TREPROSTINIL ZENTIVA 5 mg/ml SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the Patient

Treprostinil Zentiva 1 mg/ml Solution for Infusion EFG

Treprostinil Zentiva 2.5 mg/ml Solution for Infusion EFG

Treprostinil Zentiva 5 mg/ml Solution for Infusion EFG

Treprostinil Zentiva 10 mg/ml Solution for Infusion EFG

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

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

What is Treprostinil Zentiva

The active substance of this medicine is treprostinil.

Treprostinil belongs to a group of medicines whose action is similar to that of natural prostacyclins. Prostacyclins are hormone-like substances that reduce blood pressure by relaxing blood vessels, so they widen and allow blood to flow more easily. Prostacyclins can also prevent blood clotting.

What Treprostinil Zentiva is used for

Treprostinil is used to treat idiopathic or hereditary pulmonary arterial hypertension (PAH) in patients with moderate symptoms. Pulmonary arterial hypertension is a disease where blood pressure is too high in the blood vessels between the heart and lungs. This causes difficulty breathing, dizziness, fatigue, fainting, palpitations or abnormal heartbeats, dry cough, chest pain, and swelling of ankles or legs.

Treprostinil is initially administered by continuous subcutaneous infusion (under the skin). Some patients may not tolerate this administration because it causes them local pain and swelling. The doctor will decide if Treprostinil Zentiva can be administered to them through continuous intravenous infusion directly into a vein with the insertion of a central venous tube (catheter) connected to an external pump. Your doctor will determine which option is best for you.

How Treprostinil Zentiva works

Treprostinil reduces blood pressure in the pulmonary artery by improving circulation and reducing the heart's workload. Improved blood circulation increases oxygen supply to the body and requires less effort from the heart, so it works more efficiently. Treprostinil improves symptoms associated with PAH and exercise capacity in patients with reduced activity.

2. What you need to know before you use Treprostinil Zentiva

Do not use Treprostinil Zentiva:

• 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". In this disease, the blood vessels that carry blood through the lungs become swollen and blocked, increasing pressure in the blood vessels between the heart and lungs;
• if you have severe liver failure;
• if you have a heart problem, for example:

• a heart attack (myocardial infarction) in the last six months,
• severe changes in heart rate,
• severe coronary heart disease or unstable angina,
• a diagnosed heart defect, such as a faulty heart valve that causes the heart to malfunction,
• any untreated or closely monitored heart disease;

• if you have a high specific risk of bleeding, for example, due to active stomach ulcers, injuries, or other bleeding disorders;
• if you have had a stroke in the last 3 months or any interruption of blood supply to the brain.

Warnings and precautions

Talk to your doctor before starting Treprostinil Zentiva:

• if you have any liver disease;
• if you have been told you are clinically obese (BMI over 30 kg/m2);
• if you have human immunodeficiency virus (HIV) infection;
• if you have high blood pressure in the liver veins (portal hypertension);
• if you have a congenital heart defect that affects how blood circulates through it.

During treatment with this medicine, tell your doctor:

• if your blood pressure drops (hypotension);
• if you experience a rapid increase in breathing difficulties or persistent cough (may be related to pulmonary congestion, asthma, or other disease), consult your doctor immediately;
• if you experience excessive bleeding, as treprostinil can increase the risk by preventing blood clotting;
• if you have a fever while receiving treprostinil intravenously, or if the infusion site becomes red, swollen, or painful to the touch, as it may be a sign of infection.

Other medicines and Treprostinil Zentiva

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Tell your doctor if you are taking:

• medicines to treat high blood pressure(antihypertensive medicines or other vasodilators)
• medicines used to increase the amount of urine produced(diuretics), including furosemide
• medicines that interrupt blood clotting(anticoagulants), such as warfarin, heparin, or nitric oxide
• any non-steroidal anti-inflammatory drug (NSAID) (such as aspirin or ibuprofen)
• medicines that may increase or decrease the effect of treprostinil (such as 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 or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Treprostinil is not recommended during pregnancy, unless your doctor considers it essential. The safety of this medicine for use during pregnancy has not been established.

Treprostinil is not recommended during breastfeeding, unless your doctor considers it essential. You are advised to stop breastfeeding if you are prescribed treprostinil, as it is unknown whether this medicine is excreted in breast milk.

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

Driving and using machines

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

Treprostinil Zentiva contains sodium

Treprostinil Zentiva 1 mg/ml Solution for Infusion EFG

This medicine contains up to 74.16 mg of sodium (main component of table/cooking salt) in each 20 ml vial. This is equivalent to 3.71% of the maximum recommended daily sodium intake for an adult.

Treprostinil Zentiva 2.5 mg/ml Solution for Infusion EFG

This medicine contains up to 75.08 mg of sodium (main component of table/cooking salt) in each 20 ml vial. This is equivalent to 3.75% of the maximum recommended daily sodium intake for an adult.

Treprostinil Zentiva 5 mg/ml Solution for Infusion EFG

This medicine contains up to 78.16 mg of sodium (main component of table/cooking salt) in each 20 ml vial. This is equivalent to 3.91% of the maximum recommended daily sodium intake for an adult.

Treprostinil Zentiva 10 mg/ml Solution for Infusion EFG

This medicine contains up to 75 mg of sodium (main component of table/cooking salt) in each 20 ml vial. This is equivalent to 3.75% of the maximum recommended daily sodium intake for an adult.

3. How to use Treprostinil Zentiva

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

Treprostinil Zentiva is administered as a continuous infusion:

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

In both cases, treprostinil will be delivered through the tube by an external portable pump.

