Esmocard Lio

Package Leaflet: Information for the Patient

ESMOCARD LYO

2500 mg, powder for concentrate for solution for infusion

(Esmolol hydrochloride)

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

• You should keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

• 1. What ESMOCARD LYO is and what it is used for
• 2. What you need to know before you are given ESMOCARD LYO
• 3. How ESMOCARD LYO is given
• 4. Possible side effects
• 5. How to store ESMOCARD LYO
• 6. Contents of the pack and other information

1. What ESMOCARD LYO is and what it is used for

ESMOCARD LYO belongs to a group of medicines called beta-blockers. These medicines slow the heart rate and lower blood pressure.
ESMOCARD LYO is used for the short-term treatment of rapid heart rate.
ESMOCARD LYO is also used during or immediately after surgery, if the patient has high blood pressure and/or rapid heart rate.

2. What you need to know before you are given ESMOCARD LYO

Your doctor will not give you ESMOCARD LYO if:

• you are allergic to esmolol hydrochloride - symptoms of an allergic reaction include shortness of breath, wheezing, rash, itching, or swelling of the face and lips,
• you have a very slow heart rate (less than 50 beats per minute),
• you have a fast or alternating fast and slow heart rhythm,
• you have a heart condition called heart block - heart block is a condition where the electrical impulses that control the heart rate are disrupted,
• you have low blood pressure,
• you have problems with blood flow to the heart,
• you have severe heart failure symptoms,
• you are taking or have recently taken verapamil - you must not be given ESMOCARD LYO within 48 hours of stopping verapamil,
• you have symptoms of severe heart failure,
• you have an untreated adrenal gland disorder called pheochromocytoma (a tumor that can cause a sudden increase in blood pressure, severe headache, excessive sweating, and rapid heart rate),
• you have high blood pressure in the lungs (pulmonary hypertension),
• you have a sudden worsening of asthma symptoms,
• you have an increased level of acid in the blood (a condition called metabolic acidosis).

Warnings and precautions

ESMOCARD LYO MUST BE RECONSTITUTED/DILUTED BY A DOCTOR OR NURSE BEFORE USE.
Before you start using ESMOCARD LYO, you should discuss it with your doctor or nurse.
Your doctor will take special care when using this medicine:

• If you are being treated for certain heart rhythm disorders, called supraventricular arrhythmias, and:
• you have other heart problems,
• you are taking other heart medicines. Using ESMOCARD LYO in these cases may lead to severe reactions, including death. These include:
• loss of consciousness,
• shock (a condition where the heart does not pump enough blood),
• heart attack (heart stoppage).
• If you experience low blood pressure (excessive lowering of blood pressure), which can cause dizziness or fainting, especially when standing up. These symptoms usually go away after reducing the dose or stopping the medicine. Usually, during treatment with ESMOCARD LYO, blood pressure and ECG are monitored. Low blood pressure usually returns to normal within 30 minutes after stopping ESMOCARD LYO.
• If you have a slow heart rate before taking the medicine.
• If your heart rate decreases below 50-55 beats per minute - in this case, your doctor may recommend a lower dose or stop using ESMOCARD LYO.
• If you have heart failure.
• If you have problems with the electrical impulses that control the heart rate (atrioventricular block).
• If you have an adrenal gland disorder called pheochromocytoma, which is treated with medicines called alpha-blockers.
• If you are being treated for high blood pressure caused by low body temperature (hypothermia).
• If you have narrowing of the airways or wheezing, as in asthma.
• If you have diabetes or low blood sugar (hypoglycemia) - you will need special monitoring, as ESMOCARD LYO may mask the symptoms of low blood sugar and enhance the effects of antidiabetic medicines.
• If you experience skin changes at the injection site. These may be caused by the solution leaking around the injection site. In this case, your doctor will inject into a different vein.
• If you have a certain type of chest pain (angina) called Prinzmetal's angina.
• If you have low blood volume (with low blood pressure), as this may lead to circulatory collapse.
• If you have circulation problems, such as Raynaud's disease or pain, fatigue, and sometimes burning pain in the legs.
• If you have kidney problems. In case of kidney disease or the need for dialysis, high levels of potassium in the blood (hyperkalemia) may occur. This can cause severe heart problems.
• If you are allergic or at risk of anaphylactic reaction (severe allergic reaction), as ESMOCARD LYO may worsen allergies and make them harder to treat.
• If you or a family member have a history of psoriasis (a condition where scaly patches appear on the skin).
• If you have an overactive thyroid gland.

