Esmocard

Package leaflet: Information for the patient

ESMOCARD 100 mg/10 ml injection solution

Esmolol hydrochloride
Generic medicine
Read this entire leaflet carefully before using this medicine because it
contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor. See section 4.

Contents of this leaflet:

1. What ESMOCARD 100 mg/10 ml injection solution is and what it is used for
2. What you need to know before using ESMOCARD 100 mg/10 ml injection solution
3. How to use ESMOCARD 100 mg/10 ml injection solution
4. Possible side effects
5. How to store ESMOCARD 100 mg/10 ml injection solution
6. Contents of the pack and other information

1. What ESMOCARD 100 mg/10 ml solution for injection is and what it is used for

ESMOCARD 100 mg/10 ml belongs to the group of beta-blockers. These medicines
slow down the heart rate and reduce blood pressure.
ESMOCARD 100 mg/10 ml is used for short-term treatment if your heart beats
too fast.
ESMOCARD 100 mg/10 ml is also used during or immediately after surgery if
your blood pressure becomes too high and/or your heart beats too fast.

2. What you need to know before using ESMOCARD 100 mg/10 ml injection solution

The doctor will not administer ESMOCARD 100 mg/10 ml if

• you are allergic to esmolol hydrochloride. Signs of an allergic reaction include difficulty breathing, 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 irregularly alternating fast-slow heart rhythm
• you suffer from a condition called “severe heart block.” Heart block is a problem with the electrical signals controlling the heartbeat
• you have low blood pressure
• you have a condition affecting blood flow to the heart
• you have symptoms of severe heart failure
• you are taking or have recently taken verapamil. You must not receive ESMOCARD 100 mg/10 ml within 48 hours after stopping verapamil
• you have an untreated adrenal gland disorder called phaeochromocytoma. Phaeochromocytoma originates in the adrenal gland and may be accompanied by sudden high blood pressure, severe headache, sweating, and increased heart rate
• you have high blood pressure in the lungs (pulmonary hypertension)
• you have rapidly worsening asthma symptoms
• you have increased levels of acid in your body (a condition called metabolic acidosis)
  If any of the above conditions apply to you, ESMOCARD 100 mg/10 ml will not be administered. If you are unsure whether any of these conditions apply to you, consult your doctor or nurse before receiving ESMOCARD 100 mg/10 ml.

Warnings and precautions
Before being given ESMOCARD 100 mg/10 ml, speak to your doctor or nurse. The doctor will exercise particular caution when using this medicine if:

• you have been treated for certain heart rhythm disorders called supraventricular arrhythmias and:
• you have other heart problems or
• you are taking other heart medications
  The use of ESMOCARD 100 mg/10 ml in these cases may lead to serious, potentially fatal reactions, including:
• Loss of consciousness
• Shock (when the heart does not pump enough blood)
• Heart attack (cardiac arrest)
• you develop low blood pressure (hypotension). Signs of this condition may include dizziness or lightheadedness, especially when standing up. This condition is rapidly reversible by reducing the dose or stopping the medication. Usually, during treatment with ESMOCARD 100 mg/10 ml, your blood pressure and electrocardiogram (ECG) will be continuously monitored. Typically, low blood pressure improves within 30 minutes after stopping treatment with ESMOCARD 100 mg/10 ml
• you have a low heart rate before treatment
• your heart rate drops below 50–55 beats per minute. In this case, the doctor may reduce the dose or discontinue treatment with ESMOCARD 100 mg/10 ml
• you suffer from heart failure
• you have problems with the electrical signals controlling your heartbeat (heart block)
• you have an adrenal gland disorder called phaeochromocytoma that has been treated with medications known as alpha-receptor blockers
• you are taking medications to treat high blood pressure (hypertension) caused by low body temperature (hypothermia)
• you have a lung disease causing narrowing of the airways or wheezing, such as asthma
• you have diabetes (high blood sugar levels) or low blood sugar levels (hypoglycaemia). In this case, you will require special monitoring because esmolol may mask the symptoms of low blood sugar. ESMOCARD 100 mg/10 ml may enhance the effects of your diabetes medications
• you develop skin problems. These may be caused by leakage of the solution around the injection site. If this occurs, the doctor will use a different vein for injection
• you have a specific type of angina (chest pain) called “Prinzmetal’s angina”
• you have reduced blood volume (with low blood pressure). You may be more prone to circulatory collapse
• you have circulatory problems, such as pale skin of the fingers (Raynaud’s disease) or pain, fatigue, and sometimes burning sensations in the legs
• you have kidney problems. If you have kidney disease or require dialysis, you may have high potassium levels in the blood (hyperkalaemia). This can cause serious heart problems
• you have any allergies or are at risk of anaphylactic reactions (severe allergic reactions). ESMOCARD 100 mg/10 ml may worsen allergies and make them difficult to treat
• you or a family member has a history of psoriasis (a condition where the skin develops scaly patches)
• you have a condition called hyperthyroidism (overactive thyroid gland). Dosage adjustment is usually not necessary if you have liver problems.
  If any of the above conditions apply to you (or if you are unsure), consult your doctor or nurse before receiving this medicine. Monitoring and therapy adjustments may be necessary.
  For athletes: using this drug without a therapeutic need constitutes doping and may result in a positive anti-doping test.

