Introduction
Galantamine is a reversible, competitive acetylcholinesterase inhibitor and allosteric nicotinic receptor modulator approved for the treatment of mild to moderate Alzheimer's disease. Derived from natural sources including snowdrop (Galanthus spp.) and daffodil bulbs, it represents an important therapeutic option in the management of cognitive decline associated with Alzheimer's dementia.
Mechanism of Action
Galantamine exerts its therapeutic effects through dual mechanisms: 1. Acetylcholinesterase inhibition: Reversibly and competitively inhibits acetylcholinesterase in the synaptic cleft, increasing acetylcholine availability 2. Allosteric nicotinic modulation: Potentiates the response of nicotinic receptors to acetylcholine through allosteric binding sites
This dual action enhances cholinergic neurotransmission in the cerebral cortex and hippocampus, areas critically involved in memory and learning that demonstrate significant cholinergic deficit in Alzheimer's disease.
Indications
- Treatment of mild to moderate dementia of the Alzheimer's type
- Off-label: Cognitive enhancement in other forms of dementia (evidence limited)
Dosage and Administration
Initial therapy: 4 mg twice daily (8 mg total daily dose) for 4 weeks Maintenance titration: Increase to 8 mg twice daily (16 mg total daily dose) for ≥4 weeks Maximum dose: 12 mg twice daily (24 mg total daily dose) Special populations:- Renal impairment: Maximum 16 mg daily for CrCl <9 mL/min
- Hepatic impairment: Maximum 16 mg daily for moderate hepatic impairment (Child-Pugh 7-9); contraindicated in severe impairment
- Geriatric: No dosage adjustment required based on age alone
- Extended-release formulation: Available as 8, 16, and 24 mg capsules taken once daily
Pharmacokinetics
Absorption: Rapid and complete (90% bioavailability); food slows absorption but does not affect extent Distribution: Volume of distribution 175 L; protein binding 18% Metabolism: Hepatic via CYP2D6 and CYP3A4; extensive first-pass metabolism Elimination: Half-life ~7 hours; renal excretion (95%, with 20% as unchanged drug) Steady-state: Achieved within 1 weekContraindications
- Hypersensitivity to galantamine or any product components
- Severe hepatic impairment (Child-Pugh score >9)
- Severe renal impairment (CrCl <9 mL/min)
Warnings and Precautions
Black Box Warning:- Cholinesterase inhibitors may cause bradycardia and syncope; increased risk in patients with supraventricular cardiac conduction disorders or taking other medications that decrease heart rate
- Gastrointestinal effects: May cause nausea, vomiting, diarrhea, and weight loss
- Peptic ulcer disease: Use with caution in patients at risk for gastrointestinal bleeding
- Bladder outflow obstruction: May exacerbate symptoms
- Seizure disorders: May lower seizure threshold
- Asthma/COPD: May increase bronchial secretions and cause bronchospasm
- Surgery: May exaggerate neuromuscular blockade effects of succinylcholine
Drug Interactions
Major interactions:- Paroxetine: Strong CYP2D6 inhibitor; may increase galantamine levels by 40%
- Ketoconazole: Strong CYP3A4 inhibitor; may increase galantamine levels by 30%
- Other cholinesterase inhibitors: Additive cholinergic effects
- Anticholinergic agents: May reduce galantamine efficacy
- Beta-blockers, calcium channel blockers: May potentiate bradycardic effects
Adverse Effects
Very common (>10%):- Nausea (24%)
- Vomiting (13%)
- Diarrhea (9%)
- Weight loss (7%)
- Dizziness, headache, abdominal pain, dyspepsia, fatigue, anorexia
- Bradycardia, syncope (particularly in patients with cardiac conduction abnormalities)
- Gastrointestinal bleeding
- Seizures
- Severe skin reactions
- QT interval prolongation
Monitoring Parameters
Baseline:- Cognitive assessment (MMSE, ADAS-cog)
- Weight and nutritional status
- Renal and hepatic function
- Cardiac evaluation (ECG if risk factors present)
- Cognitive and functional status every 3-6 months
- Weight monitoring monthly for first 6 months
- Gastrointestinal symptoms
- Heart rate (particularly in patients with cardiac risk factors)
- Adverse effect profile
Patient Education
- Take with food to minimize gastrointestinal upset
- Maintain adequate fluid intake to prevent dehydration
- Do not abruptly discontinue without medical supervision
- Report any signs of gastrointestinal bleeding (black stools, abdominal pain)
- Monitor weight regularly and report significant weight loss
- Inform all healthcare providers about galantamine use, especially before surgery
- Be aware of potential dizziness; use caution when changing positions
- Allow 4-6 weeks to assess initial response to therapy
- Extended-release capsules should be swallowed whole, not crushed or chewed
References
1. FDA Prescribing Information: Razadyne (galantamine) [Revised 2021] 2. Birks JS. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev. 2006;(1):CD005593. 3. Wilkinson DG, Francis PT, Schwam E, et al. Cholinesterase inhibitors used in the treatment of Alzheimer's disease: the relationship between pharmacological effects and clinical efficacy. Drugs Aging. 2004;21(7):453-478. 4. Loy C, Schneider L. Galantamine for Alzheimer's disease and mild cognitive impairment. Cochrane Database Syst Rev. 2006;(1):CD001747. 5. Hansen RA, Gartlehner G, Webb AP, et al. Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer's disease: a systematic review and meta-analysis. Clin Interv Aging. 2008;3(2):211-225. 6. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Galantamine; [updated 2023]. 7. Micromedex Solutions [Internet]. Greenwood Village (CO): Truven Health Analytics. Galantamine; [updated 2023].