Esmolol hydrochloride Hikma

Package Leaflet – Information for the User

ESMOLOL HYDROCHLORIDE HIKMA 10 mg/ml Injection Solution

Generic Medicine
Please read this leaflet carefully before you start 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.
• If you experience any side effects, including those not listed in this leaflet, please inform your doctor or nurse. See section 4.

Contents of this leaflet

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

1. What Esmololo cloridrato Hikma is and what it is used for

Esmololo cloridrato Hikma contains a medicine called esmolol. It belongs to a
group of medicines known as “beta-blockers”. It works by controlling the rate and force of
your heartbeat. It may also help reduce blood pressure.
It is used to treat:

• heart problems when your heart is beating too fast
• heart problems and high blood pressure occurring during or immediately after surgery

2. What you need to know before taking Esmolol hydrochloride Hikma

Do not take Esmolol hydrochloride Hikma if:

• you are allergic to esmolol, to other beta-blocking medicines, or to any of the excipients of this medicine (listed in section 6). Symptoms of an allergic reaction include shortness of breath, dyspnea, 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 heart rate or an alternating slow-fast rhythm
• you suffer from a condition called "severe heart block." Heart block is a problem affecting the electrical impulses controlling your heartbeat
• you have low blood pressure
• you have problems with blood flow to your heart
• you have symptoms of severe heart failure
• you are taking or have recently taken verapamil. You must not be administered Esmolol within 48 hours after stopping verapamil.
• you have an untreated disease of a gland called phaeochromocytoma. Phaeochromocytoma originates in the adrenal gland and may cause 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 (metabolic acidosis)

Esmolol hydrochloride Hikma will not be administered to you if any of the above conditions apply. If you are unsure whether you suffer from any of these conditions, speak with your doctor or nurse before receiving Esmolol hydrochloride Hikma.

Warnings and precautions

Talk to your doctor or nurse before receiving Esmolol hydrochloride Hikma.

Your doctor will pay special attention when using this medicine if:

• you are being treated for certain heart rhythm disorders called supraventricular arrhythmias and you
  . have other heart problems or
  . are taking other heart medications
  The use of Esmolol hydrochloride Hikma under these conditions may lead to serious reactions, which can be fatal, including:
  . loss of consciousness
  . shock (when your heart does not pump enough blood)
  . cardiac arrest (heart attack)
• you experience low blood pressure (hypotension). Symptoms may include dizziness or lightheadedness, especially when standing. Low blood pressure usually improves within 30 minutes after stopping treatment with Esmolol hydrochloride Hikma.
• you have a slow heart rate before treatment
• your heart rate drops below 50–55 beats per minute. If this occurs, your doctor may administer a reduced dose or discontinue treatment with Esmolol hydrochloride Hikma.
• you suffer from heart failure
• you have problems with the electrical impulses controlling your heartbeat (heart block)
• you have a glandular disorder called phaeochromocytoma that has been treated with medications known as alpha-blockers
• you are being treated for high blood pressure (hypertension) caused by low body temperature (hypothermia)
• you have narrowed airways or shortness of breath, as occurs in asthma
• you suffer from diabetes or low blood sugar levels. Esmolol hydrochloride Hikma may enhance the effects of diabetes medications
• you develop skin problems. This may be caused by leakage of the solution at the injection site. If this occurs, your doctor will use a different vein for administration.
• you suffer from a specific type of angina (chest pain) called "Prinzmetal's angina."
• you have a low blood volume (with low blood pressure). You may be more likely to develop circulatory collapse.
• you have circulatory problems, such as pale 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 renal dialysis, you may develop high levels of potassium in the blood (hyperkalemia). This can cause serious heart problems.
• you have any allergies or are at risk of anaphylactic reactions (severe allergic reactions). Esmolol hydrochloride Hikma may make allergies more severe and difficult to treat.
• you or a family member has a history of psoriasis (a skin condition causing scaly patches).
• you have a condition called hyperthyroidism (overactive thyroid gland)

Dosage adjustment is generally not required if you have liver problems.
If any of the above conditions apply to you (or if you are unsure), speak with your doctor or nurse before receiving this medicine. You may need to be closely monitored, and your treatment may need to be adjusted.

