Leaflet: information for the user

Tresuvi 1mg/ml solution for infusion EFG

Tresuvi 2.5mg/ml solution for infusion EFG

Tresuvi 5mg/ml solution for infusion EFG

Tresuvi 10mg/ml solution for infusion EFG

Treprostinilo

Read this leaflet carefully before starting to use this medicine, because it contains important information for you.

-Keep this leaflet, as you may need to read it again.

-If you have any doubts, consult your doctor or pharmacist.

-This medicine has been prescribed only for you, and you must not give it to other people, even if they have the same symptoms as you, as it may harm them.

-If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1.What Tresuvi is and for what it is used

2.What you need to know before starting to use Tresuvi

3.How to use Tresuvi

4.Possible side effects

5.Storage of Tresuvi

6.Contents of the pack and additional information

What is Tresuvi

The active ingredient of Tresuvi is treprostinilo.

Treprostinilo belongs to a group of medications whose action is similar to that of natural prostacyclins. Prostacyclins are substances similar to hormones that reduce blood pressure by relaxing blood vessels, allowing blood to flow more easily. Prostacyclins can also prevent blood coagulation.

What is Tresuvi used for

Treprostinilo is used to treat idiopathic or hereditary pulmonary arterial hypertension (PAH) in patients with moderate symptoms. Pulmonary arterial hypertension is a disease in which blood pressure is too high in the blood vessels between the heart and lungs. This causes difficulty breathing, dizziness, fatigue, fainting, palpitations or abnormal heartbeats, dry cough, chest pain, and swelling of the ankles or legs.

Tresuvi is initially administered in the form of a continuous subcutaneous infusion (under the skin). Some patients may not tolerate this administration because it causes pain and swelling. The doctor will decide if it is possible to administer this medication through a continuous intravenous infusion (directly into a vein) with the insertion of a central intravenous catheter (catheter) connected to an external pump, or, depending on their condition, to an implanted pump surgically placed under the skin of the abdomen. The doctor will decide which option is best for you.

How Tresuvi works

Tresuvi reduces arterial pressure in the pulmonary artery by improving blood flow and reducing heart workload. Improved blood flow leads to better oxygen supply to the body and reduced heart effort, making the heart work more efficiently. Tresuvi improves symptoms associated with PAH and exercise capacity in patients who are limited in terms of activity.

Do not use Tresuvi:

•if you are allergic to treprostinil or any of the other ingredients in this medicine (listed in section 6).

-if you have been diagnosed with a condition called pulmonary veno-occlusive disease. In this condition, the blood vessels that carry blood to the lungs become swollen and blocked, increasing the pressure in the blood vessels between the heart and lungs.

-if you have severe liver disease

-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 angina

•a heart defect, such as a faulty heart valve that causes the heart to malfunction

•any heart disease that is not being treated or closely monitored by a doctor

-if you have a specific risk of bleeding; for example, active stomach ulcers, injuries or other bleeding conditions

-if you have had a stroke in the last three months, or any interruption to the 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 greater than 30 kg/m2)

-you have HIV (human immunodeficiency virus)

-you have high blood pressure in the veins of the liver (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 drops (hypotension)

-if you experience a rapid increase in breathing difficulties or persistent cough (which may be related to congestion in the lungs, asthma or other conditions); consult your doctor immediately.

-if you have excessive bleeding, as treprostinil may increase the risk of bleeding by preventing blood clotting

-if you experience fever while receiving treprostinil by intravenous infusion, or if the site of intravenous administration becomes red, swollen and/or painful to the touch, as this could be a sign of infection

Other medicines and Tresuvi

Inform your doctor if you are taking/using, have taken/used recently or may need to take/use any other medicine. Inform your doctor if you are taking:

-medicines used to treat high blood pressure (anti-hypertensive 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 medicines containing nitric oxide

-any non-steroidal anti-inflammatory (NSAID) (e.g., aspirin, 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 treprostinil dose

Pregnancy and breastfeeding

This medicine is not recommended for use if you are pregnant, think you may be pregnant or intend 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 for use during breastfeeding, unless your doctor considers it essential. You are advised to stop 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 intend to become pregnant, consult your doctor before using this medicine.

Driving and operating machinery

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

Tresuvi contains sodium

Inform your doctor if you follow a low-sodium diet. Your doctor will take into account that one vial of Tresuvi contains the following amounts of sodium:

Tresuvi 1mg/ml infusion solution:

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

Tresuvi 2.5mg/ml infusion solution:

This medicine containsa maximum of37.3mg of sodium (main component of table salt/for cooking) in each 10ml vial. This is equivalent to 1.9% of the recommended maximum daily sodium intake for an adult.

Tresuvi 5mg/ml infusion solution:

This medicine containsa maximum of39.1mg of sodium (main component of table salt/for cooking) in each 10ml vial. This is equivalent to 2.0% of the recommended maximum daily sodium intake for an adult.

