Trepulmix

Package leaflet: Information for the user

Trepulmix 1 mg/ml solution for infusion, 2.5 mg/ml solution for infusion, 5 mg/ml solution for infusion, 10 mg/ml solution for infusion

treprostinil
Please read 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 questions, ask your doctor.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Trepulmix is and what it is used for

What Trepulmix is
The active substance of Trepulmix is treprostinil.
Treprostinil belongs to a class of medicines that act similarly to natural prostacyclins.
Prostacyclins are hormone-like substances that reduce blood pressure by relaxing and thus dilating blood vessels, thereby improving blood flow.
Prostacyclins may also help prevent blood clotting.

What Trepulmix is used for
Trepulmix is indicated for the treatment of adult patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent or recurrent CTEPH after surgical treatment (with WHO functional class III or IV), to improve exercise capacity and disease symptoms.
Chronic thromboembolic pulmonary hypertension is a condition in which 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 swollen ankles or legs.

How Trepulmix works
Trepulmix reduces blood pressure in the pulmonary artery, improving blood flow and reducing the workload of the heart. Improved blood flow results in increased oxygen delivery to the body and reduced strain on the heart, allowing the heart to function more effectively. Trepulmix improves symptoms associated with CTEPH and enhances exercise capacity in patients with limited physical activity.

2. What you need to know before using Trepulmix

Do not use Trepulmix

• if you are allergic to treprostinil or to 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". This is a condition in which the blood vessels carrying blood to the lungs become swollen and blocked, causing increased pressure in the blood vessels between the heart and the lungs;
• if you have severe liver disease;
• if you have a heart condition, for example: a heart attack (myocardial infarction) within the last six months; serious disturbances in heart rate; severe coronary artery disease or unstable angina; you have been diagnosed with a heart defect, such as a heart valve defect impairing heart function; any untreated or poorly controlled heart disease;
• if you are at high risk of bleeding, for example, if you have active stomach ulcers, injuries, or other bleeding conditions;
• if you have had a stroke within the last 3 months or any other condition that interrupted blood supply to the brain.

Warnings and precautions
Talk to your doctor before using Trepulmix if:

• you suffer from any liver disease;
• you suffer from a kidney disease;
• you have been medically diagnosed with obesity (Body Mass Index/BMI greater than 30 kg/m²);
• you are on a low-sodium diet.

During treatment with Trepulmix, inform your doctor:

• if your blood pressure drops (hypotension);
• if you experience a rapid worsening in breathing difficulty or a persistent cough (this may be related to pulmonary congestion, asthma, or other conditions); seek immediate medical attention;
• if you experience excessive bleeding, as treprostinil may increase this risk by inhibiting blood clotting.

Children and adolescents
Trepulmix must not be used in children and adolescents.

Other medicines and Trepulmix
Inform your doctor if you are taking, have recently taken, or might take any other medicines. Inform your doctor if you are taking:

• medicines used to treat high blood pressure (antihypertensives or other vasodilators);
• medicines used to increase urine production (diuretics), including furosemide;
• medicines that prevent blood clotting (anticoagulants) such as warfarin, heparin, or nitric oxide-based products;
• any non-steroidal anti-inflammatory drugs ( NSAIDs ) (e.g., acetylsalicylic acid, ibuprofen);
• any medicines that may increase or decrease the effects of Trepulmix (e.g., gemfibrozil, rifampicin, trimethoprim, deferasirox, phenytoin, carbamazepine, phenobarbital, St. John’s wort), as your doctor may need to adjust the dose of Trepulmix.

Pregnancy and breastfeeding
Trepulmix is not recommended if you are pregnant, planning pregnancy, or suspect you may be pregnant, unless your doctor considers it necessary. The safety of this medicine during pregnancy has not been established.
While being treated with Trepulmix, the use of contraception is strongly recommended.
The use of Trepulmix is not recommended during breastfeeding unless your doctor considers it necessary. If Trepulmix is prescribed to you, it is advisable to stop breastfeeding, as it is unknown whether this medicine is excreted in breast milk.
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor before taking this medicine.

Driving and using machines
Trepulmix may cause low blood pressure, accompanied by dizziness and fainting. In such cases, do not drive or operate machinery and consult your doctor.

Trepulmix contains sodium
Inform your doctor if you are on a low-sodium diet. Your doctor will take this into account.

Trepulmix 1 mg/ml infusion solution
This medicine contains 36.8 mg of sodium (a major component of table salt) per vial, equivalent to 1.8% of the maximum daily recommended sodium intake for an adult.

Trepulmix 2.5 mg/ml infusion solution
This medicine contains 37.3 mg of sodium (a major component of table salt) per vial, equivalent to 1.9% of the maximum daily recommended sodium intake for an adult.

