Rivastigmine (DB00989): A Comprehensive Monograph on its Pharmacology, Clinical Utility, and Evolving Therapeutic Landscape

Section 1: Executive Summary

Rivastigmine is a carbamate-class cholinesterase inhibitor used for the symptomatic management of dementia. It is distinguished by its unique mechanism of action, functioning as a "pseudo-irreversible" inhibitor of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE).[1] This dual inhibition is postulated to provide a more comprehensive and sustained enhancement of cholinergic neurotransmission compared to AChE-selective agents, which may be particularly relevant as Alzheimer's disease (AD) progresses and BuChE activity becomes more prominent in acetylcholine metabolism.[4]

The primary therapeutic roles for Rivastigmine are in the treatment of mild-to-moderate dementia associated with both Alzheimer's disease and Parkinson's disease (PDD), with a higher-strength formulation also approved for severe AD.[1] Its clinical development has been critically shaped by formulation science. The initial oral formulations (capsules and solution) were associated with a high incidence of dose-limiting gastrointestinal adverse effects, such as nausea and vomiting, driven by a rapid absorption profile and high peak plasma concentrations.[5] The development of the transdermal patch was a pivotal innovation, providing continuous drug delivery that smooths the pharmacokinetic profile, lowers peak concentrations, and thereby dramatically improves the drug's tolerability.[1] This advancement allows more patients to achieve and maintain clinically effective doses, demonstrating a clear case of pharmaceutical engineering solving a clinical problem.