galantamine
Brand: Razadyne, Razadyne ER
Prototype: donepezil
Drug Class: cholinesterase inhibitor / nicotinic receptor modulator
Drug Family: antidementia
Subclass: competitive, reversible AChE inhibitor with allosteric potentiation of nicotinic receptors
Organ Systems: cns
Mechanism of Action
Competitively and reversibly inhibits AChE, increasing acetylcholine. Additionally acts as an allosteric potentiating ligand (APL) at nicotinic ACh receptors, sensitizing them to acetylcholine — a dual mechanism that may provide additional neuroprotective and cognitive benefits beyond AChE inhibition alone.
acetylcholinesterase (AChE)nicotinic acetylcholine receptors (allosteric potentiation)
Indications
- mild to moderate Alzheimer's disease dementia
Contraindications
- severe hepatic or renal impairment
Adverse Effects
Common
- nausea
- vomiting
- diarrhea
- anorexia
- weight loss
Serious
- bradycardia and syncope
- gastric ulcer perforation (less than NSAIDs but possible)
- convulsions (rare)
Pharmacokinetics (ADME)
| Absorption | well absorbed orally; bioavailability ~88-100%; food delays absorption but not total extent |
| Distribution | protein binding ~18%; Vd ~175 L |
| Metabolism | CYP2D6 and CYP3A4; active metabolites of limited clinical significance |
| Excretion | renal (~32% unchanged) |
| Half-life | 7 hours |
| Onset | weeks for clinically meaningful effect |
| Peak | 1 hour (IR); 4.5-5 hours (ER) |
| Duration | 12-24 hours |
| Protein Binding | 18% |
| Vd | 175 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| anticholinergics | pharmacodynamic antagonism reduces efficacy | moderate |
| CYP2D6 inhibitors | increase galantamine levels; may require dose reduction | moderate |
| neuromuscular blockers | may prolong action of depolarizing NMBAs | moderate |
Nursing Considerations
- Administer with food to reduce GI side effects; for ER capsule, administer once daily in the morning with food.
- Dose titration is mandatory: start 4 mg twice daily for 4 weeks, then 8 mg twice daily for 4 weeks, then increase as tolerated; this titration schedule minimizes GI adverse effects.
- Maintain adequate hydration — significant nausea/vomiting can cause dehydration; monitor fluid intake.
- In severe renal impairment (CrCl <9 mL/min) or severe hepatic impairment, galantamine is contraindicated due to markedly reduced clearance.
Clinical Pearls
- Galantamine's dual mechanism — AChE inhibition plus nicotinic receptor modulation — may theoretically provide superior cholinergic neurotransmission enhancement compared to pure AChE inhibitors, though head-to-head clinical data have not demonstrated superiority.
- Galantamine is a naturally occurring alkaloid derived from snowdrop plants (Galanthus) and daffodils; its discovery represents a pharmacological lead from traditional botanical medicine.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.