Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction
• 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 betablockade an anaesthetic with as little negative inotropic activity as possible (halothane/nitrous oxide) should be selected.

•   It may be necessary to adjust the dose of the hypoglycaemic agent in labile or insulin-dependent diabetes. Betaadrenergic blockade may prevent the appearance of signs of hypoglycaemia (tachycardia).

•   Digitalis glycosides and/or diuretics should be considered for patients with a previous history of heart failure or in patients known to have a poor cardiac reserve. Digitalis glycosides in association with beta-blockers may increase auriculo-ventricular conduction time.
•   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.

•   Like all beta-blockers, metoprolol should not be given in combination with calcium channel blockers i.e. verapamil and to a lesser extent diltiazem since this may cause bradycardia, hypotension, heart failure and asystole and may increase auriculo- ventricular conduction time. However, combinations of antihypertensive drugs may often be used with benefit to improve control of hypertension. Calcium blockers of the verapamil type should not be administered intravenously to patients receiving beta blockers (see section 4.3).

•   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. Beta-blockers used in conjunction with clonidine increase the risk of re ou d hyperte sio . If combination treatment with clonidine is to be discontinued, metoprolol should be withdrawn several days before clonidine.

•   The effects of metoprolol and other antihypertensive drugs on blood pressure are usually additive, and care should be taken to avoid hypotension.

•   NSAIDs (especially indometacin) may reduce the antihypertensive effects of beta- blockers possibly by inhibiting renal prostaglandin synthesis and/or causing sodium and fluid retention.

•   Care should also be taken when beta-blockers are given in combination with sympathetic ganglion blocking agents, other beta-blockers (ie eye drops) or MAO inhibitors. Concomitant administration of tricyclic antidepressants, barbiturates and phenothiazines as well as other antihypertensive agents may increase the blood pressure lowering effect.

•   Class 1 anti-arrhythmic drugs, e.g. disopyramide, quinidine and amiodarone may have potentiating effects on atrialconduction time and induce negative inotropic effect. Concurrent use of propafenone may result in significant increases in plasma concentrations and half-life of metoprolol. Plasma propafenone concentrations are unaffected. Dosage reduction of metoprolol may be necessary.

•   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.

•   The administration of adrenaline (epinephrine) or noradrenaline (norepinephrine) to patients undergoing betablockade can result in an increase in blood pressure and bradycardia, although this is less likely to occur with beta1-selective drugs. As beta- blockers may affect the peripheral circulation, care should be exercised when drugs with similar activity eg ergotamine are given concurrently. Concurrent use of moxisylyte may result in possible severe postural hypotension.
•   The effect of adrenaline (epinephrine) in the treatment of anaphylactic reactions may be weakened in patients receiving beta blockers (see also section 4.4).

•   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.

•   Enzyme inducing agents (eg rifampicin) may reduce plasma concentrations of metoprolol, whereas enzyme inhibitors (eg cimetidine, hydralazine and alcohol), selective serotonin reuptake inhibitors (SSRIs) as paroxetine, fluoxetine and sertraline, diphenhydramine, hydroxychloroquine, celecoxib, terbinafine may increase plasma concentrations of hepatically metabolised beta-blockers.

•   Metoprolol may impair the elimination of lidocaine.

•   Prostaglandin synthetase inhibiting drugs may decrease the hypotensive effects of beta-blockers.

•   Cocaine may inhibit the therapeutic effects of beta-blockers and increase the risk of hypertension, excessive bradycardia, and possibly heart block.

•   Concurrent use of oestrogens may decrease the antihypertensive effect of beta- blockers because oestrogeninduced fluid retention may lead to increased blood pressure.

•   Concurrent use of 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.
Concurrent use requires careful monitoring.

•   Concurrent use of aldesleukin may result in an enhanced hypotensive effect.

•   Concurrent use of alprostadil may result in an enhanced hypotensive effect.

•   There is an increased risk of bradycardia following concomitant use of mefloquine with metoprolol.

•   Concomitant use with anxiolytics and hypnotics may result in an enhanced hypotensive effect.

•   Concomitant use with corticosteroids may result in antagonism of the hypotensive effect.

•   The manufacturer of tropisetron advises caution in concomitant administration due to the risk of ventricular arrhythmias.