Chemical formula: C₁₅H₂₅NO₃ Molecular mass: 267.364 g/mol PubChem compound: 4171
Metoprolol interacts in the following cases:
Care should also be taken when beta-blockers are given in combination with sympathetic ganglion blocking agents, other beta blockers or MAO inhibitors.
Metoprolol will antagonise the beta1-effects of sympathomimetic agents but should have little influence on the bronchodilator effects of beta2-agonists at normal therapeutic doses.
Concomitant use of metoprolol with corticosteroids may result in antagonism of the hypotensive effect.
Metoprolol is a metabolic substrate for the Cytochrome P450 isoenzyme CYP2D6. Drugs that act as enzyme-inducing and enzyme-inhibiting substances may exert an influence on the plasma level of metoprolol. Enzyme inducing agents (e.g. rifampicin) may reduce plasma concentrations of metoprolol.
Concomitant administration of metoprolol with tricyclic antidepressants, barbiturates and phenothiazines as well as other antihypertensive agents may increase the blood pressure lowering effect.
During concomitant ingestion of alcohol and metoprolol the concentration of blood alcohol may reach higher levels and may decrease more slowly. The concomitant ingestion of alcohol may enhance hypotensive effects.
It may be necessary to adjust the dose of the hypoglycaemic agent in labile or insulin-dependent diabetes. Beta-adrenergic blockade may prevent the appearance of signs of hypo-glycaemia (tachycardia).
Digitalis glycosides in association with beta-blockers may increase in auriculo-ventricular conduction time.
Calcium channel blockers (such as dihydropyridine derivatives e.g. nifedipine) should not be given in combination with metoprolol because of the increased risk of hypotension and heart failure. In patients with latent cardiac insufficiency, treatment with beta-blocking agents may lead to cardiac failure.
Concurrent use of oestrogens may decrease the antihypertensive effect of beta-blockers because oestrogeninduced fluid retention may lead to increased blood pressure.
Anaesthetic drugs may attenuate reflex tachycardia and increase the risk of hypotension. Metoprolol therapy should be reported to the anaesthetist before the administration of a general anaesthetic. If possible, withdrawal of metoprolol should be completed at least 48 hours before anaesthesia. However, for some patients undergoing elective surgery, it may be desirable to employ a beta-blocker as premedication. By shielding the heart against the effect of stress, metoprolol may prevent excessive sympathetic stimulation which is liable to provoke such cardiac disturbance as arrhythmias or acute coronary insufficiency during induction and intubation. Anaesthetic agents causing myocardial depression, such as cyclopropane and trichlorethylene, are best avoided. In a patient under beta-blockade an anaesthetic with as little negative inotropic activity as possible (halothane/nitrous oxide) should be selected.
Concomitant use of metoprolol with anxiolytics and hypnotics may result in an enhanced hypotensive effect.
Metoprolol is a metabolic substrate for the Cytochrome P450 isoenzyme CYP2D6. Drugs that act as enzyme-inducing and enzyme-inhibiting substances may exert an influence on the plasma level of metoprolol. Enzyme inhibitors (e.g. cimetidine, alcohol and hydralazine) may increase plasma concentrations of metoprolol.
Prostaglandin synthetase inhibiting drugs may decrease the hypotensive effects of beta-blockers.
Concurrent use of metoprolol with aldesleukin may result in an enhanced hypotensive effect.
Concurrent use of metoprolol with alprostadil may result in an enhanced hypotensive effect.
Concurrent use of metoprolol with xanthines, especially aminophylline or theophylline, may result in mutual inhibition of therapeutic effects. Xanthine clearance may also be decreased especially in patients with increased theophylline clearance induced by smoking.
Enzyme inhibitors (e.g. cimetidine, hydralazine and alcohol), selective serotonin reuptake inhibitors (SSRIs) as paroxetine, fluoxetine and sertraline, diphenhydramine, hydroxychloroquine, celecoxib, terbinafine may increase plasma concentrations of hepatically metabolized beta blockers.