In case of liver function disorders, a change in dose is usually not necessary.
If any of the above points apply to you (or if you are unsure), you should discuss this with your doctor or nurse before taking this medicine. Your doctor may examine you carefully and change your treatment.

ESMOCARD LYO and other medicines

Tell your doctor or nurse about all the medicines you are taking now or have recently taken, as well as any medicines you plan to take, including those available without a prescription, herbal medicines, or natural products. Your doctor will assess whether the medicines you are taking affect the action of ESMOCARD LYO.
In particular, you should inform your doctor or nurse if you are taking any of the following medicines:

• medicines that lower blood pressure or slow the heart rate,
• medicines used to treat heart rhythm disorders or chest pain (angina), such as verapamil and diltiazem - you must not be given ESMOCARD LYO within 48 hours of stopping verapamil,
• nifedipine used to treat chest pain (angina), high blood pressure, and Raynaud's disease,
• medicines used to treat both heart rhythm disorders (such as quinidine, disopyramide, amiodarone) and heart failure (such as digoxin, digitoxin, digitalis glycosides),
• medicines used to treat diabetes, including insulin and oral antidiabetic medicines,
• so-called ganglion blockers (e.g., trimethaphan),
• painkillers, such as nonsteroidal anti-inflammatory drugs (NSAIDs),
• flecainide (a painkiller),
• amisulpride, a medicine used for mental disorders,
• tricyclic antidepressants (such as imipramine and amitriptyline) or other medicines used for mental disorders,
• barbiturates (such as phenobarbital, used to treat epilepsy) or phenothiazines (such as chlorpromazine, used to treat mental disorders),
• clozapine, which is used to treat mental disorders,
• epinephrine, which is used to treat allergic reactions,
• medicines used to treat asthma,
• medicines used to treat colds or nasal congestion, which constrict the nasal mucosa,
• reserpine, which is used to treat high blood pressure,
• clonidine, which is used to treat high blood pressure and migraines,
• moxonidine, which is used to treat high blood pressure,
• ergot derivatives, mainly used to treat Parkinson's disease,
• warfarin, which is used as an anticoagulant,
• morphine, which is a strong painkiller,
• suxamethonium chloride (also known as succinylcholine or scoline) or mivacurium, used to relax muscles, usually during surgery - your doctor will take special care when giving ESMOCARD LYO during surgery, along with anesthetics and other medicines.

If you are unsure whether any of the above points apply to you, you should consult your doctor or nurse before taking ESMOCARD LYO.
Tests that may be performed while using ESMOCARD LYO
Using medicines like ESMOCARD LYO for a long time may cause a decrease in the strength of heart contractions. Since ESMOCARD LYO is used for a limited time, the occurrence of such an effect is unlikely.
During administration, your doctor will monitor your condition and reduce the dose or stop using ESMOCARD LYO if a decrease in the strength of heart contractions occurs.
During administration of ESMOCARD LYO, your doctor will also recommend blood pressure measurements.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, ask your doctor for advice before taking this medicine.
There is limited data on the safety of ESMOCARD LYO in pregnant women. However, there is no evidence of increased risk of birth defects in humans.
Due to the lack of experience, ESMOCARD LYO should not be used during pregnancy.
You should inform your doctor about breastfeeding. ESMOCARD LYO may pass into human milk, so you must not be given ESMOCARD LYO if you are breastfeeding.
Before taking any medicine, you should consult your doctor or nurse.

3. How to use ESMOCARD LYO

ESMOCARD LYO MUST BE RECONSTITUTED/DILUTED BEFORE USE.
Your doctor will adjust the dose individually for each patient - will give an initial dose, and then a maintenance dose. Will determine the dosing schedule and modify the dose if side effects occur.
ESMOCARD LYO is given intravenously by infusion by a doctor or nurse. The solution with a concentration of 50 mg/ml should be administered using a perfusion pump exclusively into a large vein or central catheter.
The duration of use depends on the effect and possible side effects.
Your doctor will determine the duration of treatment.
A change in the dose of ESMOCARD LYO is usually not necessary if you have liver function disorders.
If you have kidney problems, your doctor will take special care.

Elderly

Your doctor will start treatment with a lower dose.

Use in children and adolescents

The safety and efficacy of ESMOCARD LYO in children and adolescents have not been established. ESMOCARD LYO should not be used in children and adolescents under 18 years of age.

Overdose of ESMOCARD LYO

Since ESMOCARD LYO is administered by a trained and qualified person, overdose is unlikely. However, if this happens, your doctor will stop the administration of ESMOCARD LYO and, if necessary, provide additional treatment.

