TRESUVI 1 mg /Ml Infusion Solution

Зміст інструкції

1. What is Tresuvi and what is it used for
2. What you need to know 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

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

Equivalent medicinal product
Read this leaflet carefully before using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Tresuvi is and what it is used for
• 2. What you need to know before you use 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 is Tresuvi and what is it used for

What is Tresuvi
The active ingredient of Tresuvi is treprostinil.
Treprostinil belongs to a group of medicines that act in a similar way to prostacyclins found in
nature. Prostacyclins are hormone-like substances that lower blood pressure by causing relaxation and therefore dilation of blood vessels; this allows blood to flow more easily. Prostacyclins can also affect the prevention of blood clotting.

What is Tresuvi used for
Tresuvi is used to treat idiopathic or hereditary pulmonary arterial hypertension (PAH) in patients with
moderate severity of symptoms. Pulmonary arterial hypertension is a condition in which blood pressure in the blood vessels between the heart and the lungs is too high and causes shortness of breath, dizziness,
fatigue, fainting, palpitations or irregular heartbeat, dry cough, chest pain and swelling in the
ankles or legs.
Tresuvi is initially administered as a continuous subcutaneous (under the skin) infusion.
Some patients may become unable to tolerate this due to pain and local swelling at the injection site.
The doctor will decide whether Tresuvi can be administered by continuous intravenous
infusion directly into a vein with the insertion of a venous central line that is
connected to an external pump or, depending on their condition, to a pump surgically implanted
under the skin of the abdomen. The doctor will decide which is the best option for you.
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How does Tresuvi work
Tresuvi lowers blood pressure within the pulmonary artery by improving blood circulation and reducing the workload on the heart. Improved blood circulation leads to better
oxygen supply to the body and reduces the strain on the heart, making it work more efficiently. Tresuvi
improves the symptoms associated with PAH and the ability to move in patients who are limited in terms of
physical activity.

2. What you need to know before using 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 condition called “pulmonary veno-occlusive disease”. This is a disease in which the blood vessels that carry blood through the lungs become swollen and obstructed, resulting in increased pressure in the blood vessels between the heart and the lungs;
• if you suffer from a severe liver disease;
• if you have a heart problem, for example: a heart attack (myocardial infarction) in the last six months; significant changes in heart rate; severe coronary artery disease or unstable angina; you have been diagnosed with a heart defect, such as a faulty heart valve causing heart malfunction; any heart disease that is not treated or not under close medical supervision;
• if you have a specific high risk of bleeding, for example in case of active gastric ulcers, injuries or other bleeding conditions;
• if you have had a stroke in the last 3 months or any other interruption of blood flow to the brain.

Warnings and precautions
Talk to your doctor before using Tresuvi

• if you suffer from any liver disease;
• if you have been told you are obese from a medical point of view (body mass index [BMI] greater than 30 kg/m²);
• if you have an infection with (human immunodeficiency virus);
• if you have high blood pressure in the veins of the liver (portal hypertension);
• if you have a congenital heart defect that affects the way blood flows through the heart.

During therapy with Tresuvi, inform your doctor:

• if your blood pressure drops (hypotension);
• if you experience a rapid increase in breathing difficulties or persistent cough (this may be related to pulmonary congestion, asthma or other conditions), in which case you should consult your doctor immediately;
• if you have excessive bleeding, as treprostinil may increase the risk of bleeding, as it prevents blood clotting;
• if you develop a fever while using treprostinil intravenously, or if the intravenous 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, have recently taken or might take any other medicines. Tell your
doctor if you are taking:
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• medicines used to treat high blood pressure(antihypertensive drugs or other vasodilators);
• medicines used to increase the amount of urine(diuretics) including furosemide;
• medicines that block blood clotting(anticoagulants), such as warfarin, heparin or nitric oxide-based products;
• any non-steroidal anti-inflammatory drug (NSAID) (e.g. acetylsalicylic acid, ibuprofen);
• medicines that can 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 the dose of Tresuvi.

Pregnancy and breastfeeding
Tresuvi is not recommended if you are pregnant, suspect you might be pregnant or are planning a pregnancy, unless
it is considered essential by your doctor. The safety of this medicine for use during
pregnancy has not been established.
Contraception is strongly recommended during therapy with Tresuvi.
The use of Tresuvi is not recommended during breastfeeding, unless it is considered
necessary by your doctor. It is advisable to stop breastfeeding if you have been prescribed Tresuvi,
as it is not known whether this medicine passes into breast milk.
If you are pregnant, suspect you might be pregnant or are planning a pregnancy or if you are breastfeeding
with breast milk, ask your doctor for advice before using this medicine.

