Tresuvi

Package leaflet: Information for the user

Tresuvi, 1 mg/ml, solution for infusion
Tresuvi, 2.5 mg/ml, solution for infusion
Tresuvi, 5 mg/ml, solution for infusion
Tresuvi, 10 mg/ml, solution for infusion
Treprostinil

Please read all of this leaflet carefully before using this medicine, because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor.
• This medicine has been prescribed for a specific person. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet:

1. What Tresuvi is and what it is used for
2. Important information before using Tresuvi
3. How to use Tresuvi
4. Possible side effects
5. How to store Tresuvi
6. Contents of the pack and other information

1. What Tresuvi is and what it is used for

What Tresuvi is
The active substance in Tresuvi is treprostinil.
Treprostinil belongs to a group of medicines that act similarly to naturally occurring prostacyclins. Prostacyclins are hormone-like substances that reduce blood pressure by relaxing blood vessels, causing them to widen, which allows blood to flow more easily. Prostacyclins may also help prevent blood from clotting.

What Tresuvi is used for
Tresuvi is used to treat idiopathic or hereditary pulmonary arterial hypertension (PAH) in patients with moderate symptoms. Pulmonary arterial hypertension is a condition in which blood pressure in the blood vessels between the heart and lungs is too high, leading to breathlessness, dizziness, fatigue, fainting, palpitations or irregular heartbeat, dry cough, chest pain, and swelling of the ankles and legs.

At the beginning of treatment, Tresuvi is administered by continuous subcutaneous infusion (infusion under the skin). Some patients do not tolerate this method due to pain and swelling at the infusion site. Your doctor will decide whether, instead of this route, Tresuvi can be administered by continuous intravenous infusion directly into a vein via a central venous catheter connected to an external pump, or, depending on the patient's condition, via a pump surgically implanted under the skin of the abdomen. Your doctor will determine which option is best for you.

How Tresuvi works
Tresuvi reduces blood pressure in the pulmonary arteries, improving blood flow and reducing the workload of the heart. Improved blood flow enhances oxygen delivery to the body and reduces strain on the heart muscle, thereby improving cardiac efficiency. Tresuvi alleviates symptoms associated with pulmonary arterial hypertension and improves exercise tolerance in patients who must limit their physical activity.

2. Important information before using Tresuvi

When not to use Tresuvi:

• if the patient is allergic to treprostinil or any of the other ingredients of this medicine (listed in section 6);
• if the patient has been diagnosed with pulmonary veno-occlusive disease. This is a condition in which the blood vessels in the lungs become swollen and blocked, leading to increased blood pressure in the blood vessels between the heart and lungs;
• if the patient has severe liver disease;
• if the patient has heart disease, for example:
  • heart attack (myocardial infarction) within the last six months;
  • serious heart rhythm disorders;
  • severe coronary artery disease or unstable angina pectoris;
  • diagnosed heart defect, e.g. heart valve defect causing impaired heart function;
  • any untreated heart disease or heart disease not under close medical supervision;
• if the patient has a specific high risk of bleeding – e.g. active peptic ulcer, trauma, or other types of bleeding;
• if the patient has had a stroke within the last 3 months or any other type of cerebrovascular event.

Warnings and precautions
Before starting treatment with Tresuvi, discuss with your doctor if the patient:

• has any liver disease;
• has medically diagnosed obesity (BMI above 30 kg/m²);
• is infected with HIV (human immunodeficiency virus);
• has high blood pressure in the liver veins (portal hypertension);
• has a congenital heart defect that alters the direction of blood flow through the heart.

During treatment with Tresuvi, inform the doctor if the patient:

• develops low blood pressure (hypotension);
• experiences sudden worsening of breathing difficulties or persistent cough (this may be due to pulmonary congestion, asthma, or other conditions). Contact the doctor immediately.
• experiences excessive bleeding, as treprostinil may increase the risk of bleeding by inhibiting blood coagulation;
• develops fever during intravenous treprostinil administration, or redness, swelling, and/or tenderness at the intravenous infusion site, as these may be signs of infection.

Tresuvi and other medicines
Tell the doctor about all medicines the patient is currently taking or has recently taken,
as well as any medicines the patient plans to use. Inform the doctor if the patient is taking:

• medicines used to treat high blood pressure (antihypertensives or other vasodilators);
• medicines used to increase urine output (diuretics), including furosemide;
• medicines used to prevent blood clots (anticoagulants), such as warfarin, heparin, or nitric oxide-releasing agents;
• any non-steroidal anti-inflammatory drugs ( NSAIDs ) (e.g. acetylsalicylic acid, ibuprofen);
• any medicines that may increase or decrease the effect of treprostinil (e.g. gemfibrozil, rifampicin, trimethoprim, deferasirox, phenytoin, carbamazepine, phenobarbital, St. John's wort), as it may be necessary for the doctor to adjust the dose of Tresuvi.