Missed dose of ESMOCARD LYO

Since ESMOCARD LYO is administered by a trained and qualified person, it is unlikely that a dose will be missed. However, if you have any doubts, you should talk to your doctor or nurse as soon as possible.

Stopping use of ESMOCARD LYO

Sudden stopping of ESMOCARD LYO may cause a return of symptoms, such as rapid heart rate (tachycardia) or high blood pressure (hypertension).
To avoid this, your doctor will gradually stop the administration of the medicine. In patients with coronary heart disease (e.g., angina or heart attack in the past), your doctor will take special care when stopping ESMOCARD LYO.
If you have any further questions about the use of this medicine, you should ask your doctor or nurse.

4. Possible side effects

Like all medicines, ESMOCARD LYO can cause side effects, although not everybody gets them.
Most side effects go away within 30 minutes of stopping ESMOCARD LYO. The side effects that have been reported with ESMOCARD LYO are listed below.
If you experience any of the following side effects (which may be serious), you should tell your doctor or nurse immediately. It may be necessary to stop the infusion.
Very common(may affect at least 1 in 10 people):

• lowering of blood pressure (can be quickly corrected by reducing the dose of ESMOCARD LYO or stopping the administration) - your doctor will recommend frequent blood pressure measurements during treatment
• excessive sweating

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

• loss of appetite
• feeling of anxiety or depression
• dizziness
• drowsiness
• headache
• tingling or numbness
• concentration problems
• feeling of disorientation or agitation
• feeling of weakness
• feeling of fatigue (exhaustion)
• nausea or vomiting
• irritation and hardening of the skin at the injection site

Uncommon(may affect up to 1 in 100 people):

• abnormal thoughts
• sudden loss of consciousness
• feeling of fainting or fainting
• seizures (convulsions)
• speech problems
• vision problems
• slow heart rate
• problems with the electrical impulses that control the heart rate
• increased pressure in the pulmonary arteries
• heart failure (a condition where the heart does not pump enough blood)
• heart rhythm problems, sometimes called palpitations (extra beats)
• heart rhythm problems (nodal rhythm)
• heart problems caused by poor blood flow through the blood vessels of the heart muscle (angina)
• poor circulation in the arms or legs
• pallor or sudden flushing (especially of the face and neck)
• fluid in the lungs
• shortness of breath or difficulty breathing
• wheezing
• nasal congestion
• rhonchi/stridor during breathing, audible during medical examination
• taste problems
• indigestion
• constipation
• dryness of the mucous membranes of the mouth
• abdominal pain
• skin discoloration
• redness of the skin
• muscle or tendon pain, including around the shoulders, shoulder blades, and ribs
• difficulty urinating (urinary retention)
• chest pain
• feeling of cold or high temperature (fever)
• pain and swelling (edema) of the vein at the injection site
• burning sensation at the injection site

Rare(may affect up to 1 in 1,000 people):

• significant decrease in heart rate (sinus arrest)
• absence of electrical activity of the heart (asystole)
• fragility of blood vessels with an area of hot red skin (thrombophlebitis)
• skin necrosis caused by the solution leaking around the injection site

Unknown(frequency cannot be estimated from the available data)

• increased level of potassium in the blood (hyperkalemia)
• increased level of acid in the body (metabolic acidosis)
• increased heart rate (accelerated ventricular rhythm)
• coronary artery spasm
• circulatory failure (cardiac arrest)
• psoriasis (scaly patches on the skin)
• swelling of the skin of the face, arms, legs, tongue, or throat (angioedema)
• hives
• vein inflammation or blisters at the injection site

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 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, you can help provide more information on the safety of this medicine.

5. How to store ESMOCARD LYO

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label after EXP. The expiry date refers to the last day of that month.
There are no special precautions for storage of the medicinal product.
Storage conditions (during use): 25 °C.
The reconstituted, diluted solution is physically and chemically stable for 24 hours at 25 °C. From a microbiological point of view, the product should be used immediately after opening and dilution. If not, the user is responsible for the use and administration. This time should not normally exceed 24 hours at 2 to 8°C, unless the opening, reconstitution, and dilution have been carried out under controlled and validated aseptic conditions.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What ESMOCARD LYO contains

The active substance is esmolol hydrochloride.
One 50 ml vial contains 2500 mg of esmolol hydrochloride. The product does not contain any other ingredients.
Each ml of the reconstituted concentrate for solution for infusion contains 50 mg of esmolol hydrochloride (50 mg/ml).
Each ml of the diluted solution for infusion contains 10 mg of esmolol hydrochloride (10 mg/ml).

