Galantamine
Galantamine
Generic Name
Galantamine
Mechanism
- Reversible, competitive inhibition of acetylcholinesterase (AChE): blocks AChE, increasing acetylcholine (ACh) concentration in synaptic clefts.
- Positive allosteric modulation of α4β2 nAChRs: facilitates ACh binding and potentiates nicotinic signaling, contributing to its cognitive‑enhancing properties.
- Resulting pharmacodynamic effect: improved cortical cholinergic transmission, leading to modest benefits in memory, attention, and executive function in AD patients.
Pharmacokinetics
| Parameter | Detail |
| Absorption | Rapid oral absorption, peak plasma concentration (Tₘₐₓ) 3–6 h post‑dose. |
| Bioavailability | Approximately 60–70 % (varies with food; reduced by high‑fat meals). |
| Distribution | Volume of distribution ≈ 50 L; blood‑brain barrier penetration ~10 %. |
| Protein binding | ~50 % to plasma albumin. |
| Metabolism | Primarily hepatic via non‑CYP pathways (massive phase II conjugation) and minor CYP2D6/CYP2E1 oxidation. |
| Elimination | Excreted unmetabolized (~30 %) and as conjugates (~60 %). Renal clearance 4–10 mL/min. |
| Half‑life | 6–20 h, allowing once‑daily dosing for extended‑release formulation. |
| Formulations | Immediate‑release tablets (4 mg and 8 mg), extended‑release tablets (8 mg once daily), and oral liquid (pre‑filled syringe 10 mg/mL). |
Indications
- Primary: Mild to moderate Alzheimer’s disease (AD) – multi‑modal cholinergic support improves cognition and functional status.
- Off‑label: Limited evidence for mild‑to‑moderate vascular dementia and other neuro‑degenerative disorders, but not approved for these indications.
Contraindications
| Category | Specifics |
| Contraindicated | Allergy/intolerance to galantamine or any formulation component. Severe hepatic impairment (Child‑Pugh C). |
| Warnings |
• Bradycardia, atrioventricular block, QT prolongation. • Severe gastrointestinal distress (vomiting, diarrhea). • Hypersensitivity reactions (rash, anaphylaxis). • Use with caution in: heart or valvular disease, renal/hepatic dysfunction, pregnancy/lactation (category C). |
| Precautions |
• Comprehensive cardiac evaluation before initiation. • Monitor renal and hepatic function if comorbid conditions exist. |
Dosing
| Formulation | Starting Dose | Titration | Max Recommended Dose |
| Immediate‑Release Tablets | 8 mg once daily (split into 4 mg BID). | Increase by 4 mg/day every 4 weeks, as tolerated. | 8 mg BID (16 mg/day) or 8 mg TID (24 mg/day) for moderate AD. |
| Extended‑Release Tablets (XR) | 8 mg once daily for 7 days. | Increase to 8 mg BID after 7 days if tolerated; then 8 mg TID after 14 days. | 8 mg TID (24 mg/day). |
| Oral Solution | 10 mg/mL (10 mL, 100 mg) once daily with food for patients who cannot swallow tablets. | Same titration as XR. | 100 mg/day or 150 mg/day (2‑dose). |
• Administration Tips:
• Take with a meal to mitigate GI upset.
• Do not exceed the maximum daily dose.
• Patients on over‑the‑counter anticholinergics should discontinue prior to galantamine initiation.
Adverse Effects
- Common (≥ 5 %)
- Gastro‑intestinal: nausea, vomiting, diarrhea, abdominal pain, anorexia.
- Neurologic: headache, dizziness, insomnia, muscle cramps.
- Metabolic: weight loss, increased sweating, altered taste.
- Serious (≤ 1 %)
- Cardiac: marked bradycardia, atrioventricular block, syncope, QT prolongation.
- Allergic: anaphylaxis, angioedema.
- Seizures (rare).
- Severe GI bleeding (reported in isolated cases).
Monitoring
- Baseline – ECG, pulse, blood pressure, liver enzymes, creatinine, electrolytes, MMSE or MoCA score.
- During Therapy –
- Cardiac: monitor heart rate, rhythm at each dose escalation or before starting if cardiac disease.
- Renal/Hepatic: periodic LFTs and serum creatinine; adjust if impairment is noted.
- Cognitive: MMSE/MoCA annually to assess benefit and titration.
- Adverse Effects: record GI symptoms, weight changes, urinary frequency.
- Follow‑up – Every 4–6 weeks during titration, then quarterly.
Clinical Pearls
1. Multi‑modal advantage – Unlike other cholinesterase inhibitors, galantamine’s nicotinic receptor modulation may provide additional cognitive benefits, especially in attention‑related deficits.
2. Extended‑release reduces GI toxicity – XR tablets deliver steadier plasma levels, markedly lowering nausea and vomiting compared with immediate‑release forms.
3. Bradycardia vigilance – Start at the lowest dose (8 mg BID), especially in patients with digoxin or β‑blockers; re‑check ECG after each dose escalation.
4. Contraindicated with CYP2D6 inducers – Although galantamine is minimally metabolized by CYP2D6, strong inducers can lower plasma levels; avoid co‑prescribing with carbamazepine, phenobarbital, or phenytoin.
5. Patient education – Emphasize taking the medication with food, being consistent, and reporting new GI or cardiac symptoms promptly—early detection prevents serious complications.
6. Transition from rivastigmine – When switching, maintain the existing rivastigmine dose for 5–7 days, then start galantamine at 8 mg BID and titrate per the schedule, monitoring for potential additive GI side effects.
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• Reference-Friendly Summary:
Galantamine is a reversible acetylcholinesterase inhibitor and nicotinic positive allosteric modulator, approved for mild‑to‑moderate Alzheimer’s disease. Key PK: oral bioavailability ~60 %, half‑life 6–20 h, hepatic conjugation. Standard dosing: 8 mg BID (immediate‑release) or XR 8 mg once daily with a taper to TID. Major adverse effects include GI upset and bradycardia. Monitoring of cardiac rhythm, renal/hepatic function, and cognitive status is essential for safe, effective use.