For athletes: Using this medicine without a therapeutic need constitutes doping and may result in a positive anti-doping test.

Other medicines and Esmolol hydrochloride Hikma

Tell your doctor if you are taking, have recently taken, or might take any other medicines, including over-the-counter medicines, herbal products, and natural remedies. Your doctor will check whether any other medicines you are taking could interfere with the action of Esmolol hydrochloride Hikma.

In particular, inform your doctor or nurse if you are taking any of the following medicines:

• medicines that may lower blood pressure or reduce heart rate
• medicines used to treat heart rhythm disorders or chest pain (angina), such as verapamil or diltiazem. You must not take Esmolol hydrochloride Hikma 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 agents
• medicines known as ganglion-blocking agents (such as trimethaphan)
• medicines used as painkillers, such as non-steroidal anti-inflammatory drugs (NSAIDs)
• Floctafennine, a painkiller
• Amisulpride, a medicine used to treat mental disorders
• Tricyclic antidepressants (such as imipramine and amitriptyline) or any other medicines for mental disorders
• 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, known as "nasal decongestants"
• Reserpine, used to treat high blood pressure
• Clonidine, used to treat high blood pressure and migraine
• Moxonidine, used to treat high blood pressure
• Ergotamine 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 your muscles, usually during surgery. Your doctor will also pay particular attention when using Esmolol hydrochloride Hikma during surgery, especially when you are receiving anesthetics or other treatments.

If you are unsure whether any of the above conditions apply to you, talk to your doctor, nurse, or pharmacist before taking Esmolol hydrochloride Hikma.

Tests you may undergo while receiving Esmolol hydrochloride Hikma

Long-term use of medicines like Esmolol hydrochloride Hikma may reduce the strength of your heartbeat.
Since Esmolol hydrochloride Hikma is used only for a short period, this is unlikely to occur. During treatment, you will be closely monitored, and treatment with Esmolol hydrochloride Hikma will be reduced or stopped if your heartbeat weakens.

Your doctor will also monitor your blood pressure while you are receiving Esmolol hydrochloride Hikma.

Pregnancy and breastfeeding

Ask your doctor or pharmacist for advice before taking any medicine.

Esmolol hydrochloride Hikma must not be administered to you if you are pregnant or think you may be pregnant.

Inform your doctor if you are breastfeeding. Esmolol hydrochloride Hikma may pass into breast milk; therefore, it must not be administered if you are breastfeeding.

Esmolol hydrochloride Hikma contains sodium

This medicinal product contains less than 1 mmol of sodium (23 mg) per vial and is therefore essentially "sodium-free."

3. How to take Esmolol hydrochloride Hikma

Recommended dose
Your doctor will decide how much medicine you need and for how long it will be administered.
Esmolol hydrochloride Hikma is generally not administered for longer than 24 hours.

How Esmolol hydrochloride Hikma is administered
Esmolol hydrochloride Hikma is ready for use. It will be given to you as a slow injection (infusion) through a needle inserted into a vein in your arm.
Esmolol hydrochloride Hikma must not be mixed with sodium bicarbonate or other medicines.
The treatment consists of 2 stages:

• Stage 1: a higher dose is given over one minute. This rapidly increases the levels in your blood.
• Stage 2: a lower dose is then administered over four minutes.
• Stages 1 and 2 may then be repeated and adjusted according to your heart's response. As soon as improvement is observed, stage 1 (the higher dose) will be stopped and stage 2 (the lower dose) will be reduced as deemed necessary.
• After a stable condition has been achieved, another heart medication may be administered while your dose of Esmolol hydrochloride Hikma is gradually reduced. If your heart rate or blood pressure increases during or immediately after a procedure, higher doses of Esmolol hydrochloride Hikma may be given for a short period of time.