Beta-blockers used in conjunction with clonidine increase the risk of “rebound hypertension”. If combination treatment with clonidine is to be discontinued, metoprolol should be withdrawn several days before clonidine.
Class I antiarrhythmic drugs, e.g. disopyramide, quinidine and amiodarone may have potentiating effects on atrial conduction time and induce negative inotropic effect.
The administration of adrenaline (epinephrine) or noradrenaline (norepinephrine) to patients undergoing beta-blockade can result in an increase in blood pressure and bradycardia, although this is less likely to occur with beta1-selective drugs.
The effect of adrenaline (epinephrine) in the treatment of anaphylactic reactions may be weakened in patients receiving beta blockers.
As beta-blockers may affect the peripheral circulation, care should be exercised when drugs with similar activity e.g. ergotamine are given concurrently.
NSAIDs (especially indometacin) may reduce the antihypertensive effects of beta-blockers possibly by inhibiting renal prostaglandin synthesis and/or causing sodium and fluid retention.
Metoprolol may impair the elimination of lidocaine.
There is an increased risk of bradycardia following concomitant use of mefloquine with metoprolol.
Concurrent use of metoprolol with moxisylyte may result in possible severe postural hypotension.
As with all beta-blockers particular caution is called for when metoprolol is administered together with prazosin for the first time as the co-administration of metoprolol and prazosin may produce a first dose hypotensive effect.
Concurrent use of propafenone may result in significant increases in plasma concentrations and halflife of metoprolol. Plasma propafenone concentrations are unaffected. Dosage reduction of metoprolol may be necessary.
Enzyme inducing agents (e.g. rifampicin) may reduce plasma concentrations of metoprolol.
In the presence of liver cirrhosis, the bioavailability of metoprolol may be increased, and dosage should be adjusted accordingly.
Metoprolol, due to the negative effect on conduction time, should only be given with caution to patients with first-degree heart block.
Patients with anamnestically known psoriasis should take beta-blockers only after careful consideration as the medicine may cause aggravation of psoriasis.
Beta blockers may unmask myasthenia gravis.
It is recommended that metoprolol should not be administered during pregnancy or lactation unless it is considered that the benefit outweighs the possible risk to the foetus/infant. Should therapy with metoprolol be employed, special attention should be paid to the foetus, neonate and breast fed infant for any undesirable effects such as slowing of the heart rate.
Metoprolol has, however, been used in pregnancy associated hypertension under close supervision after 20 weeks gestation. Although the drug crosses the placental barrier and is present in cord blood no evidence of foetal abnormalities has been reported. However, there is an increased risk of cardiac and pulmonary complications in the neonate in the postnatal period.
Beta blockers reduce placental perfusion and may cause foetal death and premature birth. Intrauterine growth retardation has been observed after longtime treatment of pregnant women with mild to moderate hypertension. Beta blockers have been reported to cause bradycardia in the foetus and the newborn child, there are also reports of hypoglycaemia and hypotension in newborn children.
Animal experiments have shown neither teratogenic potential nor other adverse events on the embryo and/or foetus relevant to the safety assessment of the product. Treatment with metoprolol should be discontinued 48-72 hours before the calculated birth date. If this is not possible, the newborn child should be monitored for 24-48 hours post partum for signs and symptoms of beta blockade (e.g. cardiac and pulmonary complications).
The concentration of metoprolol in breast milk is approximately three times higher than the one in the mother’s plasma. The risk of adverse effects in the breastfeeding baby would appear to be low after administration of therapeutic doses of the medicinal product (except in individuals with poor metabolic capacity). Cases of neonatal hypoglycaemia and bradycardia have been described with beta-blockers with low plasma protein binding. Metoprolol is excreted in human milk. Even though the metoprolol concentration in milk is very low, breast-feeding should be discontinued during treatment with metoprolol. In case of treatment during breast feeding, infants should be monitored carefully for symptoms of beta blockade.