Tresuvi 10mg/ml infusion solution:

This medicine containsa maximum of37.4mg of sodium (main component of table salt/for cooking) in each 10ml vial. This is equivalent to 1.9% of the recommended maximum daily sodium intake for an adult.

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

Tresuvi is administered in the form of continuous infusion:

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

or

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

In both cases, a portable pump placed outside the body (external) pumps treprostinilthrough the tube.

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

Flush the infusion line while it is connected may cause an accidental overdose.

Alternatively, Tresuvi can be administered by intravenous infusion through an implantable infusion pump, which is usually inserted surgically under the skin of the abdomen. In this case, the pump and catheters are completely inside the body (internal), and you will have to attend periodically at the hospital or clinic (e.g., every 4 weeks) to have the internal reservoir recharged.

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 should also indicate who to contact in case of an emergency.

Tresuvi is diluted only when administered in the form of continuous intravenous infusion:

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

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

Adult patients

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

Patients with obesity

If you are obese (30% or more above 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".

Older patients

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

Use in children and adolescents

Data are limited for children and adolescents.

Dose adjustment

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

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

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

How to prevent bloodstream infections with Tresuvi by intravenous route?

Like any long-term intravenous treatment, there is a risk of contracting bloodstream infections. Your doctor will inform you how to prevent them.

If you use more Tresuvi than you should

If you receive an accidental overdose of this medication, you may experience nausea, vomiting, diarrhea, low blood pressure (dizziness, fainting, or fainting), skin redness, and/or headaches.

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

If you interrupt treatment with Tresuvi

Always use treprostinil according to your doctor's or specialist's instructions at the hospital. Do not interrupt treatment with Tresuvi unless your doctor tells you to do so.

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

If you have any other doubts about the use of this medication, ask your doctor.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

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

• Widening of blood vessels with redness
• Pain or tenderness around the site of administration
• Discoloration of the skin or bruises around the site of administration
• Headaches
• Skin eruptions
• Nausea
• Diarrhea
• Jaw pain

Common (may affect up to 1 in 10 people)

• Dizziness
• Vomiting
• Drowsiness or fainting 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 urine, bleeding gums, or blood in stools
• Joint pain
• Muscle pain
• Pain in legs and/or arms

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

• Infection at the site of administration
• Abscess at the site of administration
• Decrease in blood clotting cells (platelets) (thrombocytopenia)
• Bleeding at the site of administration
• Infection of tissues under the skin (cellulitis)
• Bone pain
• Skin eruptions with discoloration or raised bumps

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

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

• Vein inflammation (thrombophlebitis)
• Bloodstream bacterial infection (bacteremia)* (see section 3)
• Septicemia (severe bacterial infection of the blood)

*Fatal or potentially fatal cases of bloodstream infection have been reported

Reporting of side effects

If you experience any type of side effect, consult your doctor, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: https://www.notificaRAM.es.

By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

No special storage conditions are required.

Do not use this medication after the expiration date that appears on the box and vial after CAD. The expiration date is the last day of the month indicated.

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

During continuous subcutaneous infusion, a single, undiluted Tresuvi vial (syringe) should be used within 14 days.

During continuous intravenous infusion, a single, diluted Tresuvi vial (syringe) should be used within 24 hours.

During continuous intravenous infusion via 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.

The unused diluted solution should be discarded.

Instructions for use can be consulted in section 3, "How to use Tresuvi".

Medications should not be disposed of through drains or trash. Deposit the containers and unused medications at the SIGRE point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and unused medications. In this way, you will help protect the environment.

Content of Tresuvi

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.

Appearance of the product and contents of the package

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

• Tresuvi 1 mg/ml infusion solution has a rubber stopper closure capsule of color yellow.

• Tresuvi 2.5 mg/ml infusion solution has a rubber stopper closure capsule of color blue.

• Tresuvi 5 mg/ml infusion solution has a rubber stopper closure capsule of color green.

• Tresuvi 10 mg/ml infusion solution has a rubber stopper closure capsule of color red.

Each box contains one vial.

Marketing Authorization Holder

Amomed Pharma GmbH

Leopold-Ungar-Platz 2

1190 Vienna

Austria

Responsible for manufacturing

AOP Orphan Pharmaceuticals GmbH

Leopold-Ungar-Platz 2

1190 Vienna

Austria

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

AOP Orphan Pharmaceuticals Iberia S.L.U.

Calle de Cólquide nº6, Edif. Prisma – Portal 2, 1st floor

28231, Las Rozas, Madrid

Spain

This medicinal product is authorized in the member states of the European Economic Area with the following names:

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

Bulgaria Tresuvi 1/2.5/ 5/ 10 mg/ ml ?????????? ???????

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 Δι?λυμα για ?γχυση

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

Finland Tresuvi 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

Last review date of this leaflet: 08/2023

Other sources of information

The detailed information about this medicinal product is available on the website of the {Spanish Agency of Medicines and Medical Devices (AEMPS) ( http://www.aemps.gob.es/ )