Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction
Propranolol modifies the tachycardia of hypoglycaemia. Caution must be exercised in the concurrent use of propranolol and hypoglycaemic therapy in diabetic patients.
Propranolol may prolong the hypoglycaemic response to insulin (see sections 4.3 and 4.4).
Simultaneous administration of rizatriptan and propranolol can cause an increased rizatriptan AUC and Cmax by approximately 70-80%. The increased rizatriptan exposure is presumed to be caused by inhibition of first-passage metabolism of rizatriptan through inhibition of monoamine oxidase-A. If both drugs are to be used, a rizatriptan dose of 5 mg has been recommended.
Class I anti-arrhythmic drugs (e.g. disopyramide) and amiodarone may have potentiating effect on atrial-conduction time and induce negative inotropic effect.
Digitalis glycosides in association with beta-blockers may increase atrioventricular conduction time.
Combined use of beta-blockers and calcium channel blockers with negative inotropic effects (e.g. verapamil, diltiazem) can lead to an exaggeration of these effects particularly in patients with impaired ventricular function and/or SA or AV conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac failure.
Neither the beta-blocker nor the calcium channel blocker should be administered intravenously within 48 hours of discontinuing the other.
Concomitant therapy with dihydropyridine calcium channel blockers, e.g. nifedipine, may increase the risk of hypotension, and cardiac failure may occur in patients with latent cardiac insufficiency.
Concomitant use of sympathomimetic agents e.g. adrenaline, may counteract the effect of beta-blockers. Caution must be exercised in the parenteral administration of preparations containing adrenaline to patients taking beta-blockers as, in rare cases, vasoconstriction, hypertension and bradycardia may result.
Administration of propranolol during infusion of lidocaine may increase the plasma concentration of lidocaine by approximately 30%. Patients already receiving propranolol tend to have higher lidocaine levels than controls. The combination should be avoided.
Concomitant use of cimetidine or hydralazine will increase plasma levels of propranolol, and concomitant use of alcohol may increase the plasma levels of propranolol.
Beta-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are co-administered, the beta-blocker should be withdrawn several days before discontinuing clonidine. If replacing clonidine with beta- blocker therapy, the introduction of beta-blockers should be delayed for several days after clonidine administration has stopped.
Caution must be exercised if ergotamine, dihydroergotamine or related compounds are given in combination with propranolol, since vasospastic reactions have been reported in a few patients.
Concomitant use of prostaglandin synthetase inhibiting drugs e.g., ibuprofen and indometacin, may decrease the hypotensive effects of propranolol.
Concomitant administration of propranolol and chlorpromazine may result in an increase in plasma levels of both drugs. This may lead to an enhanced antipsychotic effect for chlorpromazine and an increased antihypertensive effect for propranolol.
Caution must be exercised when using anaesthetic agents with propranolol. The anaesthetist should be informed and the choice of anaesthetic should be an agent with as little negative inotropic activity as possible. Use of beta-blockers with anaesthetic drugs may result in attenuation of the reflex tachycardia and increase the risk of hypotension. Anaesthetic agents causing myocardial depression are best avoided.
Pharmacokinetic studies have shown that the following agents may interact with propranolol due to effects on enzyme systems in the liver which metabolise propranolol and these agents: quinidine, propafenone, rifampicin, theophylline, warfarin, thioridazine and dihydropyridine calcium channel blockers such as nifedipine, nisoldipine, nicardipine, isradipine, and lacidipine. Owing to the fact that blood concentrations of either agent may be affected, dosage adjustments may be needed according to clinical judgement (see also the interaction above concerning the concomitant therapy with dihydropyridine calcium channel blockers).