Dabigatran etexilate orion: detailed information

Package leaflet: Information for the patient

Dabigatran etexilate Orion, 110 mg, hard capsules
Dabigatranum etexilatum
Please read the entire leaflet carefully 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 further questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are similar.
If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

What Dabigatran etexilate Orion is and what it is used for
Important information before taking Dabigatran etexilate Orion
How to take Dabigatran etexilate Orion
Possible side effects
How to store Dabigatran etexilate Orion
Contents of the pack and other information

1. What Dabigatran etexilate Orion is and what it is used for

Dabigatran etexilate Orion 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.

Dabigatran etexilate Orion is used in adults for:

preventing the formation of blood clots in veins after hip or knee replacement surgery
preventing stroke (blood clots in the brain) and other blood clots in 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 legs and lungs, and preventing recurrence of such clots.

Dabigatran etexilate Orion is used in children for:

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

2. Important information before taking Dabigatran etexilate Orion

When not to take Dabigatran etexilate Orion

if the patient is allergic to dabigatran etexilate or any of the other ingredients of this medicine (listed in section 6)
if the patient has severe kidney function impairment
if the patient is currently experiencing bleeding
if the patient has a disease of any internal organ which increases the risk of major bleeding (e.g. gastric ulcer, brain injury or intracranial haemorrhage, recent brain or eye surgery)
if the patient has an increased tendency to bleed, 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 where heparin is administered via the catheter to maintain its patency, or during a procedure called catheter ablation for atrial fibrillation to restore normal heart rhythm
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 Dabigatran etexilate Orion, 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 the following:

if the patient has an increased risk of bleeding, such as:
if the patient has recently experienced bleeding
if the patient has undergone a surgical tissue biopsy within the last month
if the patient has suffered a serious injury (e.g. bone fracture, head injury, or any injury requiring surgical treatment)
if the patient has oesophagitis or gastritis
if the patient has gastro-oesophageal reflux disease (acid reflux)
if the patient is taking medicines that may increase the risk of bleeding. See below "Dabigatran etexilate Orion and other medicines"
if the patient is taking non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, ibuprofen, piroxicam
if the patient has an infection of the heart (bacterial endocarditis)
if the patient has reduced kidney function or is dehydrated (feeling thirsty and passing reduced amounts of dark (concentrated) or 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 if the patient has been diagnosed with a condition that increases the risk of myocardial infarction
if the patient has liver disease affecting blood test results. In such cases, use of this medicine is not recommended.

When to exercise particular caution when taking Dabigatran etexilate Orion

if the patient needs to undergo surgery: In such cases, temporary discontinuation of Dabigatran etexilate Orion is necessary due to the increased risk of bleeding during and immediately after surgery. It is very important to take Dabigatran etexilate Orion before and after surgery exactly as directed by the doctor.
if the surgical procedure 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 Dabigatran etexilate Orion before and after surgery exactly as directed by the doctor.
The patient should immediately inform the doctor if numbness or weakness in the legs, or bowel or bladder problems occur after the anaesthetic wears off, as urgent medical attention is required.
if the patient has fallen or sustained an injury during treatment, especially if the head was injured. Immediate medical attention should be sought. 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 a change in treatment is necessary.

Dabigatran etexilate Orion 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, the patient should tell the doctor before taking Dabigatran etexilate Orion 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 Dabigatran etexilate Orion depending on the condition for which the medicine was prescribed. See section 3.
medicines used to prevent rejection of a transplanted organ (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 called 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 unknown what effect Dabigatran etexilate Orion has on pregnancy and the unborn child. This medicine should not be taken during pregnancy unless the doctor considers it safe. Women of childbearing potential should use effective contraception to prevent pregnancy while taking Dabigatran etexilate Orion.
Breastfeeding is not recommended during treatment with Dabigatran etexilate Orion.

Driving and using machines
Dabigatran etexilate Orion has no effect or negligible effect on the ability to drive and use machines.

Excipients
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. this medicine is considered "sodium-free".

3. How to take Dabigatran etexilate Orion

Dabigatran etexilate Orion capsules can be used in adults and children aged 8 years or older who are able to swallow capsules whole. Other age-appropriate pharmaceutical forms 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 the doctor.
Dabigatran etexilate Orion should be taken according to the following recommendations:

Prevention of blood clots after surgery (joint replacement) of the hip or knee
The recommended dose is 220 mg once daily (taken as 2 capsules of 110 mg).
If kidney 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 medications containing amiodarone, quinidine, or verapamil, the recommended dose of Dabigatran etexilate Orion is 150 mg once daily (taken as 2 capsules of 75 mg).
Patients taking medications containing verapamil who also have reduced kidney function by more than half should take a reduced dose of 75 mg of Dabigatran etexilate Orion due to an increased risk of bleeding.

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

After knee joint replacement surgery
Treatment with Dabigatran etexilate Orion should begin with one capsule taken within 1 to 4 hours after completion of the surgical procedure. Then, two capsules once daily should be taken for a total of 10 days.

