfarin. The overall incidence was low.

Treatment of blood clots in the veins of your legs and lungs, including

prevention of recurrence of blood clots in the veins of your legs and/or lungs

Frequent (may affect up to 1 in 10 people):

• Bleeding may occur from the nose, stomach, or intestine, from the rectum, from the penis/vagina or urinary tract (including blood in the urine that turns the urine pink or red), or under the skin
• Indigestion

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

• Bleeding
• Bleeding may occur in a joint or in a wound
• Bleeding may occur from hemorrhoids
• Decrease in the number of red blood cells in the blood
• Formation of hematomas
• Coughing up blood or sputum with blood spots
• Allergic reaction
• Sudden change in skin color and physical appearance
• Itching
• Ulcer in the stomach or intestine (including ulcer in the esophagus)
• Inflammation of the esophagus and stomach
• Reflux of gastric juice into the esophagus
• Feeling of nausea
• Vomiting
• Abdominal pain or stomach pain
• Frequent loose or liquid stools
• Anomalies in liver function tests
• Increased liver enzymes

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

• Bleeding may occur at the site of a surgical incision, or at the site of an injection, or at the site of a catheter in a vein or from the brain

• Decrease in the number of platelets in the blood
• Severe allergic reaction that causes difficulty breathing or dizziness
• Severe allergic reaction that causes swelling of the face or throat
• Skin rash with dark red, prominent, and itchy bumps, caused by an allergic reaction
• Difficulty swallowing

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

• Difficulty breathing or wheezing
• Decrease in the amount of hemoglobin in the blood (the substance present in red blood cells)
• Decrease in the proportion of blood cells
• Decrease in the number or even absence of white blood cells (which help fight infections)
• Yellowish discoloration of the skin or whites of the eyes, caused by liver or blood problems
• Hair loss

In the clinical trial program, the rate of heart attacks with dabigatran etexilate was higher than with warfarin. The overall incidence was low. No imbalance in the rate of heart attacks was observed in patients treated with dabigatran compared to patients treated with placebo.

Treatment of blood clots and prevention of recurrence of blood clots in children

Frequent (may affect 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 with dark red, prominent, and itchy bumps, caused by an allergic reaction
• Sudden change in skin color and physical appearance
• Formation of hematomas
• Nasal bleeding
• Reflux of gastric juice into the esophagus
• Vomiting
• Feeling of nausea
• Frequent loose or liquid stools
• Indigestion
• Hair loss
• Increased liver enzymes

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

• Decrease in the number of white blood cells (which help fight infections)
• Bleeding may occur in the stomach or intestine, from the brain, from the rectum, from the penis/vagina or urinary tract (including blood in the urine that turns the urine pink or red), or under the skin
• Decrease in the amount of hemoglobin in the blood (the substance present in red blood cells)
• Decrease in the proportion of blood cells
• Itching
• Coughing up blood or sputum with blood spots
• Abdominal pain or stomach pain
• Inflammation of the esophagus and stomach
• Allergic reaction
• Difficulty swallowing
• Yellowish discoloration of the skin or whites of the eyes, caused by liver or blood problems

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

• Absence of white blood cells (which help fight infections)
• Severe allergic reaction that causes difficulty breathing or dizziness
• Severe allergic reaction that causes swelling of the face or throat
• Difficulty breathing or wheezing
• Bleeding
• Bleeding may occur in a joint or in a wound, in a surgical incision, at the site of an injection, or at the site of a catheter in a vein
• Bleeding may occur from hemorrhoids
• Ulcer in the stomach or intestine (including ulcer in the esophagus)
• Anomalies in liver function tests

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Bigetra

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date stated on the carton or blister after "EXP". The expiration date is the last day of the month indicated.

Do not store above 30°C. Store in the original packaging to protect from light and moisture.

Medicines should not be disposed of via wastewater or household waste. Place the packaging and any unused medicines in the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Bigetra

The active ingredient is dabigatran. Each hard capsule contains 110 mg of dabigatran etexilate (in the form of mesilate).

The other ingredients are tartaric acid, arabic gum, hypromellose, dimethicone, talc, and hydroxypropylcellulose.

The capsule shell contains carrageenan, potassium chloride, titanium dioxide (E171), indigo carmine (E132), water, and hypromellose.

The black printing ink contains shellac, iron oxide black (E172), and potassium hydroxide.

Appearance and Package Contents of the Product

Bigetra 110 mg is presented in the form of hard capsules with a blue opaque cap with "D110" printed in black and a blue opaque body, which contain yellowish granules.

This medicine is presented in cardboard boxes containing 10, 30, 60, 100, or 180 hard capsules in Poliamide/Aluminum/PVC//Aluminum blisters.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Adamed Laboratorios, S.L.U.

c/ de las Rosas de Aravaca, 31 - 2ª planta

28023 Madrid

Spain

Manufacturer

Adamed Pharma S.A.

Ul. Marszalka Jósefa Pilsudskiego 5

95-200 Pabianice, Lodzkie

Poland

This medicine is authorized in the Member States of the European Economic Area under the following names:

Date of the last revision of this leaflet: February 2024

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)