Brands, Medical Use, Clinical Data
- Nootropic Agents
- Cholinergic Agents
Brands / Synonyms
Ena 713 Free Base; Exelon; Rivastigmine Hydrogen Tartrate; Rivastigmine [Usan:Inn]
For the treatment of mild to moderate Alzheimer's disease.
Rivastigmine is a parasympathomimetic and a reversible cholinesterase inhibitor. Rivastigmine is indicated for the treatment of mild to moderate dementia of the Alzheimer's type. Pathological changes in Dementia of the Alzheimer type involve cholinergic neuronal pathways that project from the basal forebrain to the cerebral cortex and hippocampus. These pathways are thought to be intricately involved in memory, attention, learning, and other cognitive processes. While the precise mechanism of rivastigmine's action is unknown, it is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by cholinesterase. If this proposed mechanism is correct, rivastigmine's effect may lessen as the disease process advances and fewer cholinergic neurons remain functionally intact.
Mechanism of Action
Rivastigmine increases the concentration of acetylcholine through reversible inhibition of its hydrolysis by cholinesterase. This acts to enhance cholinergic function.
Biotrnasformation / Drug Metabolism
Rivastigmine is rapidly metabolized by cholinesterase-mediated hydrolysis.
Exelon® (rivastigmine tartrate) is contraindicated in patients with known
hypersensitivity to rivastigmine, other carbamate derivatives or other components of the formulation.
Effect of Exelon® (rivastigmine tartrate) on the Metabolism of Other
Drugs: Rivastigmine is primarily metabolized through hydrolysis by esterases. Minimal metabolism occurs via
the major cytochrome P450 isoenzymes. Based on in vitro studies, no pharmacokinetic drug interactions with
drugs metabolized by the following isoenzyme systems are expected: CYP1A2, CYP2D6, CYP3A4/5, CYP2E1, CYP2C9, CYP2C8,
or CYP2C19. No pharmacokinetic interaction was observed between rivastigmine and digoxin, warfarin, diazepam, or
fluoxetine in studies in healthy volunteers. The elevation of prothrombin time induced by warfarin is not affected by
administration of Exelon.
Effect of Other Drugs on the Metabolism of Exelon: Drugs that induce or inhibit CYP450
metabolism are not expected to alter the metabolism of rivastigmine. Single dose pharmacokinetic studies demonstrated
that the metabolism of rivastigmine is not significantly affected by concurrent administration of digoxin, warfarin,
diazepam, or fluoxetine. Population PK analysis with a database of 625 patients showed that the pharmacokinetics of
rivastigmine were not influenced by commonly prescribed medications such as antacids (n=77), antihypertensives
(n=72), β-blockers (n=42), calcium channel blockers (n=75), antidiabetics (n=21),
nonsteroidal anti-inflammatory drugs (n=79), estrogens (n=70), salicylate analgesics (n=177), antianginals (n=35),
and antihistamines (n=15).
Use with Anticholinergics: Because of their mechanism of action, cholinesterase
inhibitors have the potential to interfere with the activity of anticholinergic medications.
Use with Cholinomimetics and Other Cholinesterase Inhibitors: A synergistic effect may
be expected when cholinesterase inhibitors are given concurrently with succinylcholine, similar neuromuscular
blocking agents or cholinergic agonists such as bethanechol.