Tuxanuva

Package Leaflet: Information for the Patient

Tuxanuva, 110 mg, Hard Capsules

Dabigatran Etexilate

Read the Package Leaflet Carefully Before Taking the Medication, as it Contains Important Information for the Patient.

• Keep this package leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medication has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this package leaflet, inform your doctor or pharmacist. See section 4.

Table of Contents of the Package Leaflet

• 1. What is Tuxanuva and What is it Used For
• 2. Important Information Before Taking Tuxanuva
• 3. How to Take Tuxanuva
• 4. Possible Side Effects
• 5. How to Store Tuxanuva
• 6. Contents of the Pack and Other Information

1. What is Tuxanuva and What is it Used For

Tuxanuva contains dabigatran etexilate as the active substance and belongs to a group of medications called anticoagulants. Its action involves blocking a substance in the body responsible for blood clot formation.
Tuxanuva is used in adults to:

• prevent the formation of blood clots in the veins after hip or knee replacement surgery
• prevent the formation of blood clots in the brain (stroke) and other blood vessels in the patient's body, if the patient has a type of irregular heartbeat called atrial fibrillation not caused by heart valve problems and at least one additional risk factor
• treat blood clots in the veins of the legs and lungs and prevent the recurrence of blood clots in the veins of the legs and lungs.

Tuxanuva is used in children to:

• treat blood clots and prevent the recurrence of blood clots.

2. Important Information Before Taking Tuxanuva

When Not to Take Tuxanuva

• if you are allergic to dabigatran etexilate or any of the other ingredients of this medication (listed in section 6)
• if you have severe kidney impairment
• if you are currently bleeding
• if you have a disease of any internal organ that increases the risk of major bleeding (e.g., stomach ulcer disease, brain injury or bleeding into the brain, recent brain or eye surgery)

if you have an increased tendency to bleed. This may be congenital, of unknown cause, or caused by the use of other medications.

• if you are taking anticoagulant medications (e.g., warfarin, rivaroxaban, apixaban, or heparin), except when switching anticoagulant treatment and heparin is administered to maintain catheter patency in a vein or artery or during restoration of normal heart function using a procedure called catheter ablation in atrial fibrillation
• if you have severe liver impairment or liver disease that may lead to death
• if you are taking oral ketoconazole or itraconazole, medications used to treat fungal infections
• if you are taking oral cyclosporine, a medication used to prevent organ rejection
• if you are taking dronedarone, a medication used to treat heart rhythm disorders
• if you are taking a combination medication containing glecaprevir and pibrentasvir, an antiviral medication used to treat hepatitis C
• if you have a mechanical heart valve that requires continuous anticoagulation.

Warnings and Precautions

Before starting Tuxanuva, discuss it with your doctor. If you have experienced symptoms or undergone surgery during treatment with Tuxanuva, consult your doctor.
The patient should inform the doctorif they have or have had any medical conditions or diseases, especially those listed below:

• if you have an increased risk of bleeding, such as:
• if you have recently experienced bleeding
• if you have undergone surgical biopsy within the last month
• if you have had a serious injury (e.g., bone fracture, head injury, or any injury requiring surgical treatment)
• if you have esophageal or gastric inflammation
• if you have gastroesophageal reflux disease
• if you are taking medications that may increase the risk of bleeding. See "Tuxanuva and Other Medications" below
• if you are taking anti-inflammatory medications, such as diclofenac, ibuprofen, or piroxicam
• if you have an infection of the heart (bacterial endocarditis)
• if you have kidney impairment or are dehydrated (feeling thirsty and producing decreased amounts of dark, concentrated urine)
• if you are over 75 years old
• if you are an adult and weigh 50 kg or less
• only in the case of use in children: if the child has an infection around or in the brain.
• in the case of a previous heart attack or if the patient has been diagnosed with conditions that increase the risk of heart attack.
• if you have liver disease that affects blood test results. In such cases, the use of this medication is not recommended.