After hip joint replacement surgery
Treatment with Dabigatran etexilate Orion should begin with one capsule taken within 1 to 4 hours after completion of the surgical procedure. Then, two capsules once daily should be taken for a total of 28 to 35 days.

Prevention of blood clots in blood vessels of the brain and body by preventing clot formation due to irregular heart function, and treatment and prevention of recurrent blood clots in the veins of the legs 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 is 220 mg, taken as one 110 mg capsule twice daily.
Patients taking medications containing verapamil should receive a reduced dose of Dabigatran etexilate Orion 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 a dose of 220 mg, taken as one 110 mg capsule twice daily.

Treatment with this medicine may be continued if the patient requires restoration of normal heart rhythm through a procedure called cardioversion. Dabigatran etexilate Orion should be taken according to the doctor's instructions.

In 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 Dabigatran etexilate Orion after the doctor confirms adequate control of blood coagulation. Dabigatran etexilate Orion should be taken according to the doctor's instructions.

Treatment and prevention of recurrent blood clots in children
Dabigatran etexilate Orion should be taken twice daily, one dose in the morning and one in the evening, approximately at the same time each day. The interval between doses should be as close as possible to 12 hours.
The recommended dose depends on body weight and age. The doctor will determine the correct dose and may adjust it during treatment. All other prescribed medications should be continued unless the doctor advises otherwise.

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

Table 1: Dosing table for Dabigatran etexilate Orion capsules

Body weight and age ranges		Single dose in mg	Total daily dose in mg
Body weight in kg	Age in years	Single dose in mg	Total daily dose in mg
from 11 to less than 13 kg	from 8 to less than 9 years	75	150
from 13 to less than 16 kg	from 8 to less than 11 years	110	220
from 16 to less than 21 kg	from 8 to less than 14 years	110	220
from 21 to less than 26 kg	from 8 to less than 16 years	150	300
from 26 to less than 31 kg	from 8 to less than 18 years	150	300
from 31 to less than 41 kg	from 8 to less than 18 years	185	370
from 41 to less than 51 kg	from 8 to less than 18 years	220	440
from 51 to less than 61 kg	from 8 to less than 18 years	260	520
from 61 to less than 71 kg	from 8 to less than 18 years	300	600
from 71 to less than 81 kg	from 8 to less than 18 years	300	600
81 kg or more	from 10 to less than 18 years	300	600

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 Dabigatran etexilate Orion
Dabigatran etexilate Orion can 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.
Switching anticoagulant medication
Do not switch anticoagulant medication without receiving detailed instructions from your doctor.
Taking more Dabigatran etexilate Orion than prescribed
Taking too high a dose of this medicine increases the risk of bleeding. If a patient has taken too many capsules, contact a doctor immediately. Specific treatment methods are available.
Missed dose of Dabigatran etexilate Orion
Prevention of blood clots after surgery (hip or knee replacement)
Continue taking the missed daily dose of Dabigatran etexilate Orion 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 blood vessels of the brain and body by preventing formation of clots caused by irregular heart rhythm, 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 Dabigatran etexilate Orion
Dabigatran etexilate Orion should be taken according to the doctor's instructions. Do not stop taking this medicine 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 gastrointestinal discomfort occurs after taking Dabigatran etexilate Orion.
If you have any further doubts regarding the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Dabigatran etexilate Orion affects the blood clotting system, therefore most of the
side effects are related to symptoms such as bruising or bleeding. Severe or major
bleeding may occur, which is the most serious side effect and, regardless of location, may
lead to disability, be life-threatening, or even result in death. In some cases, these
bleedings may not be visible.
If bleeding that does not stop spontaneously occurs, or symptoms of excessive
bleeding (unusual weakness, fatigue, paleness, dizziness, headache or unexplained
swelling) appear, contact your doctor immediately. The doctor may decide to place the patient
under close observation or change the treatment.
In case of a serious allergic reaction, which may cause difficulty
in breathing or dizziness, contact your doctor immediately.
The possible side 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 ):

decrease in haemoglobin levels in the blood (a substance in red blood cells)
abnormal liver function test results in laboratory tests.

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

bleeding may occur from the nose, into the stomach or intestines, from the penis/vagina or urinary tract (including pink or red-coloured urine due to presence of blood), from haemorrhoids, from the rectum, under the skin, into a joint, due to injury or after injury or surgery
formation of haematomas or bruising occurring after surgery
blood in stool detected in laboratory tests
decrease in the number of red blood cells in the blood
decrease in the number of blood cells
allergic reaction
vomiting
frequent passage of loose or watery stools
nausea
presence of discharge from the wound (oozing of fluid from the surgical wound)
increased liver enzyme activity
yellowing of the skin or whites of the eyes caused by liver or blood disease.

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

bleeding
bleeding may occur 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 site of intravenous catheter insertion
coughing up blood or blood-tinged sputum
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 causing difficulty breathing or dizziness
severe allergic reaction causing swelling of the face or throat
skin rash consisting of dark red, raised, itchy bumps occurring as a result of 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 the wound
fluid discharge from the surgical wound.