Trepulmix 5 mg/ml infusion solution
This medicine contains 39.1 mg of sodium (a major component of table salt) per vial, equivalent to 2.0% of the maximum daily recommended sodium intake for an adult.

Trepulmix 10 mg/ml infusion solution
This medicine contains 37.4 mg of sodium (a major component of table salt) per vial, equivalent to 1.9% of the maximum daily recommended sodium intake for an adult.

3. How to use Trepulmix

Use this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor.

Trepulmix is administered undiluted as a continuous subcutaneous infusion (under the skin) through a small tube (cannula) inserted into the abdomen or thigh.
Trepulmix is delivered through the tube by a portable pump.
Before you leave the hospital or clinic, your doctor will explain how to prepare Trepulmix and at what rate the pump should deliver the treprostinil dose. You will also be given instructions on the correct use of the pump and what to do in case of malfunction. You will be informed who to contact in an emergency.
Flushing the infusion line while it is still connected may cause accidental overdose.

Adult patients
Trepulmix is available as an infusion solution at concentrations of 1 mg/ml, 2.5 mg/ml, 5 mg/ml, or 10 mg/ml. Your doctor will determine the appropriate infusion rate and dose based on your condition.

Elderly patients
No special dose adjustments are required for these patients.

Patients with hepatic or renal impairment
Your doctor will determine the appropriate infusion rate and dose based on your condition.

Infusion rate
The infusion rate may be decreased or increased individually only under medical supervision.
Adjusting the infusion rate aims to establish an effective maintenance rate that improves CTEPH symptoms while minimizing adverse effects.

If your symptoms worsen, if you require complete bed rest, are confined to bed or chair, or if any physical activity causes discomfort or your symptoms occur even at rest, do not increase the dose without consulting your doctor. Trepulmix may no longer be sufficient to treat your condition, and additional treatment may be necessary.

If you use more Trepulmix than you should
If you accidentally use more Trepulmix than prescribed, you may experience nausea, vomiting, diarrhea, low blood pressure (dizziness, mild confusion, or fainting), flushed skin and/or headache.
If any of these effects become severe, contact your doctor or hospital immediately. Your doctor may reduce or stop the infusion until symptoms resolve. Trepulmix infusion solution will then be reintroduced at the dose recommended by your doctor.

If you stop treatment with Trepulmix
Always use Trepulmix exactly as instructed by your doctor or hospital specialist. Do not stop treatment with Trepulmix unless your doctor advises you to do so.
Sudden discontinuation or abrupt dose reductions of Trepulmix may cause recurrence of pulmonary arterial hypertension, potentially leading to rapid and severe deterioration of your condition.

If you have any questions about how to use 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
• pain around the infusion site
• reaction around the infusion site
• bleeding or bruising around the infusion site
• headache
• nausea
• diarrhoea
• jaw pain

Common (may affect up to 1 in 10 people)

• dizziness
• mild confusion or fainting due to low blood pressure
• skin rashes
• infection at the infusion site
• pus around the infusion site (abscess)
• muscle pain (myalgia)
• joint pain (arthralgia)
• swelling of feet, ankles, legs or fluid retention
• hot flush
• pain in arms and/or legs

Uncommon (may affect up to 1 in 100 people)

• swollen eyelids (eyelid oedema)
• indigestion
• vomiting
• skin itching
• rash
• back pain
• reduced appetite
• fatigue

Additional possible side effects observed in patients with pulmonary arterial hypertension (PAH):

• episodes of bleeding such as nosebleeds, coughing up blood, blood in urine, bleeding from gums, blood in faeces

Other possible side effects observed in clinical practice:

• decrease in platelets (cells responsible for blood clotting) (thrombocytopenia)
• bone pain
• skin rashes with colour change or formation of lumps
• infection of the skin and underlying tissue (cellulitis)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor. You can also report side effects directly through the national reporting system detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Trepulmix

Keep this medicine out of the sight and reach of children.
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 that month.
This medicine does not require any special storage conditions.
A vial of Trepulmix must be used or discarded within 30 days of first opening.
During continuous subcutaneous infusion, a single reservoir (syringe) of undiluted Trepulmix must be used within 72 hours.
Do not use this medicine if you notice any damage to the vial, change in colour, or signs of deterioration.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Trepulmix contains

• The active substance is treprostinil.

Trepulmix 1 mg/ml solution for infusion
Each ml of solution contains 1 mg of treprostinil (as sodium salt).
Each 10 ml vial of solution contains 10 mg of treprostinil (as sodium salt).
Trepulmix 2.5 mg/ml solution for infusion
Each ml of solution contains 2.5 mg of treprostinil (as sodium salt).
Each 10 ml vial of solution contains 25 mg of treprostinil (as sodium salt).
Trepulmix 5 mg/ml solution for infusion
Each ml of solution contains 5 mg of treprostinil (as sodium salt).
Each 10 ml vial of solution contains 50 mg of treprostinil (as sodium salt).
Trepulmix 10 mg/ml solution for infusion
Each ml of solution contains 10 mg of treprostinil (as sodium salt).
Each 10 ml vial of solution contains 100 mg of treprostinil (as sodium salt).

