rivastigmine
Brand: Exelon, Exelon Patch
Prototype: donepezil
Drug Class: cholinesterase inhibitor
Drug Family: antidementia
Subclass: carbamate acetylcholinesterase and butyrylcholinesterase inhibitor
Organ Systems: cns
Mechanism of Action
Inhibits both acetylcholinesterase and butyrylcholinesterase, increasing acetylcholine availability at cholinergic synapses. Inhibits AChE via pseudo-irreversible carbamylation (slowly reversible over hours), distinguishing it from competitive inhibitors. The transdermal formulation achieves more consistent plasma levels with fewer GI side effects than oral formulations.
acetylcholinesterase (AChE)butyrylcholinesterase (BuChE)
Indications
- Alzheimer's disease dementia (mild to severe)
- Parkinson's disease dementia (first FDA-approved treatment for this indication)
Contraindications
- hypersensitivity to rivastigmine or carbamate derivatives
Adverse Effects
Common
- nausea
- vomiting
- diarrhea
- anorexia
- weight loss
- dizziness (oral worse than patch)
- application site reactions (patch)
Serious
- severe vomiting with dehydration
- bradycardia and syncope
- gastric ulcer exacerbation
- convulsions (rare)
Pharmacokinetics (ADME)
| Absorption | oral: bioavailability ~36%; food delays and reduces peak concentration; transdermal: sustained steady-state levels |
| Distribution | protein binding ~40%; Vd ~1.8-2.7 L/kg; crosses BBB |
| Metabolism | hydrolysis by cholinesterases to inactive decarbamylated metabolite; minimal CYP involvement |
| Excretion | primarily renal (as metabolites) |
| Half-life | 1.5 hours (but AChE inhibition lasts 9-12 hours) |
| Onset | weeks to months for clinical effect |
| Peak | 1 hour (oral); sustained with transdermal |
| Duration | 12-24 hours per dose/patch |
| Protein Binding | 40% |
| Vd | 1.8-2.7 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| anticholinergics | pharmacodynamic antagonism; reduces cholinesterase inhibitor efficacy | moderate |
| beta-blockers | additive bradycardia | moderate |
| NSAIDs | increased GI side effects and ulcer risk | moderate |
Nursing Considerations
- GI side effects (nausea, vomiting, diarrhea) are the primary reason for discontinuation; administering oral doses with food and starting at the lowest dose with slow titration minimizes these effects.
- The transdermal patch (Exelon Patch) significantly reduces GI adverse effects versus oral formulation; instruct on proper application (rotate sites, do not cut patch, remove old patch before applying new).
- Patch dosing error: 4.6 mg/24h and 9.5 mg/24h are the therapeutic doses; the 13.3 mg/24h patch is for severe AD only — confirm the correct patch strength is prescribed and applied.
- Monitor for bradycardia in patients with sick sinus syndrome or conduction disturbances; rivastigmine's cholinergic effect on the SA node can slow heart rate.
Clinical Pearls
- Rivastigmine is the only cholinesterase inhibitor FDA-approved for Parkinson's disease dementia (PDD), where cholinergic deficit is particularly prominent; cognitive fluctuation and visual hallucinations may improve.
- The patch formulation of rivastigmine achieves lower but more consistent plasma levels than oral dosing, resulting in clinically meaningful reductions in nausea and vomiting — the transdermal route is now strongly preferred.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.