indication

For the treatment of mild to moderate dementia associated with Parkinson's disease or of the Alzheimer's type.

pharmacology

Rivastigmine is a parasympathomimetic and a reversible cholinesterase inhibitor. An early pathophysiological feature of Alzheimer's disease that is associated with memory loss and cognitive deficits is a deficiency of acetylcholine as a result of selective loss of cholinergic neurons in the cerebral cortex, nucleus basalis, and hippocampus. Tacrine is postulated to exert its therapeutic effect by enhancing cholinergic function. 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 progresses and fewer cholinergic neurons remain functionally intact.

mechanism of action

Rivastigmine is a carbamate derivative that is structurally related to physostigmine, but not to donepezil and tacrine. The precise mechanism of rivastigmine has not been fully determined, but it is suggested that rivastigmine binds reversibly with and inactivates chlolinesterase (eg. acetylcholinesterase, butyrylcholinesterase), preventing the hydrolysis of acetycholine, and thus leading to an increased concentration of acetylcholine at cholinergic synapses. The anticholinesterase activity of rivastigmine is relatively specific for brain acetylcholinesterase and butyrylcholinesterase compared with those in peripheral tissues.

biotransformation

Rivastigmine is rapidly metabolized by cholinesterase-mediated hydrolysis.

half life

1.5 hours

route of elimination

Rivastigmine is extensively metabolized primarily via cholinesterase-mediated hydrolysis to the decarbamylated metabolite NAP226-90. Renal excretion of the metabolites is the major route of elimination. Less than 1% of the administered dose is excreted in the feces.

drug interactions

Amantadine: Possible antagonism of action

Amitriptyline: Possible antagonism of action

Amoxapine: Possible antagonism of action

Azatadine: Possible antagonism of action

Benzatropine: Possible antagonism of action

Biperiden: Possible antagonism of action

Brompheniramine: Possible antagonism of action

Chlorpheniramine: Possible antagonism of action

Chlorpromazine: Possible antagonism of action

Chlorprothixene: Possible antagonism of action

Cimetidine: Possible antagonism of action

Clemastine: Possible antagonism of action

Clomipramine: Possible antagonism of action

Clozapine: Possible antagonism of action

Cyclizine: Possible antagonism of action

Cyclobenzaprine: Possible antagonism of action

Cyproheptadine: Possible antagonism of action

Darifenacin: Possible antagonism of action

Desipramine: Possible antagonism of action

Dicyclomine: Possible antagonism of action

Dimenhydrinate: Possible antagonism of action

Diphenhydramine: Possible antagonism of action

Disopyramide: Possible antagonism of action

Doxepin: Possible antagonism of action

Flavoxate: Possible antagonism of action

Flupenthixol: Possible antagonism of action

Glutethimide: Possible antagonism of action

Glycopyrrolate: Possible antagonism of action

Hydroxyzine: Possible antagonism of action

Hyoscyamine: Possible antagonism of action

Imipramine: Possible antagonism of action

Isocarboxazid: Possible antagonism of action

Loxapine: Possible antagonism of action

Maprotiline: Possible antagonism of action

Meclizine: Possible antagonism of action

Meperidine: Possible antagonism of action

Mesoridazine: Possible antagonism of action

Methotrimeprazine: Possible antagonism of action

Mirtazapine: Possible antagonism of action

Moclobemide: Possible antagonism of action

Nortriptyline: Possible antagonism of action

Olanzapine: Possible antagonism of action

Orphenadrine: Possible antagonism of action

Oxybutynin: Possible antagonism of action

Perphenazine: Possible antagonism of action

Phenelzine: Possible antagonism of action

Pimozide: Possible antagonism of action

Procainamide: Possible antagonism of action

Prochlorperazine: Possible antagonism of action

Promethazine: Possible antagonism of action

Propericiazine: Possible antagonism of action

Quetiapine: Possible antagonism of action

Quinidine: Possible antagonism of action

Thioproperazine: Possible antagonism of action

Thioridazine: Possible antagonism of action

Tizanidine: Possible antagonism of action

Trazodone: Possible antagonism of action

Trifluoperazine: Possible antagonism of action

Trihexyphenidyl: Possible antagonism of action

Trimethobenzamide: The therapeutic effects of the anticholinergic, Trimethobenzamide, and/or the acetylcholinesterase inhibitor (central), Rivastigmine, may be reduced due to antagonism. Monitor therapeutic effects of both agents.

Trospium: The therapeutic effects of the anticholinergic, Trospium, and/or the acetylcholinesterase inhibitor (central), Rivastigmine, may be reduced due to antagonism. Monitor therapeutic effects of both agents.