Danengo

Package leaflet: Information for the patient

Danengo, 110 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 doubts, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are identical.
• If the patient experiences any adverse reactions, including any adverse reactions 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 after hip or knee replacement surgery.
• preventing the formation of blood clots in the brain (stroke) and in other blood vessels in patients with a type of irregular heart rhythm called 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.

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 kidney function impairment.
• if the patient is currently experiencing bleeding.
• if the patient has an internal organ disease that increases the risk of major bleeding (e.g. gastric ulcer, brain injury or intracranial hemorrhage, recent surgery on the brain or eyes).
• 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 procedure called catheter ablation for atrial fibrillation.
• if the patient has severe liver function impairment or liver disease that may lead to death.
• if the patient is taking oral ketoconazole or itraconazole, 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 fixed-dose 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 Danengo, discuss this with your doctor. If symptoms occur or the patient has undergone a surgical procedure while taking this medicine, consult a doctor.
The patient should inform the doctor if they currently have or have previously had any medical conditions or diseases, especially those listed below:

• if the patient has an increased risk of bleeding, such as:
• if the patient has recently experienced bleeding.
• if the patient has undergone a surgical 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 (acid reflux into the esophagus).
• if the patient is taking medicines that may increase the risk of bleeding. See below "Danengo with other medicines".
• if the patient is taking nonsteroidal anti-inflammatory drugs such as diclofenac, ibuprofen, piroxicam.
• if the patient has an infection within 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 frothy urine).
• if the patient is over 75 years of age.
• if the patient is an adult weighing 50 kg or less.
• only when used in children: if the child has an infection around or within the brain.
• if the patient has had a previous heart attack or has conditions diagnosed that increase the risk of heart attack.
• if the patient has liver disease affecting blood test results. In such a case, Danengo is not recommended.

When to exercise special caution when taking Danengo

• if the patient needs to undergo surgery: in such a case, 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 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 legs or problems with bowel or bladder function occur after the anesthesia wears off, as urgent medical care may be needed.
• if the patient falls or injures themselves during treatment, especially if the head is injured. Immediate medical attention should be sought. The doctor will assess whether there may be 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 their doctor, who will decide whether a change in treatment is necessary.

Danengo with 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, the patient should 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, itraconazol), unless these medicines are applied only topically 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 Danengo was prescribed. See section 3.
• Medicines used to prevent rejection of transplanted organs (e.g. tacrolimus, cyclosporine).
• A fixed-dose 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 and the unborn child. Do not take Danengo during pregnancy unless your doctor determines it is safe. Women of childbearing potential should avoid becoming pregnant while taking Danengo.
Breastfeeding must 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.
Other age-appropriate formulations are available for treating 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.
Take Danengo exactly as directed below:

Prevention of blood clots after hip or knee replacement surgery (arthroplasty)
The recommended dose is 220 mg once daily (taken as 2 capsules of 110 mg).
If renal function is reduced by more than half, or in patients aged 75 years or older, the recommended dose is 150 mg once daily (taken as 2 capsules of 75 mg).
In patients taking medicines containing amiodarone, quinidine, or verapamil, the recommended dose of Danengo is 150 mg once daily (taken as 2 capsules of 75 mg).
Patients taking medicines containing verapamil and who have renal function reduced by more than half should take a reduced dose of Danengo 75 mg due to an increased risk of bleeding.

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

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

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

Prevention of thromboembolic events in blood vessels of the brain and body by preventing clot formation due to abnormal heart function, and treatment and prevention of recurrence of blood clots in leg veins and lungs
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 Danengo at a reduced dose of 220 mg, taken as one 110 mg capsule twice daily, due to a possible 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 rhythm through a procedure called cardioversion. Danengo should be taken exactly as prescribed 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 Danengo after the doctor confirms adequate control of blood coagulation. Danengo should be taken exactly as prescribed by the doctor.