What ESMOCARD LYO looks like and contents of the pack

Each vial contains 2500 mg of white or almost white powder.
The vial is made of colorless type I glass.
One pack of ESMOCARD LYO, 2500 mg powder for concentrate for solution for infusion, contains 1 vial.

Marketing authorization holder and manufacturer

Marketing authorization holder

Orpha-Devel Handels und Vertriebs GmbH
Wintergasse 85/1B
A-3002 Purkersdorf
Austria

Manufacturer

AOP Orphan Pharmaceuticals GmbH
Leopold-Ungar-Platz 2
1190 Vienna
Austria

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Belgium:
ESMOCARD 2500 mg Poudre pour solution à diluer pour solution pour perfusion
Czech Republic:
ESMOCARD LYO 2500 mg prášek pro koncentrát pro infuzní roztok
Denmark:
ESMOCARD LYO 2500 mg Pulver til koncentrat til infusionsvæske, opløsning
Finland:
ESMOCARD 2500 mg Kuiva-aine välikonsentraatiksi infuusionestettä varten, liuos
France:
ESMOCARD 2500 mg Poudre pour solution à diluer pour solution pour perfusion
Germany:
ESMOCARD LYO 2500 mg Pulver zur Herstellung einer Infusionslösung
Greece:
ESMOCARD LYO 2500 mg κόνις για πυκνό σκεύασμα για παρασκευή διαλύματος
προς έγχυση
Hungary:
ESMOCARD LYO 2500 mg por oldatos infúzióhoz való koncentrátumhoz
Ireland:
ESMOCARD LYO 2500 mg powder for concentrate for solution for infusion
Italy:
ESMOCARD 2500 mg polvere per concentrato per soluzione per infusione
Netherlands:
Esmolol HCl LYO Orpha 2500 mg poeder voor concentraat voor oplossing voor
infusie
Slovakia:
ESMOCARD LYO 2500 mg prášok na infúzny koncentrát
Slovenia:
ESMOCARD LYO 2500 mg prašek za koncentrat za raztopino za infundiranje
Sweden:
ESMOCARD 2500 mg Pulver till koncentrat till infusionsvätska, lösning
United Kingdom: Esmolol hydrochloride 250 mg powder for concentrate for solution for infusion

Date of last revision of the leaflet: 09/2021.

The following information is intended for healthcare professionals only:

This section contains practical information about administration. You should read the "Summary of Product Characteristics" to get full information about dosing and administration, contraindications, warnings, etc.

ESMOCARD LYO, 2500 mg, powder for concentrate for solution for infusion MUST NOT BE ADMINISTERED WITHOUT RECONSTITUTION/DILUTION.

The solution after reconstitution/dilution should be used immediately after opening.
Administration of ESMOCARD LYO, the reconstitution/dilution of which has been performed incorrectly, may cause death.

Dosing

Supraventricular Tachycardia

The dose of ESMOCARD LYO should be individualized. An initial dose is required, followed by a maintenance dose.
Effective dose of ESMOCARD LYO ranges from 50 to 200 micrograms/kg/min, although higher doses, such as 300 micrograms/kg/min, have also been used. In a few patients, the average effective dose was 25 micrograms/kg/min.

Schema for initiation and maintenance of treatment

Loading dose
500 micrograms/kg/min for 1 minute in infusion,
THEN 50 micrograms/kg/min for 4 minutes
Response
Continue administration
50 micrograms/kg/min in infusion
Inadequate response within 5 minutes
Repeat 500 micrograms/kg/min for 1 minute
Increase maintenance infusion to 100 micrograms/kg/min for 4 minutes
Response
Continue administration
100 micrograms/kg/min in infusion
Inadequate response within 5 minutes
Repeat 500 micrograms/kg/min for 1 minute
Increase maintenance infusion to 150 micrograms/kg/min for 4 minutes
Response
Continue administration
150 micrograms/kg/min in infusion
Inadequate response
Repeat 500 micrograms/kg/min for 1 minute
Increase maintenance infusion to 200 micrograms/kg/min and maintain
At the time of achieving the desired therapeutic effect or safety endpoint (e.g., lowered blood pressure), the loading infusion should be omitted, and the maintenance infusion dose increased by 25 micrograms/kg/min or less, rather than 50 micrograms/kg/min. If necessary, the interval between dose increases can be extended from 5 to 10 minutes.
ESMOCARD LYO should be discontinued if the heart rate and blood pressure rapidly approach or exceed the safety limit, and then, after the heart rate and blood pressure return to acceptable values, administration should be resumed at a lower dose, without a loading infusion.