• The other components are: Sodium citrate, sodium chloride, sodium hydroxide, hydrochloric acid, metacresol and water for injections. See section 2 “Trepulmix contains sodium”.

Description of the appearance of Trepulmix and package contents
Trepulmix is a clear, colourless to yellowish solution, available in a 10 ml clear glass vial sealed with a coloured rubber stopper and closure cap:
Trepulmix 1 mg/ml solution for infusion
Trepulmix 1 mg/ml solution for infusion with a yellow rubber stopper.
Trepulmix 2.5 mg/ml solution for infusion
Trepulmix 2.5 mg/ml solution for infusion with a blue rubber stopper.
Trepulmix 5 mg/ml solution for infusion
Trepulmix 5 mg/ml solution for infusion with a green rubber stopper.
Trepulmix 10 mg/ml solution for infusion
Trepulmix 10 mg/ml solution for infusion with a red rubber stopper.
Each carton contains one vial.
Not all pack sizes may be marketed.

Marketing Authorization Holder
SciPharm Sàrl
7, Fausermillen
L-6689 Mertert
Luxembourg

Manufacturer
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:

België/Belgique/Belgien Lietuva
AOP Orphan Pharmaceuticals GmbH (Austria) AOP Orphan Pharmaceuticals GmbH (Austrija)
Tél/Tel: +43 1 5037244 Tel: +43 1 5037244

България Luxembourg/Luxemburg
AOP Orphan Pharmaceuticals GmbH (Австрия) AOP Orphan Pharmaceuticals GmbH (Austria)
Teл.: +43 1 5037244 Tél/Tel: +43 1 5037244

Česká republika Magyarország
AOP Orphan Pharmaceuticals GmbH (Rakousko) AOP Orphan Pharmaceuticals GmbH (Ausztria)
Tel: +43 1 5037244 Tel.: +43 1 5037244

Danmark Malta
AOP Orphan Pharmaceuticals GmbH (Østrig) AOP Orphan Pharmaceuticals GmbH (L-Awstrija)
Tlf: +43 1 5037244 Tel: +43 1 5037244

Deutschland Nederland
AOP Orphan Pharmaceuticals Germany GmbH AOP Orphan Pharmaceuticals GmbH (Oostenrijk)
Tel: +49 89 99 740 7600 Tel: +43 1 5037244

Eesti Norge
AOP Orphan Pharmaceuticals GmbH (Austria) AOP Orphan Pharmaceuticals GmbH (Østerrike)
Tel: +43 1 5037244 Tlf: +43 1 5037244

Ελλάδα Österreich
AOP Orphan Pharmaceuticals GmbH (Αυστρία) AOP Orphan Pharmaceuticals GmbH
Τηλ: +43 1 5037244 Tel: +43 1 5037244

España Polska
AOP Orphan Pharmaceuticals Iberia S.L. AOP Orphan Pharmaceuticals GmbH (Austria)
Tel: +34 91 395 40 84 Tel.: +43 1 5037244

France Portugal
AOP Orphan Pharmaceuticals GmbH (Autriche) AOP Orphan Pharmaceuticals GmbH (Austria)
Tél: +43 1 5037244 Tel: +43 1 5037244

Hrvatska România
AOP Orphan Pharmaceuticals GmbH (Austrija) AOP Orphan Pharmaceuticals GmbH (Austria)
Tel: +43 1 5037244 Tel: +43 1 5037244

Ireland Slovenija
AOP Orphan Pharmaceuticals GmbH (Austria) AOP Orphan Pharmaceuticals GmbH (Avstrija)
Tel: +43 1 5037244 Tel: +43 1 5037244

Ísland Slovenská republika
AOP Orphan Pharmaceuticals GmbH (Austurríki) AOP Orphan Pharmaceuticals GmbH (Rakúsko)
Sími: +43 1 5037244 Tel: +43 1 5037244

Italia Suomi/Finland
AOP Orphan Pharmaceuticals GmbH (Austria) AOP Orphan Pharmaceuticals GmbH (Itävalta)
Tel: +43 1 5037244 Puh/Tel: +43 1 5037244

Κύπρος Sverige
AOP Orphan Pharmaceuticals GmbH (Αυστρία) AOP Orphan Pharmaceuticals GmbH (Österrike)
Τηλ: +43 1 5037244 Tel: +43 1 5037244

Latvija
AOP Orphan Pharmaceuticals GmbH (Austrija)
Tel: +43 1 5037244

More detailed information on this medicinal product is available on the website of the European Medicines Agency, https://www.ema.europa.eu/. In addition, links to other websites on rare diseases and their therapeutic treatments are provided.