Pregnancy and breastfeeding
Tresuvi is not recommended for use if the patient is pregnant, planning to become pregnant, or suspects she may be pregnant, unless the doctor considers it necessary. The safety of Tresuvi in pregnant women has not been established.
Use of contraception is recommended during treatment with Tresuvi.
Tresuvi is not recommended for use in breastfeeding women unless the doctor considers it necessary.
If Tresuvi is prescribed, breastfeeding should be discontinued, as it is unknown whether this medicine passes into breast milk.
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult her doctor before taking this medicine.

Driving and operating machinery
Tresuvi may cause low blood pressure with dizziness or fainting. In such cases, the patient must not drive or operate machinery and should consult the doctor for advice.

Tresuvi contains sodium
Inform the doctor if the patient is on a low-sodium diet. The doctor will take into account that one vial of Tresuvi contains the following amount of sodium:
Tresuvi 1 mg/ml infusion solution:
The medicine contains up to 36.8 mg of sodium (the main component of table salt) in each 10 ml vial. This corresponds to 1.8% of the maximum recommended daily dietary sodium intake for adults.
Tresuvi 2.5 mg/ml infusion solution:
The medicine contains up to 37.3 mg of sodium (the main component of table salt) in each 10 ml vial. This corresponds to 1.9% of the maximum recommended daily dietary sodium intake for adults.
Tresuvi 5 mg/ml infusion solution:
The medicine contains up to 39.1 mg of sodium (the main component of table salt) in each 10 ml vial. This corresponds to 2.0% of the maximum recommended daily dietary sodium intake for adults.
Tresuvi 10 mg/ml infusion solution:
The medicine contains up to 37.4 mg of sodium (the main component of table salt) in each 10 ml vial. This corresponds to 1.9% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Tresuvi

This medicine should always be used as directed by the doctor. If in doubt, consult your
doctor.
Tresuvi is administered by continuous infusion:

• subcutaneously (under the skin) via a thin tube (cannula) placed in the abdomen or thigh; or
• intravenously via a tube (catheter) usually placed in the neck, chest, or groin.

In both cases, Tresuvi is delivered through the tube using a portable pump
placed outside the patient's body (an external pump).
Before the patient leaves the hospital or clinic, the doctor will instruct the patient on how to prepare Tresuvi
and at what rate the pump should deliver treprostinil.
Flushing the connected infusion line may lead to accidental overdose.
Tresuvi may also be administered intravenously using an implanted infusion pump, usually
surgically placed under the skin of the abdomen. In such cases, the pump and tubing are entirely inside
the patient's body (intracorporeally), and periodic visits to the hospital or clinic (e.g., every
4 weeks) will be necessary to refill the pump's internal reservoir.
Additionally, the patient will receive instructions on how to properly use the pump and what to do if
the pump stops working. These instructions should also include guidance on whom to contact in an emergency.
Tresuvi must be diluted only when administered by continuous intravenous infusion:
Administration by intravenous infusion using an external portable pump: treprostinil should be diluted
only with sterile water for injections or 0.9% sodium chloride for injections (as directed by
the doctor).
Administration by intravenous infusion using an implanted infusion pump: the patient must attend
periodic visits (e.g., every 4 weeks) at the hospital or clinic, where a trained healthcare professional
will dilute the treprostinil solution with 0.9% sodium chloride for injections and refill the
pump's internal reservoir.
Adult patients
Tresuvi, solution for infusion, is available in concentrations of 1 mg/mL; 2.5 mg/mL; 5 mg/mL; or 10 mg/mL. The doctor
will determine the infusion rate and dose appropriate for the patient's clinical condition.
Patients with obesity
In patients with obesity (body weight exceeding ideal body weight by 30% or more), the doctor will determine
the initial and subsequent doses based on the patient's ideal body weight. See also section 2
"Warnings and precautions".
Elderly patients
The doctor will determine the infusion rate and dose appropriate for the patient's clinical condition.
Use in children and adolescents
Limited data are available on the use of this medicine in children and adolescents.
Dose adjustment
The infusion rate may be individually increased or decreased for each patient only under
medical supervision.
The goal of dose adjustment is to establish an effective maintenance dose that alleviates PAH symptoms
while minimizing adverse effects.
If symptoms worsen or the patient requires complete rest or is confined to bed or chair, or if any physical exertion
causes discomfort and symptoms occur at rest, do not increase the dose without consulting the doctor. This medicine may be insufficient in managing the patient's symptoms, and alternative treatment may be necessary.
Preventing bloodstream infections during intravenous administration of Tresuvi
As with any long-term intravenous therapy, there is a risk of bloodstream infection. The doctor should
train the patient on how to prevent such infections.
Use of more than the recommended dose of Tresuvi
In case of accidental overdose of this medicine, the patient may experience nausea, vomiting, diarrhea,
low blood pressure (dizziness, lightheadedness, or fainting), sudden facial flushing, and (or) headache.
If any of these symptoms become severe, contact the doctor immediately or go to the hospital. The doctor may
reduce the infusion rate or temporarily discontinue the infusion until symptoms resolve. Tresuvi administration will then be
resumed at the dose recommended by the doctor.
Stopping treatment with Tresuvi
This medicine should always be used as directed by the doctor or hospital specialist. Do not
stop using Tresuvi unless instructed by the doctor.
Sudden discontinuation or abrupt reduction in treprostinil dosage may result in recurrence of pulmonary arterial
hypertension symptoms, possibly with sudden and severe deterioration in the patient's condition.
If you have any further questions about the use of this medicine, consult your doctor.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.

