TREPULMIX 2.5 mg/ml SOLUTION FOR INFUSION

2. What you need to know before you use 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 disease called "pulmonary veno-occlusive disease"; This is a disease where the blood vessels that carry blood through the lungs become swollen and blocked, causing higher pressure in the blood vessels between the heart and lungs;
• if you have severe liver disease;
• if you have a heart problem, such as:

• a heart attack (myocardial infarction) in the last 6 months;
• severe irregular heartbeat;
• severe ischemic heart disease or unstable angina;
• a heart defect, such as a faulty heart valve that makes the heart work poorly;
• any heart disease that is not being treated or is not under close medical supervision.
• • if you have a high risk of bleeding, such as active stomach ulcers, wounds, or other bleeding conditions;
  • if you have had a stroke in 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 liver disease;
• have kidney disease;
• have been told you are medically obese (BMI over 30 kg/m2);
• are on a low-sodium diet.

During treatment with Trepulmix, tell 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 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 from clotting.

Children and adolescents

Trepulmix should not be used in children and adolescents.

Other medicines and Trepulmix

Tell your doctor if you are taking, have recently taken, or might take 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 urination(diuretics), including furosemide;
• medicines that prevent blood clotting(anticoagulants) such as warfarin, heparin, or nitric oxide products;
• any non-steroidal anti-inflammatory drug (NSAID) (e.g., acetylsalicylic acid or ibuprofen);
• medicines that may increase or decrease the effects of Trepulmix (e.g., gemfibrozil, rifampicin, trimethoprim, deferasirox, phenytoin, carbamazepine, phenobarbital, hypericum), as your doctor may need to adjust the dose of Trepulmix.

Pregnancy and breastfeeding

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

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

Trepulmix is not recommended during breastfeeding, unless your doctor considers it essential. You should stop breastfeeding if you are prescribed Trepulmix, as it is not known whether this medicine passes into breast milk.

If you are pregnant, breastfeeding, think you may be pregnant, or plan to become pregnant, ask your doctor for advice before taking this medicine.

Driving and using machines

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

Trepulmix contains sodium

Tell 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 (main component of table/cooking salt) in each vial. This is equivalent to 1.8% of the maximum recommended daily sodium intake for an adult.

Trepulmix 2.5 mg/ml solution for infusion

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

Trepulmix 5 mg/ml solution for infusion

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

Trepulmix 10 mg/ml solution for infusion

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

3. How to use Trepulmix

Follow the instructions for administration of this medicine exactly as told by your doctor. If you are unsure, ask your doctor again.

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

Trepulmix is driven through the tube by a portable pump.

Before you leave the hospital or clinic, your doctor will tell you how to prepare Trepulmix and the rate at which the pump should administer treprostinil. You will also be given information on how to use the pump correctly and what to do if it stops working. You will also be told who to contact in case of an emergency.

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

Adult patients

Trepulmix 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 dose suitable for your condition.

Elderly patients

No special dose adjustment is needed in these patients.

Patients with severe liver or kidney disease

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

Infusion rate

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 CTEPH while minimizing adverse reactions.

If your symptoms worsen or if you need to rest completely, or if you are confined to bed or a 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 need another treatment.

If you use more Trepulmix than you should

If you accidentally overdose on Trepulmix, you may experience nausea, vomiting, diarrhea, low blood pressure (dizziness, lightheadedness, or fainting), flushing of the skin, and/or headache.

If any of these effects worsen, you should contact your doctor or hospital immediately. Your doctor may reduce or interrupt the infusion until your symptoms have disappeared. The Trepulmix solution for infusion will be reintroduced at the dose recommended by your doctor.

If you stop treatment with Trepulmix

Always use Trepulmix following the instructions of your doctor or hospital specialist. Do not stop using Trepulmix unless your doctor has told you to.

Sudden withdrawal or rapid reduction of the dose of Trepulmix can cause pulmonary hypertension to return, with the possibility of rapid and severe worsening of your condition.

If you have any further questions on 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
• 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
• abscess (pus) around the infusion site
• muscle pain (myalgia)
• joint pain (arthralgia)
• swelling of feet, ankles, legs, or fluid retention
• flushing
• 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):

• bleeding episodes such as: nosebleeds, coughing up blood, blood in urine, bleeding gums, blood in stool

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 rash with discoloration or raised areas
• infection of the tissue under the skin (cellulitis)

Reporting of side effects

If you experience any side effects, talk to your doctor, even if they are not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Trepulmix

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 carton and vial after "EXP". The expiry date is the last day of the month shown.

This medicine does not require any special storage conditions.

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

During continuous subcutaneous infusion, a single reservoir (syringe) of undiluted Trepulmix should be used within 72 hours.

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Packaging Contents and Additional Information

Trepulmix Composition

• The active ingredient 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

One 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 ingredients are:
• Sodium citrate, sodium chloride, sodium hydroxide, hydrochloric acid, metacresol, and water for injectable preparations. See section 2 "Trepulmix contains sodium".

Product Appearance and Packaging Contents

Trepulmix is a clear, colorless to slightly yellowish solution, available in a 10 ml transparent glass vial sealed with a rubber stopper and a color-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 box contains one vial.

Only certain pack sizes may be marketed.

Marketing Authorization Holder

SciPharm Sàrl

7, Fausermillen

L-6689 Mertert

Luxembourg

Manufacturer

AOP Orphan Pharmaceuticals GmbH

Leopold-Ungar-Platz

21190 Vienna

Austria

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

Date of Last Revision of this Leaflet:.

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