Levosimendan zentiva

Package leaflet: Information for the user

Levosimendan Zentiva, 2.5 mg/mL, concentrate for solution for infusion
Levosimendanum
Please read all of this leaflet carefully before this medicine is administered, because it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or nurse. If you experience any side effects, including any not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

1. What Levosimendan Zentiva is and what it is used for
2. Important information before using Levosimendan Zentiva
3. How to use Levosimendan Zentiva
4. Possible side effects
5. How to store Levosimendan Zentiva
6. Contents of the pack and other information

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

Levosimendan Zentiva is a concentrated medicine that must be diluted before intravenous infusion.
Levosimendan increases the force with which the heart pumps blood and allows blood vessels to relax. Levosimendan reduces pulmonary congestion and facilitates blood and oxygen flow throughout the body. Levosimendan helps relieve breathlessness caused by severe heart failure.
Levosimendan Zentiva is used in short-term, additional treatment of acute decompensated severe chronic heart failure in adult patients who still have difficulty breathing despite taking other medicines that remove excess fluid from the body.

2. Important information before using the medicine

Levosimendan Zentiva
When not to use Levosimendan Zentiva:

• if the patient is allergic (hypersensitive) to levosimendan or to any of the other ingredients of this medicine (listed in section 6);
• if the patient has very low blood pressure and a rapid heartbeat;
• if the patient has a heart condition that impairs filling or emptying of the heart;
• if the patient has severe kidney or liver disease;
• if the patient has ever been informed by a doctor about having a heart rhythm disorder called torsades de pointes.

Warnings and precautions

• if the patient has any kidney or liver disease;
• if the patient has a low number of blood cells and chest pain;
• if the patient has a rapid heartbeat, irregular heart rhythm, or if the doctor has ever informed the patient about having atrial fibrillation or abnormally low blood potassium levels, levosimendan should be used with great caution.

If the patient has any of the above conditions or symptoms, discuss this with the doctor before starting treatment with Levosimendan Zentiva.

Children and adolescents
This medicine should not be used in children and adolescents under 18 years of age.

Levosimendan Zentiva and other medicines
Tell the doctor about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
If the patient is receiving other intravenous medicines used for heart conditions, the use of levosimendan may cause a drop in blood pressure.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a baby, she should consult a doctor before using this medicine.
It is unknown whether levosimendan affects the unborn child. The doctor must decide whether the benefits to the patient outweigh the risks to the unborn child.
There is evidence that levosimendan passes into human milk. Breastfeeding should be avoided during treatment with levosimendan to prevent potential cardiovascular adverse effects in infants.

Levosimendan Zentiva contains alcohol
This medicine contains 98% v/v alcohol. This corresponds to 3848 mg per 5 mL in the vial, equivalent to 98 mL of beer or 41 mL of wine.
The alcohol content may affect the ability to drive or operate machinery. It may influence judgment and reaction speed.
If the patient has epilepsy or liver problems, he or she should talk to a doctor or pharmacist before starting this medicine.
The alcohol content may affect the action of other medicines. If the patient is taking other medicines, he or she should consult a doctor or pharmacist.
If the patient is pregnant or breastfeeding, she should talk to a doctor or pharmacist before starting this medicine.
If the patient is alcohol-dependent, he or she should consult a doctor or pharmacist before taking this medicine.
Since this medicine is usually administered slowly over 24 hours, the effect of alcohol may be reduced.

3. How to use Levosimendan Zentiva

Levosimendan Zentiva is administered as an intravenous infusion (drip infusion). Therefore, Levosimendan Zentiva must be given in a hospital setting where a doctor can monitor the patient.
The doctor will decide on the dose of Levosimendan Zentiva.
The doctor will assess the patient's response to levosimendan (e.g. by measuring pulse or arterial blood pressure, performing an ECG, and asking about well-being).
The doctor may adjust the dose if considered necessary. The doctor may monitor the patient's condition for 4–5 days after completion of the levosimendan infusion.
The patient may receive a rapid infusion lasting ten minutes, followed by a slower infusion lasting up to 24 hours.
The doctor should periodically check how the patient is responding to levosimendan. The doctor may reduce the infusion rate if blood pressure drops, heart rate becomes too fast, or the patient feels unwell. Inform the doctor or nurse if the patient experiences rapid heartbeat, dizziness, or if the effect of levosimendan seems too strong or too weak.
If the doctor considers that the patient requires more levosimendan and no adverse effects are occurring, the infusion rate may be increased.
The doctor will continue the levosimendan infusion for as long as necessary to support heart function. This usually lasts 24 hours.
The effect on the heart persists for at least 24 hours after the end of the levosimendan infusion. This effect may last for 7–10 days after the end of the infusion.
If more Levosimendan Zentiva has been administered than recommended
If an excessive dose of Levosimendan Zentiva is given, a decrease in arterial blood pressure and increased heart rate may occur. The doctor will provide appropriate treatment based on the patient's condition.
If you have any further questions about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Very common (occur in more than 1 in 10 patients):