Driving and using machines
Tresuvi can cause low blood pressure with dizziness or fainting. If this happens, do not drive or use
machines and ask your doctor for advice.

Tresuvi contains sodium
Tell your doctor if you are on a low-sodium diet. Your doctor will take into account that
one vial of Tresuvi contains the following amounts of sodium:
Tresuvi 1 mg/ml solution for infusion:
this medicine contains 36.8 mg of sodium (the main component of table salt) per vial
of 10 ml. This is equivalent to 1.8% of the recommended maximum daily intake with the diet of an
adult.
Tresuvi 2.5 mg/ml solution for infusion:
this medicine contains 37.3 mg of sodium (the main component of table salt) per vial
of 10 ml. This is equivalent to 1.9% of the recommended maximum daily intake with the diet of an
adult.
Tresuvi 5 mg/ml solution for infusion:
this medicine contains 39.1 mg of sodium (the main component of table salt) per vial
of 10 ml. This is equivalent to 2.0% of the recommended maximum daily intake with the diet of an
adult.
Tresuvi 10 mg/ml solution for infusion:
this medicine contains 37.4 mg of sodium (the main component of table salt) per vial
of 10 ml. This is equivalent to 1.9% of the recommended maximum daily intake with the diet of an
adult.

3. How to use Tresuvi

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Use this medicine following the doctor's instructions exactly. If you have any doubts, consult your doctor.

Method of administration
Tresuvi is administered as a continuous infusion:

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

In both cases Tresuvi is pushed through the tube by a portable pump positioned outside the body
(external).
Before leaving the hospital or clinic, the doctor will tell you how to prepare Tresuvi and at what rate the pump
must deliver treprostinil.
Flushing the infusion line while it is connected can cause accidental overdose.
Alternatively, Tresuvi can be administered intravenously via an implantable infusion pump
usually surgically inserted under the skin of the abdomen. In this case, the
pump and the tube are both completely inside the body (internal pump) and you will need to go
periodically (e.g. every 4 weeks) to the hospital or clinic to refill the internal reservoir.
In any case, you must also be given information on how to use the pump correctly and on what
to do if it stops working. You should also be told who to contact in case of emergency.
Tresuvi is diluted only if administered with continuous intravenous infusion.

For intravenous infusion with a portable external pump:the treprostinil solution must be diluted only
with sterile water for injectable preparations or with 0.9% sodium chloride for injectable preparations
(as indicated by the doctor).

For intravenous infusion with an implantable pump:you will need to go periodically (e.g.
every 4 weeks) to the hospital or clinic, where healthcare professionals must dilute the treprostinil solution with 0.9% sodium chloride for injectable preparations and refill the internal reservoir.
Adult patients
Tresuvi is available as an infusion solution of 1 mg/ml, 2.5 mg/ml, 5 mg/ml or 10 mg/ml. The doctor
will determine the infusion rate and the appropriate dose for your condition.
Overweight patients
If you are overweight (weight equal to or greater than 30% of your ideal body weight) the doctor will establish the initial dose and subsequent doses based on your ideal body weight. Also refer to paragraph 2,
“Warnings and precautions”.
Elderly patients
The doctor will determine the infusion rate and the appropriate dose according to your condition.

Use in children and adolescents
Limited data are available for children and adolescents.
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Dosage adjustment
The infusion rate can be reduced or increased on an individual basis only under medical supervision.
Adjusting the infusion rate aims to establish an effective maintenance rate
that improves the symptoms of PAH while minimizing side effects.
If your symptoms worsen or if you need complete rest, or if you are confined to bed or a chair, or if
any physical activity causes discomfort and symptoms occur at rest, do not increase the dose without
consulting a doctor. This medicine may no longer be sufficient to treat your condition and
another treatment may be necessary.

How can bloodstream infections be preventedduring treatment with Tresuvi via
intravenous route?
As with any long-term intravenous treatment, there is a risk of contracting bloodstream infections. The doctor will tell you what to do to avoid this happening.

If you use more Tresuvi than you should
In case of accidental overdose of this medicine, nausea, vomiting, diarrhea, low blood pressure (dizziness, lightheadedness or fainting), skin flushing and/or headache may occur.
If any of these effects become severe, contact your doctor or hospital immediately. The doctor may
reduce or stop the infusion until the symptoms disappear. The Tresuvi infusion solution will then be
reintroduced at a dose level recommended by the doctor.

