Betaloc

Overdose

Symptoms

Symptoms of overdose may include hypotension, cardiac insufficiency, bradycardia and bradyarrhythmia, cardiac conduction disturbances and bronchospasm.

Management

Care should be provided at a facility that can provide appropriate supporting measures, monitoring and supervision.

Atropine, adrenostimulating drugs or pacemaker to treat bradycardia and conduction disorders.

Hypotension, acute cardiac failure, and shock to be treated with suitable volume expansion, injection of glucagon (if necessary, followed by an intravenous infusion of glucagon), intravenous administration of adrenostimulating drugs such as dobutamine, with α1 receptor agonistic drugs added in presence of vasodilation. Intravenous use of Ca2+ can also be considered.

Bronchospasm can usually be reversed by bronchodilators.

Shelf life

4 years.

Betaloc price

Average cost of Betaloc 100 mg per unit in online pharmacies is from 0.78$ to 1.12$, per pack from 58$ to 88$.

Incompatibilities

Not applicable.

List of excipients

Sodium chloride and water for injections.

Undesirable effects

The following events have been reported as adverse events in clinical trials or reported from routine use.

The following definitions of frequencies are used:

Very common (>1/10), common (>1/100 to <1/10), uncommon ((>1/1,000 to <1/100), rare ((>1/10,000 to <1/1,000) and very rare (<1/10,000).

System Organ Class	Frequency	Undesirable Effect
Infections and infestations	Very rare	Gangrene in patients with pre existing severe peripheral circulatory disorders
Blood and lymphatic system disorders	Very rare	Thrombocytopenia
Psychiatric disorders	Uncommon	Depression, insomnia, nightmares
	Rare	Nervousness, anxiety
	Very rare	Confusion, hallucinations
Nervous system disorders	Common	Dizziness, headache
	Uncommon	Concentration impairment, somnolence, paraesthesiae
	Very rare	Amnesia/memory impairment, taste disturbances
Eye disorders	Rare	Disturbances of vision, dry and/or irritated eyes, conjunctivitis
Ear and labyrinth disorders	Very rare	Tinnitus
Cardiac disorders	Common	Bradycardia, palpitations
	Uncommon	Deterioration of heart failure symptoms, cardiogenic shock in patients with acute myocardial infarction*, first degree heart block
	Rare	Disturbances of cardiac conduction, cardiac arrhythmias, increased existing AV block
Vascular disorders	Common	Postural disorders (very rarely with syncope)
	Rare	Raynauds phenomenon
	Very rare	Increase of pre-existing intermittent claudication
Respiratory, thoracic and mediastinal disorders	Common	Dyspnoea on exertion
	Uncommon	Bronchospasm
	Rare	Rhinitis
Gastrointestinal disorders	Common	Nausea, abdominal pain, diarrhoea, constipation
	Uncommon	Vomiting
	Rare	Dry mouth
Hepatobiliary disorders	Very rare	Hepatitis
Skin and subcutaneous tissue disorders	Uncommon	Rash (in the form of psoriasiform urticaria and dystrophic skin lesions), increased sweating
	Rare	Loss of hair
	Very rare	Photosensitivity reactions, aggravated psoriasis
Musculoskeletal and connective tissue disorders	Very rare	Arthralgia
	Uncommon	Muscle cramps
Reproductive system and breast disorders	Rare	Impotence/sexual dysfunction
General disorders and administration site disorders	Very common	Fatigue
	Common	Cold hands and feet
	Uncommon	Precordial pain, oedema
Investigations	Uncommon	Weight gain
	Rare	Liver function test abnormalities, positive anti-nuclear antibodies (not associated with SLE).

* Excess frequency of 0.4 % compared with placebo in a study of 46,000 patients with acute myocardial infarction where the frequency of cardiogenic shock was 2.3 % in the metoprolol group and 1.9 % in the placebo group in the subset of patients with low shock risk index. The corresponding excess frequency for patients in Killip class I was 0.7% (metoprolol 3.5% and placebo 2.8%). The shock risk index was based on the absolute risk of shock in each individual patient derived from age, sex, time delay, Killip class, blood pressure, heart rate, ECG abnormality, and prior history of hypertension. The patient group with low shock risk index corresponds to the patients in which metoprolol is indicated for use in acute myocardial infarction.

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. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme.

Website: www.mhra.gov.uk/yellowcard.

Preclinical safety data

Pre-clinical information has not been included because the safety profile of metoprolol tartrate has been established after many years of clinical use. Please refer to section 4.

Pharmacotherapeutic group

Beta blocking agents, selective

Pharmacodynamic properties

Pharmacotherapeutic group: Beta blocking agents, selective

ATC code: C07AB02

Mechanism of action

Metoprolol is a competitive beta-adrenoceptor antagonist. It acts preferentially to inhibit beta-adrenoceptors (conferring some cardioselectivity), is devoid of intrinsic sympathomimetic activity (partial agonist activity) and possesses beta-adrenoceptor blocking activity comparable in potency with propranolol.

Pharmacodynamic effects

A negative chronotrophic effect on the heart is a consistent feature of metoprolol administration. Thus, cardiac output and systolic blood pressure rapidly decrease following acute administration.

Clinical efficacy and safety

The intention to treat trial COMMIT included 45,852 patients admitted to hospital within 24 hours of the onset of symptoms of suspected acute myocardial infarction with supporting ECG abnormalities (i.e. ST elevation, ST depression or left bundle-branch block). Patients were randomly allocated to metoprolol (up to 15 mg intravenous then 200 mg oral) or placebo and treated until discharge or up to 4 weeks in hospital. The two co-primary outcomes were: (1) composite of death, reinfarction or cardiac arrest; and (2) death from any cause during the scheduled treatment period. Neither of the co-primary outcomes was significantly reduced by metoprolol. However, metoprolol treatment was associated with fewer people having reinfarction and ventricular fibrillation but an increased rate of cardiogenic shock during the first day after admission. There was substantial net hazard in haemodynamically unstable patients. There was moderate net benefit in those who were stable, particularly after days 0-1.

Pharmacokinetic properties

Biotransformation

Metoprolol undergoes oxidative metabolism in the liver primarily by the CYP2D6 isoenzyme.

Elimination

Metoprolol is eliminated mainly by hepatic metabolism, the average elimination half-life is 3.5 hours (range 1-9 hours). Rates of metabolism vary between individuals, with poor metabolisers (approximately 10%) showing higher plasma concentrations and slower elimination than extensive metabolisers. Within individuals, however, plasma concentrations are stable and reproducible.

Date of revision of the text

30th December 2016

Marketing authorisation holder

AstraZeneca UK Ltd.,

600 Capability Green,

Luton, LU1 3LU, UK.

Special precautions for storage

Protect from light. Store below 25°C.

Nature and contents of container

5 ml glass ampoule.

Marketing authorisation number(s)

PL 17901/0106

Special precautions for disposal and other handling

No special requirements.

Date of first authorisation/renewal of the authorisation

Date of first authorisation: 28th May 2002

Date of renewal of authorisation: 16th July 2005