LEVOSIMENDAN ZENTIVA 2.5 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Levosimendan Zentiva2.5 mg/ml concentrate for 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.
• If you experience any side effects, talk to your doctor, or pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

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

Levosimendan Zentiva is presented as a concentrate that must be diluted before administration by intravenous infusion.

Levosimendan works by increasing the heart's pumping force and allowing the blood vessels to relax. Levosimendan will reduce lung congestion and facilitate blood and oxygen circulation in your body. Levosimendan helps alleviate the breathing difficulties of severe heart failure.

Levosimendan is indicated for the short-term additional treatment of heart failure in adults who continue to have difficulty breathing despite taking other medications to remove fluid from the body.

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

Do not use Levosimendan Zentiva

• If you are allergic (hypersensitive) to levosimendan or any of the other ingredients of this medicine (listed in section 6).
• If you have low blood pressure or tachycardia (abnormally high heart rate).
• If you have severe kidney or liver damage.
• If you have any heart disease that makes it difficult for the heart to fill and empty.
• If your doctor has told you that you have had an arrhythmia called Torsades de Pointes.

Warnings and precautions

• If you have liver or kidney disease.
• If you have anemia and chest pain at the same time.
• If you have tachycardia, abnormal heart rate, your doctor has told you that you have atrial fibrillation or have abnormally low potassium levels in your blood, your doctor should use levosimendan with caution.

Talk to your doctor before starting to use levosimendan if you have any of the diseases or symptoms mentioned above.

Children and adolescents

This medicine should not be given to children and adolescents under 18 years of age.

Other medicines and Levosimendan Zentiva

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.

If you have been given other intravenous heart medicines, the administration of levosimendan may cause a drop in blood pressure.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

It is not known if levosimendan affects your baby. Your doctor will decide if the benefit outweighs any possible risk to the baby.

There are indications that levosimendan passes into breast milk. You should not breastfeed while being treated with levosimendan to avoid possible cardiovascular side effects in the baby.

Levosimendan Zentiva contains alcohol

This medicine contains 98% alcohol by volume. This is up to 3,848 mg in each 5 ml vial, equivalent to 98 ml of beer or 41 ml of wine.

The amount of alcohol in this medicine may affect your ability to drive and use machines as it may alter your judgment and reaction speed.

If you suffer from epilepsy or liver problems, talk to your doctor or pharmacist before taking this medicine.

The amount of alcohol in this medicine may alter the effect of other medicines. Talk to your doctor or pharmacist if you are taking other medicines.

If you are pregnant or breastfeeding, talk to your doctor or pharmacist before taking this medicine.

If you are addicted to alcohol, talk to your doctor or pharmacist before taking this medicine.

Since this medicine is usually administered slowly over 24 hours, the effects of alcohol may be reduced.

3. How to use Levosimendan Zentiva

Levosimendan should be administered by intravenous infusion (drip). For this reason, it should only be administered in a hospital where your doctor can monitor you. Your doctor will decide the dose of levosimendan to be administered. Your doctor will follow your response to treatment (for example, by measuring your heart rate, blood pressure, electrocardiogram, and your subjective feelings), and will modify the dose if necessary. Your doctor may want to monitor you for 4-5 days after the end of levosimendan administration.

You may receive a rapid infusion for ten minutes, followed by a slower infusion for up to 24 hours.

Your doctor will assess your response to levosimendan at different times. This way, the infusion can be decreased if your blood pressure drops or your heart rate becomes too fast or you do not feel well. If you feel that your heart is racing, you feel dizzy or have the impression that the effect of levosimendan is too strong or too weak, you should inform your doctor or nurse.

If your doctor considers that you need a higher dose of levosimendan and you are not experiencing side effects, the infusion can be increased.

Your doctor will continue the levosimendan infusion for as long as necessary to help your heart. It is usually recommended to infuse levosimendan for 24 hours.

The effect on your heart function will continue for 24 hours after the infusion of the product has ended. The effect may continue for 7-10 days after the end of the infusion.

If you use more Levosimendan Zentiva than you should

An overdose of levosimendan will cause a drop in blood pressure and an increase in heart rate. Your doctor will know how to treat you according to your history.

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 up to 1 in 10 people)

• Abnormally high heart rate.
• Headache.
• Low blood pressure.

Common (may affect up to 1 in 10 people)

• Potassium levels in the blood are low.
• Insomnia.
• Dizziness.
• An abnormal heart rhythm called atrial fibrillation (as a consequence of heart palpitations instead of a proper heartbeat).
• Extra heartbeats.
• Heart failure.
• Decreased oxygen supply to the heart through the blood.
• Nausea.
• Constipation.
• Diarrhea.
• Vomiting.
• Decreased hemoglobin.

