Treprostinil TilloMed

Package leaflet: Information for the user

Treprostinil Tillomed 1 mg/ml, 2.5 mg/ml, 5 mg/ml, 10 mg/ml solution for infusion

Generic medicine
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, consult 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, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Treprostinil Tillomed is and what it is used for

What Treprostinil Tillomed is
The active substance of Treprostinil Tillomed 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 causing relaxation and thus dilation of blood vessels, improving blood flow. Prostacyclins may also prevent blood clotting.

What Treprostinil Tillomed is used for
Treprostinil Tillomed is used for the treatment of idiopathic or hereditary pulmonary arterial hypertension (PAH) in patients with moderate symptoms.
Pulmonary arterial hypertension is a disease in which the blood pressure is too high in the blood vessels between the heart and the lungs. It causes shortness of breath, dizziness, fatigue, fainting, palpitations or cardiac arrhythmias, dry cough, chest pain, and swelling of the ankles or legs.

Treprostinil Tillomed is initially administered as a continuous subcutaneous infusion (under the skin). Some patients may no longer be able to tolerate it due to local pain and swelling. Your doctor will decide whether Treprostinil Tillomed should be administered instead as a continuous intravenous infusion directly into a vein via a central venous catheter connected to an external pump. Your doctor will determine the best option for you.

How Treprostinil Tillomed works
Treprostinil Tillomed reduces blood pressure in the pulmonary artery, improving blood circulation and reducing the workload on the heart. Improved blood flow leads to better oxygen delivery to the body and reduced strain on the heart, allowing the heart to function more effectively. Treprostinil improves symptoms associated with PAH and increases exercise capacity in patients with limited physical ability.

2. What you need to know before using Treprostinil Tillomed

Do not use Treprostinil Tillomed

• If you are allergic (hypersensitive) to treprostinil or to 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 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:
  • myocardial infarction (a heart attack) within the last six months
  • severe disturbances in heart rate
  • severe coronary artery disease or unstable angina
  • you have been diagnosed with a heart defect, such as a valvular defect causing impaired heart function
  • any untreated heart disease or heart disease not under close medical supervision.
• If you are at high specific risk of bleeding – for example, if you have active gastric ulcers, injuries, or other bleeding conditions.
• If you have had a stroke within the last three months or any other condition that has interrupted blood flow to the brain.

Warnings and precautions
Talk to your doctor before using Treprostinil Tillomed

• If you have liver disease
• If you have kidney disease
• If you are obese (BMI greater than 30 kg/m²)
• If you are infected with human immunodeficiency virus (HIV)
• If you have high blood pressure in the hepatic veins (portal hypertension)
• If you have a congenital heart defect affecting blood circulation

During treatment with Treprostinil Tillomed, inform your doctor:

• If your blood pressure decreases (hypotension)
• If you experience a rapid worsening of breathing difficulty or persistent cough (this may be due to pulmonary congestion, asthma, or other conditions); seek immediate medical attention
• If you experience excessive bleeding, as treprostinil may increase this risk by preventing blood clotting
• If you develop fever during intravenous administration of treprostinil or if the intravenous infusion site becomes red, swollen, and/or painful to touch, as this could be a sign of infection.

Other medicines and Treprostinil Tillomed
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 Drug ( NSAID ) (e.g., acetylsalicylic acid, 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 the dose of treprostinil.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before taking this medicine.
The use of treprostinil is not recommended during pregnancy, if you are planning a pregnancy, or if you think you may be pregnant, unless your doctor considers it necessary. The safety of using this medicine during pregnancy has not been established.
The use of treprostinil is not recommended during breastfeeding unless your doctor considers it necessary. If treprostinil is prescribed to you, it is advisable to stop breastfeeding, as it is not known whether this medicine is excreted in breast milk.
The use of an effective contraceptive method is strongly recommended during treatment with treprostinil.

