LEVOSIMENDAN REIG JOFRE

Package leaflet: Information for the user

Levosimendan Reig Jofre, 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 so that you can read it again if necessary.
• If you have any further questions, please consult your doctor or nurse.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, inform your doctor or nurse immediately. See section 4.

Contents of the leaflet

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

1. What Levosimendan Reig Jofre is and what it is used for

Levosimendan Reig Jofre is a medicine in the form of a concentrate that must be diluted before
being administered to the patient as an intravenous infusion.
Levosimendan Reig Jofre increases the force with which the heart pumps blood and causes blood vessels to relax. As a result, Levosimendan Reig Jofre reduces pulmonary congestion and improves blood and oxygen flow throughout the body. Levosimendan Reig Jofre helps relieve breathlessness caused by severe heart failure.
Levosimendan Reig Jofre is used in the treatment of heart failure in patients who continue to experience breathing difficulties despite treatment with other medicines that remove excess fluid from the body.
Levosimendan Reig Jofre is used in adults.

2. Important information before using Levosimendan Reig Jofre

When not to use Levosimendan Reig Jofre:

• if the patient is allergic to levosimendan or 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 severe kidney or liver disease;
• if the patient has a heart condition that impairs filling or emptying of the heart;
• if the patient has ever been informed by a doctor of having an abnormal heart rhythm called torsades de pointes.

Warnings and precautions
Please discuss the following with your doctor or nurse before starting treatment with Levosimendan Reig Jofre.

• if the patient has low blood pressure;
• if the patient has reduced blood volume (hypovolemia);
• if the patient has any kidney or liver disease;
• if the patient has a low number of blood cells (anemia) and chest pain;
• if the patient has a rapid heartbeat, an irregular heart rhythm, or if the doctor has ever informed the patient of having atrial fibrillation or abnormally low potassium levels in the blood, Levosimendan Reig Jofre should be used with great caution.

Children and adolescents
Levosimendan Reig Jofre must not be used in children and adolescents under 18 years of age.

Levosimendan Reig Jofre and other medicines
Tell your doctor about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, including those available without a prescription.
If the patient is receiving other intravenous heart medications, using Levosimendan Reig Jofre may cause a drop in blood pressure.
Tell your doctor if the patient is taking isosorbide mononitrate, as Levosimendan Reig Jofre may intensify the drop in blood pressure upon standing.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine. It is not known whether using Levosimendan Reig Jofre affects the unborn child. The doctor will decide whether the benefits to the mother outweigh the potential risks to the child.
It has been shown that Levosimendan Reig Jofre passes into human breast milk. Breastfeeding must be avoided during treatment with Levosimendan Reig Jofre to prevent possible adverse effects on the infant's cardiovascular system.

Levosimendan Reig Jofre contains alcohol
This medicine contains 3925 mg of alcohol (absolute ethanol) in each 5 mL vial, which corresponds to 98% v/v alcohol. This amount of alcohol is equivalent to 99.2 mL of beer or 41.3 mL of wine.
The amount of alcohol in this medicine may affect the ability to drive or operate machinery, as it may impair judgment and reaction speed.
If the patient has epilepsy or liver problems, he or she should consult a doctor or pharmacist before using this medicine.
The amount of alcohol in this medicine may alter the effects 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 consult a doctor or pharmacist before using this medicine.
If the patient is alcohol-dependent, he or she should consult a doctor or pharmacist before using this medicine.
Since this medicine is usually administered slowly over more than 24 hours, the effects of alcohol may be reduced.

3. How to use Levosimendan Reig Jofre

Levosimendan Reig Jofre will be administered as an intravenous infusion (via drip). Therefore, Levosimendan Reig Jofre must only be given in a hospital setting where a physician can monitor the patient.
The physician will decide the appropriate dose of the medicine to administer. The physician will assess the patient's response to Levosimendan Reig Jofre (e.g. by measuring pulse, blood pressure, performing an ECG, and asking about well-being). If necessary, the physician may adjust the dose of the medicine. The physician may wish to monitor the patient for up to 4-5 days after completion of Levosimendan Reig Jofre infusion.
The patient may first receive a rapid infusion lasting 10 minutes, followed by a slower intravenous infusion lasting up to 24 hours.
Periodically, the physician will assess the patient's response to Levosimendan Reig Jofre. If the patient experiences a drop in blood pressure, increased heart rate, or feels unwell, the physician may reduce the infusion rate. Inform the physician or nurse if palpitations, dizziness, or the sensation that the effect of Levosimendan Reig Jofre is too strong or too weak occur.
The physician may increase the infusion rate if a higher dose of Levosimendan Reig Jofre is required and the patient does not experience adverse effects.
The physician will continue the Levosimendan Reig Jofre infusion for as long as cardiac support is needed. This usually lasts 24 hours.
The effect of Levosimendan Reig Jofre on the heart persists for at least 24 hours after the infusion ends. The medicine may remain active for 7-10 days after the infusion ends.

Renal impairment
Caution should be exercised when administering Levosimendan Reig Jofre to patients with mild or moderate renal impairment. Levosimendan Reig Jofre should not be used in patients with severe renal impairment (see section 2).

