TRESUVI 2.5 mg/ml SOLUTION FOR INFUSION

2. What you need to know before you use Tresuvi

Do not use Tresuvi:

• if you are allergic to treprostinil or any of the other ingredients of this medicine (listed in section 6).
  • if you have been diagnosed with a disease called "pulmonary veno-occlusive disease". In this disease, the blood vessels that carry blood through the lungs become swollen and blocked, increasing the pressure in the blood vessels between the heart and lungs.
  • if you have severe liver failure
  • if you have a heart problem, for example:
• a heart attack (myocardial infarction) in the last six months
• severe changes in heart rate
• severe coronary heart disease or unstable angina
• a diagnosis of heart defect, such as a defective heart valve that causes the heart to malfunction
• any heart disease that is not being treated or is under close medical supervision
  • if you are at specific risk of bleeding; for example, active stomach ulcers, injuries, or other bleeding conditions
  • if you have had a stroke in the last 3 months, or any interruption of blood supply to the brain

Warnings and precautions

Consult your doctor before starting to use Tresuvi if:

• you have any liver disease
• you have been told that you are clinically obese (BMI over 30 kg/m2)
• you have an HIV infection (human immunodeficiency virus)
• you have high blood pressure in the liver veins (portal hypertension)
• you have a congenital heart defect that affects the way blood circulates through it

During treatment with this medicine, inform your doctor:

• if your blood pressure decreases (hypotension)
• if you experience a rapid increase in breathing difficulties or persistent cough (may be related to congestion in the lungs, asthma, or other conditions); consult your doctor immediately.
• if you experience excessive bleeding, as treprostinil may increase the risk by preventing blood clotting
• if you develop a fever while receiving treprostinil intravenously, or if the infusion site becomes red, swollen, and/or painful to the touch, as this could be a sign of infection

Other medicines and Tresuvi

Tell your doctor if you are taking/using, have recently taken/used, or might take/use any other medicines. Tell your doctor if you are taking:

• medicines used to treat high blood pressure (antihypertensive medicines or other vasodilators)
• medicines used to increase the amount of urine excreted (diuretics), including furosemide
• medicines that prevent blood clotting (anticoagulants), such as warfarin, heparin, or nitric oxide medications
• any non-steroidal anti-inflammatory drug (NSAID) (e.g., acetylsalicylic acid, ibuprofen)
  • medicines that may increase or decrease the effect of treprostinil (e.g., gemfibrozil, rifampicin, trimethoprim, deferasirox, phenytoin, carbamazepine, phenobarbital, St. John's Wort), as your doctor may need to adjust your dose of treprostinil

Pregnancy and breastfeeding

This medicine is not recommended if you are pregnant, think you may be pregnant, or plan to become pregnant, unless your doctor considers it essential. The safety of this medicine for use during pregnancy has not been established.

It is highly recommended to use contraceptive methods during treatment with treprostinil.

This medicine is not recommended during breastfeeding, unless your doctor considers it essential. You are advised to discontinue breastfeeding if you are prescribed treprostinil, as it is unknown whether this medicine passes into breast milk.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Driving and using machines

This medicine may cause low blood pressure with dizziness and fainting. In such cases, do not drive or use machines, and consult your doctor.

Tresuvi contains sodium

Tell your doctor if you are on a controlled sodium diet. Your doctor will take into account that a vial of Tresuvi contains the following amounts of sodium:

Tresuvi 1 mg/ml solution for infusion:

This medicine contains a maximum of 36.8 mg of sodium (main component of table/cooking salt) in each 10 ml vial. This is equivalent to 1.8% of the maximum recommended daily sodium intake for an adult.

Tresuvi 2.5 mg/ml solution for infusion:

This medicine contains a maximum of 37.3 mg of sodium (main component of table/cooking salt) in each 10 ml vial. This is equivalent to 1.9% of the maximum recommended daily sodium intake for an adult.

Tresuvi 5 mg/ml solution for infusion:

This medicine contains a maximum of 39.1 mg of sodium (main component of table/cooking salt) in each 10 ml vial. This is equivalent to 2.0% of the maximum recommended daily sodium intake for an adult.

Tresuvi 10 mg/ml solution for infusion:

This medicine contains a maximum of 37.4 mg of sodium (main component of table/cooking salt) in each 10 ml vial. This is equivalent to 1.9% of the maximum recommended daily sodium intake for an adult.

