Trepulmix 1 mg/ml solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Trepulmix 1mg/ml solution for infusion

Trepulmix 2.5mg/ml solution for infusion

Trepulmix 5mg/ml solution for infusion

Trepulmix 10mg/ml solution for infusion

treprostinil

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the 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 adverse 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 in Trepulmix is treprostinil.

Treprostinil belongs to a group of medicines that act similarly to natural prostacyclins. Prostacyclins are hormone-like substances that lower blood pressure by relaxing blood vessels, causing them to widen and allowing blood to flow more easily. Prostacyclins may also help prevent blood from clotting.

What Trepulmix is used for

Trepulmix is used to treat adult patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent or recurrent CTEPH after surgical treatment (severity classified as World Health Organization [WHO] functional class [FC] III or IV), to improve exercise capacity and disease symptoms. Chronic thromboembolic pulmonary hypertension is a condition in which blood pressure is too high in the blood vessels between the heart and the lungs, causing shortness of breath, dizziness, fatigue, fainting, palpitations or abnormal heartbeats, dry cough, chest pain, and swollen ankles or legs.

How Trepulmix works

Trepulmix reduces blood pressure in the pulmonary artery by improving blood flow and decreasing the workload of the heart. By improving blood flow, oxygen delivery to the body increases and strain on the heart decreases, allowing the heart to function more effectively. Trepulmix improves symptoms associated with CTEPH and exercise capacity in patients with activity limitations.

2. What you need to know before using Trepulmix

Do not use Trepulmix

• 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 condition in which the blood vessels carrying blood through the lungs become swollen and blocked, leading to 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 heart rhythm disturbances;
  • severe ischemic heart disease or unstable angina;
  • you have been diagnosed with a heart defect, such as a faulty heart valve causing improper heart function;
  • any heart disease that is not being treated or is not under close medical supervision.
  • if you have a specific high risk of bleeding, for example, active stomach ulcers, wounds, or other bleeding conditions;
  • if you have had a stroke within the last 3 months or any other interruption of blood supply to the brain.

Warnings and precautions

Talk to your doctor before starting Trepulmix if you:

• have any liver disease;
• have any kidney disease;
• have been diagnosed as medically obese (BMI greater than 30 kg/m²);
• are on a low-sodium diet.

During your treatment with Trepulmix, inform your doctor:

• if your blood pressure decreases (hypotension);
• if you experience a rapid worsening of breathing difficulty or persistent cough (this may be related to lung congestion, asthma, or another condition); contact your doctor immediately;
• if you experience excessive bleeding, as treprostinil may increase the risk by preventing blood from clotting.

Children and adolescents

Trepulmix must not be used in children and adolescents.

Other medicines and Trepulmix

Tell your doctor if you are taking, have recently taken, or might need to 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 the rate of urination (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 or ibuprofen);
• medicines that may increase or reduce 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 to become pregnant, or think you may be pregnant, unless considered essential by your doctor. The safety of this medicine during pregnancy has not been established.

The use of contraceptive methods is strongly recommended during treatment with treprostinil.

The use of Trepulmix during breastfeeding is not recommended, unless considered essential by your doctor. You are advised to stop breastfeeding if Trepulmix is prescribed, 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 taking this medicine.

Driving and use of machines

Trepulmix may cause low blood pressure with dizziness or fainting. If this occurs, do not drive or operate machinery and consult your doctor.

Trepulmix contains sodium

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

Trepulmix 1 mg/ml solution for infusion

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

Trepulmix 2.5 mg/ml solution for infusion

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

Trepulmix 5 mg/ml solution for infusion

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

Trepulmix 10 mg/ml solution for infusion

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

3. How to use Trepulmix

Follow exactly the administration instructions for this medicine given by your doctor. If in doubt, consult your doctor again.

Trepulmix is administered undiluted by continuous subcutaneous infusion (under the skin) through a small tube (cannula) placed in your abdomen or thigh;

Trepulmix is delivered through the tube by a portable pump.

Before leaving the hospital or clinic, your doctor will instruct you on how to prepare Trepulmix and the rate at which the pump should deliver treprostinil. You should also be provided with information on how to use the pump correctly and what to do if it stops working. In addition, you should be informed whom to contact in case of an emergency.

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

Adult patients

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

Elderly patients

No special dose adjustment is required in these patients.

Patients with severe hepatic or renal disease

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

Infusion rate

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

The aim of adjusting the infusion rate is to establish an effective maintenance rate that improves the symptoms of CTEPH while minimizing adverse reactions.