If you stop treatment with Tresuvi
Always use Tresuvi as indicated by your doctor or hospital specialist. Do not stop Tresuvi unless the interruption has been recommended by your doctor.
Abrupt discontinuation or a sudden reduction in the dose of treprostinil can cause the return
of pulmonary arterial hypertension with the potential risk of rapid and serious deterioration of your
condition.
If you have any doubts about the use of this medicine, consult 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)

• Dilation of blood vessels with redness of the skin
• Pain or tenderness around the infusion site
• Change in skin color or bruising around the infusion site
• Headache
• Skin rashes
• Nausea
• Diarrhea
• Jaw pain

Pag. 5to 8
Common (may affect up to 1 in 10 people)

• Dizziness
• Vomiting
• Feeling lightheaded or fainting due to low blood pressure
• Feeling of 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

Not known (frequency cannot be estimated from available data)

• Infection at the infusion site
• Abscess at the infusion site
• Decrease in blood cells (platelets) that help blood clotting (thrombocytopenia)
• Bleeding at the infusion site
• Infection of the subcutaneous tissues (cellulitis)
• Bone pain
• Skin rashes with change in skin color or raised bumps
• Heart failure with excessive volume of blood pumped by the heart leading to shortness of breath, fatigue, swelling of the legs and abdomen, and persistent cough (high-output heart failure)

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

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

* Cases of life-threatening or fatal bacterial blood infection have been reported

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. You can also report side effects directly through the national reporting system
at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects you can help provide more information on the safety of this
medicine.

5. How to store Tresuvi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and vial after
“EXP.” The expiry date refers to the last day of that month.
Do not use this medicine if you notice damage to the vial, discoloration or other signs of deterioration. A
vial of Tresuvi must be used or discarded within 30 days of first opening.
This medicine does not require any special storage conditions.
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Shelf life during continuous subcutaneous infusion
The chemical-physical and microbiological stability of a single reservoir (syringe) of undiluted treprostinil
administered via subcutaneous infusion has been demonstrated for up to 14 days at 37°C. Other
storage times and conditions are the responsibility of the user.

Shelf life during continuous intravenous infusion
The chemical-physical and microbiological stability of a single reservoir (syringe) of diluted treprostinil
administered via intravenous infusion has been demonstrated for up to 24 hours at 37°C (at concentrations of
0.004 mg/ml) in polyvinyl chloride, polypropylene and glass. To minimize the risk of bloodstream infections,
the maximum duration of use of diluted treprostinil must not exceed 24 hours. Other storage times and
conditions after first opening are the responsibility of the user.
During continuous intravenous infusion with implantable infusion pumps, diluted Tresuvi introduced into the
pump reservoir must be used within a maximum of 30 days. The healthcare professional will advise you
how long it will be before the next reservoir refill.
Any remaining diluted solution must be discarded.
For instructions for use, see section 3 “How to use Tresuvi”.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Tresuvi contains
The active ingredient is treprostinil (1 mg/ml, 2.5 mg/ml, 5 mg/ml, 10 mg/ml).
Each ml contains 1 mg of treprostinil, as treprostinil sodium.
Each ml contains 2.5 mg of treprostinil, as treprostinil sodium.
Each ml contains 5 mg of treprostinil, as treprostinil sodium.
Each ml contains 10 mg of treprostinil, as treprostinil sodium.
The other ingredients are:
Sodium citrate, hydrochloric acid (for pH adjustment), metacresol, sodium hydroxide, sodium chloride and
water for injections.

Description of Tresuvi and contents of the pack
Tresuvi is a clear, colorless to slightly yellow solution free from visible particles, available in a
10 ml transparent glass vial sealed with a rubber stopper and a colored closure cap
with code:

• 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 Authorisation Holder and Manufacturer
Marketing Authorisation Holder
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Orpha-Devel Handels und Vertriebs GmbH
Wintergasse 85/1B
3002 Purkersdorf
Austria

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

This medicinal product is authorised in the Member States of the European Economic Areawith the following
names:
Austria Treprostinil Orpha-Devel, Infusionslösung
Belgium Tresuvi, Solution for perfusion
Croatia Tresuvi, Otopina za infuziju
Estonia Tresuvi, Infusioonilahus
France Treposuvi, Solution pour perfusion
Germany Tresuvi, Infusionslösung
Ireland Treposuvi, Solution for infusion
Italy Tresuvi, Soluzione per infusione
Latvia Treposuvi, šķīdums infūzijām
Lithuania Tresuvi, Infuzinis tirpalas
Malta Tresuvi, Solution for infusion
Netherlands Treposuvi, Oplossing voor infusie
Sweden Tresuvi, Infusionsvätska, lösning
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