Package leaflet: Information for the patient

Tuxanuva, 150 mg, hard capsules
Dabigatranum etexilatum
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

Keep this leaflet as you may need to read it again.
If you have any further questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm others, even if their symptoms are the same.
If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet

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 that is responsible for blood clot formation.
Tuxanuva is used in adults to:

prevent the formation of blood clots in the brain (stroke) and other blood vessels in the body in patients with an irregular heartbeat known as non-valvular atrial fibrillation and at least one additional risk factor
treat blood clots in the veins of the legs and lungs, and to prevent recurrence of blood clots in the veins of the legs and lungs.

Tuxanuva is used in children to:

treat blood clots and to prevent 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. This may be congenital, of unknown cause, or caused by taking other medicines
if the patient is taking anticoagulant medicines (e.g. warfarin, rivaroxaban, apixaban, or heparin), except when switching anticoagulant therapy, when heparin is administered to maintain catheter patency in a vein or artery, or during restoration of normal heart rhythm by a procedure called catheter ablation in 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 ongoing anticoagulant therapy.

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, 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 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 of 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 previously had a heart attack or has conditions diagnosed to increase the risk of heart attack
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 with 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 surgery requires insertion of a catheter or administration of an 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 should 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 attention is required.
if the patient has fallen or sustained an injury while on treatment, especially if the head was injured. Immediate medical evaluation is necessary. 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 their doctor, who will decide whether a change in treatment is needed.

Tuxanuva and other medicines
Inform 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 to the skin
medicines used to treat heart rhythm disorders (e.g. amiodarone, dronedarone, quinidine, verapamil). In patients taking verapamil-containing medicines, the doctor may recommend a lower dose of Tuxanuva depending on the condition for which it 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 (SSRIs) or serotonin-noradrenaline reuptake inhibitors (SNRIs)
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, 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 use effective contraception to prevent pregnancy while taking Tuxanuva.
Breastfeeding is not recommended during treatment with Tuxanuva.

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

Tuxanuva contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. 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. There are other age-appropriate formulations available for treating children under 8 years of age.
This medicine should always be taken as prescribed by the doctor. In case of doubt, consult the doctor.
Tuxanuva should be taken according to the following recommendations:
Prevention of blood clots in blood vessels of the brain and body by preventing the formation of clots that occur due to irregular heart function, and treatment of blood clots in the veins of the legs and lungs, as well as prevention of recurrence of such clots
The recommended dose is 300 mg taken as one 150 mg capsule twice daily.
In patients aged 80 years or older, the recommended dose is 220 mg taken as one 110 mg capsule twice daily.
Patients taking medicines containing verapamil should receive Tuxanuva at a reduced dose of 220 mg taken as one 110 mg capsule twice daily due to the potential increased risk of bleeding.
In patients with potentially increased risk of bleeding, the doctor may recommend treatment with 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 through a procedure called cardioversion or through a procedure called catheter ablation for atrial fibrillation. Tuxanuva should be taken as directed by the doctor.
In the case of implantation of a medical device (stent) into a blood vessel to maintain its patency using a procedure known as percutaneous coronary intervention with stent implantation, the patient may receive treatment with Tuxanuva after the doctor has confirmed adequate control of blood coagulation. Tuxanuva should be taken as directed by the doctor.
Treatment of blood clots 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 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, crush, 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 unscrew the cap.
Immediately after removing a capsule for dosing, replace the cap on the bottle and close it tightly.

Changing treatment during use of Tuxanuva
Do not change the dose or stop treatment without first obtaining detailed 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.
Missing a dose of Tuxanuva
A missed dose may be taken if there is still at least 6 hours before the next scheduled dose.
If less than 6 hours remain until the next scheduled dose, do not take the missed dose. Do not take a double dose to make up for a missed dose.
Stopping treatment with Tuxanuva
Tuxanuva should be taken as directed by your doctor. Do not stop taking this medicine without first consulting your doctor, as the risk of developing blood clots 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 all medicines, 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 are related to symptoms such as bruising or bleeding.
Severe or extensive bleeding may occur, which is the most serious adverse reaction. Regardless of location, it may lead to disability, be life-threatening, or even result in death. In some cases, these bleedings may not be visible.

If 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 thromboembolism in blood vessels of the brain and body by preventing the formation of clots that occur due to abnormal heart function

Common (may occur in up to 1 in 10 people):

bleeding may occur from the nose, into the stomach or intestines, from the penis/vagina or urinary tract (including pink or red urine due to 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, rectum or into the brain
formation of haematomas
coughing up blood or blood-stained 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 color 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 a surgical incision site, wound, injection site, or catheter insertion site into a vein
severe allergic reaction causing difficulty breathing or dizziness
severe allergic reaction causing swelling of the face or throat
skin rash characterized by dark red, raised, itchy bumps due to an allergic reaction
decrease in the proportion of red blood cells in the blood
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
decrease in number or even absence of white blood cells (which help fight infections)
hair loss.

In clinical trials, the number of heart attacks was numerically higher with dabigatran etexilate than with warfarin. The overall number of occurrences was small.

Treatment of blood clots in the legs and lungs, and prevention of recurrent 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 blood) or under the skin
indigestion.

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

bleeding
bleeding may occur into a joint or following injury
bleeding from haemorrhoids may occur
decrease in the number of red blood cells in the blood
formation of haematomas
coughing up blood or blood-stained sputum
allergic reaction
sudden change in skin color and appearance
itching
stomach or intestinal ulcer (including oesophageal ulceration)
inflammation of the oesophagus and stomach
regurgitation of 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 a surgical incision site, injection site, or catheter insertion site into a vein, 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 characterized by 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 the blood (a substance in red blood cells)
decrease in the proportion of red blood cells in the blood
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 heart attacks was numerically higher with dabigatran etexilate than with warfarin. The overall number of occurrences was small. No difference in the number of heart attacks was observed between patients treated with dabigatran etexilate and those 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 characterized by dark red, raised, itchy bumps due to an allergic reaction
sudden change in skin color 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, from the brain, from the anus, from the penis/vagina or urinary tract (including pink or red urine due to blood), or under the skin
decrease in haemoglobin levels in the blood (a substance in red blood cells)
decrease in the proportion of red blood cells in the 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 catheter insertion site into a vein
bleeding from haemorrhoids may occur
stomach or intestinal ulcer (including oesophageal ulceration)
abnormal liver function test results in laboratory tests.

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

5. How to store Tuxanuva

Keep this medicine out of 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. Store in the outer packaging to protect from moisture.
Medicines must not be disposed of via the sewage system. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment.

6. Contents of the packaging 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 150 mg of dabigatran etexilate.
Other components: tartaric acid (in the form of pellets), hypromellose (2910), talc, hydroxypropylcellulose (353 cps - 658 cps), sodium croscarmellose, 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 150 mg is a hard capsule of size "0" (21.5 mm ± 0.4 mm), with a white opaque cap printed with "MD" and a white opaque body printed with "150", both in black ink, containing a mixture of pellets ranging from white to pale yellow and pale yellow granules.
Tuxanuva 150 mg is available in blisters made of OPA/aluminum/PE + desiccant/aluminum/PE, packed in cardboard boxes containing 10, 30, or 60 hard capsules.
Tuxanuva 150 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