LEVOSIMENDAN EVER PHARMA 2.5 mg/ml CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you start using Levosimendan EVER Pharma

Do not use Levosimendan EVER Pharma

• if you are allergic (hypersensitive) to levosimendan or any of the other components of this medicine (listed in section 6),
• if you have low blood pressure or tachycardia (abnormally high heart rate),
• if you have any 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 an arrhythmia called Torsades de Pointes.

Warnings and precautions

Talk to your doctor or nurse before you start using this medicine if:

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

Talk to your doctor or nurse if you are not sure 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 of age.

Other medicines and Levosimendan EVER Pharma

Tell your doctor if you are using, have recently used, or might use 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.

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

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. It is not known if levosimendan affects your baby. Some negative reproductive effects have been observed in animals, so the use of levosimendan is not recommended during pregnancy and in women who may become pregnant and do not use contraceptives.

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

Levosimendan EVER Pharma contains alcohol (ethanol)

This medicine contains up to 3.925 mg of alcohol (ethanol) in each 5 ml vial, equivalent to 98% ethanol (alcohol). The amount of this medicine is equivalent to 99.2 ml of beer or 41.3 ml of wine.

It is harmful to those suffering from alcoholism.

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

3. How to use Levosimendan EVER Pharma

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 by intravenous infusion.

The dose and duration of treatment will be individualized according to your clinical condition and response.

Normally, you will receive a rapid infusion (loading dose of 6-12 micrograms/kg) over ten minutes, followed by a slower infusion (continuous infusion of 0.1 micrograms/kg/min) for up to 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 (e.g., by measuring your heart rate, blood pressure, electrocardiogram, and subjective sensations) and modify the dose if necessary.

Tell your doctor or nurse if you feel that 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 decrease the infusion if your blood pressure drops 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, the infusion may 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 at least 24 hours after the infusion of levosimendan is stopped. The effect may continue for up to 9 days after the infusion is finished. 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 stopped.

Renal impairment

Levosimendan should be used with caution in patients with mild or moderate renal impairment. Levosimendan should not be used in patients with severe renal impairment (creatinine clearance <30 ml min) (see section 2. "what you need to know before start using levosimendan ever pharma").< p>

Hepatic impairment

Levosimendan should be used with caution in patients with mild to moderate hepatic impairment, although it does not seem necessary to adjust the dose in these patients. Levosimendan should not be used in patients with severe hepatic impairment (see section 2. "What you need to know before you start using Levosimendan EVER Pharma").

If you use more Levosimendan EVER Pharma than you should

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

4. Possible side effects

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

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

Abnormally high heart rate,

Headache,

Drop in blood pressure.

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

Decrease in potassium levels in the blood,

Insomnia,

Dizziness,

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

Extra heartbeats,

Heart failure,

Decreased oxygen supply to the heart,

Nausea,

Constipation,

Diarrhea,

Vomiting,

Decrease in hemoglobin.

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

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

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Medicines and Healthcare Products Agency (AEMPS) website (http://www.aemps.gob.es/). By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Levosimendan EVER Pharma

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

Do not use Levosimendan EVER Pharma after the expiry date which is stated on the vial or carton. The expiry date is the last day of the month stated.

Store in a 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 the storage instructions are followed, the product can be used until the expiry date stated.

After dilution

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

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

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. Contents of the pack and further information

Composition of Levosimendan EVER Pharma

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

Appearance and pack size

The concentrate is a clear yellow or orange solution, free from visible particles, for dilution before administration.

Nature and contents of the container:

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

Pack sizes:

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

Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer

Marketing authorisation holder:

EVER Valinject GmbH

Oberburgau, 3

4866 Unterach am Attersee

Austria

Manufacturer:

PHARMIDEA SIA

Rupnicu Street 4

2114 Olaine

Latvia

You can request more information about this medicine from the local representative of the marketing authorisation holder:

EVER Pharma Therapeutics Spain, S.L.

C/Toledo 170

28005 Madrid

Spain

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

Estonia Levosimendan Auxilia

France Levosimendan Pharmidea 2.5 mg/ml, solution à diluer pour perfusion

Spain Levosimendan EVER pharma 2.5 mg/ml concentrado para solucion para perfusion EFG

Poland Levosimendan Mercapharm

Portugal Levossimendano EVER Pharma 2.5 mg/ml concentrado para solução para perfusão

Date of last revision of this leaflet:November 2022

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

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This information is intended only for healthcare professionals:

Levosimendan EVER Pharma 2.5 mg/ml Concentrate for Solution for Infusion EFG

Instructions for use and handling

Levosimendan EVER Pharma 2.5 mg/ml Concentrate for Solution for Infusion is designed for single use.

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

Compatibility of levosimendan with 5% glucose solutions in PVC, PE, PP, and PE/PP copolymer containers has been demonstrated for 24 hours at room temperature or refrigerated. Compatibility has also been demonstrated with different types of intravenous bags and tubes made of PVC and non-PVC materials. The diluted product does not require protection from light.

Levosimendan EVER Pharma 2.5 mg/ml Concentrate for Solution for Infusion should not be diluted to concentrations higher than 0.05 mg/ml, as this may cause opalescence and precipitation.

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

It has been demonstrated that Levosimendan EVER Pharma is compatible with the following medicines when administered simultaneously in connected intravenous lines:

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

Posology and method of administration

Levosimendan EVER Pharma 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 EVER Pharma should be diluted before administration.

The infusion is for intravenous use only and can be administered by peripheral or central route.

See the summary of product characteristics for information on posology.