Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction
The hypotensive effect of labetalol can be reduced when used in combination with inhibitors of prostaglandin synthesis (NSAIDs). Dosage adjustments may therefore be required. Further interactions may occur with other blood pressure lowering agents.

Labetalol fluoresces in alkaline solutions with an excitation wavelength of 334 nm and a fluorescence wavelength of 412 nm, and can therefore interact with the analysis of certain fluorescent substances including catecholamines.

The presence of labetalol metabolites in the urine may indicate falsely elevated levels of urinary catecholamines, metadrenaline, normetadrenaline and vanillylmandelic acid (VMA) when measured by fluorimetric or photometric methods. When patients with suspected pheochromocytoma who are treated with labetalol hydrochloride are screened, a specific method such as high-performance liquid chromatography with solid phase extraction should be used to determine catecholamine levels.

Labetalol has been shown to reduce the absorption of radioisotopes of metaiodobenzylguanidine (MIBG). Care should therefore be taken when interpreting the results of MIBG scintigraphy.

Concurrent administration of labetalol and adrenaline may result in bradycardia and hypertension (see section 4.4 Special warnings and precautions for use).

Caution should be observed if labetalol is used concurrently with class I antiarrhythmics or calcium antagonists of the verapamil type.

Increased risk of myocardial depression in combination with class I antiarrhythmics (e.g.
disopyramide and quinidine) and amiodarone (class II antiarrhythmic).

Risk of pronounced bradycardia and hypotension in combination with calcium antagonists with a negative inotropic effect (e.g. verapamil, diltiazem). Particularly for patients with impaired ventricular function and/or conduction disturbances. When making the transition from a calcium antagonist to a beta blocker (or vice versa), new intravenous therapy must not be initiated until at least 48 hours have elapsed from the discontinuation of the previous therapy.
Concurrent treatment with dihydropyridine-derived calcium antagonists (e.g. nifedipine) can increase the risk of hypotension and cause heart failure in patients with latent cardiac insufficiency. The atrioventricular conduction time may be prolonged by the concurrent use of digitalis glycosides and beta blockers. Labetalol can amplify the effect of digoxin in regards to the reduction of ventricular frequency.

Beta blockers, especially nonselective beta blockers, can increase the risk of hypoglycaemia in diabetic patients, mask the symptoms of hypoglycaemia (e.g. tachycardia and tremor) and delay the normalisation of blood sugar following insulin-induced hypoglycaemia. Dose adjustments of oral antidiabetics and insulin may be required.

Caution must be observed in connection with general anaesthesia in patients using beta blockers. Beta blockers reduce the risk of arrhythmias during anaesthesia but can cause a reduction in reflex tachycardia and increase the risk of hypotension during anaesthesia. The negative inotropic effect of the anaesthetic agent should be as small as possible. Cardiac function must be monitored closely; bradycardia due to vagal dominance should be corrected with the intravenous administration of 1- 2 mg atropine.

When beta blockers and clonidine are discontinued in patients taking both agents, a gradual withdrawal of the beta blocker must be made several days prior to the withdrawal of clonidine. The purpose of this measure is to reduce the potential recurring hypertensive crisis resulting from the withdrawal of clonidine. Thus, when changing from clonidine to a beta blocker it is important to gradually withdraw clonidine and initiate beta blocker therapy several days after the withdrawal of clonidine.

Concurrent use of acetylcholinesterase inhibitors may increase the risk of bradycardia.

Concurrent treatment with alpha adrenergic agonists (e.g. phenylpropanolamine and adrenaline) can increase the risk of elevated blood pressure, while concurrent treatment with beta adrenergic agonists results in a mutual reduction of effect (antidote effect).

Concurrent use of ergotamine derivatives can increase the risk of vasospastic reactions in some patients.

Labetalol has been shown to increase the bioavailability of imipramine by over 50 %, due to the inhibition of its 2-hydroxylation. Concurrent treatment with labetalol and imipramine can increase the effect of imipramine. Concurrent use of tricyclic antidepressants can increase the incidence of tremor.

Caution must be observed when prescribing oral labetalol as cimetidine can increase its bioavailability. Improved blood pressure lowering may be achieved with concurrent use of e.g.
nitrates, antipsychotics (phenothiazine derivatives such as chlorpromazine) and other antipsychotics and antidepressants.