3. How to use Tresuvi

Follow the instructions for administration of this medicine exactly as indicated by your doctor. In case of doubt, consult your doctor again.

Tresuvi is administered as a continuous infusion:

• subcutaneously (under the skin) through a small tube (cannula) placed in the abdomen or thigh;

or

• intravenously through a tube (catheter) that is usually placed in the neck, chest, or groin.

In both cases, a portable pump located outside your body (external) pumps treprostinil through the tube.

Before leaving the hospital or clinic, your doctor will inform you how to prepare this medicine and at what speed the pump should administer the treprostinil.

Flushing the infusion line while it is connected can cause an accidental overdose.

Alternatively, Tresuvi can be administered intravenously through an implantable infusion pump, which is usually surgically inserted under the abdominal skin. In this case, the pump and catheters are entirely inside your body (internal), and you will need to attend the hospital or clinic periodically (e.g., every 4 weeks) to have the internal reservoir refilled.

In either case, you will also be given information on how to use the pump correctly and what to do if it stops working. The information will also indicate who to contact in case of an emergency.

Tresuvi is diluted only when administered as a continuous intravenous infusion:

For intravenous infusion with an external portable pump:You should only dilute the treprostinil solution with sterile water for injection or sodium chloride 0.9% solution for injection (as indicated by your doctor).

For intravenous infusion with an implantable infusion pump:You will need to attend the hospital or clinic periodically (e.g., every 4 weeks), where healthcare professionals will dilute your treprostinil solution with sodium chloride 0.9% solution for injection and refill the internal reservoir.

Adult patients

Tresuvi is available as a solution for infusion of 1 mg/ml, 2.5 mg/ml, 5 mg/ml, or 10 mg/ml. Your doctor will determine the infusion rate and the suitable dose for your disease.

Overweight patients

If you are overweight (30% or more than your ideal body weight), your doctor will determine the initial dose and subsequent doses based on your ideal body weight. See also section 2, "Warnings and precautions".

Elderly patients

Your doctor will determine the infusion rate and the suitable dose for your disease.

Use in children and adolescents

There are limited data available for children and adolescents.

Dose adjustment

The infusion rate can be reduced or increased individually only under medical supervision.

The goal of adjusting the infusion rate is to establish an effective maintenance rate that improves the symptoms of PAH and minimizes any undesirable effects.

If your symptoms increase or if you need complete rest, or are confined to bed or a chair, or if any physical activity causes you discomfort and your symptoms appear at rest, do not increase the dose without consulting your doctor. This medicine may no longer be sufficient to treat your disease, and other treatment may be necessary.

How can bloodstream infections with Tresuvi by intravenous route be avoided?

As with any long-term intravenous treatment, there is a risk of contracting bloodstream infections. Your doctor will indicate how to avoid them.

If you use more Tresuvi than you should

If you accidentally receive an overdose of this medicine, you may experience nausea, vomiting, diarrhea, low blood pressure (dizziness, fainting), flushing of the skin, and/or headache.

If any of these symptoms become severe, you should contact your doctor or hospital immediately. The doctor may reduce the dose or interrupt the administration until the symptoms disappear. Then, the administration of treprostinil will be resumed with the dose recommended by your doctor.

If you stop using Tresuvi

Always use treprostinil according to the instructions of your doctor or hospital specialist. Do not stop using Tresuvi unless your doctor tells you to do so.

Sudden withdrawal or rapid reductions in the dose of treprostinil can cause the reappearance of pulmonary arterial hypertension with the possibility of rapid and severe deterioration of your condition.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Very common (may affect more than 1 in 10 people)

• vasodilation with flushing
• pain or sensitivity to the touch around the infusion site
• discoloration of the skin or bruising around the infusion site
• headache
• skin rash
• nausea
• diarrhea
• jaw pain

Common (may affect up to 1 in 10 people)

• dizziness
• vomiting
• fainting or dizziness due to low blood pressure
• itching or redness of the skin
• swelling of feet, ankles, legs, or fluid retention
• bleeding episodes, such as nosebleeds, coughing up blood, blood in the urine, bleeding gums, blood in the 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 blood clotting cells (platelets) (thrombocytopenia)
• bleeding at the infusion site
• infection of the tissues under the skin (cellulitis)
• bone pain
• skin rash with discoloration or raised bumps

heart failure with a high volume of blood pumped by the heart over a period, causing difficulty breathing, fatigue, swelling of the legs and abdomen, and persistent cough (high-output heart failure)