Before leaving the hospital or clinic, your doctor will tell you how to prepare treprostinil and at what speed the pump should deliver treprostinil.

Flushing the infusion tube while connected can cause an accidental overdose.

In any case, you should also be given information on how to use the pump correctly and what to do if it stops working. The information should also tell you who to contact in case of an emergency.

Treprostinil is diluted only when administered with continuous intravenous infusion.

For intravenous infusion with an external portable pump:The treprostinil solution should only be diluted with sterile water for injection or 0.9% sodium chloride solution for infusion (as indicated by your doctor).

Adult patients

Treprostinil Zentiva 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 suitable dose for your disease.

Overweight patients

If you are overweight (weigh 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 infusion rate and suitable dose for your disease.

Use in children and adolescents

There are limited data available for children and adolescents.

Dose adjustment

The infusion rate in each individual patient may be reduced or increased only under medical supervision.

The goal of adjusting the infusion rate is to establish an effective maintenance rate that improves PAH symptoms while minimizing side effects.

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

How can bloodstream infections be avoided during intravenous administration of treprostinil?

As with any long-term intravenous treatment, there is a risk of contracting bloodstream infections. Your doctor will tell you how to avoid them.

If you use more Treprostinil Zentiva than you should

If treprostinil is accidentally administered in excess, you may experience nausea, vomiting, diarrhea, low blood pressure (dizziness, fainting), flushing, and/or headache.

If any of these symptoms become severe, you should contact your doctor or hospital immediately. The doctor may reduce the dose or interrupt administration until the symptoms disappear. Then, the administration of Treprostinil Zentiva will be resumed with the dose recommended by your doctor.

In case of overdose, consult your doctor immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount used.

If you stop using Treprostinil Zentiva

Always use treprostinil exactly as your doctor or hospital specialist has told you. Do not stop using treprostinil unless your doctor tells you to.

Sudden interruption or rapid reduction of the treprostinil dose can cause PAH to recur, 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 side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

• vasodilation with flushing
• pain or pain on palpation around the infusion site
• skin color changes or bruising around the infusion site
• headache
• skin rash
• nausea
• diarrhea
• jaw pain

Common side effects (may affect up to 1 in 10 people)

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

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

• infection at the infusion site
• abscess at the infusion site
• reduction of blood clotting cells (platelets) in the blood (thrombocytopenia)
• bleeding at the infusion site
• bone pain
• skin rash with discoloration or bumps (maculopapular rash)
• infection of the tissue under the skin (cellulitis)
• excessive blood flow from the heart that causes difficulty breathing, fatigue, swelling of legs and abdomen due to fluid accumulation, persistent cough.

Other side effects associated with intravenous administration

• vein inflammation (thrombophlebitis)
• bacterial infection in the bloodstream (bacteremia)* (see section 3)
• septicemia (severe bacterial infection of the blood)

• Potentially fatal or fatal cases of bacterial infection in the bloodstream have been reported.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Treprostinil Zentiva

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

Do not use Treprostinil Zentiva if you notice damage to the vial, color change, or other signs of deterioration.

Treprostinil vials should be discarded 30 days after first opening.

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

During continuous intravenous infusion with external portable pumps, a single treprostinil reservoir (syringe) should be used within 24 hours.

The diluted solution should be discarded if not used.

For instructions on use, see section 3: How to use Treprostinil Zentiva.

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

Composition of Treprostinil Zentiva

The active substance is treprostinil 1 mg/ml, 2.5 mg/ml, 5 mg/ml, 10 mg/ml.

The other components are: sodium chloride, metacresol, sodium citrate, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), water for injectable preparations.

Appearance and Packaging of the Product

Treprostinil Zentiva 1 mg/ml Solution for Infusion EFG

Clear to slightly yellowish transparent solution, practically free from visible particles, filled in a glass vial with a bromobutyl rubber stopper, with an aluminum cap and a yellow plastic flip-off cap, containing 20 ml of solution for infusion.

Treprostinil Zentiva 2.5 mg/ml Solution for Infusion EFG

Clear to slightly yellowish transparent solution, practically free from visible particles, filled in a glass vial with a bromobutyl rubber stopper, with an aluminum cap and a blue plastic flip-off cap, containing 20 ml of solution for infusion.

Treprostinil Zentiva 5 mg/ml Solution for Infusion EFG

Clear to slightly yellowish transparent solution, practically free from visible particles, filled in a glass vial with a bromobutyl rubber stopper, with an aluminum cap and a green plastic flip-off cap, containing 20 ml of solution for infusion.

Treprostinil Zentiva 10 mg/ml Solution for Infusion EFG

Clear to slightly yellowish transparent solution, practically free from visible particles, filled in a glass vial with a bromobutyl rubber stopper, with an aluminum cap and a red plastic flip-off cap, containing 20 ml of solution for infusion.

The vials are packaged in a cardboard box.

Package size: 1 vial

Marketing Authorization Holder and Manufacturer:

Marketing Authorization Holder:

Zentiva, k.s.

U kabelovny 130,

Dolní Mecholupy,

102 37 Prague 10

Czech Republic

Manufacturer[1]

Tillomed Malta Limited,

Malta Life Sciences Park,

LS2.01.06 Industrial Estate,

San Gwann, SGN 3000, Malta

SGS Pharma Magyarorszag Kft

Derkovits Gyula Utca 53,

Budapest XIX, 1193

Hungary

[1] Only the site that actually performs the release will be indicated on the marketed product.

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

Zentiva Spain S.L.U.

Avenida de Europa, 19, Edificio 3, Planta 1.

28224 Pozuelo de Alarcón, Madrid

Spain

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Date of the last revision of this leaflet: September 2024