Danengo

Package leaflet: Information for the patient

Danengo, 75 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, as you may need to read it again.
• 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. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

1. What Danengo is and what it is used for
2. Important information before taking Danengo
3. How to take Danengo
4. Possible side effects
5. How to store Danengo
6. Contents of the pack 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 responsible for blood clot formation.
Danengo is used in adults for:

• preventing the formation of blood clots in veins following hip or knee replacement surgery.

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 currently has bleeding.
• if the patient has an internal organ disease that increases the risk of major bleeding (e.g. gastric ulcer, brain injury or intracranial bleeding, recent brain or eye surgery).
• if the patient has an increased tendency to bleed, which 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 a catheter ablation procedure for atrial fibrillation to restore normal heart rhythm.
• if the patient has severe impairment of liver function 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 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 an artificial heart valve implanted, which requires continuous use of blood-thinning medicines.

Warnings and precautions
Before starting treatment with Danengo, discuss this with your doctor. If symptoms occur or the patient has undergone surgery during treatment with this medicine, consult a doctor.
The patient should inform the doctor if they have or have 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 oesophagus or stomach.
• if the patient has gastro-oesophageal reflux (backflow of stomach acid into the oesophagus).
• if the patient is taking medicines that may increase the risk of bleeding. See below "Danengo with 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] 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 has conditions diagnosed as 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 special 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 injection into the spine (e.g. for epidural or spinal anaesthesia 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 the bowel or bladder occur after the anaesthetic wears off, as urgent medical care is required.
• if the patient falls or injures themselves 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 immune system disorder causing increased risk of blood clots), the patient should inform the doctor, who will decide whether treatment needs to be changed.

Danengo with 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 must inform the doctor before taking Danengo 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 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 Danengo depending on the condition for which the medicine was prescribed. See also 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-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 unknown what effect Danengo has on pregnancy and the unborn child. This medicine should not be taken during pregnancy unless the doctor determines it is safe. Women of childbearing potential should avoid becoming pregnant while taking Danengo.
Breastfeeding should not be undertaken during treatment with Danengo.

Driving and operating machinery
Danengo has no effect or a negligible effect on the ability to drive 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.
There are other age-appropriate pharmaceutical forms available for treating children under 8 years of age.
This medicine should always be taken according to the doctor's instructions. If in doubt, consult your doctor.
Take Danengo exactly as described below:

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 each).
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 each).
In patients taking medicines containing amiodarone, quinidine, or verapamil, the recommended dose of Danengo is 150 mg once daily (taken as 2 capsules of 75 mg each).
Patients taking verapamil-containing medicines who also have renal function reduced by more than half should take a reduced dose of 75 mg of Danengo due to an increased risk of bleeding.

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

After knee replacement surgery
Treatment with Danengo should be initiated by taking one capsule within 1 to 4 hours after completion of surgery. Then, take 2 capsules once daily for a total of 10 days.

After hip replacement surgery
Treatment with Danengo should be initiated by taking one capsule within 1 to 4 hours after completion of surgery. Then, take 2 capsules once daily for a total of 28 to 35 days.

Treatment of blood clots and prevention of recurrence 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 your doctor advises otherwise.

Table 1 shows the single and total daily doses of Danengo in milligrams (mg).
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 can 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.

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 into 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 receiving detailed instructions from your doctor.

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

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

Treatment 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 the missed dose.

Stopping Danengo treatment
Danengo should be taken as directed by the doctor. Do not stop taking Danengo without first consulting your doctor, as the risk of developing a blood clot 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 effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Danengo affects the blood clotting system; therefore, most adverse effects are related to symptoms such as bruising or bleeding.
Serious or extensive 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 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. Your 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.

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):

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

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

• Bleeding from the nose, stomach or intestines, penis or vagina or urinary tract (including pink or red urine due to presence of blood), from haemorrhoids, from the rectum, under the skin, into joints, following injury or after a surgical procedure
• Bruising or haematomas occurring after surgery
• Blood in stool detected in laboratory tests
• Decreased number of red blood cells in the blood
• Decreased proportion 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 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
• Decreased platelet count in the blood
• Decreased red blood cell count 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 not known (frequency cannot be estimated from available data):

• Difficulty breathing or wheezing
• Decreased or even absent 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):

• Decreased number of red blood cells in the blood
• Decreased platelet count in the blood
• Skin rash consisting of dark red, raised, itchy bumps due to an allergic reaction
• Sudden change in skin colour and appearance
• Bruising
• 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):

• Decreased white blood cell count (which help fight infections)
• Bleeding into the stomach or intestines, brain, rectum, penis or vagina or urinary tract (including pink or red urine due to presence of blood), or under the skin
• Decreased haemoglobin levels in the blood (substance in red blood cells)
• Decreased proportion of blood cells
• 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 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 into joints, from wounds, surgical incision sites, injection sites, or sites of intravenous catheter insertion
• Bleeding from haemorrhoids
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Abnormal liver function test results in laboratory examinations

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 the Department of Monitoring Adverse Drug Reactions at 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 effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps provide more information on the safety of the medicine.

5. How to store Danengo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton, blister, or container label after: EXP. The expiry date refers to the last day of the stated month.
Blister:
No special temperature storage instructions for this medicine.
Store in the original packaging to protect from light and moisture.
Container:
No special temperature storage instructions 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 the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the package and other information

What Danengo contains

• The active substance is dabigatran etexilate. Each hard capsule contains 75 mg of dabigatran etexilate (as mesylate).
• The other components (excipients) are:

contents of the capsule: tartaric acid (pellets), hypromellose (6 mPa*s), hydroxypropylcellulose (470 mPa*s), and talc;
capsule shell: titanium dioxide (E 171), carrageenan, potassium chloride, hypromellose (type 2910);
printing ink: shellac, iron oxide black (E 172), potassium hydroxide.

What Danengo looks like and contents of the pack

Danengo 75 mg hard capsules: The capsule cap is white or almost white, the capsule body is white or almost white, with a black "75" printed longitudinally, approximately 18 mm in length.
The capsule contents are off-white to pale yellow pellets.

Danengo 75 mg hard capsules are available in cardboard packs containing:

• 10 x 1, 30 x 1, 60 x 1, 100 x 1, or multipacks containing 100 (2 packs of 50 x 1) or 180 (3 packs of 60 x 1) hard capsules in perforated, single-dose, peelable blisters.
• 60 hard capsules in a container with a child-resistant cap, or 3 containers each containing 60 hard capsules with a 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 about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warszawa
telephone: + 48 22 573 75 00