Use in the elderly
Your doctor will start your treatment with a reduced dose.

Use in children
Children up to 18 years of age must not receive Esmolol hydrochloride Hikma.

If you receive more Esmolol hydrochloride Hikma than you should
Since Esmolol hydrochloride Hikma is administered by trained and qualified personnel, it is unlikely that you will receive too much. However, if this happens, your doctor will stop Esmolol hydrochloride Hikma and administer alternative treatment if necessary.

If you think you have missed a dose of Esmolol hydrochloride Hikma
Since Esmolol hydrochloride Hikma is administered by trained and qualified personnel, it is unlikely that a dose will be missed. However, if you think a dose has been missed, speak to your doctor, nurse, or pharmacist as soon as possible.

If you stop receiving Esmolol hydrochloride Hikma
Stopping Esmolol hydrochloride Hikma abruptly may cause symptoms of rapid heartbeat (tachycardia) and rebound high blood pressure (hypertension). To avoid this, your doctor must stop your treatment gradually. If you are aware of having coronary artery disease (which may be associated with a history of angina or heart attack), your doctor will pay particular attention when discontinuing treatment with Esmolol hydrochloride Hikma.

If you have any doubts about how to use this medicine, speak to your doctor or nurse.

4. Possible side effects

Like all medicines, this medicinal product can cause side effects, although not everyone experiences them.
Most of the side effects disappear within 30 minutes after stopping treatment with Esmolol hydrochloride Hikma.
Immediately inform your doctor or nurse if you notice any of the side effects, which may also be serious. It may also be necessary to stop the infusion.
The following side effects have been reported with Esmolol hydrochloride Hikma:

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

• Drop in blood pressure. This effect can be rapidly corrected by reducing the dose of Esmolol hydrochloride Hikma or by stopping treatment. Your blood pressure will be monitored frequently during treatment.
• Excessive sweating

Common (may affect less than 1 in 10 people)

• Loss of appetite
• Feeling of anxiety or depression
• Dizziness
• Drowsiness
• Headache
• Tingling or "pins and needles"
• Difficulty concentrating
• Feeling confused or agitated
• Feeling unwell (nausea and vomiting)
• Feeling of weakness
• Feeling of tiredness (fatigue)
• Irritation and hardening of the skin at the site where Esmolol hydrochloride Hikma was administered

Uncommon (may affect less than 1 in 100 people)

• Abnormal thoughts
• Sudden loss of consciousness
• Feeling faint or fainting
• Seizures (epileptic fits or convulsions)
• Speech problems
• Vision problems
• Reduced heart rate
• Problems with the electrical impulses controlling your heartbeat
• Increased pressure in the lung arteries
• Inability of the heart to pump enough blood (heart failure)
• Interruption of heart rhythm sometimes known as palpitations (ventricular extrasystoles)
• Heart rhythm disturbances (nodal rhythm)
• Chest discomfort due to reduced blood flow through the blood vessels of the heart muscle (angina pectoris)
• Poor circulation in the legs or arms
• Pale or flushed appearance
• Fluid in the lungs
• Shortness of breath or chest tightness making breathing difficult
• Dyspnea
• Nasal congestion
• Abnormal crackles/noises when breathing
• Changes in taste sensation
• Indigestion
• Constipation
• Dry mouth
• Stomach area pain
• Skin discoloration
• Skin redness
• Muscle or tendon pain, including around the shoulder blades and ribs
• Problems passing urine (urinary retention)
• Feeling of chills or elevated temperature (fever)
• Pain and swelling (edema) of the veins at the site where Esmolol hydrochloride Hikma was administered
• Burning sensation or bruising at the injection site

Very rare (may affect less than 1 in 10,000 people)

• Severe reduction in heart rate (sinus arrest)
• Absence of electrical activity in the heart (asystole)
• Softening of blood vessels with an area of red, warm skin (thrombophlebitis)
• Dead skin caused by leakage of solution around the administration site