When to Exercise Particular Caution When Taking Tuxanuva

• if you need to undergo surgery: In this case, it is necessary to discontinue Tuxanuva temporarily due to the increased risk of bleeding during and after surgery. It is very important to take Tuxanuva before and after surgery exactly as your doctor has advised.

if the surgical procedure requires the insertion of a catheter or injection into the spine (e.g., for spinal or epidural anesthesia or pain relief):

• It is very important to take Tuxanuva before and after surgery exactly as your doctor has advised.
• You should immediately inform your doctor if you experience numbness or weakness in your lower limbs or problems with your bowels or bladder after the anesthesia has worn off, as urgent medical attention is required.
• if you have fallen or injured yourself during treatment, especially if you have injured your head. You should immediately seek medical attention. Your doctor will examine you to determine if there is an increased risk of bleeding.
• if you have a condition called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), you should inform your doctor, who will decide whether to change your treatment.

Tuxanuva and Other Medications

Tell your doctor or pharmacist about all medications you are currently taking or have recently taken, as well as any medications you plan to take.
In particular, you must tell your doctor before taking Tuxanuva if you are taking any of the following medications:

• medications that reduce blood clotting (e.g., warfarin, phenprocoumon, acenocoumarol, heparin, clopidogrel, prasugrel, ticagrelor, rivaroxaban, acetylsalicylic acid)
• medications used to treat fungal infections (e.g., ketoconazole, itraconazole), unless they are used only on the skin
• medications used to treat heart rhythm disorders (e.g., amiodarone, dronedarone, quinidine, verapamil). In patients taking medications containing amiodarone, quinidine, or verapamil, the doctor may recommend a lower dose of Tuxanuva, depending on the condition for which it was prescribed. See section 3.
• medications used to prevent organ rejection (e.g., tacrolimus, cyclosporine)
• a combination medication containing glecaprevir and pibrentasvir (an antiviral medication used to treat hepatitis C)
• anti-inflammatory and pain-relieving medications (e.g., acetylsalicylic acid, ibuprofen, diclofenac)
• St. John's Wort, a herbal medication used to treat depression
• antidepressant medications called selective serotonin reuptake inhibitors or selective norepinephrine reuptake inhibitors
• rifampicin or clarithromycin (antibiotics)
• antiviral medications used to treat AIDS (e.g., ritonavir)
• certain medications used to treat epilepsy (e.g., carbamazepine, phenytoin).

Pregnancy and Breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a child, ask your doctor or pharmacist for advice before taking this medication.
Tuxanuva should not be taken during pregnancy unless your doctor considers it necessary. Women of childbearing age should avoid becoming pregnant while taking Tuxanuva.
Do not breastfeed while taking Tuxanuva.

Driving and Using Machines

Tuxanuva has no or negligible influence on the ability to drive and use machines.

Tuxanuva Contains Sodium

This medication contains less than 1 mmol (23 mg) of sodium per tablet, which means it is essentially "sodium-free".

3. How to Take Tuxanuva

Tuxanuva capsules can be used in adults and children aged 8 years or older who can swallow the capsules whole. There are other age-appropriate formulations for the treatment of children under 8 years of age.
This medication should always be taken exactly as your doctor has advised. If you are unsure, ask your doctor.

Take Tuxanuva as Follows:

