Galantamine
Did You Know...
Volume IV, Number 4 | July/August 2001
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Galantamine (Reminyl®; Janssen), is a tertiary alkaloid isolated from the bulbs of the daffodil and is a competitive and reversible inhibitor of acetylcholinesterase. It is FDA-approved for the treatment of mild-to-moderate dementia of the Alzheimer's type. The exact mechanism of galantamine's action is unknown, however, it is thought to exert its therapeutic effect by enhancing cholinergic function and thereby increasing the concentration of acetylcholine.
Peak levels of galantamine are reached about 1 hour after oral administration. It is well absorbed orally (90% bioavailability) and plasma protein binding is 18%. The volume of distribution of galantamine is 175 L. The elimination half-life is approximately 1 hour, while the terminal elimination half-life is approximately 7 hours. About 20 to 50% of the galantamine dose is excreted unchanged in the urine and two metabolites, epigalantamine and galanthamione, have been detected in plasma and urine.
Galantamine is metabolized by the cytochrome P-450 2D6 and 3A4; therefore, agents that inhibit or induce these isozymes may impact the hepatic clearance of galantamine. The clearance of galantamine is decreased when given with amitriptyline, fluoxetine, fluvoxamine, and quinidine. Potent inhibitors (e.g., ketoconazole, paroxetine, and erythromycin) may increase the AUC of galantamine. Galantamine has no effect on the pharmacokinetics of warfarin or digoxin.
Adverse effects of galantamine include nausea, vomiting, diarrhea, anorexia, and weight loss. (See Table 1). Administration with food, use of anti-emetics, and ensuring adequate fluid intake may reduce the severity or occurrence of nausea and vomiting. Other adverse events that occurred in at least 2% of treated patients include fatigue, syncope, dizziness, headache, tremor, abdominal pain, dyspepsia, bradycardia, depression, insomnia, somnolence, anemia, rhinitis, urinary tract infection, and hematuria.
Table 1: Adverse Drug Reactions Associated with Alzheimer Medications
| Donepezil* (Aricept®) | Galantamine* (Reminyl®) | Rivastigmine* (Exelon®) |
Tacrine† | |
|---|---|---|---|---|
| Nausea | 6% | 24% | 17% | 28% |
| Vomiting | 5% | 13% | 14% | 28% |
| Diarrhea | 9% | 9% | -- | 16% |
| Dizziness | -- | 9% | 9% | 12% |
| Weight decrease | -- | 7% | -- | 3% |
| Anorexia | 3% | 9% | 5% | 9% |
Derived from individual
product labeling: *Maintenance phase; † Titration phase
The recommended starting dose (See table 2) of
galantamine is 8 mg/day, administered in two divided doses
preferably with the morning and evening meal. If this dose
is well tolerated after a minimum of four weeks, the dose
should be increased to 16 mg/day (8 mg twice daily). A further
increase to 24 mg/day (12 mg twice daily) should be attempted
only after a minimum of four weeks at the previous dose. In
clinical trials, galantamine was shown to be effective at
doses of 16 to 32 mg/day. The dose of galantamine should not
exceed 16 mg/day in patients with moderate hepatic impairment,
and it should not be administered in patients with severe
hepatic or renal impairment.
Table 2. Dosage Administration
| Donepezil | Galantamine | Rivastigmine | Tacrine | |
|---|---|---|---|---|
| Initial Dose | 5 mg QD | 4 mg BID | 1.5 mg BID | 10 mg QID |
| Titration | Increase to 10 mg QD after 4 to 6 weeks | Titrate slowly over intervals of 4 weeks |
Increase to 3 mg BID, 4.5 mg BID, then 6 mg BID daily at 2-week intervals as tolerated | Increase to 20 mg QID, then 30 mg QID, and 40 mg QID at 4-week intervals as tolerated (monitor transaminase levels) |
| Maximum Dose | 24 mg/day | 6 mg BID (12 mg/day) | (160 mg/day) |
|
| Time of Administration | Bedtime | Morning and evening | Morning and evening | Ideally administered between meals QID |
| Food | With or without | Take with food | Take with food | Between meals if possible, can be taken with food to improve tolerability, but reduces plasma levels 30 to 40% |
| Product Formulations | Tablet | Tablet | Capsule | Capsule |
QD = once daily; BID = twice daily; QID = four times daily
Galantamine, approved February 2001, is indicated for mild-to-moderate dementia of the Alzheimer's type. It is available as a 4-, 8-, and 12 mg tablet (See Table 3). The initial dose of galantamine is 4 mg twice daily and may be increased to a maximum dose of 24 mg/day. Gastrointestinal effects appear to be the most common adverse effects, however, by taking the recommended dose and taking galantamine with food, these adverse effects may be diminished.
Table 3: Cost Comparison (AWP) for 30-day supply
| Donepezil (Aricept®) | 5 mg | $131.31 |
| 10 mg | $131.31 | |
| Galantamine (Reminyl®) | 4 mg | $129.60 |
| 8 mg | $129.60 | |
| 12 mg | $129.60 | |
| Rivastigmine (Exelon®) | 1.5 mg | $134.14 |
| 3 mg | $134.14 | |
| 4.5 mg | $134.14 | |
| 6 mg | $134.14 | |
| Tacrine (Cognex®) | 10 mg | $152.75 |
| 20 mg | $152.75 | |
| 30 mg | $152.75 | |
| 40 mg | $152.75 |