Tuxanuva

Package leaflet: Information for the patient

Tuxanuva, 75 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, 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 give it to others. This medicine may harm others, even if their symptoms are similar.
• If the patient experiences any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

1. What Tuxanuva is and what it is 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 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:

• prevention of blood clots in veins following hip or knee replacement surgery.

Tuxanuva is used in children for:

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

2. Important information before taking Tuxanuva

When NOT to take Tuxanuva

• if the patient is allergic to dabigatran etexilate or to any of the other ingredients of this medicine (listed in section 6)
• if the patient has severe impairment of kidney function
• 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. stomach ulcer, brain injury or intracranial hemorrhage, 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 during a switch in 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 impairment of liver function 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 combination medicine containing glecaprevir and pibrentasvir, an antiviral medicine used to treat hepatitis C virus infection
• if the patient has a mechanical heart valve, which requires continuous use of blood-thinning medicines.

Warnings and precautions
Before starting Tuxanuva, discuss this with your doctor. If symptoms occur while being treated with Tuxanuva or if the patient has undergone surgery, seek medical advice.
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 tissue biopsy within the past month
• if the patient has sustained a serious injury (e.g. bone fracture, head injury, or any injury requiring surgical treatment)
• if the patient has inflammation of the esophagus or stomach
• if the patient has gastroesophageal reflux (acid reflux into the esophagus)
• if the patient is taking medicines that may increase the risk of bleeding. See below “Tuxanuva and other medicines”
• if the patient is taking nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, ibuprofen, piroxicam
• if the patient has an infection within the heart (bacterial endocarditis)
• if the patient has impaired 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 has conditions diagnosed as increasing 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 when taking Tuxanuva

• if the patient needs to undergo surgery: In such cases, temporary discontinuation of Tuxanuva is necessary due to 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 anesthesia 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 numbness or weakness in the legs or problems with bowel or bladder function occur after the anesthesia wears off, as urgent medical care may be needed.
• if the patient 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 the 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 or has recently taken, as well as any medicines the patient 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 it was prescribed. See also section 3.
• medicines used to prevent rejection of transplanted organs (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 plans to become pregnant, 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 considers it safe. Women of childbearing potential should avoid becoming pregnant while taking Tuxanuva.
Breastfeeding should not be performed during treatment with Tuxanuva.

Driving and operating machinery
Tuxanuva has no effect or has 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 your doctor. If in doubt, consult your doctor.
Take Tuxanuva exactly as directed below:

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

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

After knee joint replacement surgery
Start taking Tuxanuva by taking one capsule within 1 to 4 hours after completion of the surgical procedure. Then take two capsules once daily for a total of 10 days.

After hip joint replacement surgery
Start taking Tuxanuva by taking one capsule within 1 to 4 hours after completion of the surgical procedure. Then take two capsules once daily for a total of 28 to 35 days.

Treatment and prevention of recurrence of 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 ideally be 12 hours.

The recommended dose depends on body weight and age. Your doctor will determine the correct dose. Your doctor may adjust the dose during treatment. Continue taking all other prescribed medicines unless your 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

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 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 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 unscrew the cap.
• Immediately after removing a capsule for dosing, the cap should be replaced and the bottle closed tightly.

Changing treatment while taking Tuxanuva
Do not change the dose or stop treatment without receiving 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 taking the missed daily dose of Tuxanuva at the usual time the next day. Do not take a double dose to make up for a missed dose.

Treatment 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 as directed 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 gastrointestinal discomfort occurs after taking Tuxanuva.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Serious adverse effects
Tuxanuva affects the blood clotting system; therefore, most adverse effects involve symptoms such as bruising or bleeding.
Severe or major bleeding may occur, which is the most serious adverse effect. Regardless of location, it may lead to disability, be life-threatening, or even result in death. In some cases, these bleedings may not be visible.

• If 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 monitoring or change the treatment.
• In case of a severe allergic reaction, which may cause difficulty breathing or dizziness, contact your doctor immediately.

Other adverse effects
The possible adverse effects listed below are grouped according to their frequency of occurrence.
Prevention of blood clots after hip or knee replacement surgery
Common (may occur in up to 1 in 10 people):

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

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

• bleeding from the nose, stomach or intestines, penis/vagina or urinary tract (including pink or red urine due to presence of blood), from haemorrhoids, rectum, under the skin, into joints, following injury or after a surgical procedure
• formation of bruises or haematomas after a surgical procedure
• blood in stool detected in laboratory tests
• decrease in the number of red blood cells in the blood
• decrease in the proportion of red blood cells in the blood
• allergic reaction
• vomiting
• frequent passage of loose or watery stools
• nausea
• discharge from the wound (fluid leakage from the surgical wound)
• increased liver enzyme activity
• yellowing of the skin or whites of the eyes due to liver or blood disease.

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

• bleeding
• bleeding into the brain, from the surgical incision site, injection site, or site of intravenous catheter insertion may occur
• 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 a surgical procedure
• severe allergic reaction causing difficulty breathing or dizziness
• severe allergic reaction causing swelling of the face or throat
• skin rash consisting of dark red, raised, itchy bumps due to an allergic reaction
• sudden change in skin colour and appearance
• itching
• stomach or intestinal ulcer (including oesophageal ulceration)
• inflammation of the oesophagus and stomach
• regurgitation of stomach contents into the oesophagus (reflux)
• abdominal pain or stomach pain
• indigestion
• difficulty swallowing
• fluid discharge from the wound
• fluid discharge from the surgical wound.

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

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

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 due to an allergic reaction
• sudden change in skin colour and appearance
• formation of haematomas
• nosebleeds
• regurgitation of stomach contents into the oesophagus (reflux)
• vomiting
• nausea
• frequent passage of loose or watery stools
• indigestion
• hair loss
• increased liver enzyme activity.

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

• decrease in the number of white blood cells (which help fight infections)
• bleeding may occur into the stomach or intestines, brain, rectum, penis/vagina or urinary tract (including pink or red 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 proportion of red blood cells in the blood
• 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 due to 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 joints, from wounds, surgical incision sites, injection sites, or sites of intravenous catheter insertion
• bleeding from haemorrhoids may occur
• stomach or intestinal ulcer (including oesophageal ulceration)
• abnormal liver function test results.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects 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 effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps provide more information on the safety of this medicine.

5. How to store 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 wastewater. 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 75 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 75 mg is a hard capsule of size “2” (17.5 mm ± 0.4 mm), with a white opaque cap printed with “MD” and a white opaque body printed with “75” in black ink, containing a mixture of white to pale yellow pellets and pale yellow granules.
Tuxanuva 75 mg is available in blisters made of OPA/Aluminium/PE + desiccant/Aluminium/PE, in cardboard boxes containing 10, 30, or 60 hard capsules.
Tuxanuva 75 mg is also available in PP bottles of 120 mL or 150 mL with child-resistant closure and a desiccant in the form of silica gel, 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 medicine, please contact the local representative of the Marketing Authorisation Holder:
Stada Poland Sp. z o.o.
ul. Krakowiaków 44
02-255 Warsaw
Tel. +48 22 737 79 20