Prevention of blood clots after hip or knee replacement surgery
The recommended dose is 220 mg once daily(taken as 2 capsules of 110 mg each).
If kidney function is severely impairedor in patients aged 75 years or older,
the recommended dose is 150 mg once daily(taken as 2 capsules of 75 mg each).
In patients taking medications containing amiodarone, quinidine, or verapamil, the recommended dose of Tuxanuva is 150 mg once daily(taken as 2 capsules of 75 mg each).
Patients taking medications containing verapamilwith severely impaired kidney functionshould take a reduced dose of 75 mgof Tuxanuva due to the increased risk of bleeding.
In both types of surgery, do not start treatment if there is bleeding from the surgical site. If it is not possible to start treatment the day after surgery, start with a dose of 2 capsules once daily.
After knee replacement surgery
Tuxanuva treatment should be started with a dose of 1 capsule within 1 to 4 hours after the completion of surgery. Then, take 2 capsules once daily for a total of 10 days.
After hip replacement surgery
Tuxanuva treatment should be started with a dose of 1 capsule within 1 to 4 hours after the completion of surgery. Then, take 2 capsules once daily for a total of 28 to 35 days.
Prevention of blood clots in the brain and body due to irregular heart rhythm and treatment of blood clots in the legs and lungs and prevention of recurrence of blood clots in the legs and lungs
The recommended dose is 300 mgtaken as one 150 mg capsule twice daily.
In patients aged 80 years or older, the recommended dose is 220 mgtaken as one 110 mg capsule twice daily.
Patients taking medications containing verapamilshould receive a reduced dose of Tuxanuva of 220 mgtaken as one 110 mg capsule twice dailydue to the increased risk of bleeding.
In patients with a potentially increased risk of bleeding, the doctor may recommend a dose of 220 mgtaken as one 110 mg capsule twice daily.
Treatment can be continued if the patient requires restoration of normal heart function using a procedure called cardioversion. Tuxanuva should be taken as advised by your doctor.
In the 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 Tuxanuva treatment after the doctor has confirmed that blood clotting is under control. Tuxanuva should be taken as advised by your doctor.
Treatment of blood clots and prevention of recurrence of blood clots in children
Tuxanuva should be taken twice daily, one dose in the morning and one dose in the evening, at approximately the same time each day. The interval between doses should be approximately 12 hours.
The recommended dose depends on the patient's weight and age. The doctor will determine the correct dose. The doctor may adjust the dose during treatment. Continue to take all other medications unless your doctor advises you to stop taking any of them.
Table 1 shows the single and total daily doses of Tuxanuva in milligrams (mg). The doses depend on the patient's weight in kilograms (kg) and age in years.

Table 1: Tuxanuva Dosing Table in Capsule Form

Doses that require combining more than one capsule:
300 mg:
two 150 mg capsules or
four 75 mg capsules
260 mg:
one 110 mg capsule and one 150 mg capsule or
one 110 mg capsule and two 75 mg capsules
220 mg:
two 110 mg capsules
185 mg:
one 75 mg capsule and one 110 mg capsule
150 mg:
one 150 mg capsule or
two 75 mg capsules

How to Take Tuxanuva

Tuxanuva 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.

Instructions for Opening the Bottle

• To open the bottle, press and twist the cap
• Immediately after removing a capsule, replace the cap on the bottle and close it tightly.

Changing Treatment During Tuxanuva Use

Do not change the dose of Tuxanuva or treatment without receiving detailed instructions from your doctor.

Taking More Than the Recommended Dose of Tuxanuva

Taking too much of this medication increases the risk of bleeding. If you have taken too many Tuxanuva capsules, contact your doctor immediately. Specific treatments are available.

Missing a Dose of Tuxanuva

Prevention of blood clots after hip or knee replacement surgery
Continue taking the missed daily dose of Tuxanuva at the same time the next day. Do not take a double dose to make up for the missed dose.
Use in adults: Prevention of blood clots in the brain and body due to irregular heart rhythm and treatment of blood clots in the legs and lungs and prevention of recurrence of blood clots in the legs and lungs
Use in children: Treatment of blood clots and prevention of recurrence of blood clots in children
The missed dose can be taken up to 6 hours before the next scheduled dose.
If there are less than 6 hours until the next scheduled dose, do not take the missed dose. Do not take a double dose to make up for the missed dose.

Stopping Tuxanuva Treatment

Tuxanuva should be taken as advised by your doctor. Do not stop taking this medication without consulting your doctor first, as the risk of blood clot formation may be higher if treatment is stopped prematurely. Contact your doctor if you experience nausea after taking Tuxanuva.
If you have any further questions about the use of this medication, ask your doctor or pharmacist.