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

Treprostinil Tillomed contains sodium
Treprostinil Tillomed 1 mg/ml solution for infusion
This medicine contains 74.16 mg of sodium (the main component of table salt) in each 20 ml vial. This corresponds to 3.71% of the maximum daily recommended dietary intake for an adult.
Treprostinil Tillomed 2.5 mg/ml solution for infusion
This medicine contains 75.08 mg of sodium (the main component of table salt) in each 20 ml vial. This corresponds to 3.75% of the maximum daily recommended dietary intake for an adult.
Treprostinil Tillomed 5 mg/ml solution for infusion
This medicine contains 78.16 mg of sodium (the main component of table salt) in each 20 ml vial. This corresponds to 3.91% of the maximum daily recommended dietary intake for an adult.
Treprostinil Tillomed 10 mg/ml solution for infusion
This medicine contains 75 mg of sodium (the main component of table salt) in each 20 ml vial. This corresponds to 3.75% of the maximum daily recommended dietary intake for an adult.

3. How to use Treprostinil Tillomed

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

Treprostinil Tillomed is administered by continuous infusion:

• either subcutaneously (under the skin) through a thin tube (cannula) inserted into the abdomen or thigh
• or intravenously through a tube (catheter) usually inserted into the neck, chest, or groin.

In both cases, treprostinil is delivered through the tube by an external portable pump placed outside the body.

Before leaving the hospital or clinic, your doctor will inform you how to prepare treprostinil and at which rate the pump should deliver the treprostinil dose.

Flushing the infusion cannula while it is connected may cause accidental overdose of the medicine.

You must also be provided with information on the correct use of the pump and what to do in case of pump malfunction. Among the information provided, you will be told whom to contact in an emergency.

Treprostinil must be diluted only when administered by continuous intravenous infusion:

For intravenous infusion via an external portable pump: the treprostinil solution must be diluted only with sterile water for injection or with 0.9% sodium chloride for injection (as directed by the doctor).

Adult patients
Treprostinil Tillomed is available as an infusion solution at concentrations of 1 mg/ml, 2.5 mg/ml, 5 mg/ml, and 10 mg/ml. Your doctor will determine the appropriate infusion rate and dose according to your condition.

Overweight patients
If you are overweight (exceeding 30% or more of your ideal body weight), your doctor will determine the initial and subsequent doses based on your ideal body weight.
See also section 2 “Warnings and precautions”.

Elderly patients
Your doctor will determine the appropriate infusion rate and dose according to your condition.

Children and adolescents
Available data on the use of this medicine in children and adolescents are limited.

Dose adjustment
The infusion rate may be increased or decreased individually only under medical supervision.

The aim of adjusting the infusion rate is to establish an effective maintenance rate that improves symptoms of pulmonary arterial hypertension while minimizing potential adverse effects.

If your symptoms worsen, or if you require complete bed rest or are confined to bed or chair, or if any physical activity increases your symptoms, or if symptoms occur even at rest, do not increase the dose without consulting your doctor. It is possible that treprostinil is no longer sufficient to treat your disease, and additional treatment may be necessary.

How can bloodstream infections be prevented during intravenous treprostinil treatment?
As with any long-term intravenous treatment, there is a risk of bloodstream infections. Your doctor will instruct you on how to avoid this.

If you use more Treprostinil Tillomed than you should
If you accidentally receive more treprostinil than prescribed, you may experience nausea, vomiting, diarrhea, low blood pressure (dizziness, confusion, or fainting), flushing, and/or headache.

If any of these effects become severe, contact your doctor or go to the hospital immediately. Your doctor may reduce or stop the infusion until symptoms resolve. The Treprostinil Tillomed infusion solution will then be restarted at a dose level recommended by your doctor.

If you stop treatment with Treprostinil Tillomed
Always use Treprostinil Tillomed exactly as instructed by your doctor or hospital specialist. Do not stop treatment with treprostinil unless instructed by your doctor.

Sudden discontinuation or abrupt dose reductions of treprostinil may cause a recurrence of pulmonary arterial hypertension, possibly leading to rapid and severe deterioration of your condition.

