DANENGO

Patient Information Leaflet

Danengo, 150 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 ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Leaflet Contents

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

1. What Danengo is and what it is used for

Danengo 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 involved in blood clot formation.
Danengo is used in adults for:

• preventing blood clots in the brain (stroke) and in other blood vessels of the body in patients who have 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 such clots.

Danengo is used in children for:

• treatment of blood clots and prevention of recurrence of blood clots.

2. Important information before taking Danengo

When not to take Danengo

• 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 impairment of kidney function.
• if the patient is currently experiencing bleeding.
• if the patient has an internal organ disease that increases the risk of major bleeding (e.g. stomach 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, when heparin is administered through the catheter to maintain its patency, or during restoration of normal heart rhythm by a procedure called catheter ablation in atrial fibrillation.
• if the patient has severe impairment of liver function or liver disease that may lead to death.
• if the patient is taking ketoconazole or itraconazole orally, medicines used to treat fungal infections.
• if the patient is taking cyclosporine, a medicine used to prevent rejection of a transplanted organ.
• 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 Danengo, discuss this with your doctor or pharmacist. 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 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 “Danengo and other medicines”.
• if the patient is taking nonsteroidal anti-inflammatory drugs 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) and/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 heart attack or if the patient has been diagnosed with conditions increasing the risk of heart attack.
• if the patient has liver disease affecting blood test results. In such cases, Danengo is not recommended.

When to exercise particular caution when taking Danengo

• if the patient needs to undergo surgery: in such cases, temporary discontinuation of Danengo is necessary due to increased risk of bleeding during and immediately after surgery. It is very important to take Danengo exactly as directed by the doctor before and after surgery.

• if surgery requires insertion of a catheter or administration of a spinal injection (e.g. for epidural or spinal anesthesia or for pain relief):

• it is very important to take Danengo 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 anesthesia 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 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 the doctor, who will decide whether treatment adjustment is needed.

Danengo and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. In particular, tell the doctor before taking Danengo 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 medicines are used only topically on 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 Danengo depending on the condition for which it was prescribed. See section 3.
• Medicines used to prevent rejection of a transplanted organ (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 Danengo has on pregnancy or the unborn child. Do not take Danengo during pregnancy unless the doctor determines it is safe. Women of childbearing potential should avoid becoming pregnant while taking Danengo.
Breastfeeding is not recommended during treatment with Danengo.

Driving and using machines
Danengo has no effect or has a negligible effect on the ability to drive vehicles and operate machinery.

3. How to take Danengo

Danengo can be used in adults and children aged 8 years or older who are able to swallow capsules whole.
Other age-appropriate formulations are available for the treatment of children under 8 years of age.
This medicine should always be taken exactly as prescribed by the doctor. In case of doubt, consult your doctor.
Danengo should be taken according to the following recommendations:
Prevention of thromboembolism in blood vessels of the brain and body by preventing the formation of blood clots that occur due to irregular heart function, and 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 older, the recommended dose of Danengo is 220 mg taken as one 110 mg capsule twice daily.
Patients taking medicines containing verapamil should receive a reduced dose of Danengo 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 Danengo at a dose of 220 mg taken as one 110 mg capsule twice daily.
Treatment with Danengo may be continued if the patient requires restoration of normal heart function through a procedure called cardioversion or through a procedure called catheter ablation for atrial fibrillation. Danengo 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 called percutaneous coronary intervention with stent implantation, the patient may receive treatment with Danengo after the doctor has confirmed adequate control of blood coagulation. Danengo should be taken as directed by the doctor.
Treatment of blood clots and prevention of recurrent blood clots in children
Danengo 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 the doctor advises otherwise.
Table 1 shows the single and total daily doses of Danengo in milligrams (mg).
The doses depend on the patient's body weight in kilograms (kg) and age in years.
Table 1: Dosing table for Danengo capsules

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

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

Instructions for opening blisters
The pictogram below shows how to remove Danengo capsules from the blister pack.
To remove a capsule from the blister:

1. Hold the blister by the edges and separate one blister cell from the rest of the blister by gently bending and tearing along the perforation around it.
2. Lift the edge of the foil and completely peel it back.
3. Push the capsule out onto your hand.
4. Swallow the capsule whole with a glass of water.
   • Do not push the capsule through the blister foil.
   • Do not peel back the foil until the capsule is needed.

Instructions for opening the container

• To open the container, press down and turn the cap.
• After removing a capsule and taking the dose, immediately close the container tightly with the cap.

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

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

Missed dose of Danengo
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 until 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 Danengo treatment
Danengo should be taken exactly as prescribed by the doctor. Do not stop taking Danengo without first consulting your doctor, as the risk of blood clot formation may be higher if treatment is stopped prematurely. Contact your doctor if you experience gastrointestinal discomfort after taking Danengo.