Treatment 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 your 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: Dosage 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: as two 110 mg capsules
185 mg: as one 75 mg capsule and one 110 mg capsule
150 mg: as 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 crush,
chew or empty the pellets from the capsule, as this may increase the risk of bleeding.
Instructions for opening blisters
The following pictogram illustrates 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 strip by gently bending and tearing along the perforation around it.
2. Lift the edge of the foil and completely peel it off.
3. Push the capsule out onto your hand.
4. Swallow the capsule whole with a glass of water.
   • Do not push capsules through the blister foil.
   • Do not peel off 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 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
Prevention of blood clots after hip or knee replacement surgery
Continue taking the missed daily dose of Danengo at the usual time on the following day. Do not take a double dose to make up for a missed dose.
Use in adults: Prevention of blood clots in the brain and body by preventing formation of clots caused by 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
Use in children: Treatment of blood clots and prevention of recurrence of blood clots
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, 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 as prescribed by the doctor. Do not stop taking Danengo without first consulting your doctor, as the risk of developing a blood clot may be greater if treatment is stopped prematurely. Contact your doctor if gastrointestinal discomfort occurs 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 experiences them.
Danengo affects the blood clotting system; therefore, most adverse effects involve symptoms such as bruising or bleeding.
Severe or major bleeding may occur, which is the most serious adverse effect. Regardless of location, it may lead to disability, be life-threatening, or even result in death. In some cases, these bleedings may not be visible.
If 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 (a substance in red blood cells)
• Abnormal liver function test results

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

• Bleeding may occur from the nose, into the stomach or intestines, from the 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 a joint, following injury or after a surgical procedure
• Development of haematomas or bruising after surgery
• Blood in stool detected in laboratory tests
• Decreased number of red blood cells in the blood
• Decreased blood cell count
• Allergic reaction
• Vomiting
• Frequent passage of loose or watery stools
• Nausea
• Discharge from the wound (leakage of fluid from the 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, from the injection site, or from the site of intravenous catheter insertion
• Blood-tinged discharge from the intravenous catheter insertion site
• Coughing up blood or blood-tinged sputum
• Decreased platelet count in the blood
• Decreased number of red blood cells 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
• Discharge of fluid from the wound
• Discharge of fluid from the surgical wound

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

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

Prevention of blood clots in blood vessels of the brain and body by preventing formation of clots 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 urinary tract (including pink or red urine due to presence of blood), or under the skin
• Decreased 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 haematomas
• Coughing up blood or blood-tinged sputum
• Decreased platelet count in the blood
• Decreased haemoglobin levels in the blood (a substance in red blood cells)
• 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)
• Vomiting
• Difficulty swallowing
• Abnormal liver function test results

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

• Bleeding into a joint, from the surgical incision site, from a wound, from the 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
• Decreased blood cell count
• Increased 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
• Decreased 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 low.

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 under the skin
• Indigestion

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

• Bleeding
• Bleeding into a joint or following injury
• Bleeding from haemorrhoids
• Decreased number of red blood cells in the blood
• Formation of haematomas
• Coughing up blood or blood-tinged sputum
• 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)
• Nausea
• Vomiting
• Abdominal pain or stomach pain
• Frequent passage of loose or watery stools
• Abnormal liver function test results
• Increased liver enzyme activity

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

• Bleeding from the surgical incision site, from the injection site, from the site of intravenous catheter insertion, or into the brain
• Decreased platelet count 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

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

• Difficulty breathing or wheezing
• Decreased haemoglobin levels in the blood (a substance in red blood cells)
• Decreased blood cell count
• Decreased 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 compared to those receiving placebo.

Treatment and prevention of recurrence of 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
• Formation of haematomas
• 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 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 under the skin
• Decreased haemoglobin levels in the blood (a substance in red blood cells)
• Decreased blood cell count
• Itching
• Coughing up blood or blood-tinged 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 into a joint, from a wound, from the surgical incision site, from the injection site, or from the site of intravenous catheter insertion
• Bleeding from haemorrhoids
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Abnormal liver function test results

Reporting of adverse effects
If you experience any adverse effects, including any not listed in this leaflet, tell your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring of 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 effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps provide more information on the safety of this 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 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 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 packaging and other information

What Danengo contains

• The active substance is dabigatran etexilate. Each hard capsule contains 110 mg of dabigatran etexilate (as mesilate).
• The other components (excipients) are: capsule contents: tartaric acid (pellets), hypromellose (6 mPa*s), hydroxypropylcellulose (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 110 mg hard capsules: the capsule cap is blue, the body is blue, printed longitudinally in black with "110", approximately 19 mm in length.
The capsule contents are off-white to pale yellow pellets.
Danengo 110 mg hard capsules are available in cardboard packs containing:

• 10 x 1, 30 x 1, 60 x 1, 100 x 1, or bulk packs of 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 cap.

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 Warsaw, Poland
telephone: +48 22 573 75 00