As with all beta-blockers, metoprolol can affect patient’s ability to drive and operate machinery. It should be taken into account that occasionally dizziness and fatigue may occur. Patient should be warned accordingly. If affected, patients should not drive or operate machinery.
Frequency estimates: 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); very rare (<1/10,000); not known (cannot be estimated from the available data).
Very rare: Thrombocytopenia, agranulocytosis
Rare: Depression, nightmares, Nervousness, anxiety, impotence
Very rare: Hallucinations, personality disorder, Amnesia/memory impairment
Common: Dizziness, headache
Rare: Alertness decreased, somnolence or insomnia, paraesthesia
Very rare: Visual disturbance (e.g. blurred vision, dry eyes and/or eye irritation)
Very rare: Tinnitus, and, in doses exceeding those recommended, "hearing disorders (e.g. hypoacusis or deafness)
Common: Bradycardia
Rare: Heart failure, cardiac arrhythmias, palpitation
Very rare: Cardiac conduction disorders, precordial pain
Not known: Increase in existing intermittent claudication
Common: Orthostatic hypotension (occasionally with syncope)
Rare: Oedema, Raynaud’s phenomenon
Very rare: Gangrene in patients with pre existing severe peripheral circulatory disorders
Common: Exertional dyspnoea
Rare: Bronchospasm (which may occur in patients without a history of obstructive lung disease)
Very rare: Rhinitis
Common: Nausea and vomiting, abdominal pain
Rare: Diarrhoea or constipation
Very rare: Dry mouth
Not known: Retroperitoneal fibrosis*
Not known: Hepatitis
Rare: Skin rash (in the form of urticaria, psoriasiform and dystrophic skin lesions)
Very rare: Photosensitivity, hyperhidrosis, alopecia, worsening of psoriasis
Not known: Occurrence of antinuclear antibodies (not associated with SLE)
Rare: Muscle cramps
Very rare: Arthritis
Very rare: Disturbances of Libido and potency
Not known: Peyronie’s disease*
Common: Fatigue
Very rare: Dysgeusia (Taste disturbances)
Very rare: Weight increase, liver function test abnormal
* (relationship to Metoprolol has not been definitely established).
Beta-blockers may mask the symptoms of thyrotoxicosis or hypoglycaemia.
The following adverse reactions have been reported during post-approval use of metoprolol: confusional state, an increase in blood triglycerides and a decrease in high density lipoprotein (HDL). Because these reports are from a population of uncertain size and are subject to confounding factors, it is not possible to reliably estimate their frequency.
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).
Very rare: Gangrene in patients with pre existing severe peripheral circulatory disorders
Very rare: Thrombocytopenia
Uncommon: Depression, insomnia, nightmares
Rare: Nervousness, anxiety
Very rare: Confusion, hallucinations
Common: Dizziness, headache
Uncommon: Concentration impairment, somnolence, paraesthesiae
Very rare: Amnesia/memory impairment, taste disturbances
Rare: Disturbances of vision, dry and/or irritated eyes, conjunctivitis
Very rare: Tinnitus
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
Common: Postural disorders (very rarely with syncope)
Rare: Raynauds phenomenon
Very rare: Increase of pre-existing intermittent claudication
Common: Dyspnoea on exertion
Uncommon: Bronchospasm
Rare: Rhinitis
Common: Nausea, abdominal pain, diarrhoea, constipation
Uncommon: Vomiting
Rare: Dry mouth
Very rare: Hepatitis
Uncommon: Rash (in the form of psoriasiform urticaria and dystrophic skin lesions), increased sweating
Rare: Loss of hair
Very rare: Photosensitivity reactions, aggravated psoriasis
Very rare: Arthralgia
Uncommon: Muscle cramps
Rare: Impotence/sexual dysfunction
Very common: Fatigue
Common: Cold hands and feet
Uncommon: Precordial pain, oedema
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.
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