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

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Danengo affects the blood clotting system, so most adverse reactions are related to symptoms such as bruising or bleeding.
Severe or major bleeding may occur, which is the most serious adverse reaction. 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 you experience bleeding 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 you under close observation or change your treatment.
In case of a serious allergic reaction, which may cause difficulty breathing or dizziness, contact your doctor immediately.

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

Prevention of thromboembolism in blood vessels of the brain and body by preventing the formation of clots that occur due to 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 or vagina, or from the urinary tract (including pink or red 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 haemorrhoids, from the rectum, or into the brain
• Formation of bruises
• Coughing up blood or blood-stained sputum
• Decrease in the number of platelets in the blood
• Decrease in haemoglobin content in the blood (the substance in red blood cells)
• Allergic reaction
• Sudden change in skin color and appearance
• Itching
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Inflammation of the oesophagus and stomach
• Regurgitation of food from the stomach into the oesophagus (reflux)
• Vomiting
• Difficulty swallowing
• Abnormal liver function test results in laboratory tests

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

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

Frequency 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 studies, the number of heart attacks with dabigatran etexilate was numerically higher than with warfarin. The overall number of events was small.

Treatment of blood clots in the legs and lungs, and prevention of recurrence of blood clots in the legs and/or 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 or vagina or urinary tract (including pink or red 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 injury
• Bleeding from haemorrhoids may occur
• Decrease in the number of red blood cells in the blood
• Formation of bruises
• Coughing up blood or blood-stained sputum
• Allergic reaction
• Sudden change in skin color and appearance
• Itching
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Inflammation of the oesophagus and stomach
• Regurgitation of food from the stomach into the oesophagus (reflux)
• Nausea
• Vomiting
• Abdominal pain or stomach pain
• Frequent passage of loose or watery stools
• Abnormal liver function test results in laboratory tests
• Increase in liver enzyme activity

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

• Bleeding may occur from a surgical incision site, or from an injection site or site of intravenous catheter insertion, or bleeding from 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 characterized by dark red, raised, itchy bumps due to an allergic reaction
• Difficulty swallowing

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

• Difficulty breathing or wheezing
• Decrease in haemoglobin content in the blood (substance in red blood cells)
• Decrease in blood cell count
• 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 studies, the number of heart attacks with dabigatran etexilate was numerically higher than with warfarin. The overall number of events was low. No difference in the number of heart attacks 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 characterized by dark red, raised, itchy bumps due to an allergic reaction
• Sudden change in skin color and appearance
• Formation of bruises
• Nosebleeds
• Regurgitation of food from the stomach into the oesophagus (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 anus, from the penis or vagina or urinary tract (including pink or red urine due to presence of blood), or bleeding under the skin
• Decrease in haemoglobin content in the blood (substance in red blood cells)
• Decrease in blood cell count
• 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 disease or blood disorders

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

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

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

5. How to store Danengo

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton, blister, or container label following EXP. The expiry date refers to the last day of the stated month.
Blister:
No special temperature storage requirements for this medicine.
Store in the original packaging to protect from light and moisture.
Container:
No special temperature storage requirements for this medicine.
Store in the original packaging to protect from light and moisture.
Keep the container tightly closed.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

What Danengo contains

• The active substance is dabigatran etexilate. Each hard capsule contains 150 mg of dabigatran etexilate (as mesilate).
• The other ingredients (excipients) are: capsule contents: tartaric acid (pellets), hypromellose (6 mPa*s), hydroxypropyl cellulose (470 mPa*s), and talc; capsule shell: titanium dioxide (E 171), indigo carmine (E 132), carrageenan, potassium chloride, hypromellose (type 2910); printing ink: shellac, black iron oxide (E 172), potassium hydroxide.

What Danengo looks like and contents of the pack
Danengo 150 mg hard capsules: The capsule cap is blue, the body is white or almost white, printed longitudinally in black with the mark "150", approximately 24 mm in length.
The capsule contents consist of off-white to pale yellow pellets.
Danengo 150 mg hard capsules are available in cardboard boxes containing:

• 10 x 1, 30 x 1, 60 x 1, 100 x 1, or multi-packs of 100 (2 packs of 50 x 1) or 180 (3 packs of 60 x 1) hard capsules in peelable, single-dose perforated blisters.
• 60 hard capsules in a child-resistant closure container or 3 containers each containing 60 hard capsules with child-resistant closure.

Not all pack sizes may be marketed.
Marketing Authorisation Holder
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany
Manufacturer/Importer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warsaw, Poland
telephone: +48 22 573 75 00