Package leaflet: Information for the patient

Tuxanuva, 110 mg, hard capsules
Dabigatran etexilate
Please read the entire leaflet carefully 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. This medicine may harm others, even if their symptoms are identical.
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 Tuxanuva is and what it is used for
Important information before taking Tuxanuva
How to take Tuxanuva
Possible side effects
How to store Tuxanuva
Contents of the pack and other information

1. What Tuxanuva is and what it is used for

Tuxanuva 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.
Tuxanuva is used in adults for:

preventing blood clots in veins after hip or knee replacement surgery
preventing blood clots in the brain (stroke) and in other blood vessels in the body 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 such clots.

Tuxanuva is used in children for:

treating blood clots and preventing recurrence of blood clots.

2. Important information before taking Tuxanuva

When NOT to take Tuxanuva

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 that 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, heparin is administered to maintain catheter patency in a vein or artery, or during catheter ablation procedures 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 organ transplant rejection
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 Tuxanuva, discuss this with your doctor. If symptoms occur while taking Tuxanuva or if the patient has undergone a surgical procedure, contact 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 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 gastroesophageal reflux (acid reflux into the oesophagus)
if the patient is taking medicines that may increase the risk of bleeding. See below “Tuxanuva 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 in the heart (bacterial endocarditis)
if the patient has kidney function impairment or is dehydrated (feeling thirsty and passing reduced amounts of dark (concentrated)/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 previous myocardial infarction or has conditions diagnosed to increase 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 special caution when taking Tuxanuva

if the patient needs to undergo surgery: In such cases, temporary discontinuation of Tuxanuva is necessary due to the increased risk of bleeding during and immediately after surgery. It is very important to take Tuxanuva exactly as directed by the doctor before and after surgery.
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 Tuxanuva exactly as directed by the doctor before and after surgery.
The patient must immediately inform the doctor if they experience numbness or weakness in the lower limbs, or problems with bowel or bladder function after the anaesthesia wears off, as urgent medical care is required.
if the patient has fallen or sustained an injury during treatment, especially if the head was injured. Immediate medical evaluation 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 their doctor, who will decide whether a change in treatment is necessary.

Tuxanuva and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take. In particular, tell the doctor before taking Tuxanuva 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 are applied only topically to the skin
medicines used to treat heart rhythm disorders (e.g. amiodarone, dronedarone, quinidine, verapamil). For patients taking medicines containing amiodarone, quinidine, or verapamil, the doctor may recommend a lower dose of Tuxanuva depending on the condition for which the medicine was prescribed. See section 3.
medicines used to prevent organ transplant rejection (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 (antibiotics)
antiviral medicines used to treat AIDS (e.g. ritonavir)
certain medicines used to treat epilepsy (e.g. carbamazepine, phenytoin).

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
It is not known what effect Tuxanuva has on pregnancy or the unborn child. Tuxanuva should not be taken during pregnancy unless the doctor determines it is safe. Women of childbearing potential should avoid becoming pregnant while taking Tuxanuva.
Breastfeeding should not be undertaken during treatment with Tuxanuva.

Driving and operating machinery
Tuxanuva has no effect or a negligible effect on the ability to drive and operate machinery.

Tuxanuva contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to take Tuxanuva

Tuxanuva capsules 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 as prescribed by the doctor. If in doubt, consult your doctor.
Take Tuxanuva 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 medications containing amiodarone, quinidine, or verapamil, the recommended dose of Tuxanuva is 150 mg once daily (taken as 2 capsules of 75 mg).
Patients taking verapamil-containing medications who also have reduced renal function by more than half should take a reduced dose of Tuxanuva 75 mg due to increased risk of bleeding.

In both types of surgery, treatment should not be initiated if there is 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 replacement surgery
Initiate Tuxanuva with one capsule taken 1 to 4 hours after completion of surgery. Then take two capsules once daily for a total of 10 days.

After hip replacement surgery
Initiate Tuxanuva with one capsule taken 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 the brain and body by preventing clot formation due to abnormal 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 verapamil-containing medications should receive Tuxanuva at a reduced dose of 220 mg taken as one 110 mg capsule twice daily due to potential increased risk of bleeding.
In patients with potentially increased risk of bleeding, the doctor may recommend treatment with Tuxanuva at 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 via a procedure called cardioversion. Tuxanuva should be taken as directed by the doctor.

In patients undergoing implantation of a medical device (stent) into a blood vessel to maintain its patency using a procedure called percutaneous coronary intervention with stent implantation, treatment with Tuxanuva may be initiated once the doctor has confirmed adequate control of blood coagulation. Tuxanuva should be taken as directed by the doctor.

Treatment and prevention of recurrent blood clots in children
Tuxanuva 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 medications should be continued unless the doctor advises otherwise.

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

Table 1: Dosing table for Tuxanuva 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 a 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 Tuxanuva
Tuxanuva 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 the bottle

To open the bottle, press down and twist off the cap.
Immediately after removing a capsule and taking the dose, the cap should be replaced and the bottle tightly closed.

Changing treatment while taking Tuxanuva
Do not change the dose or stop treatment without first obtaining specific instructions from your doctor.