There have been reports of a heart rhythm disorder called ventricular fibrillation (as a consequence of heart palpitations instead of a proper heartbeat) in patients who received levosimendan.

Tell your doctor immediately if you experience any side effects. Your doctor may reduce or stop the levosimendan infusion.

If you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Reporting of side effects

If you experience any side effects, talk to your doctor, or pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the Spanish Medicines and Healthcare Products Agency: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Levosimendan Zentiva

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 after EXP. The expiry date refers to the last day of that month.

Storage conditions

Store in a refrigerator (2°C - 8°C). Do not freeze.

The product is a clear, yellow or orange solution, without visible particles.

Storage conditions after dilution:

Chemical and physical stability has been demonstrated for 48 hours at 25°C.

From a microbiological point of view, unless the method of opening/reconstitution/dilution precludes the risk of microbial contamination, the product should be used immediately.

If not used immediately, in-use storage times and conditions are the responsibility of the user.

6. Contents of the pack and further information

Composition of Levosimendan Zentiva

• The active substance is levosimendan.
• One 5 ml vial of concentrate for solution for infusion contains 12.5 mg of levosimendan.

• The other ingredients are: povidone, citric acid, anhydrous ethanol.

Appearance and packaging

Pack size: 1 colourless (type I) glass vial of 5 ml.

Levosimendan Zentiva 2.5 mg/ml concentrate for solution for infusion is a clear, yellow or orange solution, free from visible particles, in a 6 ml type I glass vial, closed with a 20 mm rubber stopper and sealed with a 20 mm flip-off MT cap.

Marketing authorisation holder and manufacturer

Marketing authorisation holder

Zentiva, k.s.,

U kabelovny 130,

Prague 10 - Dolní Mecholupy,

102 37 Czech Republic

Manufacturer[1]

MIAS Pharma Limited

Suite 2, Stafford House,

Strand Road,

Portmarnock,

Co. Dublin,

Ireland

or

Tillomed Malta Limited,

Malta Life Sciences Park,

LS2.01.06 Industrial Estate,

San Gwann, SGN 3000, Malta

You can obtain further information on this medicine from the local representative of the marketing authorisation holder:

Zentiva Spain S.L.U.,

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

28224 Pozuelo de Alarcón, Madrid

Spain

This medicine is authorised in the Member States of the European Economic Area under the following names:

Austria: Levosimendan Tillomed 2.5 mg / ml Konzentrat zur Herstellung einer Infusionslösung

Czech Republic: Levosimendan Zentiva

Denmark: Levosimendan Tillomed

Finland: Levosimendaani Tillomed 2.5 mg/ml infuusiokonsentraatti, liuosta varten

France: LÉVOSIMENDAN TILLOMED 2.5 mg/ml, solution à diluer pour perfusion

Germany: Levosimendan Tillomed 2.5 mg / ml Konzentrat zur Herstellung einer Infusionslösung

Italy: Levosimendan Tillomed

Norway: Levosimendan Tillomed

Poland: Levosimendan Zentiva

Portugal: Levossimendano Tillomed 2.5 mg/ml concentrado para solução para perfusão

Slovakia: Levosimendan Zentiva 2.5 mg/ml koncentrát na infúzny roztok

Slovenia: Levosimendan Tillomed 2.5 mg/ml koncentrat za raztopino za infundiranje

Spain: Levosimendán Zentiva 2.5 mg/ml concentrado para solución para perfusión EFG

Sweden: Levosimendan Tillomed

Date of last revision of this leaflet:November 2021

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency for Medicines and Healthcare Products (AEMPS) http://www.aemps.gob.es/

This information is intended for healthcare professionals only:

Instructions for use and handling

Levosimendan Zentiva 2.5 mg/ml concentrate for solution for infusion is designed exclusively for single use.

Levosimendan Zentiva 2.5 mg/ml concentrate for solution for infusion should not be diluted to concentrations higher than 0.05 mg/ml as indicated below, as this may cause opalescence and precipitation.

As with other parenteral products, the diluted solution should be inspected visually for particles and discoloration before administration.

• To prepare the 0.025 mg/ml infusion, mix 5 ml of levosimendan concentrate with 500 ml of 5% glucose solution.
• To prepare the 0.05 mg/ml infusion, mix 10 ml of levosimendan concentrate with 500 ml of 5% glucose solution.

Posology and method of administration

Levosimendan is for hospital use only. It should be administered in a hospital setting where there are monitoring facilities and experience with the use of inotropic agents.

Levosimendan should be diluted before administration.

The infusion should be administered exclusively by intravenous route, either by peripheral or central route.

Refer to the summary of product characteristics for information on posology.

[1] In the printed leaflet, only the actual site will appear