4. Possible Side Effects

Like all medications, Tuxanuva can cause side effects, although not everybody gets them.

Severe Side Effects

Tuxanuva affects the blood clotting system, so most side effects are related to symptoms such as bruising or bleeding.
Severe or massive bleeding may occur, which is the most serious side effect and can lead to disability, be life-threatening, or even cause death.
In some cases, this bleeding may not be visible.

• In the event of bleeding that does not stop on its own or symptoms of excessive bleeding (exceptional weakness, fatigue, pallor, dizziness, headache, or unexplained swelling), contact your doctor immediately. Your doctor may decide to monitor you closely or change your medication.
• In the event of a severe allergic reaction that may cause difficulty breathing or dizziness, contact your doctor immediately.

Other Side Effects

Possible side effects listed below are grouped by frequency of occurrence.
Prevention of blood clots after hip or knee replacement surgery
Common(may affect up to 1 in 10 people):

• decreased hemoglobin levels in the blood (a substance in red blood cells)
• abnormal liver function test results. Uncommon(may affect 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 urine discoloration due to blood), or bleeding under the skin
• formation of hematomas or bruising after surgery
• blood in the stool as detected by laboratory tests
• decreased red blood cell count
• decreased red blood cell percentage
• allergic reaction
• vomiting
• diarrhea
• nausea
• wound secretion (oozing from the surgical wound)
• increased liver enzyme activity
• jaundice of the skin or eyes due to liver or blood disease. Rare(may affect up to 1 in 1,000 people):
• bleeding
• bleeding may occur into the brain, from the surgical wound, from the injection site, or from the catheter insertion site
• bleeding from the catheter insertion site
• coughing up blood or sputum stained with blood
• decreased platelet count
• decreased red blood cell count after surgery
• severe allergic reaction causing difficulty breathing or dizziness
• severe allergic reaction causing facial or throat swelling
• skin rash in the form of dark red, raised, itchy bumps due to an allergic reaction
• sudden change in skin color or appearance

Unknown(frequency cannot be estimated from the available data):

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

Prevention of blood clots in the brain and body due to irregular heart rhythm
Common(may affect 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 urine discoloration due to blood), or bleeding under the skin
• decreased red blood cell count
• abdominal pain or stomach pain
• nausea
• diarrhea
• vomiting. Uncommon(may affect up to 1 in 100 people):
• bleeding
• bleeding may occur from the surgical wound, from the injection site, or from the catheter insertion site
• formation of hematomas
• coughing up blood or sputum stained with blood
• decreased platelet count
• decreased hemoglobin levels in the blood (a substance in red blood cells)
• allergic reaction
• sudden change in skin color or appearance
• itching
• stomach or intestinal ulcers (including esophageal ulcers)
• esophageal or gastric inflammation
• gastroesophageal reflux disease
• abdominal pain or stomach pain
• diarrhea
• abnormal liver function test results

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

• bleeding may occur into the joint, from the surgical wound, from the injection site, or from the catheter insertion site
• severe allergic reaction causing difficulty breathing or dizziness
• severe allergic reaction causing facial or throat swelling
• skin rash in the form of dark red, raised, itchy bumps due to an allergic reaction
• decreased red blood cell percentage
• increased liver enzyme activity
• jaundice of the skin or eyes due to liver or blood disease.

Unknown(frequency cannot be estimated from the available data):

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

Treatment of blood clots in the legs and lungs and prevention of recurrence of blood clots in the legs and lungs
Common(may affect 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 urine discoloration due to blood), or bleeding under the skin
• nausea.

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

• bleeding
• bleeding may occur into the joint or due to injury
• bleeding from the surgical wound
• decreased red blood cell count
• formation of hematomas
• coughing up blood or sputum stained with blood
• allergic reaction
• sudden change in skin color or appearance
• itching
• stomach or intestinal ulcers (including esophageal ulcers)
• esophageal or gastric inflammation
• gastroesophageal reflux disease
• nausea
• vomiting
• abdominal pain or stomach pain
• diarrhea
• abnormal liver function test results
• increased liver enzyme activity.