If your symptoms worsen, or if you need complete rest, are confined to bed or chair, or if any physical activity causes discomfort and you experience symptoms at rest, do not increase the dose without consulting a doctor. It may be that Trepulmix is no longer sufficient to treat your disease and that you require additional treatment.

If you use more Trepulmix than you should

If you have an accidental overdose of Trepulmix, you may experience nausea, vomiting, diarrhoea, hypotension (dizziness, lightheadedness, or fainting), skin flushing and/or headache.

If any of these effects worsen, you must contact your doctor or hospital immediately. Your doctor may reduce or interrupt the infusion until your symptoms have resolved. Trepulmix infusion solution will then be restarted at the dose recommended by your doctor.

If you stop using Trepulmix

Always use Trepulmix exactly as directed by your doctor or hospital specialist. Do not stop using Trepulmix unless your doctor has advised you to do so.

Abrupt withdrawal or sudden reductions in the dose of Trepulmix may cause pulmonary arterial hypertension to return, 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 adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

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

• widening of blood vessels
• pain around the infusion site
• reaction around the infusion site
• bleeding or bruising around the infusion site
• headache
• nausea
• diarrhea
• jaw pain

Common (may affect up to 1 in 10 people)

• dizziness
• lightheadedness or fainting due to low blood pressure
• skin rash
• 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 flushes
• pain in arms and/or legs

Uncommon (may affect up to 1 in 100 people)

• swollen eyelids (eyelid edema)
• indigestion
• vomiting
• itching of the skin
• rash
• back pain
• decreased appetite
• fatigue

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

• hemorrhagic episodes such as: nosebleeds, coughing up blood, blood in the urine, bleeding from the gums, blood in the stools

Other possible side effects observed in clinical practice:

• a decrease in blood cells responsible for blood clotting (platelets) in the blood (thrombocytopenia)
• bone pain
• skin rashes with discoloration or raised areas
• infection of the tissue beneath the skin (cellulitis)

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, even if they are adverse effects not listed in this leaflet. You can also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Trepulmix

Keep this medicine out of 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 the month indicated.

This medicine does not require any special storage conditions.

A vial of Trepulmix must be used or discarded within 30 days after first opening.

During continuous subcutaneous infusion, a single reservoir (syringe) of undiluted Trepulmix must be used within 14 days.

Do not use this medicine if you notice damage to the vial, discoloration, or any other signs of deterioration.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This helps protect the environment.

6. Contents of the pack and other information

Composition of Trepulmix

• The active substance is treprostinil.

Trepulmix 1 mg/ml solution for infusion

Each ml of solution contains 1 mg of treprostinil (as the sodium salt).

Each 10 ml vial of solution contains 10 mg of treprostinil (as the sodium salt).

Trepulmix 2.5 mg/ml solution for infusion

Each ml of solution contains 2.5 mg of treprostinil (as the sodium salt).

Each 10 ml vial of solution contains 25 mg of treprostinil (as the sodium salt).

Trepulmix 5 mg/ml solution for infusion

Each ml of solution contains 5 mg of treprostinil (as the sodium salt).

Each 10 ml vial of solution contains 50 mg of treprostinil (as the sodium salt).

Trepulmix 10 mg/ml solution for infusion

Each ml of solution contains 10 mg of treprostinil (as the sodium salt).

Each 10 ml vial of solution contains 100 mg of treprostinil (as the 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".

Nature of the product and pack contents

Trepulmix is a clear, colourless to slightly yellow solution, supplied in a 10 ml clear glass vial sealed with a rubber stopper and a colour-coded cap:

Trepulmix 1 mg/ml solution for infusion

Trepulmix 1 mg/ml solution for infusion has a yellow rubber stopper.

Trepulmix 2.5 mg/ml solution for infusion

Trepulmix 2.5 mg/ml solution for infusion has a blue rubber stopper.

Trepulmix 5 mg/ml solution for infusion

Trepulmix 5 mg/ml solution for infusion has a green rubber stopper.

Trepulmix 10 mg/ml solution for infusion

Trepulmix 10 mg/ml solution for infusion has a red rubber stopper.

Each carton contains one vial.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder

SciPharm Sàrl

7, Fausermillen

L-6689 Mertert

Luxembourg

Manufacturer

AOP Orphan Pharmaceuticals GmbH

Leopold-Ungar-Platz

21190 Vienna

Austria

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet: .

Detailed information on this medicine is available on the website of the European Medicines Agency: https://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicinal products.