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.
4 years.
Not applicable.
Sodium chloride and water for injections.
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.
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
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.
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.
30th December 2016
AstraZeneca UK Ltd.,
600 Capability Green,
Luton, LU1 3LU, UK.
Protect from light. Store below 25°C.
5 ml glass ampoule.
PL 17901/0106
No special requirements.
Date of first authorisation: 28th May 2002
Date of renewal of authorisation: 16th July 2005