Other medicines and ESMOCARD 100 mg/10 ml injection solution
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines, including those without a prescription, herbal medicines, or natural products. Your doctor will check whether the medicines you are taking may affect how ESMOCARD 100 mg/10 ml works. In particular, inform your doctor or nurse if you are taking any of the following medicines:

• Medicines that may lower blood pressure or slow heart rate
• Medicines used to treat heart rhythm disorders or chest pain (angina), such as verapamil and diltiazem. You must not receive ESMOCARD 100 mg/10 ml within 48 hours after stopping verapamil
• Nifedipine, used to treat chest pain (angina), high blood pressure, and Raynaud’s disease
• Medicines used to treat heart rhythm disorders (such as quinidine, disopyramide, amiodarone) and heart failure (such as digoxin, digitoxin, digitalis)
• Medicines used to treat diabetes, including insulin and oral antidiabetic drugs
• Medicines known as ganglion blockers (e.g., trimethaphan)
• Medicines used as painkillers, such as non-steroidal anti-inflammatory drugs (NSAIDs)
• Floctafennine, a painkiller
• Amisulpride, a medicine used to treat mental health disorders
• Tricyclic antidepressants (such as imipramine and amitriptyline) or any other medicines for mental health conditions
• Barbiturates (such as phenobarbital, used to treat epilepsy) or phenothiazines (such as chlorpromazine, used to treat mental disorders)
• Clozapine, used to treat mental disorders
• Epinephrine, used to treat allergic reactions
• Medicines used to treat asthma
• Medicines used to treat colds or nasal congestion, also known as nasal decongestants
• Reserpine, used to treat high blood pressure
• Clonidine, used to treat high blood pressure and headaches
• Moxonidine, used to treat high blood pressure
• Ergot derivatives, medicines mainly used to treat Parkinson’s disease
• Warfarin, used to thin the blood
• Morphine, a strong painkiller
• Succinylcholine chloride (also known as suxamethonium or scoline) or mivacurium, used to relax muscles, usually during surgery
  Your doctor will also exercise particular caution when using ESMOCARD 100 mg/10 ml during surgical procedures, especially when anaesthetics and other treatments are administered.
  If you have any doubts about whether any of these restrictions may apply to your case, consult your doctor or nurse before receiving ESMOCARD 100 mg/10 ml.

Tests you may undergo during treatment with ESMOCARD 100 mg/10 ml
Long-term use of medicines like ESMOCARD 100 mg/10 ml may reduce the strength of the heartbeat.
Since ESMOCARD 100 mg/10 ml is used only for a limited time, this is unlikely to occur. During treatment, you will be closely monitored, and if the strength of your heartbeat decreases, treatment with ESMOCARD 100 mg/10 ml will be reduced or stopped.
During treatment with ESMOCARD 100 mg/10 ml, your doctor will also monitor your blood pressure.

Pregnancy and breastfeeding
Consult your doctor before using this medicine if you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding.
Available data on the use of esmolol in humans are insufficient to confirm its safety during pregnancy. However, in humans, there are no indicators of an increased risk of birth defects.
Due to the lack of experience with the use of ESMOCARD 100 mg/10 ml, it is not recommended during pregnancy.
Inform your doctor if you are breastfeeding. ESMOCARD 100 mg/10 ml may pass into breast milk; therefore, you must not be administered ESMOCARD 100 mg/10 ml if you are breastfeeding.
Consult your doctor before taking any medicine.

ESMOCARD 100 mg/10 ml injection solution contains sodium
ESMOCARD 100 mg/10 ml contains approximately 7.88 mg of sodium per vial. This information may be important if you are on a low-sodium diet.

3. How to use ESMOCARD 100 mg/10 ml solution for injection

The dosage must be individually adjusted. A starting dose followed by a maintenance dose is recommended. Your doctor will determine the dosing schedule and, if necessary, adjust the dosage according to any possible adverse effects.
ESMOCARD 100 mg/10 ml is administered by infusion. It is given intravenously by a doctor or nurse.
The duration of use depends on the effect achieved and the possible occurrence of adverse effects. Your doctor will determine the duration of treatment.

• Usually, no dose adjustment of ESMOCARD 100 mg/10 ml is required if you have liver problems.
  If you have kidney problems, your doctor will take appropriate precautions.

Elderly patients
Your doctor will start treatment with a lower dose.
Use in children and adolescents
The safety and efficacy of ESMOCARD 100 mg/10 ml have not been established in children and adolescents. ESMOCARD 100 mg/10 ml must not be administered to children under 18 years of age.

If you are given more ESMOCARD 100 mg/10 ml solution for injection than you should
Since ESMOCARD 100 mg/10 ml is administered by a trained and qualified person, it is unlikely that you will receive too much. However, if this were to happen, your doctor would stop ESMOCARD 100 mg/10 ml and, if necessary, provide additional treatment.

If you think a dose of ESMOCARD 100 mg/10 ml has not been administered to you
Since ESMOCARD 100 mg/10 ml is administered by a trained and qualified person, it is unlikely that a dose will be missed. However, if you believe a dose has not been given, inform your doctor or nurse as soon as possible.

When administration of ESMOCARD 100 mg/10 ml solution for injection is stopped
Sudden discontinuation of ESMOCARD 100 mg/10 ml may cause recurrence of symptoms such as fast heartbeat (tachycardia) and high blood pressure (hypertension). To avoid this, your doctor must stop treatment gradually. If you suffer from coronary heart disease (which may be associated with a history of angina or heart attack), your doctor will pay particular attention when stopping treatment with ESMOCARD 100 mg/10 ml.

If you have any questions about the use of ESMOCARD 100 mg/10 ml, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Most of the side effects disappear within 30 minutes after stopping treatment with ESMOCARD 100 mg/10 ml. The following side effects have been observed with ESMOCARD 100 mg/10 ml:
Contact your doctor or nurse immediately if you notice any of the following side effects, as they may be serious. It may also be necessary to stop the infusion.
Very common (may affect more than 1 in 10 people):

• Decrease in blood pressure. This can be rapidly corrected by reducing the dose of ESMOCARD 100 mg/10 ml or by stopping treatment. Your blood pressure will be monitored frequently during treatment.
• Excessive sweating

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

• Loss of appetite
• Feelings of anxiety or depression
• Dizziness
• Drowsiness
• Headache
• Tingling or prickling sensations like "pins and needles"
• Difficulty concentrating
• Feelings of confusion or agitation
• Feeling unwell (nausea and vomiting)
• Feeling of weakness
• Feeling of tiredness (fatigue)
• Irritation and hardening of the skin at the injection site of ESMOCARD 100 mg/10 ml

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

• Abnormal thoughts
• Sudden loss of consciousness
• Fainting or feeling faint
• Seizures (epilepsy or convulsions)
• Speech disorders
• Visual disturbances
• Slowing of the heart rate
• Problems with the electrical signals controlling the heartbeat
• Increased pressure in the lung arteries
• Inability of the heart to pump enough blood (heart failure)
• Heart rhythm problems, sometimes known as "palpitations" (ventricular extrasystoles)
• Irregular heartbeat (nodal rhythm)
• Chest discomfort caused by reduced blood flow through the vessels of the heart muscle (angina pectoris)
• Poor circulation in arms or legs
• Pale or flushed skin
• Fluid in the lungs
• Shortness of breath or breathing difficulties due to chest tightness
• Wheezing
• Stuffy nose
• Abnormal rattling or crackling sounds during breathing
• Changes in taste sensation
• Indigestion
• Constipation
• Dry mouth
• Stomach area pain
• Changes in skin color
• Skin redness
• Muscle or tendon pain, including around the shoulder blades and ribs
• Difficulty urinating (urinary retention)
• Chest pain
• Feeling of cold or elevated body temperature (fever)
• Pain and swelling (edema) of the vein during injection of ESMOCARD 100 mg/10 ml
• Burning sensation at the injection site

Very rare (may affect up to 1 in 10,000 people):

• Severe reduction in heart rate (sinus arrest)
• Absence of electrical activity in the heart (asystole)
• Painful veins with a warm, red area of skin (thrombophlebitis)
• Dead skin due to leakage of solution around the injection site

Not known (frequency cannot be estimated from the available data):

• Increased potassium levels in the blood (hyperkalaemia)
• Increased levels of acids in the body (metabolic acidosis)
• Increased heart contraction rate (accelerated idioventricular rhythm)
• Spasm of the heart arteries
• Interruption of normal blood circulation (cardiac arrest)
• Psoriasis (a skin disease causing scaly patches)
• Swelling of the face, limbs, tongue or throat (angioedema)
• Hives (urticaria)
• Inflammation of a vein or blister formation at the infusion site

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, inform your doctor or nurse. You can also report side effects directly via the national reporting system at:
www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store ESMOCARD 100 mg/10 ml solution for injection

Do not store above 25°C. Keep the vial in the outer carton
to protect the medicine from light.
Keep this medicine out of the sight and reach of children.
Do not use ESMOCARD 100 mg/10 ml after the expiry date which is stated on the carton and
on the label of the vial after "Exp". The expiry date refers to the last day of that month.
The opened product is stable for 24 hours at 2-8°C. However, it should be used
immediately after opening. If not used immediately, the duration and conditions of
storage are the responsibility of the user and normally should not exceed
24 hours at 2-8°C, unless the opening has been carried out under controlled and validated
aseptic conditions.
Do not use ESMOCARD 100 mg/10 ml if you notice particles or changes in the colour of the
solution.
Do not dispose of any medicine via wastewater or household waste. Ask your doctor
how to dispose of medicines no longer required. This will help protect the
environment.

6. Package contents and other information

What ESMOCARD 100 mg/10 ml injection solution contains

• The active substance is esmolol hydrochloride.
• Each 10 ml vial of injectable solution contains 100 mg of esmolol hydrochloride. 1 ml of aqueous solution contains 10 mg of esmolol hydrochloride.
• The excipients are sodium acetate trihydrate, acetic acid 99%, hydrochloric acid 10% (for pH adjustment), and water for injections.

Description of the appearance of ESMOCARD 100 mg/10 ml injection solution and contents of the package
ESMOCARD 100 mg/10 ml injection solution is clear and colourless, available in vials containing 10 ml of solution each. The vial is made of transparent glass (type I) with a chlorobutyl rubber stopper.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Orpha-Devel Handels und Vertriebs GmbH
Wintergasse 85/1B
A-3002 Purkersdorf
Austria

Manufacturer
Amomed Pharma GmbH
Storchengasse 1
1150 Vienna
Austria
Hikma Italia S.P.A.,
Viale Certosa 10,
27100 Pavia,
Italy

This medicinal product is authorized in the European Economic Area (EEA) Member States under the following names:
Czech Republic: ESMOCARD 100mg/10ml injekčni roztok
Denmark: ESMOCARD injektionsvæske, opløsning 10 mg/ml
Estonia: ESMOCARD 10 mg/ml süstelahus
Finland: ESMOCARD 10 mg/ml injektioneste, liuos
France: ESMOCARD 100 mg/10 ml, solution injectable
Germany: ESMOCARD 100 mg/10 ml Injektionslösung
Greece: ESMOCARD 100 mg/10 ml ενέσιμο διάλυμα
Hungary: ESMOCARD 10 mg/ml oldatos injekció
Ireland: ESMOCARD 100 mg/10 ml solution for injection
Italy: ESMOCARD 100 mg/10 ml soluzione iniettabile
Latvia: ESMOCARD 100 mg/10 ml šķīdums injekcijām
Lithuania: ESMOCARD 100 mg/10 ml injekcinis tirpalas
Netherlands: ESMOLOL HCl Orpha 100 mg/10 ml oplossing voor injectie
Poland: ESMOCARD 100 mg/10 ml, roztwór do wstrzykiwań
Slovakia: ESMOCARD 100mg/10ml injekčný roztok
Slovenia: ESMOCARD 10 mg/ml raztopina za injiciranje
Sweden: ESMOCARD 10 mg/ml injektionsvätska, lösning
United Kingdom: Esmolol hydrochloride 10 mg/ml solution for injection

The following information is intended exclusively for physicians or healthcare

professionals:
This section contains practical information regarding administration. Please refer to the
Summary of Product Characteristics for complete information on dosage, route of
administration, contraindications, warnings, etc.
Esmocard 100 mg/10 ml solution for injection in 10 ml vial is a ready-to-use, pure solution for intravenous administration. The concentration of this product is 10 mg/ml of esmolol hydrochloride.
SUPRAVENTRICULAR TACHYARRHYTHMIA
The dosage of Esmocard 100 mg/10 ml must be individually titrated. An initial dose followed by a maintenance dose should be administered.
The effective dosage range of Esmocard 100 mg/10 ml is between 50 and 200 micrograms/kg/min, although doses up to 300 micrograms/kg/min have been used. In some patients, a mean effective dosage of 25 micrograms/kg/min has proven adequate.
Flowchart for initial and maintenance dosing
Infuse loading dose of
500 micrograms/kg/min for 1 minute,
THEN 50 micrograms/kg/min for 4 minutes
Response
Maintain infusion at
50 micrograms/kg/min
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
Maintain infusion at
100 micrograms/kg/min
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
Maintain infusion at
150 micrograms/kg/min
Inadequate response
Repeat 500 micrograms/kg/min for 1 minute
Increase maintenance infusion to 200 micrograms/kg/min and maintain
As the desired heart rate or safety endpoint (e.g. reduced arterial pressure) is approached, DISCONTINUE the loading infusion and reduce the incremental step in the maintenance infusion from 50 micrograms/kg/min to 25 micrograms/kg/min or less. If necessary, the titration steps interval may be increased from 5 to 10 minutes.
NB: It has not been demonstrated that maintenance doses exceeding 200 micrograms/kg/min provide significantly greater benefit, and the safety of doses exceeding 300 micrograms/kg/min has not been studied.
In case of adverse reaction, the dosage of Esmocard 100 mg/10 may be reduced or administration discontinued. Pharmacologically-related adverse reactions should resolve within 30 minutes.
If a localized reaction at the infusion site occurs, an alternative infusion site should be used and care taken to avoid possible extravasation.
Administration of Esmocard 100 mg/10 infusions for longer than 24 hours has not been adequately evaluated. Prolonged infusions exceeding 24 hours should be used with caution.

No cases have been reported in which the abrupt discontinuation of Esmocard 100 mg/10 ml
has caused withdrawal effects that may occur following sudden interruption of chronic
beta-blocker therapy in patients with coronary artery disease (CAD). However, particular
caution is recommended in patients with coronary artery disease in case of abrupt
discontinuation of Esmocard 100 mg/10 ml infusions.
PERIOPERATIVE TACHYCARDIA AND HYPERTENSION
For tachycardia and hypertension, the dosing regimen may vary as follows:
a) For intraoperative treatment – during anesthesia, when immediate control is required,
administer an 80 mg bolus injection over 15-30 seconds, followed by an infusion of 150
micrograms/kg/min. Titrate the infusion rate as needed up to 300 micrograms/kg/min.
b) At emergence from anesthesia, administer an infusion of 500 micrograms/kg/min for up
to 4 minutes, followed by an infusion of 300 micrograms/kg/min.
c) In the postoperative period, if time is available for titration, administer a loading dose
of 500 micrograms/kg/min over one minute before each titration step, to achieve a rapid
onset of action. Use titration steps of 50, 100, 150, 200, 250, and 300 micrograms/kg/min,
administered every four minutes, stopping once the desired therapeutic effect is achieved.
Switching from Esmocard 100 mg/10 ml to alternative medications
After adequate control of heart rate and clinical stability have been achieved, it may be possible
to switch to alternative medications (such as antiarrhythmics or calcium antagonists).
Dosage reduction:
When Esmocard 100 mg/10 ml is being replaced by alternative medications, the physician must
carefully consider the instructions for the chosen alternative medication and reduce the
Esmocard 100 mg/10 ml dosage as follows:

1. Within the first hour after administration of the first dose of the alternative medication,
   reduce the infusion rate of Esmocard 100 mg/10 ml by half (50%).
2. After administration of the second dose of the alternative medication, monitor the
   patient’s response closely and, if satisfactory control has been maintained during the first
   hour, discontinue the Esmocard 100 mg/10 ml infusion.
   Additional dosing information: As soon as the desired therapeutic effect or safety endpoint (e.g., reduced blood pressure) is reached, discontinue the loading dose and reduce the infusion incrementally to 12.5–25 micrograms/kg/min. If desired, the interval between titration steps may also be extended from five to ten minutes.
   If heart rate or blood pressure rapidly approaches or exceeds the safety limit, administration of Esmocard 100 mg/10 ml must be stopped; subsequently, restart without a loading infusion at a lower dose once heart rate or blood pressure has returned to an acceptable level.
   Special populations
   Elderly
   Elderly patients should be treated with caution, starting with a lower dosage. No specific studies have been conducted in the elderly. However, an analysis of data from 252 patients aged over 65 years did not reveal any changes in pharmacodynamic effects compared to those observed in patients under 65 years of age.
   Patients with renal impairment
   Particular caution is required when administering Esmocard 100 mg/10 ml by infusion in patients with renal impairment, as the acidic metabolite of Esmocard 100 mg/10 ml is eliminated via the kidneys. Elimination of the acidic metabolite is significantly reduced in patients with renal disease, with an elimination half-life increased by approximately ten times the normal levels, along with substantially elevated plasma concentrations.
   Patients with hepatic impairment
   In patients with hepatic impairment, no special precautions are required due to the predominant role of plasma esterases in the metabolism of Esmocard 100 mg/10 ml.
   Paediatric population (under 18 years of age):
   The safety and efficacy of Esmocard 100 mg/10 ml in children under 18 years of age have not yet been established. Therefore, the use of Esmocard 100 mg/10 ml is not recommended in the paediatric population.

Patient information leaflet

ESMOCARD 2500 mg powder for concentrate for solution for infusion

Esmolol hydrochloride
Generic Medicine
Please read this leaflet carefully before using this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• This medicine has been prescribed for you. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or nurse. See section 4.

Contents of this leaflet:

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

1. What ESMOCARD is and what it is used for

ESMOCARD belongs to the group of beta-blockers. These medicines slow down the heartbeat and reduce blood pressure.
ESMOCARD is used for short-term treatment when your heart beats too fast.
ESMOCARD is also used during or immediately after surgery if your blood pressure becomes too high and/or your heart beats too fast.

2. What you need to know before using ESMOCARD

Your doctor will not administer ESMOCARD if:

• you are allergic to esmolol hydrochloride. Signs of an allergic reaction include difficulty breathing, wheezing, skin 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 irregular heartbeat (fast-slow)
• you suffer from a condition called "severe heart block." Heart block is a problem with the electrical signals controlling the heartbeat
• you have low blood pressure
• you have a condition affecting blood flow to the heart
• you are taking or have recently taken verapamil. You must not receive ESMOCARD within 48 hours after stopping verapamil if you have symptoms of severe heart failure
• you have an untreated adrenal gland disease called phaeochromocytoma. Phaeochromocytoma originates in the adrenal gland and may be associated with sudden high blood pressure, severe headache, sweating, and increased heart rate
• you have high blood pressure in the lungs (pulmonary hypertension)
• you have rapidly worsening asthma symptoms
• you have increased levels of acid in your body (a condition called metabolic acidosis)

Warnings and precautions

• ESMOCARD MUST BE RECONSTITITUTED/DILUTED BY A DOCTOR OR NURSE. Before ESMOCARD is administered to you, speak to your doctor or nurse. Your doctor will pay particular attention when using this medicine if:
• you have been treated for certain heart rhythm disorders called supraventricular arrhythmias and:
• you have other heart problems or
• you are taking other heart medications. The use of ESMOCARD in these cases may lead to serious, potentially fatal reactions, including:
• loss of consciousness
• shock (when the heart does not pump enough blood)
• heart attack (cardiac arrest)
• you develop low blood pressure (hypotension). Signs of this condition may include dizziness or lightheadedness, especially when standing up. This condition is rapidly reversible by reducing the dose or stopping the medication. During treatment with ESMOCARD, your blood pressure and electrocardiogram (ECG) will normally be continuously monitored. Usually, low blood pressure improves within 30 minutes after stopping ESMOCARD treatment
• you have a low heart rate before treatment
• your heart rate drops below 50–55 beats per minute. In this case, your doctor may reduce the dose or discontinue ESMOCARD treatment
• you suffer from heart failure
• you have problems with the electrical signals controlling your heartbeat (heart block)
• you have an adrenal gland disease called phaeochromocytoma that has been treated with medications known as alpha-receptor blockers
• you are taking medications to treat high blood pressure (hypertension) caused by low body temperature (hypothermia)
• you have a lung disease causing airway narrowing or wheezing, such as asthma
• you have diabetes (high blood sugar levels) or low blood sugar levels (hypoglycaemia). In this case, you will require special monitoring because ESMOCARD may mask the symptoms of low blood sugar. ESMOCARD may also enhance the effects of your diabetes medications
• you develop skin problems. These may be caused by leakage of the solution around the injection site. If this occurs, your doctor will use a different vein for injection
• you have a specific type of angina (chest pain) called "Prinzmetal's angina"
• you have reduced blood volume (with low blood pressure). You may be more prone to circulatory collapse
• you have circulatory problems, such as pale skin of the fingers (Raynaud's disease), or pain, fatigue, or burning in the legs
• you have kidney problems. If you have kidney disease or require dialysis, you may develop high levels of potassium in the blood (hyperkalaemia). This can cause serious heart problems
• you have any allergies or are at risk of anaphylactic reactions (severe allergic reactions). ESMOCARD may worsen allergies and make them difficult to treat
• you or a family member has a history of psoriasis (when the skin produces scaly patches)
• you have a condition called hyperthyroidism (overactive thyroid gland). Dosage adjustment is usually not necessary if you have liver problems. If any of the above conditions apply to you (or if you are unsure), speak to your doctor or nurse before receiving this medicine. You may require monitoring and adjustments to your treatment. For athletes: using this medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.

Other medicines and ESMOCARD
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines, including those without a prescription, herbal remedies, or natural products. Your doctor will check that the medicines you are taking do not alter the way ESMOCARD works.
In particular, inform your doctor or nurse if you are taking any of the following medicines:

• Medicines that may 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 will not be given ESMOCARD within 48 hours after stopping verapamil
• Nifedipine, used to treat chest pain (angina), high blood pressure, and Raynaud's disease
• Medicines used to treat heart rhythm disorders (such as quinidine, disopyramide, amiodarone) and heart failure (such as digoxin, digitoxin, digitalis)
• Medicines used to treat diabetes, including insulin and oral antidiabetic drugs
• Medicines known as ganglion blockers (e.g., trimethaphan)
• Medicines used as painkillers, such as non-steroidal anti-inflammatory drugs (NSAIDs)
• Floctafénine, a painkiller
• Amisulpride, a medicine used to treat mental health disorders
• Tricyclic antidepressants (such as imipramine and amitriptyline) or any other medicines for mental health conditions
• Barbiturates (such as phenobarbital, used to treat epilepsy) or phenothiazines (such as chlorpromazine, used to treat mental disorders)
• Clozapine, used to treat mental disorders
• Epinephrine, used to treat allergic reactions
• Medicines used to treat asthma
• Medicines used for colds or nasal congestion, also known as nasal decongestants
• Reserpine, used to treat high blood pressure
• Clonidine, used to treat high blood pressure and headache
• Moxonidine, used to treat high blood pressure
• Ergot derivatives, medicines mainly used to treat Parkinson's disease
• Warfarin, used to thin the blood
• Morphine, a strong painkiller
• Suxamethonium chloride (also known as succinylcholine or scoline) or mivacurium, used to relax muscles, usually during surgery. Your doctor will also pay particular attention when using ESMOCARD during surgical procedures, especially when anaesthetics and other treatments are administered. If you have any doubts about whether any of these restrictions apply to you, speak to your doctor or nurse before receiving ESMOCARD.

Tests you may undergo during treatment with ESMOCARD
Long-term use of medicines like ESMOCARD may reduce the strength of the heartbeat.
Since ESMOCARD is used only for a limited time, this is unlikely to occur. During treatment, you will be closely monitored, and if the strength of your heartbeat decreases, ESMOCARD treatment will be reduced or stopped.
During treatment with ESMOCARD, your doctor will also monitor your blood pressure.

Pregnancy and breastfeeding
Consult your doctor before using this medicine if you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding.
Available data on the use of ESMOCARD in humans are insufficient to demonstrate its safety during pregnancy. However, there are no indicators in humans of an increased risk of birth defects.
Due to the lack of experience with ESMOCARD use, it is not recommended during pregnancy.
Inform your doctor if you are breastfeeding. ESMOCARD may pass into breast milk; therefore, ESMOCARD must not be administered if you are breastfeeding.
Consult your doctor or nurse before taking any medicine.

3. How to use ESMOCARD

ESMOCARD MUST BE RECONSTITUTED/DILUTED BEFORE USE
The dosage should be individually adjusted. It is recommended to administer an initial dose followed by a maintenance dose. Your doctor will determine the dosing regimen and adjust the dosage, if necessary, based on any possible adverse effects.
ESMOCARD is administered by infusion. It is given intravenously by a doctor or nurse. Administration of the 50 mg/ml solution using an infusion pump must strictly be performed into a large vein or via a central venous catheter.
The duration of treatment depends on the therapeutic effect and the possible occurrence of adverse effects. Your doctor will determine how long the treatment should last.
Usually, no dose adjustment of ESMOCARD is necessary if you have liver problems.
If you have kidney problems, your doctor will take appropriate precautions.
Elderly
Your doctor will start treatment with a lower dose.
Use in children and adolescents
The safety and efficacy of ESMOCARD in children and adolescents have not been established.
ESMOCARD must not be administered to children under 18 years of age.
If you are given more ESMOCARD than you should
Since ESMOCARD is administered by a trained and qualified person, it is unlikely that you will receive too much. However, if this were to happen, your doctor would stop ESMOCARD and, if necessary, provide additional treatment.
If you think a dose of ESMOCARD has not been given to you
Since ESMOCARD is administered by a trained and qualified person, it is unlikely that a dose would be missed. However, if you believe a dose has not been administered, inform your doctor or nurse as soon as possible.
When administration of ESMOCARD is stopped
Stopping ESMOCARD abruptly may cause the return of symptoms such as rapid heartbeat (tachycardia) and high blood pressure (hypertension). To avoid this, your doctor must discontinue treatment gradually. If you suffer from coronary heart disease (which may be associated with a history of angina or heart attack), your doctor will pay particular attention when stopping treatment with ESMOCARD.
If you have any doubts about the use of ESMOCARD, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Most of the side effects disappear within 30 minutes after stopping treatment with ESMOCARD. The following side effects have been observed with ESMOCARD:
Contact your doctor or nurse immediately if you notice any of the following side effects, which may be serious. It may also be necessary to stop the infusion.

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

• Decrease in blood pressure. This can be rapidly corrected by reducing the dose of ESMOCARD or stopping treatment. Your blood pressure will be monitored frequently during treatment.
• Excessive sweating

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

• Loss of appetite
• Feelings of anxiety or depression
• Dizziness
• Drowsiness
• Headache
• Tingling or prickling sensations like “pins and needles”
• Difficulty concentrating
• Confusion or agitation
• Feeling unwell (nausea and vomiting)
• Feeling of weakness
• Feeling of tiredness (fatigue)
• Irritation and hardening of the skin at the injection site during ESMOCARD administration

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

• Abnormal thoughts
• Sudden loss of consciousness
• Fainting or feeling faint
• Seizures (epilepsy or convulsions)
• Speech disorders
• Visual disturbances
• Slowing of the heartbeat
• Problems with the electrical signals controlling the heartbeat
• Increased pressure in the arteries of the lungs
• Inability of the heart to pump enough blood (heart failure)
• A problem with the heart rhythm, sometimes known as “palpitations” (ventricular extrasystoles)
• Disturbance of heart rhythm (nodal rhythm)
• Chest discomfort caused by reduced blood flow through the blood vessels of the heart muscle (angina pectoris)
• Poor circulation in arms or legs
• Pallor or flushing
• Fluid in the lungs
• Shortness of breath or breathing difficulties due to chest tightness
• Wheezing
• Nasal congestion
• Abnormal rattling/crackling sounds during breathing
• Changes in taste sensation
• Indigestion
• Constipation
• Dry mouth
• Stomach area pain
• Changes in skin colour
• Skin redness
• Muscle or tendon pain, including around the shoulder blades and ribs
• Difficulty urinating (urinary retention)
• Chest pain
• Feeling of cold or elevated body temperature (fever)
• Pain and swelling (edema) of the vein during ESMOCARD injection
• Burning sensation at the injection site

Very rare (may affect up to 1 in 10,000 people):

• Severe reduction in heart rate (sinus arrest)
• Absence of electrical activity in the heart (asystole)
• Painful veins with a warm, red area of skin (thrombophlebitis)
• Dead skin tissue due to leakage of solution around the injection site

Not known (frequency cannot be estimated from the available data):

• Increased potassium levels in the blood (hyperkalaemia)
• Increased levels of acids in the body (metabolic acidosis)
• Increased heart contraction rate (accelerated idioventricular rhythm)
• Spasm of the heart arteries
• Interruption of normal blood circulation (cardiac arrest)
• Psoriasis (a skin disease causing scaly patches)
• Swelling of the face, limbs, tongue or throat (angioedema)
• Hives (urticaria)
• Inflammation of a vein or blister formation at the infusion site

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store ESMOCARD

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label after "Exp".
The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
The recommended storage condition is at a temperature of 25°C.
The opened, reconstituted and diluted product is physically and chemically stable for 24 hours at 25°C.
From a microbiological standpoint, the product should be used immediately after opening and dilution.
Otherwise, the user is responsible for the use and administration of the medicine.
Normally, the period of use should not exceed 24 hours at a temperature of 2–8°C, unless the opening and reconstitution/dilution have been carried out under controlled and validated aseptic conditions.
Do not dispose of any medicine via wastewater or household waste.
Your pharmacist or nurse will dispose of medicines you no longer use.
This will help protect the environment.

6. Pack contents and other information

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

Description of the appearance of ESMOCARD and contents of the pack
One vial contains 2500 mg of white or almost white powder.
The vial is made of colourless glass (type I).
One pack of ESMOCARD 2500 mg powder for solution for infusion contains 1 vial.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Orpha-Devel Handels und Vertriebs GmbH
Wintergasse 85/1B
A-3002 Purkersdorf
Austria

Manufacturers
Amomed Pharma GmbH
Storchengasse 1
1150 Vienna
Austria
Hikma Italia S.P.A.,
Viale Certosa 10,
27100 Pavia,
Italy

This medicinal product is authorised in the following European Economic Area Member States
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
Estonia: ESMOCARD LYO 2500 mg infusioonilahuse kontsentraadi pulber
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
Latvia: ESMOCARD LYO 2500 mg pulveris infūziju šķīduma koncentrāta pagatavošanai
Lithuania: ESMOCARD LYO 2500 mg milteliai infuzinio tirpalo koncentratui
Netherlands: Esmolol HCl LYO Orpha 2500 mg poeder voor concentraat voor oplossing voor infusie
Norway: ESMOCARD LYO 2500 mg pulver til infusjonsvæske, oppløsning
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 2500 mg powder for concentrate for solution for infusion

The following information is intended exclusively for doctors or healthcare professionals:

Healthcare professionals:
This section contains practical information regarding administration. Please read the
Summary of Product Characteristics for complete information on dosage, administration,
contraindications, warnings, etc.
ESMOCARD 2500 mg powder for concentrate for solution for infusion MUST NOT
BE ADMINISTERED WITHOUT RECONSTITUTION/DILUTION.
The reconstituted/diluted solution for infusion must be used immediately after preparation.
Administration of ESMOCARD without proper reconstitution/dilution may result in death.

Dosage
SUPRAVENTRICULAR TACHYARRHYTHMIA
The dosage of ESMOCARD must be individually titrated. An initial dose followed by a maintenance dose should be administered.
The effective dose of ESMOCARD ranges between 50 and 200 micrograms/kg/min, although doses up to 300 micrograms/kg/min have been used. In some patients, a mean effective dose of 25 micrograms/kg/min has been sufficient.

Flowchart for initial and maintenance dosing
Infuse loading dose of
500 micrograms/kg/min for 1 minute,
THEN 50 micrograms/kg/min for 4 minutes
Response
Maintain infusion at
50 micrograms/kg/min
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
Maintain infusion at
100 micrograms/kg/min
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
Maintain infusion at
150 micrograms/kg/min
Inadequate response
Repeat 500 micrograms/kg/min for 1 minute
Increase maintenance infusion to 200 micrograms/kg/min and maintain
As the desired heart rate or safety endpoint (e.g. reduced blood pressure) is approached, STOP the loading infusion and reduce the incremental maintenance infusion from 50 micrograms/kg/min to 25 micrograms/kg/min or less. If necessary, the interval between titration steps may be increased from 5 to 10 minutes.
NOTE: It has not been demonstrated that maintenance doses exceeding 200 micrograms/kg/min provide significantly increased benefit, and the safety of doses exceeding 300 micrograms/kg/min has not been studied.
In case of adverse reaction, the dosage of ESMOCARD may be reduced or administration discontinued. Pharmacologically related adverse reactions should resolve within 30 minutes.
If a local reaction occurs at the infusion site, an alternative infusion site should be used, and care should be taken to avoid extravasation.
Administration of ESMOCARD infusions for longer than 24 hours has not been adequately evaluated. Caution is recommended when using infusions exceeding 24 hours.
No cases have been reported in which abrupt discontinuation of ESMOCARD caused withdrawal effects that may occur after sudden interruption of chronic beta-blocker therapy in patients with coronary artery disease (CAD). However, particular caution is recommended in patients with coronary artery disease when abruptly stopping ESMOCARD infusions.

PERIOPERATIVE TACHYCARDIA AND HYPERTENSION
For tachycardia and hypertension occurring in the perioperative period, the dosage regimen may vary as follows:
a) For intraoperative treatment – during anesthesia, when immediate control is required, administer an 80 mg bolus injection over 15–30 seconds, followed by an infusion of 150 micrograms/kg/min. Titrate the infusion rate as needed up to 300 micrograms/kg/min.
b) At emergence from anesthesia, administer an infusion of 500 micrograms/kg/min for up to 4 minutes, followed by an infusion of 300 micrograms/kg/min.
c) In the postoperative period, if time is available for titration, administer a loading dose of 500 micrograms/kg/min over one minute before each titration step to achieve rapid onset of action. Use titration steps of 50, 100, 150, 200, 250, and 300 micrograms/kg/min, each administered every four minutes, stopping once the desired therapeutic effect is achieved.

Transition from ESMOCARD therapy to alternative medications
After adequate heart rate control and clinical stability have been achieved, transition to alternative medications (such as antiarrhythmics or calcium antagonists) may be considered.

Dosage reduction
When replacing ESMOCARD with alternative medications, the physician must carefully consider the instructions for the chosen alternative drug and reduce the ESMOCARD infusion rate as follows:
3) Within the first hour after administering the first dose of the alternative medication, reduce the ESMOCARD infusion rate by half (50%).
2) After administering the second dose of the alternative medication, monitor the patient’s response carefully and, if satisfactory control has been maintained during the first hour, discontinue the ESMOCARD infusion.

Additional dosing information
As soon as the desired therapeutic effect or safety endpoint (e.g. reduced blood pressure) is reached, stop the loading dose and reduce the incremental infusion rate to 12.5–25 micrograms/kg/min. If desired, the interval between titration steps may be increased from five to ten minutes.
When heart rate or blood pressure rapidly approaches or exceeds the safety limit, ESMOCARD administration should be interrupted; subsequently, restart without a loading infusion at a lower dose once heart rate or blood pressure returns to an acceptable level.

Special populations
Elderly
Elderly patients should be treated with caution, starting with a lower dosage. Specific studies in the elderly have not been conducted. However, an analysis of data from 252 patients over 65 years of age did not reveal any significant changes in pharmacodynamic effects compared to patients under 65 years of age.

Patients with renal impairment
Particular caution is required when administering ESMOCARD by infusion in patients with renal impairment, as the acid metabolite of ESMOCARD is eliminated via the kidneys. Elimination of the acid metabolite is significantly reduced in patients with renal disease, with an elimination half-life increased approximately tenfold compared to normal, along with markedly elevated plasma levels.

Patients with hepatic impairment
In cases of hepatic impairment, no special precautions are required due to the primary role of plasma esterases in the metabolism of ESMOCARD.

Paediatric population (under 18 years of age):
The safety and efficacy of ESMOCARD in children under 18 years of age have not yet been established. Therefore, the use of ESMOCARD is not recommended in the paediatric population.

Method of administration
The powder must be reconstituted/diluted before use. The reconstituted/diluted powder can be administered at two different concentrations and volumes:

1. The standard concentration is 10 mg/ml, with a final volume of 250 ml
2. In some cases where a smaller volume is considered necessary, a higher concentration (50 mg/ml) may be prepared by diluting the powder to a final volume of 50 ml and then administered using an INFUSION/INFUSION PUMP. Clinical experience with this higher concentration is limited. This higher concentration must be infused only through a large vein or central catheter using an infusion pump.

INFUSION RATE CONVERSION TABLES (micrograms/kg/min to ml/min) for a diluted solution for infusion (10 mg/ml) administered via STANDARD INFUSION:

INFUSION RATE CONVERSION TABLES (micrograms/kg/min
ml/min) for a concentrated infusion solution (50 mg/ml) administered using a
INFUSION PUMP/MOTORIZED PUMP :