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

• Increased levels of potassium in the blood (hyperkalemia)
• Increased levels of acids in the body (metabolic acidosis)
• Increased rate of heart contraction (accelerated idioventricular rhythm)
• Spasms of the heart artery
• Failure of normal blood circulation (cardiac arrest)
• Psoriasis (a condition in which the skin produces scaly patches)
• Swelling of the face, limbs, tongue, or throat (angioedema)
• Hives (urticaria)
• Inflammation of the vein or formation of blisters at the infusion site

Reporting of side effects
If you experience any side effect, including those 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/it/responsabili. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Esmolol hydrochloride Hikma

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and the carton after
EXP.
Do not store above 25°C.
Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C – 8°C.
Keep the vial in the outer carton to protect from light.

6. Package contents and other information

What Esmololo Hikma contains

• The active substance is esmolol hydrochloride.
• The other ingredients are sodium acetate trihydrate, glacial acetic acid, sodium hydroxide and/or hydrochloric acid for pH adjustment, and water for injections.

Each ml of solution contains 10 mg of esmolol hydrochloride, equivalent to 8.9 mg of esmolol.
Each 10 ml vial of solution contains 100 mg of esmolol hydrochloride, equivalent to 89 mg of esmolol.
Description of the appearance of Esmolol Hikma and package contents
Esmolol Hikma is a clear, colourless to pale yellow solution, contained in 10 ml transparent type I glass vials, packed in cardboard boxes.
Packaging: 10 vials.
Marketing Authorisation Holder and Manufacturer:
Hikma Farmacêutica (Portugal) S.A.
Estrada do Rio da Mò n.8, 8A and 8B
Fervença
2705-906 Terrugem SNT
Portugal
This medicinal product is authorised in EEA Member States under the following
names:
Austria: Esmolol Hikma 10 mg/ml, Injektionslösung
Germany: Esmolol Hikma 10 mg/ml, Injektionslösung
Italy: Esmololo cloridrato Hikma
Portugal: Esmolol Hikma
Netherlands: Esmolol HCl Hikma 10 mg/ml, oplossing voor injectie
United Kingdom: Esmolol 10 mg/ml, Solution for injection
This leaflet was last revised on
The following information is intended for medical professionals only:

• Dosage and method of administration Esmolol Hikma is a ready-to-use 10 mg/ml solution recommended for intravenous administration. The dosage form is used to administer the appropriate loading dose of Esmolol Hikma or bolus dose manually via syringe. Dosage is summarised in the following tables:

Table 1
Volume of Esmolol Hikma 10 mg/ml required for a
LOADING DOSE OF 500 mcg/kg/min

Table 2
Volume of Esmolol hydrochloride Hikma 10 mg/ml required to provide
MAINTENANCE DOSES at infusion rates between 12.5 and 300 mcg/kg/min

Perioperative Tachycardia and Hypertension
For perioperative tachycardia and hypertension, the dosing regimen may vary as follows:

Intraoperative treatment – during anaesthesia when immediate control is required:

• An 80 mg bolus injection is administered 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. The infusion volume required for patients of different weights is indicated in Table 2.

Upon awakening from anaesthesia

• An infusion of 500 micrograms/kg/min is administered for 4 minutes, followed by an infusion of 300 micrograms/kg/min. The infusion volume required for patients of different weights is indicated in Table 2.

For postoperative situations when titration time is available

• A loading dose of 500 micrograms/kg/min is administered over 1 minute prior to each titration step to achieve a rapid onset of action. Use titration steps of 50, 100, 150, 250, and 300 micrograms/kg/min, each administered over 4 minutes, and stop once the desired therapeutic effect is achieved. The infusion volume required for patients of different weights is indicated in Table 2.

Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products or with sodium bicarbonate solutions.

Special precautions for disposal and handling
For single use only. Avoid contact with alkalis. The solution should be visually inspected for the presence of particles and discoloration prior to administration. Only a clear, colourless or slightly coloured solution may be used. Unused medicines or waste materials must be disposed of in accordance with local regulations.