Concore AM Drug Interactions

Combinations not recommended: Calcium antagonists of the verapamil type and to a lesser extent of the diltiazem type: In combination with bisoprolol, negative influence on contractility, atrio-ventricular conduction and blood pressure. Intravenous administration of verapamil in patients on β-blocker treatment may lead to profound hypotension and atrioventricular block.
Centrally acting antihypertensive drugs such as clonidine, methyldopa, moxonidine, rilmenidine: Concomitant use of centrally acting antihypertensive drugs with bisoprolol may lead to reduction of heart rate and cardiac output, as well as to vasodilation. Abrupt withdrawal, particularly if prior to beta-blocker discontinuation, may increase risk of "rebound hypertension".
Combinations to be used with caution: The metabolism of amlodipine takes place via the main pathway of CYP3A4 iso-enzymes of the cytochrome P450 system.
CYP3A4 inhibitors: Concomitant use of amlodipine with strong or moderate inhibitors of CYP3A4 (e.g. protease inhibitors, azole antifungals, macrolides like erythromycin or clarithromycin, verapamil or diltiazem) can be expected to increase the plasma concentrations of amlodipine to a clinically relevant extent.
CYP3A4 inducers: Upon co-administration of known inducers of the CYP3A4, the plasma concentration of amlodipine may vary. Therefore, blood pressure should be monitored and dose regulation considered both during and after concomitant medication particularly with strong CYP3A4 inducers (e.g. rifampicin, Hypericum perforatum).
Simvastatin: Combination with amlodipine may lead to an increase in simvastatin plasma level. Simvastatin doses of more than 20 mg daily are not recommended in patients treated with amlodipine.
Class-I antiarrhythmic drugs (e.g. quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): In combination with bisoprolol, the effect on atrio-ventricular conduction time and negative inotropic effect may be potentiated.
Class-III antiarrhythmic drugs (e.g. amiodarone): In combination with bisoprolol the effect on atrio-ventricular conduction time may be potentiated.
Parasympathomimetic drugs: Concomitant use with bisoprolol may increase atrio-ventricular conduction time and thus, the risk of bradycardia.
Topical beta-blocker containing preparations (e.g. eye drops for glaucoma treatment) may contribute to the systemic effects of bisoprolol.
Insulin and oral antidiabetic drugs: In combination with bisoprolol, intensification of blood sugar lowering effect may occur. Blockade of beta-adrenoceptors may mask symptoms of hypoglycemia.
Anesthetic agents: In combination with bisoprolol, the reflex tachycardia may be attenuated and the risk of hypotension may be increased.
Cardiac glycosides (digitalis): Concomitant use with bisoprolol may lead to a reduction of heart rate, or an increase of atrio-ventricular conduction time.
Non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the hypotensive effect of bisoprolol.
Beta-sympathomimetic agents (e.g. isoprenaline, dobutamine) used in combination with bisoprolol may reduce the effect of both agents.
Sympathomimetics that activate both beta- and alpha-adrenoceptors (e.g. norepinephrine, epinephrine): Combination with bisoprolol may unmask the alpha-adrenoceptor-mediated vasoconstrictor effects of these agents leading to blood pressure increase. Such interactions are considered to be more likely with nonselective beta-blockers.
Antihypertensive agents as well as other drugs with blood pressure lowering potential (e.g. tricyclic antidepressants, barbiturates, phenothiazines): Increased risk of hypotension.
There is a risk of increased tacrolimus blood levels when co-administered with amlodipine but the pharmacokinetic mechanism of this interaction is not fully understood. In order to avoid toxicity of tacrolimus, administration of amlodipine in a patient treated with tacrolimus requires monitoring of tacrolimus blood levels and dose adjustment of tacrolimus when appropriate.
No drug interaction studies have been conducted with cyclosporine and amlodipine in healthy volunteers or other populations with the exception of renal transplant patients, where variable trough concentration increases (average 0% - 40%) of cyclosporine were observed. Consideration should be given for monitoring cyclosporine levels in renal transplant patients on amlodipine, and cyclosporine dose reductions should be made as necessary.
Combinations to be considered: Mefloquine may increase the risk of decelerating the heart rate (bradycardia), if used in combination with bisoprolol.
Monoamine oxidase inhibitors (except MAO-B inhibitors): Enhanced hypotensive effect of the beta-blockers but also risk for hypertensive crisis.
Ergotamine derivatives: In combination with bisoprolol, exacerbation of peripheral circulatory disturbances.