If you have any doubts about how to use this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Very common: (may affect more than 1 in 10 people)

• dilation of blood vessels with skin flushing
• pain or sensitivity at the infusion site
• skin discoloration or bruising at the infusion site
• headache
• skin rashes
• nausea
• diarrhoea
• jaw or jawbone pain

Common: (may affect up to 1 in 10 people)

• dizziness
• malaise (vomiting)
• mental confusion or fainting due to low blood pressure
• itching or skin redness
• swelling of feet, ankles or legs or fluid retention
• episodes of bleeding such as nosebleeds, coughing up blood, blood in urine, bleeding gums, blood in stools
• joint pain (arthralgia)
• muscle pain (myalgia)
• pain in legs and/or arms

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

• infection at the infusion site
• abscess at the infusion site
• decrease in blood cells responsible for blood clotting (platelets) (thrombocytopenia)
• bleeding at the infusion site
• bone pain
• skin rashes with skin discoloration or formation of papules (maculopapular rash)
• infection of the tissue beneath the skin (cellulitis)
• excessive pumping of blood from the heart causing shortness of breath, fatigue, swelling of legs and abdomen due to fluid accumulation, persistent cough

Additional side effects associated with intravenous administration

• inflammation of the vein (thrombophlebitis)
• bacterial infection of the bloodstream (bacteraemia)* (see section 3)
• sepsis (severe bacterial infection of the blood)

* Cases of potentially life-threatening or fatal bacterial infections of the bloodstream have been reported.
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 via 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 Treprostinil Tillomed

Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage conditions.
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.
Do not use Treprostinil Tillomed if you notice that the vial is damaged, or if there is any change in colour of the product or other signs of deterioration.
A vial of treprostinil must be used or discarded within 30 days of first opening.
During continuous subcutaneous infusion, a single reservoir (syringe) of undiluted treprostinil must be used within 72 hours.
During continuous intravenous infusion using external portable pumps, a single reservoir (syringe) of diluted treprostinil must be used within 24 hours.
Any remaining diluted solution must be discarded.
For instructions on use, see section 3 "How to use Treprostinil Tillomed".
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Treprostinil Tillomed contains
The active substance is treprostinil 1 mg/ml, 2.5 mg/ml, 5 mg/ml, 10 mg/ml.
The other components of Treprostinil Tillomed are:
Sodium chloride, metacresol, sodium citrate, sodium hydroxide, hydrochloric acid, concentrate,
water for injections.

Description of the appearance of Treprostinil Tillomed and contents of the pack
Treprostinil Tillomed 1 mg/ml solution for infusion
Clear, colourless to slightly yellow solution, practically free from visible particles, contained in a 20 ml transparent glass vial closed with a 20 mm greyish-black bromobutyl rubber stopper with four equidistant 90° marks and a circle in the centre, and sealed with a 20 mm peelable seal with opaque yellow finish.

Treprostinil Tillomed 2.5 mg/ml solution for infusion
Clear, colourless to slightly yellow solution, practically free from visible particles, contained in a 20 ml transparent glass vial closed with a 20 mm greyish-black bromobutyl rubber stopper with four equidistant 90° marks and a circle in the centre, and sealed with a 20 mm peelable seal with opaque blue finish.

Treprostinil Tillomed 5 mg/ml solution for infusion
Clear, colourless to slightly yellow solution, practically free from visible particles, contained in a 20 ml transparent glass vial closed with a 20 mm greyish-black bromobutyl rubber stopper with four equidistant 90° marks and a circle in the centre, and sealed with a 20 mm peelable seal with opaque green finish.

Treprostinil Tillomed 10 mg/ml solution for infusion
Clear, colourless to slightly yellow solution, practically free from visible particles, contained in a 20 ml transparent glass vial closed with a 20 mm greyish-black bromobutyl rubber stopper with four equidistant 90° marks and a circle in the centre, and sealed with a 20 mm peelable seal with opaque red finish.

The vials are packed in an outer carton.
Pack: 1 vial/box

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Tillomed Italia S.r.l.
Viale Richard 1, Tower A
20143, Milan
Italy

Manufacturer
SGS Pharma Magyarorszag Kft.
Derkovits Gyula Utca 53,
Budapest XIX, 1193,
Hungary

Tillomed Malta Limited
Malta Life Sciences Park,
LS2.01.06 Industrial Estate,
San Gwann, SGN 3000, Malta

This medicinal product is authorised in the Member States of the European Economic Area
under the following name: