ESMOLOL HYDROCHLORIDE

Posology Esmolol hydrochloride10 mg / mL Solution for infusion is a ready-to-use 10 mg / mL solution, recommended for intravenous administration. SUPRAVENTRICULAR TACHYARRYTHMIA (except for pre-excitation syndromes) OR NON-COMPENSATORY SINUS TACHYCARDIA The Esmolol hydrochloride dosage in supraventricular tachyarrhythmias should be individually titrated as indicated in the below flow chart.

Each stage consists of an induction dose followed by a maintenance dose. The effective maintenance dose is between 50 and 200 micrograms / kg / minute, with doses of 25 to 300 micrograms / kg / minute also being used. Flow Chart for Initiation and Maintenance of Treatment Loading dosage infusion of 500 micrograms / kg / minute for 1 minute THEN a maintenance infusion of 50 micrograms / kg / minute for 4 minutes Response Maintain the infusion at 50 micrograms / kg / minute Inadequate response within 5 minutes Repeat the dose of 500 micrograms / kg / minute for 1 minute Increase the maintenance infusion to 100 micrograms / kg / minute for 4 minutes Response Maintain the infusion at 100 micrograms / kg / minute Inadequate response within 5 minutes Repeat the dose of 500 micrograms / kg / minute for 1 minute Increase the maintenance infusion to 150 micrograms / kg / minute for 4 minutes Response Maintain theinfusion at 150 micrograms / kg / minute Inadequate response Repeat the dose of 500 micrograms / kg / minute for 1 minute Increase the maintenance infusion to 200 micrograms / kg / min and maintain Loading dose Loading dose adjustment may be necessary depending on the haemodynamic response (heart rate, blood pressure) Maintenance dose For a continuous and progressive dosage an effective maintenance dose is between 50 to 200 micrograms / kg / minute.

25 micrograms / kg / minute doses may be used. Maintenance dose adjustment may be necessary depending on the desired haemodynamic response. Administration of doses greater than 200 micrograms / kg / min provides little added heart rate-lowering effect, and the rate of adverse reactions increases.

Loading dose and maintenance doses of Esmolol hydrochloride to administer for different patient weights are outlined in Table 1 and Table 2 respectively. Table 1 and 2 provide information on the respective initiation dose and maintenance dose of Esmolol hydrochloride as a function of patient weight.

5 mL / h 33 mL / h 66 mL / h 99 mL / h 132 mL / h 198 mL / h 120 9 mL / h 18 mL / h 36 mL / h 72 mL / h 108 mL / h 144 mL / h 216 mL / h 1mL of Esmolol hydrochloride is equivalent to 10 mg of esmolol. , lowered blood pressure) is approached, OMIT the loading dose and reduce the incremental dose in the maintenance infusion from 50 micrograms/kg/minute to 25 micrograms / kg / minute or lower.

If necessary, the interval between the titration steps may be increased from 5 to 10 minutes.

NOTE:

Maintenance doses in excess of 200 micrograms / kg / minute have not shown any significant benefits. The safety of doses above 300 micrograms / kg / minute has not been studied. PERIOPERATIVE TACHYCARDIA AND HYPERTENSION For perioperative tachycardia and/or hypertension the dosing regimen may vary as follows: For intraoperative treatment - during anaesthesia when immediate control is required: • A bolus injection of 80 mg is given over 15 to 30 seconds followed by a 150 micrograms / kg / minute infusion.

Titrate the infusion rate as required up to 300 micrograms / kg / minute. The volume of infusion required for different patient weights is provided in Table 2. Upon awakening from anaesthesia • An infusion of 500 micrograms / kg / minute is given for 4 minutes followed by a 300 micrograms / kg / minute infusion.

The volume of infusion required for different patient weights is provided in Table 2. For post-operative situations when time for titration is available • A loading dose of 500 micrograms / kg / minute is given over 1 minute before each titration step to produce a rapid onset of action.

Use titration steps of 50,100, 150, 200, 250 and 300 micrograms / kg / minute given over 4 minutes and stopping at the desired therapeutic effect. The volume of infusion required for different patient weights is provided in Table 2.

Recommended maximum dose: • For adequate control of blood pressure, higher dosages (250 – 300 mcg / kg / min) may be required. The safety of dosages above 300 mcg / kg / min has not been adequately studied. Potential effects to be aware of during dosing with Esmolol hydrochloride In the event of an adverse reaction, the dosage of Esmolol hydrochloride may be reduced or discontinued.

Pharmacological adverse reactions should resolve within 30 minutes. If a local infusion site reaction develops, an alternative infusion site should be used and caution should be taken to prevent extravasation. The administration […]

In case of undesirable effects, the dose of esmolol hydrochloride can be reduced or discontinued. Most of the undesirable effects observed have been mild and transient. The most important one has been hypotension. The following undesirable effects are ranked according to MedDRA System Organ Class (SOC) and to their frequency.

Note:

The frequency of occurrence of adverse events is classified as follows: Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1000 to < 1/100) Very rare (<1/10000) Not known (Cannot be estimated from the available data) Frequency System Organ Class Very common Common Uncommon Very rare Not known Metabolism and nutrition disorders Anorexia Hyperkalemia Metabolic acidosis Psychiatric Depression Thinking disorders Anxiety abnormal Nervous system disorders Dizziness 1 Somnolence Headache Paraesthesiae Disturbance in attention Confusional state Agitation Syncope Convulsion Speech disorder Eye disorders Visual impairment Cardiac disorders Bradycardia Atrioventricular block Pulmonary arterial pressure increased Cardiac Failure Ventricular extrasystoles Nodal rhythm Angina pectoris Sinus arrest Asystole Accelerated idioventricular rhythm Coronary arteriospasm Cardiac arrest.

Vascular disorders Hypotensio n Peripheral ischaemia Pallor Flushing Thrombophle bitis 2 1 Dizziness and diaphoresis are in association with symptomatic hypotension. 2 In association with Injection and Infusion site reactions. Frequency System Organ Class Very common Common Uncommon Very rare Not known Respiratory, thoracic and mediastinal disorders Dyspnoea Pulmonary oedema Bronchospasm Wheezing Nasal congestion Rhonchi Rales Gastrointestinal disorders Nausea Vomiting Dysgeusia Dyspepsia Constipation Dry mouth Abdominal pain Skin and subcutaneous tissue Diaphoresis 1 Skin discolouration 2 Skin necrosis 2 (due to Psoriasis 3 Angioedema disorders Erythema 2 extravasation) Urticaria Musculoskeletal and connective tissue disorders Musculoskeletal pain 4 Renal and urinary disorders Urinary retention General disorders and administration site conditions Asthenia Fatigue Injection site reaction Infusion site reaction Infusion site inflammation Infusion site induration Chills Pyrexia Oedema 2 Pain 2 Infusion site burning Infusion site ecchymosis Infusion site phlebitis Infusion site vesicles Blistering 2 1 Dizziness and diaphoresis are in association with symptomatic hypotension.

2 In association with Injection and Infusion site reactions. 3 Beta-blockers as a drug class can cause psoriasis in some situations, or worsen it. 4 Including midscapular pain and costochondritis Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Warnings It is recommended to continuously monitor the blood pressure and the ECG in all patients treated with esmolol hydrochloride. The use of esmolol hydrochloride for control of ventricular response in patients with supraventricular arrhythmias should be undertaken with caution when the patient is compromised haemodynamically or is taking other drugs that decrease any or all of the following: peripheral resistance, myocardial filling, myocardial contractility, or electrical impulse propagation in the myocardium.

Despite the rapid onset and offset of the effects of esmolol hydrochloride, severe reactions may occur, including loss of consciousness, cardiogenic shock, cardiac arrest. Several deaths have been reported in complex clinical states where esmolol hydrochloride was presumably being used to control ventricular rate.

The most frequently observed side effect is hypotension, which is dose related but can occur at any dose. This can be severe. In the event of a hypotensive episode the infusion rate should be lowered or, if necessary, be discontinued.

Hypotension is usually reversible (within 30 minutes after discontinuation of administration of esmolol hydrochloride). In some cases, additional interventions may be necessary to restore blood pressure. In patients with a low systolic blood pressure, extra caution is needed when adjusting the dosage and during the maintenance infusion.

Bradycardia, including severe bradycardia, and cardiac arrest has occurred with the use of esmolol hydrochloride. Esmolol hydrochloride should be used with special caution in patients with low pretreatment heart rates and only when the potential benefits are considered to outweigh the risk.

3). If the pulse rate decreases to less than 50 – 55 beats per minute at rest and the patient experiences symptoms related to bradycardia, the dosage should be reduced or administration stopped. Sympathetic stimulation is necessary in supporting circulatory function in congestive heart failure.

Beta-blockade carries the potential hazard of further depressing myocardial contractility and precipitating more severe failure. Continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure.

Caution should be exercised when using esmolol hydrochloride in patients with compromised cardiac function. At the first sign or symptom of impending cardiac failure, esmolol hydrochloride should be withdrawn. 9). 3). 3). 3). Caution is required when esmolol hydrochloride is used to treat hypertension following induced hypothermia.

Patients with bronchospastic disease should, in general, not receive beta-blockers. Because of its relative beta-1 selectivity and titratability, esmolol hydrochloride should be used with caution in patients with bronchospastic diseases.

However, since beta-1 selectivity is not absolute, esmolol hydrochloride should be carefully titrated to obtain the lowest possible effective dose. In the event of bronchospasm, the infusion should be terminated immediately and a beta-2-agonist should be administered if necessary.

If the patient already uses a beta-2-receptor stimulating agent, it may be necessary to re-evaluate the dose of this agent. Esmolol hydrochloride should be used with caution in patients with a history of wheezing or asthma. Precautions Esmolol hydrochloride should be used with caution in diabetics or in case of suspected or actual hypoglycaemia.

Beta-blockers may mask the prodromal symptoms of a hypoglycaemia such as tachycardia. However, dizziness and sweating may not be affected. 5). Infusion site reactions have occurred with the use of both esmolol hydrochloride 10 mg / mL and 20 mg / mL.

8). Infusions into small veins or through a butterfly catheter should be avoided. If a local infusion site reaction develops, an alternative infusion site should be used. Beta-blockers may increase the number and the duration of anginal attacks in patients with Prinzemetal's angina due to unopposed alpha-receptor mediated coronary artery vasoconstriction.

Non-selective beta-blockers should not be used for these patients and beta-1 selective blockers should only be used with the utmost care. In hypovolemic patients, esmolol hydrochloride can attenuate reflex tachycardia and increase the risk of circulatory collapse.

Therefore, esmolol hydrochloride should be used with caution in such patients. In patients with peripheral circulatory disorders (Raynaud's disease or syndrome, intermittent claudication), beta-blockers should be used with great caution as aggravation of these disorders may occur.

Some beta-blockers, especially those administered intravenously, including esmolol hydrochloride, have been associated with increases in serum potassium levels and hyperkalemia. The risk is increased in patients with risk factors such as renal impairment and those on haemodialysis.

[…]

1 or other beta-blockers (cross sensitivity between beta- blockers is possible); • Severe sinus bradycardia (less than 50 beats per minute); Sick sinus syndrome; severe AV-nodal conductance disorders (without pacemaker); 2nd or 3rd degree AV-block; • Cardiogenic shock; • Severe hypotension; • Decompensated heart failure; • Concomitant or recent intravenous administration of verapamil.

5); • Non-treated phaeochromocytoma; • Pulmonary hypertension; • Acute asthmatic attack; • Metabolic acidosis.