Special Alerts:

Galantamine (Reminyl®): Warnings Concerning Preliminary Safety Information From Investigational Studies with Galantamine in Patients with Mild Cognitive Impairment - January 21, 2005

Johnson & Johnson Pharmaceutical Research & Development, LLC (J&JPRD) has announced that preliminary safety information from two investigational studies conducted with galantamine (Reminyl®) in patients with mild cognitive impairment (MCI) revealed an increase in mortality as compared to placebo. The GAL-INT-11 and GAL-INT-18 studies evaluated the rate of progression from mild cognitive impairment to dementia; over 2000 patients from 16 countries were enrolled. Although rates of mortality in both the galantamine treatment group and placebo group were low, 15 patients died while receiving treatment as compared to 5 deaths which occurred in individuals receiving placebo. Cardiovascular and cerebrovascular causes were thought to be associated with these deaths. Whether other drugs in this class have similar action when used for mild cognitive impairment is not known. Galantamine is not currently approved by the Food and Drug Administration (FDA) as treatment for mild cognitive impairment.

J&JPRD is currently reviewing additional data from these studies, including information gained from individuals who had dropped out of the trials, and is discussing this information with regulatory authorities.

A complete copy of the press announcement is available at: http://www.jnj.com/news/jnj_news/20050121_150033.htm

Additional information is available at http://www.clinicalstudyresults.org/ http://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/index_advisories public e.html

Pronunciation:

(ga LAN ta meen)

U.S. Brand Names:

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Generic Available:

Canadian Brand Names:

Use:

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Lactation:

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Warnings/Precautions:

Adverse Reactions:

>10%: Gastrointestinal: Nausea (6% to 24%), vomiting (4% to 13%), diarrhea (6% to 12%)

1% to 10%:

Cardiovascular: Bradycardia (2% to 3%), syncope (0.4% to 2.2%: dose related), chest pain (1%)

Central nervous system: Dizziness (9%), headache (8%), depression (7%), fatigue (5%), insomnia (5%), somnolence (4%), tremor (3%)

Gastrointestinal: Anorexia (7% to 9%), weight loss (5% to 7%), abdominal pain (5%), dyspepsia (5%), flatulence (1%)

Genitourinary: Urinary tract infection (8%), hematuria (<1% to 3%), incontinence (1%)

Hematologic: Anemia (3%)

Respiratory: Rhinitis (4%)

<1%: Alkaline phosphatase increase, apathy, aphasia, apraxia, ataxia, atrial fibrillation, AV block, bundle branch block, convulsions, cystitis, delirium, dependent edema, diverticulitis, dysphagia, epistaxis, esophageal perforation, gastritis, gastroenteritis, heart failure, hiccups, hyperglycemia, hypertonia, hypokinesia, hypotension, involuntary muscle contractions, libido increase, melena, increased micturition frequency, muscle weakness, nocturia, palpitation, paranoid reaction, paresthesia, paroniria, postural hypotension, purpura, QT prolongation, rectal hemorrhage, renal calculi, saliva increased, supraventricular tachycardia, T-wave inversion, thrombocytopenia, urinary retention, ventricular tachycardia, vertigo, xerostomia

Postmarketing and/or case reports: Aggression, dehydration, gastrointestinal bleeding, hypokalemia, renal failure (due to dehydration)

Overdosage/Toxicology:

Drug Interactions:

Amiodarone: Concurrent use may lead to bradycardia

Anticholinergic agents (eg, atropine, benztropine, tolterodine): Galantamine may antagonize anticholinergic actions

Beta blockers without ISA activity: Concurrent use may lead to bradycardia

Cimetidine: Increased bioavailability of galantamine by 16%

Cholinergic agonists: May have synergistic effects

Digoxin: Concurrent use may lead to AV block

Diltiazem: Concurrent use may lead to bradycardia

Ketoconazole: Increased galantamine levels (AUC increased by 30%)

NSAIDs: Concurrent use may increase risk of gastrointestinal ulcer because of increased gastric acid secretion.

Paroxetine: Increased galantamine levels (AUC increased by 40%)

Succinylcholine: Concurrent use may lead to enhanced neuromuscular blockade

Verapamil: Concurrent use may lead to bradycardia

Ethanol/Nutrition/Herb Interactions:

Ethanol: Avoid ethanol (may increase CNS adverse events).

Herb/Nutraceutical: St John's wort may decrease galantamine serum levels; avoid concurrent use.

Stability:

Mechanism of Action:

Pharmacodynamics/Kinetics:

Duration: 3 hours; maximum inhibition of erythrocyte acetylcholinesterase ~40% at 1 hour post 10 mg oral dose; levels return to baseline at 30 hours

Absorption: Rapid and complete

Distribution: 1.8-2.6 L/kg; levels in the brain are 2-3 times higher than in plasma

Protein binding: 18%

Metabolism: Hepatic; linear, CYP2D6 and 3A4; metabolized to epigalanthaminone and galanthaminone both of which have acetylcholinesterase inhibitory activity 130 times less than galantamine

Bioavailability: 80% to 100%

Half-life elimination: 6-8 hours

Time to peak: 1 hour

Excretion: Urine (25%)

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Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Dosage Forms:

Solution, oral, as hydrobromide: 4 mg/mL (100 mL) [with calibrated pipette]

Tablet, as hydrobromide: 4 mg, 8 mg, 12 mg

International Brand Names: