Drug Interactions between benzgalantamine and Evotaz

Consumer information for this interaction is not currently available.

MONITOR: Since acetylcholinesterase inhibitors can cause bradycardia and heart block due to vagotonic effects on the sinoatrial and atrioventricular nodes, additive effects may occur with other agents that also possess bradycardic effects such as beta-blockers, calcium channel blockers, digitalis, some protease inhibitors (atazanavir, lopinavir-ritonavir, saquinavir), amiodarone, dronedarone, moricizine, lacosamide, and mefloquine. A group of French investigators conducted a retrospective analysis of spontaneous reports in the French Pharmacovigilance Database concerning adverse drug reactions (ADRs) associated with use of the acetylcholinesterase inhibitors donepezil, galantamine, and rivastigmine. Two hundred and five cases of potential drug-drug interaction with bradycardic drugs (beta-blockers, calcium channel blockers, amiodarone, digoxin) were identified, 73 of which were associated with serious ADRs including five deaths due to syncope, bradycardia, arrhythmia, or cardiac arrest. However, no details on the individual cases such as patient characteristics or concomitant risk factors were provided, making the contribution of a potential drug interaction difficult to evaluate. The remainder of the cases were of no apparent clinical consequences. In contrast, a phase III trial of donepezil consisting of 1035 patients reported no significant increase in risk ratios for bradycardia during concomitant use of beta-blockers, nondihydropyridine calcium channel blockers, or digoxin.

MANAGEMENT: Caution is advised if acetylcholinesterase inhibitors are used concomitantly with bradycardic drugs. Patients with underlying structural heart disease, preexisting conduction system abnormalities, ischemic heart disease, or cardiomyopathies may be at increased risk for developing cardiac conduction disturbances and atrioventricular block. Patients should be advised to notify their physician if they experience dizziness, lightheadedness, fainting, or irregular heartbeat.

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with potent inhibitors of CYP450 2D6 and/or 3A4 may increase the plasma concentrations of galantamine, which is also an active metabolite of benzgalantamine. Up to 75% of galantamine is eliminated via metabolism and in vitro studies have identified CYP450 2D6 and 3A4 as the major isoenzymes involved. The systemic exposure (AUC) of galantamine (4 mg, 8 mg, or 12 mg twice daily) increased by 40%, 45%, and 48%, respectively, when administered to healthy volunteers (n=16) also receiving the strong CYP450 2D6 inhibitor paroxetine. Similarly, the strong CYP450 3A4 inhibitor ketoconazole (200 mg twice daily) increased the AUC of galantamine (4 mg twice daily) by 30% when given concurrently to study subjects (n=16). An increase in the AUC of galantamine can increase the risk of acetylcholinesterase inhibitor-related adverse effects. One potential side effect of galantamine is bradycardia, which may increase the risk of QT prolongation. If the inhibitor being coadministered is also associated with QT prolongation (e.g., adagrasib, ceritinib, fluoxetine, ketoconazole, levoketoconazole, mifepristone), the risk of experiencing this adverse effect may be further increased.

MANAGEMENT: Caution and closer monitoring of the pharmacologic response to galantamine and its prodrug benzgalantamine is advised whenever a potent CYP450 2D6 and/or 3A4 inhibitor is added to or withdrawn from therapy. Some authorities suggest considering a reduction in the galantamine dose for patients on concurrent potent CYP450 2D6 and/or 3A4 inhibitors. Patients should be monitored more closely for acetylcholinesterase inhibitor related adverse effects including vagotonic effects on the heart rate (e.g., bradycardia, which may increase the risk of QT prolongation, and heart block), neurologic side effects (e.g., seizure activity), respiratory distress, bladder outflow obstruction, dizziness or syncope, nausea, vomiting and diarrhea. These effects may be more severe when the coadministered inhibitor shares a similar adverse effect profile with galantamine.