• abnormally rapid heartbeat
• headache
• decreased blood pressure

Common (occur in up to 1 in 10 patients):

• low blood potassium levels
• insomnia
• dizziness
• heart rhythm disorders called atrial fibrillation (a part of the heart flutters instead of beating properly)
• extra heartbeats
• heart failure
• myocardial ischaemia
• nausea
• constipation
• diarrhoea
• vomiting
• low number of blood cells

In patients receiving levosimendan, heart rhythm disturbances called ventricular fibrillation (a part of the heart flutters instead of beating properly) have been observed.
Frequency unknown (cannot be estimated from the available data): hypersensitivity
(symptoms may include rash and itching).
If any side effects occur, you must inform your doctor or nurse immediately. The doctor may reduce the infusion rate or discontinue the levosimendan infusion.
If any of the side effects become serious, or if you notice any side effects not listed in this leaflet, inform your doctor.
Reporting of side effects
If you experience any adverse reactions, including any not listed in this leaflet, you should inform your doctor or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181 C, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, additional information on the safety of this medicine can be collected.

5. How to store Levosimendan Zentiva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial or carton after "EXP". The expiry date refers to the last day of the stated month.
Storage conditions
Store in a refrigerator (2°C – 8°C). Do not freeze.
This product is a clear, yellow or orange solution free from visible particles.
Storage conditions after dilution:
Chemical and physical stability has been demonstrated for 48 hours at 25°C.
From a microbiological standpoint, unless the method of opening, reconstitution or dilution excludes the risk of microbiological contamination, the product should be used immediately. If the product is not used immediately, the responsibility for the storage duration and conditions prior to use lies with the user.

6. Contents of the pack and other information

What Levosimendan Zentiva contains
The active substance is levosimendan.
Each 5 mL vial of concentrate for solution for infusion contains 12.5 mg of levosimendan.
The other ingredients are: Povidone K-12 (E1201), Citric acid (E330), Anhydrous ethanol (E1510).

What Levosimendan Zentiva looks like and contents of the pack
Pack sizes:
1 vial (clear type I glass) with a volume of 5 mL in a cardboard box.
4 vials (clear type I glass) with a volume of 5 mL in a cardboard box.

Levosimendan Zentiva 2.5 mg/mL concentrate for solution for infusion is available as a clear, yellow or orange solution free from visible particles, packed in a 6 mL clear vial made of type I glass, closed with a 20 mm rubber stopper and sealed with a 20 mm flip-off seal.

Marketing Authorisation Holder:
Zentiva, k.s.,
U kabelovny 130,
Dolní Měcholupy,
102 37 Prague 10,
Czech Republic

Manufacturer/Importer:
MIAS Pharma Limited
Suite 2, Stafford House,
Strand Road,
Portmarnock,
Co. Dublin,
Ireland
Tillomed Malta Limited,
Malta Life Sciences Park,
LS2.01.06 Industrial Estate,
San Gwann, SGN 3000, Malta

This medicinal product is authorised in the European Economic Area member states under the following names:
Austria: Levosimendan Tillomed 2.5 mg/mL concentrate for solution for infusion
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 concentrate for solution for infusion
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

Information intended exclusively for healthcare professionals:
Instructions for use and handling
Levosimendan Zentiva 2.5 mg/mL concentrate for solution for infusion is intended for single use only.
Levosimendan Zentiva 2.5 mg/mL concentrate for solution for infusion must not be diluted to a concentration higher than 0.05 mg/mL, as specified below, otherwise opalescence and precipitation may occur.
As with all parenteral products, the diluted solution should be visually inspected for the presence of particulate matter and discoloration prior to administration.

• To prepare an infusion solution with a concentration of 0.025 mg/mL, mix 5 mL of Levosimendan Zentiva 2.5 mg/mL concentrate for solution for infusion with 500 mL of 5% glucose solution.
• To prepare an infusion solution with a concentration of 0.05 mg/mL, mix 10 mL of Levosimendan Zentiva 2.5 mg/mL concentrate for solution for infusion with 500 mL of 5% glucose solution.

Dosage and method of administration
Levosimendan Zentiva is intended for hospital use only. The medicinal product must be administered in a hospital setting where appropriate monitoring equipment and experienced personnel for administering inotropic agents are available.
Levosimendan Zentiva must be diluted before administration.
The solution is intended for intravenous infusion only and may be administered peripherally or centrally.
For information on dosage, refer to the Summary of Product Characteristics.