Concor AM Drug Interactions

In connection with amlodipine: Effects of other medicinal products on amlodipine: CYP3A4 inhibitors: Concomitant use of amlodipine with strong or moderate inhibitors of CYP3A4 (e.g. protease inhibitors like indinavir, saquinavir and ritonavir, azole antifungals such as fluconazole and itraconazole, macrolides like erythromycin or clarithromycin, verapamil or diltiazem) may give rise to significant increase in amlodipine exposure resulting in an increased risk of hypotension. The clinical translation of these PK variations may be more pronounced in the elderly. Clinical monitoring and dose adjustment may thus be required.
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). Administration of amlodipine with grapefruit or grapefruit juice is not recommended as bioavailability may be increased in some patients resulting in increased blood pressure lowering effects.
Dantrolene (infusion): In animals, lethal ventricular fibrillation and cardiovascular collapse are observed in association with hyperkalemia after administration of verapamil and intravenous dantrolene. Due to risk of hyperkalemia, it is recommended that the co-administration of calcium channel blockers such as amlodipine be avoided in patients susceptible to malignant hyperthermia and in the management of malignant hyperthermia.
Effects of amlodipine on other medicinal products: The blood pressure lowering effects of amlodipine adds to the blood pressure-lowering effects of other medicinal products with antihypertensive properties.
Tacrolimus: 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.
Cyclosporine: 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.
Simvastatin: Co-administration of multiple doses of 10 mg of amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily.
In clinical interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin, or warfarin.
In connection with bisoprolol: Combinations not recommended: Calcium antagonists of verapamil type and to a lesser extent of diltiazem type: 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, moxonodine, rilmenidine: Concomitant use of centrally acting antihypertensive drugs may lead to reduction of heartrate and cardiac output and vasodilation. Abrupt withdrawal of the drug may increase the risk of "rebound hypertension".
Combinations to be used with special caution: Calcium antagonists of the dihydropyridine type such as nifedipine: Concomitant use may increase the risk of hypotension, and an increase in the risk of a further deterioration of the ventricular pump function in patients with heart failure cannot be excluded.
Class I antiarrhythmic drugs (e.g. disopyramide, quinidine, lidocaine, phenytoin, flecainide, propafenone): Effect on atrio-ventricular conduction time and negative inotropic effect may be potentiated.
Class III antiarrhythmic drugs (e.g. amiodarone): Effect on atrio-ventricular conduction time may be potentiated.
Parasympathomimetic drugs: Concomitant use 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 add to the systemic effects of bisoprolol.
Insulin and oral antidiabetic drugs: Intensification of blood sugar lowering effect. Blockade of beta-adrenoceptors may mask symptoms of hypoglycaemia.
Anaesthetic agents: Attenuation of the reflex tachycardia and increase of the risk of hypotension (for further information on general anesthesia see Precautions).
Digitalis glycosides: Reduction of heart rate, increase of atrio-ventricular conduction time.
Non-steroidal anti-inflammatory drugs (NSAIDs): NSAIDs may reduce the hypotensive effect of bisoprolol.
Beta-sympathomimetic agents (e.g. isoprenaline, dobutamine): 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.
Concomitant use with antihypertensive agents as well as with other drugs with blood pressure lowering potential (e.g. tricyclic antidepressants, barbiturates, phenothiazines) may increase the risk of hypotension.
Combinations to be considered: Mefloquine: increased risk of bradycardia.
Monoamine oxidase inhibitors (except MAO-B inhibitors): Enhanced hypotensive effect of the beta-blockers but also risk for hypertensive crisis.