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
Treprostynil

Read the package leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor.
• This medicine 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, please inform your doctor or pharmacist. See section 4.

Package Leaflet Contents:

• 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 of Tresuvi is treprostynil.
Treprostynil belongs to a group of medicines that work in a similar way to naturally occurring prostacyclins. Prostacyclins are hormone-like substances that lower blood pressure by relaxing blood vessels, allowing blood to flow more easily. Prostacyclins may also prevent blood clotting.

What Tresuvi is used for

Tresuvi is used to treat pulmonary arterial hypertension (PAH) in patients with moderate symptoms. Pulmonary arterial hypertension is a disease in which the blood pressure in the blood vessels between the heart and lungs is too high, causing shortness of breath, dizziness, fatigue, fainting, palpitations, or irregular heartbeat, dry cough, chest pain, and swelling of the ankles and legs.
Initially, Tresuvi is given as a continuous subcutaneous infusion (under the skin). Some patients may not tolerate this method of administration due to pain and swelling at the infusion site. The doctor will decide whether Tresuvi can be given as a continuous intravenous infusion directly into a vein after inserting a central venous catheter connected to an external pump or, depending on the patient's condition, an implanted pump under the abdominal skin. The doctor will decide which option is best for the patient.

How Tresuvi works

Tresuvi lowers blood pressure in the pulmonary arteries, improving blood flow and reducing the workload on the heart. Improved blood flow leads to better oxygen supply to the body and reduces the strain on the heart muscle, improving its efficiency. Tresuvi alleviates symptoms associated with pulmonary arterial hypertension and improves exercise tolerance in patients who need to limit physical activity.

2. Important information before using Tresuvi

When not to use Tresuvi:

• if you are allergic to treprostynil or any of the other ingredients of this medicine (listed in section 6);
• if you have pulmonary veno-occlusive disease, a disease in which there is swelling of the blood vessels in the lungs and their blockage, leading to increased blood pressure in the blood vessels between the heart and lungs;
• if you have severe liver disease;
• if you have heart disease, such as:
• heart attack (myocardial infarction) within the last six months;
• severe arrhythmias;
• severe coronary artery disease or unstable angina;
• diagnosed heart valve disease, e.g., heart valve disease that impairs heart function;
• any untreated or unmonitored heart disease;
• if you have a specific high risk of bleeding, such as active peptic ulcer disease, injuries, or other types of bleeding;
• if you have had a stroke within the last three months or other cerebral circulation disorders.

Warnings and precautions

Before starting treatment with Tresuvi, you should discuss with your doctor if you:

• have any liver disease;
• have medically recognized obesity (BMI over 30 kg/m);
• are infected with HIV (human immunodeficiency virus);
• have high blood pressure in the liver veins (portal hypertension);
• have a congenital heart defect that changes the direction of blood flow through the heart.

During treatment with Tresuvi, you should tell your doctor:

• if you experience a decrease in blood pressure (hypotension);
• if you experience sudden worsening of breathing difficulties or persistent cough (may be caused by pulmonary congestion, asthma, or other diseases). You should contact your doctor immediately.
• if you experience excessive bleeding, as treprostynil may increase the risk of bleeding by inhibiting blood clotting;
• if you experience fever during intravenous administration of treprostynil or redness, swelling, and/or pain at the infusion site, as these may be signs of infection.

Tresuvi and other medicines

You should tell your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take. You should tell your doctor if you are taking:

• medicines used to treat high blood pressure(antihypertensive or other vasodilating medicines);
• medicines used to increase the amount of urine excreted(diuretics), including furosemide;
• medicines that prevent blood clots(anticoagulants), such as warfarin, heparin, or nitric oxide donors;
• any non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., acetylsalicylic acid, ibuprofen);
• medicines that may increase or decrease the effect of treprostynil (e.g., gemfibrozil, rifampicin, trimethoprim, deferasirox, phenytoin, carbamazepine, phenobarbital, St. John's Wort), as the dose of Tresuvi may need to be adjusted by your doctor.

It may be necessary to adjust the dose of Tresuvi.

Pregnancy and breastfeeding

Tresuvi is not recommended during pregnancy, if you are planning to have a baby, or if you suspect you may be pregnant, unless your doctor considers it necessary. The safety of Tresuvi in pregnant women has not been established.
During treatment with Tresuvi, contraception is recommended.
Tresuvi is not recommended during breastfeeding, unless your doctor considers it necessary. If Tresuvi is prescribed to a breastfeeding woman, breastfeeding should be discontinued, as it is not known whether this medicine passes into breast milk.
If you are pregnant, breastfeeding, suspect you may be pregnant, or plan to have a baby, you should consult your doctor before taking this medicine.

Driving and using machines

Tresuvi may cause low blood pressure with dizziness or fainting. In such cases, you should not drive or operate machinery and should consult your doctor for advice.

Tresuvi contains sodium

You should tell your doctor if you are on a low-sodium diet. Your doctor will consider that one vial of Tresuvi contains the following amount of sodium:
Tresuvi 1 mg/ml solution for infusion:
The medicine contains a maximum of 36.8 mg of sodium (the main component of common salt) per 10 ml vial. This corresponds to 1.8% of the maximum recommended daily intake of sodium in the diet for adults.
Tresuvi 2.5 mg/ml solution for infusion:
The medicine contains a maximum of 37.3 mg of sodium (the main component of common salt) per 10 ml vial. This corresponds to 1.9% of the maximum recommended daily intake of sodium in the diet for adults.
Tresuvi 5 mg/ml solution for infusion:
The medicine contains a maximum of 39.1 mg of sodium (the main component of common salt) per 10 ml vial. This corresponds to 2.0% of the maximum recommended daily intake of sodium in the diet for adults.
Tresuvi 10 mg/ml solution for infusion:
The medicine contains a maximum of 37.4 mg of sodium (the main component of common salt) per 10 ml vial. This corresponds to 1.9% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to use Tresuvi

This medicine should always be used as directed by your doctor. If you are unsure, consult your doctor.
Tresuvi is administered as a continuous infusion:

• subcutaneously (under the skin) through a thin tube (cannula) inserted into the abdomen or thigh; or
• intravenously through a tube (catheter) usually inserted into the neck, chest, or groin.

In both cases, Tresuvi is administered through a tube using a portable pump placed outside the patient's body (external pump).
Before the patient leaves the hospital or clinic, the doctor will tell the patient how to prepare Tresuvi and at what rate the pump should deliver treprostynil.
Flushing the connected infusion line may cause accidental overdose.
Tresuvi can also be administered intravenously using an implanted infusion pump, usually surgically implanted under the abdominal skin. In this case, the pump and tubes are completely inside the patient's body (intracorporeally) and periodic hospital or clinic visits (e.g., every 4 weeks) will be necessary to refill the internal reservoir of the pump.
Additionally, the patient will receive information on how to properly use the pump and what to do if the pump stops working. The information provided should also include instructions on who to contact in case of an emergency.
Tresuvi is diluted only when administered as a continuous intravenous infusion:
Intravenous administration using an external portable pump:treprostynil should be diluted exclusively with sterile water for injection or 0.9% sodium chloride for injection (as recommended by the doctor).
Intravenous administration using an implanted infusion pump:the patient must come for periodic visits (e.g., every 4 weeks) to the hospital or clinic, where a specialized healthcare professional will dilute the treprostynil solution with 0.9% sodium chloride for injection and refill the internal reservoir of the pump.
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 suitable for the patient's clinical condition.
Patients with obesity
In the case of patients with obesity (weight exceeding 30% or more of the ideal body weight), the doctor will determine the initial dose 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 suitable for the patient's clinical condition.

Use in children and adolescents

Only limited data are available on the use of Tresuvi in children and adolescents.
Dose adjustment
The infusion rate can be decreased or increased individually for each patient only under medical supervision.
The goal of dose adjustment is to establish an effective maintenance dose that alleviates PAH symptoms and minimizes the occurrence of side effects.
If symptoms worsen or the patient needs complete rest or is limited to bed or chair, or if any physical exertion causes discomfort, and symptoms occur at rest, do not increase the dose without consulting your doctor. This medicine may be insufficient to treat the patient's symptoms, and other treatment may be necessary.

Prevention of blood infections during intravenous administration of Tresuvi

Similarly, as with any long-term intravenous treatment, there is a risk of blood infection. The doctor should train the patient on how to prevent this.

Use of a higher than recommended dose of Tresuvi

In case of accidental overdose of this medicine, the patient may experience nausea, vomiting, diarrhea, low blood pressure (dizziness, feeling of emptiness in the head or fainting), sudden flushing of the face, and/or headache.
If the severity of any of these symptoms is severe, you should contact your doctor immediately or go to the hospital. The doctor may decrease the infusion rate or stop it until the symptoms subside. Administration of Tresuvi will then be resumed at the dose recommended by the doctor.

Stopping treatment with Tresuvi

This medicine should always be used as directed by your doctor or a specialist in the hospital. Do not stop using Tresuvi unless your doctor has told you to do so.
Sudden withdrawal or sudden decrease in the dose of treprostynil may cause a recurrence of pulmonary arterial hypertension symptoms with possible sudden and severe worsening of the patient's condition.
If you have any further questions about the use of this medicine, ask your doctor.

4. Possible side effects

Like all medicines, Tresuvi can cause side effects, although not everybody gets them.
Very common (may affect more than 1 in 10 people)

• vasodilation with sudden flushing of the face
• pain or tenderness around the infusion site
• discoloration or bruising around the infusion site
• headaches
• skin rash
• nausea
• diarrhea
• jaw pain

Common (may affect up to 1 in 10 people)

• dizziness
• vomiting
• feeling of emptiness in the head or fainting caused by low blood pressure
• itching or flushing of the skin
• swelling of the feet, ankles, legs, or fluid retention
• cases of bleeding, such as nosebleeds, coughing up blood, blood in urine, bleeding from the gums, or blood in stool
• joint pain
• muscle pain
• pain in the legs and/or arms

Other possible side effects (frequency cannot be estimated from the available data)

• infection at the infusion site
• abscess at the infusion site
• decrease in the number of platelets (responsible for blood clotting) (thrombocytopenia)
• bleeding at the infusion site
• infection of the tissue under the skin (cellulitis)
• bone pain
• skin rash with discoloration or raised bumps
• heart failure with a large volume of blood pumped by the heart in a given time, leading to shortness of breath, fatigue, swelling of the legs and abdomen, and persistent cough (heart failure with increased cardiac output).

Additional side effects related to intravenous administration (frequency cannot be estimated from the available data)

• phlebitis (thrombophlebitis)
• bacterial infection of the blood (bacteremia)* (see section 3)
• sepsis (severe bacterial infection of the blood).

* Cases of life-threatening or fatal bacterial infections of the blood have been reported.

Reporting side effects

If you experience any side effects, including those not listed in this package leaflet, please inform your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 4921301, fax: +48 22 4921309, website: https://smz.ezdrowie.gov.pl .
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Tresuvi

Medicines should be kept out of the sight and reach of children.

There are no special precautions for storage.
Do not use this medicine after the expiry date stated on the carton and vial after EXP.
The expiry date refers to the last day of the month stated.
Do not use this medicine if you notice damage to the vial, discoloration, or other signs of deterioration. The vial of Tresuvi should be used or discarded within 30 days of first opening.
During continuous subcutaneous infusion, one container (syringe) of undiluted Tresuvi should be used within 14 days.
During continuous intravenous infusion, one container (syringe) of diluted Tresuvi should be used within 24 hours.
During continuous intravenous infusion using an implanted infusion pump, the diluted Tresuvi solution introduced into the pump reservoir must be used within a maximum of 30 days. A specialized healthcare professional will inform the patient when to refill the pump reservoir.
Any unused diluted solution should be discarded.
Information on the use of Tresuvi can be found in section 3 "How to use Tresuvi".
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Tresuvi contains

The active substance is treprostynil 1 mg/ml, 2.5 mg/ml, 5 mg/ml, or 10 mg/ml.
The other ingredients are:
sodium citrate, sodium chloride, sodium hydroxide 1 M, hydrochloric acid 1 M (for pH adjustment), metacresol, and water for injection.

What Tresuvi looks like and contents of the pack

Tresuvi is a clear, colorless to slightly yellow solution, without visible particles, available in 10 ml glass vials type I, closed with a chlorobutyl rubber stopper coated with Teflon and a colored flip-off cap:

• Tresuvi 1 mg/ml solution for infusion has a yellowrubber cap.
• Tresuvi 2.5 mg/ml solution for infusion has a bluerubber cap.
• Tresuvi 5 mg/ml solution for infusion has a greenrubber cap.
• Tresuvi 10 mg/ml solution for infusion has a redrubber cap.

Each pack contains one vial.

Marketing authorization holder

Amomed Pharma GmbH
Leopold-Ungar-Platz 2
1190 Vienna
Austria

Manufacturer

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

This medicine is authorized 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
Date of last revision of the package leaflet:31.08.2023