Other side effects associated with the intravenous route of administration (frequency cannot be estimated from the available data)

• inflammation of the veins (thrombophlebitis)
• bacterial infection of the bloodstream (bacteremia)* (see section 3)
• septicemia (severe bacterial infection of the blood)

• Potentially life-threatening or fatal cases of bloodstream infections have been reported

Reporting of side effects

If you experience any side effects, talk to your doctor, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaRAM.es.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Tresuvi

Keep this medicine out of the sight and reach of children.

No special storage conditions are required.

Do not use this medicine after the expiry date stated on the carton and vial after EXP. The expiry date is the last day of the month indicated.

Do not use this medicine if you notice any damage to the vial, color change, or other signs of deterioration. The Tresuvi vial should be used or discarded within 30 days of first opening.

During continuous subcutaneousinfusion, a single container (syringe) of undiluted Tresuvi should be used within 14 days.

During continuous intravenousinfusion, a single container (syringe) of diluted Tresuvi should be used within 24 hours.

During continuous intravenous infusion through implantable infusion pumps, the diluted Tresuvi solution introduced into the pump reservoir should be used within a maximum of 30 days. The healthcare professional will indicate the duration of the interval until the next reservoir refill.

Any unused diluted solution should be discarded.

The instructions for use can be found in section 3, "How to use Tresuvi".

Medicines should not be disposed of via wastewater or household waste. Return the containers and any unused medicines to the pharmacy. If you have any doubts, ask your pharmacist how to dispose of the containers and any unused medicines. This will help protect the environment.

6. Packaging Contents and Additional Information

Tresuvi Contents

The active ingredient is treprostinil (1 mg/ml, 2.5 mg/ml, 5 mg/ml, 10 mg/ml).

The other components are:

Sodium citrate (E331), sodium chloride, sodium hydroxide (E-524), hydrochloric acid (for pH adjustment), metacresol, and water for injectable preparations.

Product Appearance and Packaging Contents

Tresuvi is a clear, colorless to slightly yellowish solution, without visible particles, available in a 10 ml transparent glass vial, sealed with a rubber stopper and a color-coded closure cap:

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

Each box 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

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

AOP Orphan Pharmaceuticals Iberia S.L.U.

Calle de Cólquide nº6, Edif. Prisma – Portal 2, 1º F

28231, Las Rozas, Madrid

Spain

This medication is authorized in the member states of the European Economic Area under the following names:

Austria Treposa 1/2.5/ 5/ 10 mg/ ml Infusionslösung

Bulgaria Tresuvi 1/2.5/ 5/ 10 mg/ ml инфузионен разтвор

Czech Republic Tresuvi 1/2.5/ 5/ 10 mg/ ml Infuzní roztok

Denmark Tresuvi 1/2.5/ 5/ 10 mg/ ml Infusionsvæske, opløsning

Greece Tresuvi 1/2.5/ 5/ 10 mg/ ml Διοσμητικό για έγχυση

Spain Tresuvi 1/2.5/ 5/ 10 mg/ ml Solución para perfusión

Finland Treposa 1/2.5/ 5/ 10 mg/ ml Infuusioneste, liuos

Hungary Tresuvi 1/2.5/ 5/ 10 mg/ ml Oldatos infúzió

Norway Tresuvi 1/2.5/ 5/ 10 mg/ ml Infusionsvæske, oppløsning

Poland Tresuvi 1/2.5/ 5/ 10 mg/ ml Roztwór do infuzji

Portugal Tresuvi 1/2.5/ 5/ 10 mg/ ml solução para perfusão

Romania Tresuvi 1/2.5/ 5/ 10 mg/ ml Solutie perfuzabila

Slovakia Tresuvi 1/2.5/ 5/ 10 mg/ ml Infúzny roztok

Slovenia Treprostinil Amomed 1/2.5/ 5/ 10 mg/ ml Raztopina za infundiranje

Date of the last revision of this prospectus:08/2023

Other sources of information

Detailed information about this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)