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

• bleeding may occur from the surgical wound, from the injection site, or from the catheter insertion site, or bleeding into the brain
• decreased platelet count
• severe allergic reaction causing difficulty breathing or dizziness
• severe allergic reaction causing facial or throat swelling
• skin rash in the form of dark red, raised, itchy bumps due to an allergic reaction
• difficulty swallowing.

Unknown(frequency cannot be estimated from the available data):

• difficulty breathing or wheezing
• decreased hemoglobin levels in the blood (a substance in red blood cells)
• decreased red blood cell percentage
• decrease in the number of or lack of white blood cells (which help fight infections)
• jaundice of the skin or eyes due to liver or blood disease
• hair loss. In clinical trials, the incidence of heart attacks in patients taking dabigatran etexilate was higher than in patients taking warfarin. The overall incidence was low.

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

• decreased red blood cell count
• decreased platelet count
• skin rash in the form of dark red, raised, itchy bumps due to an allergic reaction
• sudden change in skin color or appearance
• formation of hematomas
• nosebleeds
• gastroesophageal reflux disease
• vomiting
• nausea
• diarrhea
• nausea
• hair loss
• increased liver enzyme activity. Uncommon(may affect 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 anus, from the penis/vagina or urinary tract (including urine discoloration due to blood), or bleeding under the skin
• decreased hemoglobin levels in the blood (a substance in red blood cells)
• decreased red blood cell percentage
• itching
• coughing up blood or sputum stained with blood
• abdominal pain or stomach pain
• esophageal or gastric inflammation
• allergic reaction
• difficulty swallowing
• jaundice of the skin or eyes due to liver or blood disease.

Unknown(frequency cannot be estimated from the available data):

• lack of white blood cells (which help fight infections)
• severe allergic reaction causing difficulty breathing or dizziness
• severe allergic reaction causing facial or throat swelling
• difficulty breathing or wheezing
• bleeding
• bleeding may occur into the joint, from the surgical wound, from the injection site, or from the catheter insertion site
• bleeding from the surgical wound
• stomach or intestinal ulcers (including esophageal ulcers)
• abnormal liver function test results.

Reporting Side Effects

If you experience any side effects, including those not listed in this package leaflet, inform your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw
Phone: +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 authorization holder.
Reporting side effects will help to gather more information on the safety of this medication.

5. How to Store Tuxanuva

Keep this medication out of the sight and reach of children.
Do not use this medication after the expiry date stated on the carton or blister after "EXP". The expiry date refers to the last day of the month stated.
Blister:
Store in a temperature not exceeding 30°C.
Bottle:
Store in a temperature not exceeding 30°C. Store in the outer packaging to protect from moisture.
Medications should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medications no longer required. 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 mesylate, equivalent to 110 mg of dabigatran etexilate.
• The other ingredients are: tartaric acid (in the form of pellets), hypromellose (2910), talc, hydroxypropyl cellulose (353 cps - 658 cps), croscarmellose sodium, and magnesium stearate. Capsule shell: titanium dioxide and hypromellose. Black ink for printing: 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, size "1" (19.4 mm ± 0.4 mm), with a white opaque cap with the imprint "MD" and a white opaque body with the imprint "110", printed with black ink, containing a mixture of pellets that are white to light yellow and granules that are light yellow.
Tuxanuva 110 mg is available in blisters of OPA/Aluminum/PE + desiccant/Aluminum/PE, in cardboard boxes containing 10, 30, or 60 hard capsules.
Tuxanuva 110 mg is also available in PP bottles of 120 mL or 150 mL with a child-resistant closure and a desiccant in the form of silica gel, containing 60 hard capsules, in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorization 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
To obtain more detailed information on this medication, contact the local representative of the marketing authorization holder:
Stada Poland Sp. z o.o.
ul. Krakowiaków 44
02-255 Warsaw
Phone: +48 22 737 79 20

Date of Last Revision of the Package Leaflet: