Leaflet: information for the user

Levosimendan EVER Pharma 2.5 mg/ml concentrate for solution for infusion EFG

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• If you experience any side effects, consult your doctor or nurse, even if they are not listed in this leaflet. See section 4.

1. What Levosimendan EVER Pharma is and what it is used for

2. What you need to know before starting to use Levosimendan EVER Pharma

3. How to use Levosimendan EVER Pharma

4. Possible side effects

5. Storage of Levosimendan EVER Pharma

6. Contents of the pack and additional information

Levosimendan EVER Pharma is presented in a concentrated form that must be diluted before administration via intravenous infusion.

Levosimendan acts by increasing the heart's pumping force and allowing the relaxation of blood vessels. Levosimendan will reduce pulmonary congestion and facilitate the circulation of blood and oxygen throughout the body. Levosimendan helps to alleviate the difficulty of breathing associated with severe heart failure.

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

Levosimendan is used in adults.

No use LevosimendánEVERPharma

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

Warnings and Precautions

Consult your doctor or nurse before starting to use this medication if:

• You have low blood pressure,
• You are in a state of decreased blood volume (hypovolemia),
• You have a liver or kidney disease,
• Your doctor has told you that you have abnormally low levels of potassium in your blood,
• You have simultaneously low blood count (anemia) and chest pain,
• You have an abnormally fast heartbeat, abnormal heart rhythm or your doctor has told you that you have atrial fibrillation.

Consult your doctor or nurse if you are unsure if you have any of the diseases or symptoms mentioned above.

Children and Adolescents

The safety and efficacy of levosimendan have not yet been established in children and adolescents under 18 years.

Other Medications and LevosimendánEVERPharma

Inform your doctor if you are using, have used recently or may need to use any other medication, including those purchased without a prescription.

If you have been given other intravenous cardiac medications, the administration of Levosimendan may cause a drop in blood pressure.

Inform your doctor or nurse if you are taking isosorbide mononitrate (used to treat angina), as levosimendan may increase a drop in your blood pressure when standing up.

Pregnancy and Breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor before using this medication. It is unknown if levosimendan affects your baby. Some negative reproductive effects have been observed in animals, so it is not recommended to use levosimendan during pregnancy and in women who may become pregnant and are not using contraceptives.

There is evidence that levosimendan passes into breast milk. Do not breastfeed while being treated with levosimendan to avoid possible adverse cardiovascular effects in the child.

LevosimendánEVERPharma contains alcohol (ethanol)

This medication contains up to 3,925mg of alcohol (ethanol) in each 5ml vial, which is equivalent to 98% ethanol (alcohol). The amount of this medication is equivalent to 99.2ml of beer or 41.3ml of wine.

It is harmful to those who suffer from alcoholism.

It should be taken into account in pregnant women, breastfeeding women, children and high-risk groups such as patients with liver disease or epilepsy. The amount of alcohol contained in this medication may alter the effect of other medications.

Levosimendan is for hospital use only. It should be administered in a hospital setting with sufficient monitoring facilities and practical experience with the use of inotropes.

Levosimendan should be administered via intravenous infusion.

The dose and duration of treatment will be individualized based on your clinical status and response.

You will normally receive a rapid infusion (loading dose of 6-12 micrograms/kg) over 10 minutes, followed by a slower infusion (continuous infusion of 0.1 micrograms/kg/min) for a maximum of 24 hours.

Your doctor will decide the amount of levosimendan to be administered based on your body weight and renal and hepatic function.

Your doctor will monitor your response to levosimendan treatment (for example, by measuring your heart rate, blood pressure, electrocardiogram, and subjective sensations) and adjust the dose as necessary.

Inform your doctor or nurse if you feel your heart is racing, you feel dizzy, or you have the impression that the effect of levosimendan is too strong or too weak. Your doctor may reduce the infusion if your blood pressure falls or your heart rate becomes too fast or you do not feel well.

If your doctor considers that you need a higher dose of levosimendan and you are not experiencing side effects, they may increase the infusion.

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

The effect on your cardiac function will continue for at least 24 hours after stopping the levosimendan infusion. The effect may continue up to 9 days after the infusion is completed. For this reason, levosimendan should only be administered in a hospital where your doctor can monitor you for up to 4-5 days after the infusion is completed.

Renal insufficiency

Levosimendan should be used with caution in patients with mild or moderate renal insufficiency. Levosimendan should not be used in patients with severe renal insufficiency (creatinine clearance <30 ml/min) (see section 2. “What you need to know before starting to use Levosimendan EVER Pharma”).

Liver insufficiency

Levosimendan should be used with caution in patients with mild to moderate liver insufficiency, although dose adjustment is not necessary in these patients. Levosimendan should not be used in patients with severe liver insufficiency (see section 2. “What you need to know before starting to use Levosimendan EVER Pharma”).

If you use more Levosimendan EVER Pharma than you should

If you are given an excessive amount of levosimendan, your blood pressure may drop and your heart rate may increase. Your doctor will know how to treat you based on your condition.

Like all medications, this medication may produce adverse effects, although not everyone will experience them.

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

Abnormally high heart rate,

Headache,

Low blood pressure.

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

Low potassium levels in the blood,

Insomnia,

Dizziness,

Abnormal heart rhythm called atrial fibrillation (a consequence of heart palpitations instead of a normal heartbeat),

Additional heartbeats,

Heart failure,

Decreased oxygen supply to the heart,

Nausea,

Constipation,

Diarrhea,

Vomiting,

Decreased hemoglobin levels.

Cases of a heart rhythm alteration called ventricular fibrillation (a consequence of heart palpitations instead of a normal heartbeat) have been reported in patients who received levosimendan.

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

Reporting Adverse Effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicinal Products for Human Use:www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

Keep this medication out of the sight and reach of children.

Do not use Levosimendan EVER Pharma after the expiration date that appears on the vial or on the box. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2°C and 8°C). Do not freeze.

The color of the concentrate may change to orange during storage, but there is no loss of potency and if storage instructions are followed, the product can be used until the expiration date indicated.

After dilution

Chemical and physical stability in use has been demonstrated for 24 hours at 25°C and between 2°C and 8°C.

From a microbiological standpoint, the product should be used immediately. If not used immediately, storage times in use and conditions before use are the responsibility of the user and should normally not exceed 24 hours at 2-8°C, unless the dilution is performed in controlled and validated aseptic conditions.

As with all parenteral medications, visually inspect the diluted solution for particles and discoloration before administration.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of empty containers and unused medications. This will help protect the environment.

Composition of LevosimendanEVERPharma

• The active ingredient is levosimendan 2.5mg/ml. Each ml of concentrate contains 2.5mg of levosimendan.
• The other components (excipients) are: povidone, citric acid and anhydrous ethanol.

Appearance of the product and contents of the pack

The concentrate is a clear yellow or orange solution, free of visible particles, to be diluted before administration.

Nature and contents of the pack:

Solution of 5 ml in a transparent, colourless type I glass vial of 8 ml, closed with a grey rubber stopper of chlorobutyl or bromobutyl with a fluoropolymer coating, aluminium cap and PP white flip-off disc.

Pack sizes:

• 1, 4, 10 vials (glass type I) of 5 ml packed in a folded cardboard box that includes a leaflet.

Only some pack sizes may be marketed.

Marketing authorisation holder and manufacturer responsible

Marketing authorisation holder:

EVER Valinject GmbH

Oberburgau, 3

4866 Unterach am Attersee

Austria

Manufacturer responsible:

PHARMIDEA SIA

Rupnicu Street 4

2114 Olaine

Latvia

Further information about this medicinal product can be obtained by contacting the local representative of the marketing authorisation holder:

EVER Pharma Therapeutics Spain, S.L.

C/Toledo 170

28005 Madrid

Spain

This medicinal product is authorised in the member states of the European Economic Area with the following names:

EstoniaLevosimendan Auxilia

FranceLevosimendan Pharmidea 2.5 mg/ml, solution to be diluted for intravenous infusion

SpainLevosimendan EVER pharma 2.5 mg/ml concentrate for solution for intravenous infusion EFG

PolandLevosimendan Mercapharm

PortugalLevossimendano EVER Pharma 2.5 mg/ml concentrate for solution for intravenous infusion

Date of the last revision of this leaflet:November 2022

Further detailed information about this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

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This information is intended solely for healthcare professionals:

LevosimendanEVERPharma 2.5 mg/ml concentrate for solution for intravenous infusion EFG

Instructions for use and handling

LevosimendanEVERPharma 2.5 mg/ml concentrate for solution for intravenous infusion is designed for single use.

As with all parenteral medicines, visually inspect the diluted solution for particles and discoloration before administration.

Compatibility of levosimendan with 5% glucose solution in PVC, PE, PP and PE/PP copolymer containers has been demonstrated for a period of 24 hours at room temperature or refrigerated. Also, compatibility with different types of PVC and non-PVC intravenous bags and tubing has been demonstrated. The diluted product does not require protection against light.

LevosimendanEVERPharma 2.5 mg/ml concentrate for solution for intravenous infusion should not be diluted to concentrations higher than 0.05 mg/ml as indicated below, otherwise opalescence and precipitation may occur.

• To prepare a solution for intravenous infusion of 0.025 mg/ml, mix 5 ml of Levosimendan EVER Pharma 2.5 mg/ml concentrate for solution for intravenous infusion with 500 ml of 5% glucose solution.
• To prepare a solution for intravenous infusion of 0.05 mg/ml, mix 10 ml of Levosimendan EVER Pharma 2.5 mg/ml concentrate for solution for intravenous infusion with 500 ml of 5% glucose solution.

Compatibility of Levosimendan EVER Pharma with the following medicinal products has been demonstrated when administered simultaneously in intravenous lines connected:

• Furosemide 10mg/ml
• Digoxin 0.25mg/ml
• Glycerol trinitrate 0.1mg/ml

Dosage and method of administration

Levosimendan EVER Pharma is only for hospital use. It should be administered in a hospital environment with sufficient monitoring facilities and practical experience with the use of inotropes.

Levosimendan EVER Pharma should be diluted before administration.

Intravenous infusion is only for intravenous use and can be administered via peripheral or central veins.

See the summary of product characteristics for further information on dosage.