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

Missed dose of Tuxanuva
Prevention of blood clots after hip or knee replacement surgery
Continue by taking the missed daily dose of Tuxanuva 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 clot formation due to irregular heart rhythm, and treatment and prevention of recurrence of blood clots in the veins of the legs and lungs
Use in children: Treatment of blood clots 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, the missed dose should not be taken. Do not take a double dose to make up for a missed dose.

Stopping Tuxanuva
Tuxanuva should be taken exactly as prescribed by the doctor. 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 you experience indigestion after taking Tuxanuva.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
Serious adverse reactions
Tuxanuva affects the blood clotting system; therefore, most adverse reactions involve symptoms such as bruising or bleeding.
Severe or major bleeding may occur, which is the most serious adverse reaction, and 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 bleeding that does not stop spontaneously or symptoms of excessive bleeding occur (unusual weakness, fatigue, paleness, dizziness, headache, or unexplained swelling), 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 breathing or dizziness, contact your doctor immediately.

Other adverse reactions
The possible adverse reactions 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 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 urine due to presence of blood), from haemorrhoids, from the rectum, under the skin, into joints, due to injury, after injury, or after a surgical procedure
development of bruises or haematomas following a surgical procedure
blood in stool detected in laboratory tests
reduction in the number of red blood cells in blood
reduction in the proportion of red blood cells in blood
allergic reaction
vomiting
frequent passage of loose or watery stools
nausea
presence of discharge from wound (fluid oozing from 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, 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
reduction in the number of platelets in blood
reduction in the number of red blood cells in blood after a surgical procedure
severe allergic reaction causing difficulty breathing or dizziness
severe allergic reaction causing swelling of the face or throat
skin rash with 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.

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

difficulty breathing or wheezing
reduction in 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 that occur due to irregular 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/vagina or urinary tract (including pink or red urine due to presence of blood), or under the skin
reduction in the number of red blood cells in 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, rectum, or into the brain
development of haematomas
coughing up blood or blood-stained sputum
reduction in the number of platelets in blood
decrease in haemoglobin levels in 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, wound, injection site, or 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 with dark red, raised, itchy bumps due to an allergic reaction
reduction in the proportion of red 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 available data):

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

In clinical trials, the number of heart attacks with dabigatran etexilate was numerically higher than with warfarin. The overall number of occurrences was small.
Treatment 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 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
reduction in the number of red blood cells in blood
development of haematomas
coughing up blood or blood-stained 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, injection site, site of intravenous catheter insertion, or into the brain
reduction in the number of platelets in blood
severe allergic reaction causing difficulty breathing or dizziness
severe allergic reaction causing swelling of the face or throat
skin rash with dark red, raised, itchy bumps due to an allergic reaction
difficulty swallowing.

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

difficulty breathing or wheezing
decrease in haemoglobin levels in blood (a substance in red blood cells)
reduction in the proportion of red blood cells
reduction 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 heart attacks with dabigatran etexilate was numerically higher than with warfarin. The overall number of occurrences was small. No difference in the number of heart attacks was observed in patients treated with dabigatran etexilate compared to patients receiving placebo.
Treatment and prevention of recurrence of blood clots in children
Common (may occur in up to 1 in 10 people):

reduction in the number of red blood cells in blood
reduction in the number of platelets in blood
skin rash with dark red, raised, itchy bumps due to an allergic reaction
sudden change in skin colour and appearance
development 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):

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

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, surgical incision site, injection site, or 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 adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products 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 reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Tuxanuva

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 after:
"Expiry date (EXP)". The expiry date refers to the last day of the stated month.
Blister:
Store below 30°C.
Bottle:
Store below 30°C. Keep in the outer packaging to protect from moisture.
Medicines should not be disposed of via wastewater. 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 Tuxanuva contains

The active substance is dabigatran etexilate. Each hard capsule contains dabigatran etexilate in the form of dabigatran etexilate mesilate, equivalent to 110 mg of dabigatran etexilate.
Other ingredients are: tartaric acid (in the form of pellets), hypromellose (2910), talc, hydroxypropylcellulose (353 cps - 658 cps), sodium croscarmellose, and magnesium stearate.
Capsule shell: titanium dioxide and hypromellose.
Black printing ink: shellac, propylene glycol (E 1520), iron oxide black (E 172), and potassium hydroxide.

What Tuxanuva looks like and contents of the pack
Tuxanuva 110 mg is a hard capsule of size "1" (19.4 mm ± 0.4 mm), with a white opaque cap printed with "MD" and a white opaque body printed with "110" in black ink, containing a mixture of white to pale yellow pellets and pale yellow granules.
Tuxanuva 110 mg is available in blisters made of OPA/Aluminium/PE + desiccant/Aluminium/PE, packed in cardboard boxes containing 10, 30 or 60 hard capsules.
Tuxanuva 110 mg is also available in PP bottles with a child-resistant closure and a desiccant in the form of silica gel, with a capacity of 120 mL or 150 mL, containing 60 hard capsules, packed in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
STADA Arzneimittel AG
Stadastrasse 2-18
61118 Bad Vilbel
Germany

Manufacturer/Importer
Stada Arzneimittel AG
Stadastraße 2-18
61118 Bad Vilbel
Germany
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park
PLA3000 Paola
Malta

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Stada Poland Sp. z o.o.
ul. Krakowiaków 44
02-255 Warszawa
Tel. +48 22 737 79 20