Package leaflet: Information for the user

Simdax, 2.5 mg/mL, concentrate for solution for infusion
levosimendan
Please read all of this leaflet carefully before this medicine is given, because it contains
important information for you.

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 get any side effects, including any not listed in this leaflet, please tell your doctor or nurse. See section 4.

Contents of the leaflet

What Simdax is and what it is used for
What you need to know before being given Simdax
How Simdax is given
Possible side effects
How to store Simdax
Contents of the pack and other information

1. What Simdax is and what it is used for

Simdax is a medicine in the form of a concentrate that must be diluted before intravenous infusion.
Simdax increases the strength with which the heart pumps blood and allows blood vessels to relax.
As a result, it reduces lung congestion and facilitates blood and oxygen flow throughout the body. It helps
alleviate breathlessness caused by severe heart failure.
Simdax is used in short-term, additional treatment of acute decompensated severe chronic heart failure in adult patients who still experience breathing difficulties despite treatment with other medicines that remove excess fluid from the body.

2. Important information before using Simdax

When not to use Simdax:

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

Warnings and precautions

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 ever been told by a doctor of having low potassium levels in the blood;
if the patient has a low number of blood cells (anaemia) 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; Simdax should be used with great caution.

If the patient has any of the above conditions or symptoms, discuss this with the doctor or nurse before starting treatment with Simdax.
Children and adolescents
The safety and efficacy of Simdax in children and adolescents under 18 years of age have not been established.
Simdax 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 for the heart, administration of Simdax 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 not known whether Simdax affects the unborn child. In animal studies, a harmful effect on reproduction has been observed; therefore, levosimendan should not be used during pregnancy or in women of childbearing potential who are not using contraception.
It has been shown that Simdax passes into human milk. Breastfeeding must be avoided during treatment with Simdax to prevent possible adverse effects on the cardiovascular system of the infant.
Simdax contains alcohol
This medicine contains 3925 mg of alcohol (anhydrous ethanol) in each 5 mL vial, which constitutes 98% of the volume as 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 and 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 effect 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 Simdax

Simdax is intended for hospital use only. This medicine should be administered in a hospital setting where appropriate monitoring equipment and specialist expertise in the use of inotropic agents are available.
Simdax will be given as an intravenous infusion (via a drip).
The dose and duration of treatment will be adjusted according to the individual patient's clinical condition and response to treatment.
Typically, the medicine is administered as a rapid infusion (loading dose of 6 to 12 micrograms/kg) over 10 minutes, followed by a slower continuous intravenous infusion (0.1 microgram/kg/min) for up to 24 hours. The physician will determine the appropriate dose of Simdax based on the patient's body weight and kidney and liver function.
The physician will periodically assess the patient's response to Simdax (e.g. by measuring pulse or blood pressure, performing an ECG and/or asking about well-being), and adjust the dose if necessary.
Inform the doctor or nurse if palpitations, dizziness or any feeling that the effect of Simdax is too strong or too weak occurs. If the patient experiences a drop in blood pressure, increased heart rate or general malaise, the doctor may reduce the infusion rate.
The doctor may increase the infusion rate if a higher dose of Simdax is considered necessary and no adverse effects are present.
The doctor will continue the Simdax infusion for as long as cardiac support is required. This usually lasts 24 hours.
The effect of Simdax on the heart persists for at least 24 hours after the end of the infusion. The medicine may have effects lasting up to 9 days after the infusion ends. Therefore, Simdax must be used only in a hospital where the physician can monitor the patient's condition for 4–5 days after the infusion has ended.

Impaired kidney function
Caution should be exercised when administering Simdax to patients with mild or moderate renal impairment. Simdax should not be used in patients with severe renal impairment (creatinine clearance < 30 mL/min) (see section 2. Important information before using Simdax).

Impaired liver function
Caution should be exercised when administering Simdax to patients with mild or moderate hepatic impairment, although dose adjustment is not usually required in these patients. Simdax should not be used in patients with severe hepatic impairment (see section 2. Important information before using Simdax).

Overdose of Simdax
If too high a dose of Simdax is administered, a decrease in 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 or nurse.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.

Very common (occur in more than 1 in 10 people):

abnormally rapid heartbeat
headache
decreased blood pressure

Common (occur in up to 1 in 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 normally)
extra heartbeats
heart failure
myocardial ischaemia
nausea
constipation
diarrhoea
vomiting
low number of blood cells

Frequency unknown (cannot be estimated from available data):

hypersensitivity (symptoms may include rash and itching)

Heart rhythm disorders called ventricular fibrillation (a part of the heart flutters instead of beating normally) have been observed in patients receiving Simdax.

If any adverse reactions occur, inform your doctor or nurse immediately. The doctor may reduce the infusion rate or discontinue the Simdax infusion.

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, inform your doctor or nurse. Adverse reactions 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
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Simdax

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial or carton.
The expiry date refers to the last day of the stated month.
Store at 2°C – 8°C (in a refrigerator). Do not freeze.
During storage, the concentrate may change color to orange, but this does not affect its potency
and it 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 24 hours at 25°C and for 24 hours at 2°C to 8°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.
As with all parenteral preparations, the prepared solution should be inspected visually for particulate matter and discoloration prior to administration.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such practices help protect the environment.

6. Contents of the pack and other information

What Simdax contains

The active substance is levosimendan 2.5 mg/mL. Each mL of concentrate contains 2.5 mg of levosimendan.
Other ingredients: povidone, anhydrous citric acid and anhydrous ethanol.

What Simdax looks like and contents of the pack
The concentrate is a clear, yellow to orange solution for dilution before administration.
Pack sizes:

1 vial (colourless type I glass) with a volume of 5 mL, in a cardboard box.

Marketing Authorisation Holder
Orion Corporation
Orionintie 1
FI-02200 Espoo
Finland
Manufacturer
Orion Corporation, Orion Pharma
Orionintie 1
FI-02200 Espoo
Finland
For further information regarding this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Orion Pharma Poland Sp. z o.o.
[email protected]
This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Austria, France: Zimino
Denmark, Belgium, Estonia, Poland: Simdax

Information intended exclusively for healthcare professionals:

Instructions for use and handling
Simdax 2.5 mg/mL concentrate for solution for infusion is intended for single use only.
Simdax should not be diluted to a concentration higher than 0.05 mg/mL as described in 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 Simdax 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 Simdax 2.5 mg/mL concentrate for solution for infusion with 500 mL of 5% glucose solution.

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