Hepatic impairment
Caution should be exercised when administering Levosimendan Reig Jofre to patients with mild or moderate hepatic impairment, although dose adjustment is not necessary in these patients. Levosimendan Reig Jofre should not be used in patients with severe hepatic impairment (see section 2).

Administration of a higher than recommended dose of Levosimendan Reig Jofre
If an excessive dose of Levosimendan Reig Jofre is administered, a decrease in blood pressure and increased heart rate may occur. The physician will provide appropriate treatment based on the patient's condition.

4. Possible side effects

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

• abnormally rapid heartbeat
• headache
• decreased blood pressure.

Common (may occur in not more than 1 out of 10 people):

• low potassium levels in the blood
• 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.

Frequency not known (cannot be estimated from the available data):

• hypersensitivity (symptoms may include rash and itching).

In patients receiving Levosimendan Reig Jofre, heart rhythm disorders called ventricular fibrillation (a part of the heart flutters instead of beating properly) have been observed.
If side effects occur, a doctor should be informed immediately. The doctor may reduce the infusion rate or discontinue the infusion of Levosimendan Reig Jofre.
Reporting of side effects
If any side effects occur, including any side effects not listed in this leaflet, tell your doctor or nurse. Side effects can also be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181 C, 02-222 Warsaw, phone: +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 Authorisation Holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Levosimendan Reig Jofre

Keep this medicine out of the sight and reach of children.
Store in a refrigerator (2°C–8°C).
Do not freeze.
Do not use this medicine after the expiry date stated on the label or carton, following:
EXP. The expiry date refers to the last day of the stated month.
During storage, the concentrate may change colour to orange, but this does not affect its potency, and the medicine may still be used up to the indicated expiry date, provided that storage instructions have been followed.

After dilution
Chemical and physical stability has been demonstrated for the prepared solution for up to 24 hours at 25°C.
From a microbiological standpoint, the product should be used immediately. If the product is not used immediately, the user is responsible for the storage duration and conditions prior to use. The product should not be stored for longer than 24 hours at a temperature between 2°C and 8°C, unless the dilution was carried out under controlled and validated aseptic conditions.
After dilution, the medicine must never be stored or administered for longer than 24 hours.

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

6. Contents of the pack and other information

What Levosimendan Reig Jofre contains

• The active substance is levosimendan. Each mL of concentrate contains 2.5 mg of levosimendan. Each 5 mL vial contains 12.5 mg of levosimendan.
• The other ingredients are povidone, citric acid (for pH adjustment), and absolute ethanol.

What Levosimendan Reig Jofre looks like and contents of the pack
The concentrate for solution for infusion is a clear yellow or orange solution, which must be diluted before administration.
Pack sizes

• 1, 4, 10 vials (vial made of glass with a chlorobutyl rubber stopper and aluminium cap and seal), each containing 5 mL, in a cardboard box.

Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Reig Jofre Sp. z o.o.
Ostródzka Street 74N
03-289 Warsaw
Poland
e-mail: [email protected]
Telephone: +48 22 487 88 49
Manufacturer
Laboratorio Reig Jofre, S.A.
Gran Capitan, 10
Sant Joan Despí
08970 Barcelona
Spain
This medicinal product is authorised in the European Economic Area countries under the following names:
Denmark: Levosimendan Bioglan
Finland: Levosimendan Bioglan 2.5 mg/ml infuusiokonsentraatti, liuosta varten
France: LEVOSIMENDAN REIG JOFRE 2,5 mg/mL, solution à diluer pour perfusion
Spain: Levosimendan Sala 2,5 mg/ml concentrado para solución para perfusión EFG
Germany: Levosimendan Hikma 2,5 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Norway: Levosimendan Bioglan
Poland: Levosimendan Reig Jofre
Portugal: Levossimendano Reig Jofre 2,5 mg/ml concentrado para solução para perfusão
Sweden: Levosimendan Bioglan
Italy: Levosimendan Reig Jofre
Other sources of information
Detailed information on this medicinal product is available on the website of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products (URPL): www.urpl.gov.pl

Information intended exclusively for healthcare professionals:
Levosimendan Reig Jofre, 2.5 mg/mL, concentrate for solution for infusion
Instructions for use and handling
Levosimendan Reig Jofre 2.5 mg/mL, concentrate for solution for infusion is intended for single use only.
Levosimendan Reig Jofre must not be diluted to a concentration greater than 0.05 mg/mL according to the instructions below, otherwise opalescence and precipitation may occur.
As with all parenteral products, the diluted solution should be visually inspected for 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 Reig Jofre 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 Reig Jofre 2.5 mg/mL concentrate for solution for infusion with 500 mL of 5% glucose solution.

Dosage and method of administration
Levosimendan Reig Jofre is intended for hospital use only. The medicinal product should be administered in a hospital setting where appropriate monitoring equipment and experienced personnel for administration of inotropic agents are available.
Levosimendan Reig Jofre 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 Product Characteristics Summary.