Not known ( frequency cannot be estimated from the available data ):

difficulty breathing or wheezing
decrease in number or even absence of white blood cells (which help fight infections)
hair loss.

In clinical trials, the number of myocardial infarctions with dabigatran use was
quantitatively higher than with warfarin use. The overall number of such events was
low.

Prevention of blood clots in the brain and body by preventing formation of clots caused by irregular heart rhythm
Common ( may occur in up to 1 in 10 people ):

bleeding may occur from the nose, into the stomach or intestines, from the penis/vagina or urinary tract (including pink or red-coloured urine due to presence of blood), or 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 haematomas
coughing up blood or blood-tinged sputum
decrease in the number of platelets in the blood
decrease in 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 in laboratory tests.

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

bleeding may occur 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 occurring as a result of an allergic reaction
decrease in the number of blood cells
increased liver enzyme activity
yellowing of the skin or whites of the eyes caused by liver or blood disease.

Not known ( frequency cannot be estimated from the available data ):

difficulty breathing or wheezing
decrease in number or even absence of white blood cells (which help fight infections)
hair loss.

In clinical trials, the number of myocardial infarctions with dabigatran use was
quantitatively higher than with warfarin use. The overall number of such events was
low.

Treatment of blood clots in the legs and lungs, and prevention of recurrence of blood clots in the legs and lungs
Common ( may occur in up to 1 in 10 people ):

bleeding may occur from the nose, into the stomach or intestines, from the anus, from the penis/vagina or urinary tract (including pink or red-coloured urine due to presence of blood), or under the skin
indigestion.

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

bleeding
bleeding may occur into a joint or due to injury
bleeding may occur from haemorrhoids
decrease in the 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 in laboratory tests
increased liver enzyme activity.

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

bleeding may occur from the surgical incision site, from the injection site or from the site of intravenous catheter insertion, or bleeding into the brain
decrease in the number of platelets in the blood
severe allergic reaction causing difficulty breathing or dizziness
severe allergic reaction causing swelling of the face or throat
skin rash consisting of dark red, raised, itchy bumps occurring as a result of an allergic reaction
difficulty swallowing.

Not known ( frequency cannot be estimated from the available data ):

difficulty breathing or wheezing
decrease in haemoglobin levels in the blood (a substance in red blood cells)
decrease in the number of blood cells
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 or blood disease
hair loss.

In clinical trials, the number of myocardial infarctions with dabigatran use was
quantitatively higher than with warfarin use. The overall number of such events was
low. No difference in the number of myocardial infarctions was observed in patients treated with dabigatran compared to patients receiving placebo.

Treatment of blood clots and prevention of recurrent blood clots in children
Common ( may occur in up to 1 in 10 people ):

decrease in the number of red blood cells in the blood
decrease in the number of platelets in the blood
skin rash consisting of dark red, raised, itchy bumps occurring as a result of 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 ):

decrease in the number of white blood cells (which help fight infections)
bleeding may occur into the stomach or intestines, into the brain, from the rectum, from the penis/vagina or urinary tract (including pink or red-coloured urine due to presence of blood), or under the skin
decrease in haemoglobin levels in the blood (a substance in red blood cells)
decrease in the number of blood cells
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 or blood disease.

Not known ( frequency cannot be estimated from the 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 the surgical incision site, from the injection site or from the site of intravenous catheter insertion
bleeding may occur from haemorrhoids
stomach or intestinal ulcer (including oesophageal ulceration)
abnormal liver function test results in laboratory tests.

Reporting of side effects
If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. Side 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
Side effects can also be reported to the marketing authorisation holder. Reporting side effects helps provide more information on the safety of the medicine.

5. How to store Dabigatran etexilate Orion

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton or blister pack following:
"Expiry date (EXP)". The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Medicines must not be disposed of via the sewage system. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Dabigatran etexilate Orion contains

The active substance is dabigatran etexilate. Each hard capsule contains dabigatran etexilate in the form of mesilate, equivalent to 110 mg of dabigatran etexilate.
The other ingredients are: tartaric acid, hypromellose, talc, hydroxypropylcellulose, sodium croscarmellose and magnesium stearate.
The capsule shell contains titanium dioxide (E 171) and hypromellose.
The black printing ink contains shellac, propylene glycol (E 1520), iron oxide black (E 172) and potassium hydroxide.

What Dabigatran etexilate Orion looks like and contents of the pack
Dabigatran etexilate Orion 110 mg is white, opaque hard capsules, 19.4 mm in length and 6.9 mm in diameter, filled with white to pale yellow pellets. The cap is printed in black ink with the mark "MD" and the body with the number "110".
Dabigatran etexilate Orion 110 mg is available in aluminium/aluminium/LDPE/PES foil blisters in cardboard boxes containing 10, 30, 60, 100 or 180 hard capsules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Orion Corporation
Orionintie 1
02200 Espoo
Finland

Importer/Manufacturer
Orion Corporation, Orion Pharma
Orionintie 1
02200 Espoo
Finland
Orion Corporation, Orion Pharma
Joensuunkatu 7
24100 Salo
Finland

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Orion Pharma Poland Sp. z o.o.
[email protected]