Very common (may affect more than 1 in 10 patients):

• Vasodilation with sudden redness of the facial skin
• Pain or tenderness around the infusion site
• Skin discoloration or bruising around the infusion site
• Headache
• Skin rash
• Nausea
• Diarrhea
• Jaw pain

Common (may affect up to 1 in 10 patients):

• Dizziness
• Vomiting
• Feeling faint or lightheaded due to low blood pressure
• Itching or redness of the skin
• Swelling of the feet, ankles, legs, or fluid retention
• Bleeding events, such as nosebleeds, coughing up blood, blood in the urine, bleeding gums, blood in the stool
• Joint pain
• Muscle pain
• Pain in legs and/or arms

Other possible adverse reactions (frequency cannot be determined from available data):

• Infection at the infusion site
• Abscess at the infusion site
• Decrease in platelet count (thrombocytopenia) (platelets responsible for blood clotting)
• Bleeding at the infusion site
• Infection of subcutaneous tissue (cellulitis)
• Bone pain
• Skin rash with discoloration or raised nodules
• Heart failure with high cardiac output leading to breathlessness, fatigue, swelling of legs and abdomen, and persistent cough (high-output heart failure)

Additional adverse reactions related to intravenous administration (frequency cannot be determined from available data):

• Inflammation of the vein (thrombophlebitis)
• Bacterial infection of the blood (bacteremia)* (see section 3)
• Sepsis (severe bacterial blood infection)

* Life-threatening or fatal cases of bacterial blood infections have been reported.

Reporting of adverse reactions

If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02222 Warsaw, Tel: +48 22 4921301, Fax: +48 22 4921309, 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 Tresuvi

Keep this medicine out of the sight and reach of children.
No special storage instructions are required for this medicine.
Do not use this medicine after the expiry date stated on the carton and vial following the abbreviation EXP.
The expiry date refers to the last day of the stated month.
Do not use this medicine if the vial is damaged, discoloured, or if there are any other signs of deterioration in quality.
The vial of Tresuvi must be used or discarded within 30 days of first opening.
During continuous subcutaneous infusion, one container (syringe) of undiluted Tresuvi must be used within 14 days.
During continuous intravenous infusion, one container (syringe) of diluted Tresuvi must be used within 24 hours.
During continuous intravenous infusion using an implanted infusion pump, diluted Tresuvi placed in the pump reservoir must be used within a maximum of 30 days. A healthcare professional will inform the patient when the pump reservoir needs to be refilled.
Any unused portion of diluted solution must be discarded.
Instructions for use can be found in section 3, "How to use Tresuvi".
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

What Tresuvi contains
The active substance is treprostinil 1 mg/ml, 2.5 mg/ml, 5 mg/ml or 10 mg/ml.
The other components are:
sodium citrate, sodium chloride, sodium hydroxide 1 M, hydrochloric acid 1 M (for pH adjustment), metacresol and water for injections.

What Tresuvi looks like and contents of the pack
Tresuvi is a clear, colourless to slightly yellow solution free from visible solid particles, available in 10 ml colourless type I glass vials closed with a chlorobutyl rubber stopper coated with Teflon and a coloured flip-off cap:

• Tresuvi 1 mg/ml infusion solution has a yellow rubber cap.
• Tresuvi 2.5 mg/ml infusion solution has a blue rubber cap.
• Tresuvi 5 mg/ml infusion solution has a green rubber cap.
• Tresuvi 10 mg/ml infusion solution has a red rubber cap.

Each pack contains one vial.

Marketing Authorisation Holder
Amomed Pharma GmbH
Leopold-Ungar-Platz 2
1190 Vienna
Austria

Manufacturer
AOP Orphan Pharmaceuticals GmbH
Leopold-Ungar-Platz 2
1190 Vienna
Austria

This medicinal product is authorised for sale in the Member States of the European Economic Area under the following names:
Austria Treposa, Infusionslösung
Bulgaria Tresuvi, инфузионен разтвор
Czech Republic Tresuvi, infuzní roztok
Denmark Tresuvi, infusionsvæske, opløsning
Finland Treposa, infuusioneste, liuos
Greece Tresuvi, Διάλυμα για έγχυση
Spain Tresuvi, solución para perfusión
Norway Tresuvi, infusionsvæske, oppløsning
Poland Tresuvi, roztwór do infuzji
Portugal Tresuvi, solução para perfusão
Romania Tresuvi, soluţie perfuzabilǎ
Slovakia Tresuvi, infúzny roztok
Slovenia Treprostinil Amomed, raztopina za infundiranje
Hungary Tresuvi, oldatos infúzió