Tachycardia and Hypertension in the Perioperative Period

In the treatment of tachycardia and hypertension in the perioperative period, the dosing regimens may vary as follows:
a) In intraoperative treatment - during anesthesia, when immediate control is necessary, 80 mg should be administered intravenously in a bolus over 15 to 30 seconds, and then 150 micrograms/kg/min in infusion. The dose administered in infusion should be adjusted, as needed, up to 300 micrograms/kg/min.
b) After awakening from anesthesia, 500 micrograms/kg/min should be administered in infusion for up to 4 minutes, and then 300 micrograms/kg/min in infusion.
c) In the postoperative period, when there is time to adjust the dose, 500 micrograms/kg/min should be administered as a loading dose over 1 minute before each dose increase, to achieve a rapid onset of action. The following doses should be administered sequentially: 50, 100, 150, 200, 250, and 300 micrograms/kg/min over 4 minutes, maintaining the dose at which the desired therapeutic effect is achieved.

Conversion to other Medicines

After achieving adequate control of heart rate and stable clinical condition, the treatment can be switched to alternative medicinal products (e.g., antiarrhythmic or calcium channel blockers).

Dose reduction:

When switching from ESMOCARD LYO to alternative medicines, your doctor should carefully review the Summary of Product Characteristics of the chosen alternative medicine, and the dose of ESMOCARD LYO should be reduced as follows:

• 1) within the first hour of administration of the first dose of the alternative medicine, the infusion rate of ESMOCARD LYO should be reduced by half (50%),
• 2) after administration of the second dose of the alternative medicine, your doctor should monitor your response to treatment and if satisfactory control is maintained for the first hour, the infusion of ESMOCARD LYO should be discontinued.

Additional dosing information:When the desired therapeutic effect or safety endpoint (e.g., lowered blood pressure) is achieved, the loading infusion should be omitted, and the maintenance infusion dose increased by 12.5-25 micrograms/kg/min. If necessary, the interval between dose increases can be extended from 5 to 10 minutes.
ESMOCARD LYO should be discontinued if the heart rate and blood pressure rapidly approach or exceed the safety limit, and then, after the heart rate and blood pressure return to acceptable values, administration should be resumed at a lower dose, without a loading infusion.

Special populations

Elderly
Caution should be exercised in the elderly, and treatment should be started with a lower dose.
No special studies have been performed in the elderly. However, analysis of data from 252 patients over 65 years of age did not show any changes in pharmacodynamic effects compared to data from patients under 65 years of age.
Patients with renal impairment
Caution is required in patients with renal impairment when administering ESMOCARD LYO in infusion, as the acidic metabolite of ESMOCARD LYO is excreted by the kidneys. The excretion of the acidic metabolite is significantly lower in patients with impaired renal function, with approximately a tenfold increase in half-life compared to individuals with normal renal function and significantly increased plasma concentrations.
Patients with hepatic impairment
In case of hepatic impairment, no special precautions are necessary, as the esterases in red blood cells play a major role in the metabolism of ESMOCARD LYO.
Children and adolescents (under 18 years of age)
The safety and efficacy of ESMOCARD LYO in children under 18 years of age have not been established. Therefore, ESMOCARD LYO should not be used in this age group.

Method of Administration

Before use, the powder must be dissolved/diluted. The powder after dissolution/dilution can be administered in two different concentrations, in two different volumes:

• 1. The usually used concentration is 10 mg/ml, and the administered volume is 250 ml.
• 2. In certain cases, when it is necessary to administer a smaller volume, a solution with a higher concentration (50 mg/ml) can be prepared

a solution with a higher concentration (50 mg/ml) by dissolving the powder to a final volume of 50 ml and administering the medicinal product using an infusion pump. There is limited clinical experience with the use of solutions with this higher concentration. The medicinal product with a higher concentration should only be administered through a large vein or central catheter using an infusion pump.
INFUSION RATE CONVERSION TABLES(micrograms/kg body weight/min → ml/min) for dilutedinfusion solution (10 mg/ml) administered in STANDARD INFUSION:

INFUSION RATE CONVERSION TABLES(micrograms/kg body weight/min → ml/min) for concentratedinfusion solution (50 mg/ml) administered using an infusion pump :