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Medication Safety Issues
Sound-alike/look-alike issues:
Razadyne® may be confused with Rozerem™
Reminyl® may be confused with Amaryl®, Robinul®
Due to patient safety concerns regarding prescribing and dispensing errors between Reminyl® and Amaryl®, Reminyl® (galantamine) is being renamed to Razadyne® (immediate-release) and Razadyne® ER (extended-release). The brand name Reminyl® was discontinued with the July, 2005 distribution of Razadyne®.
Pronunciation
(ga LAN ta meen)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of mild-to-moderate dementia of Alzheimer's disease
Use: Unlabeled/Investigational
Severe dementia associated with Alzheimer's disease; mild-to-moderate dementia associated with Parkinson's disease; Lewy body dementia
Pregnancy Risk Factor
B
Pregnancy Considerations
In animal studies, there was a slight increased in the incident of skeletal variations when given during organogenesis. Adequate, well-controlled studies in pregnant women do not exist. Should be used in pregnancy only if benefit outweighs potential risk to the fetus.
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
Hypersensitivity to galantamine or any component of the formulation; severe liver dysfunction (Child-Pugh score 10-15); severe renal dysfunction (Clcr <9 mL/minute)
Warnings/Precautions
Concerns related to adverse effects:
• Anorexia/weight loss: May cause anorexia and/or weight loss.
• Diarrhea: May cause diarrhea.
• Nausea/vomiting: May cause nausea and/or vomiting.
• Vagotonic effects: Cholinesterase inhibitors may have vagotonic effects which may cause bradycardia and/or heart block with or without a history of cardiac disease.
Disease-related concerns:
• Cardiac conduction abnormalities: Use with caution in patients with sick-sinus syndrome, bradycardia, or conduction abnormalities. Alzheimer's treatment guidelines consider bradycardia to be a relative contraindication for use of centrally-active cholinesterase inhibitors.
• Hepatic impairment: Use with caution in patients with mild-to-moderate liver impairment; not recommended in severe impairment.
• Peptic ulcer disease: Use with caution in patients at risk of ulcer disease (eg, previous history or NSAID use); may increase gastric acid secretion. Monitor for symptoms of bleeding.
• Renal impairment: Use with caution in patients with moderate renal impairment; not recommended in severe impairment (Clcr <9 mL/minute).
• Respiratory disease: Use with caution in patients with COPD and/or asthma.
• Seizure disorder: Use with caution in patients with a history of seizure disorder.
• Urinary tract obstruction: Use with caution in patients with bladder outlet obstruction or prostatic hyperplasia; cholinomimetics may cause or worsen outflow obstructions, including possible exacerbation of BPH symptoms.
Concurrent drug therapy issues:
• Depolarizing neuromuscular-blocking agents: May exaggerate neuromuscular blockade effects of depolarizing neuromuscular-blocking agents like succinylcholine.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children.
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%)
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%)
Neuromuscular & skeletal: Tremor (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, fever, gastritis, gastroenteritis, heart failure, hiccups, hyperglycemia, hyper-/hypokinesia, hypertonia, hypotension, involuntary muscle contractions, libido increase, malaise, melena, MI, micturition frequency increased, muscle weakness, nocturia, palpitation, paranoid reaction, paresthesia, paroniria, postural hypotension, purpura, QT prolongation, rectal hemorrhage, renal calculi, saliva increased, stroke, suicide, supraventricular tachycardia, T-wave inversion, thrombocytopenia, TIA, urinary retention, ventricular tachycardia, vertigo, weakness, xerostomia
Postmarketing and/or case reports: Aggression, dehydration, gastrointestinal bleeding, hypokalemia, renal failure (due to dehydration)
Metabolism/Transport Effects
Substrate (minor) of CYP2D6, 3A4
Drug Interactions
Anticholinergics: May diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Exceptions: Paliperidone. Risk C: Monitor therapy
Antipsychotics: Acetylcholinesterase Inhibitors (Central) may enhance the neurotoxic (central) effect of Antipsychotics. Severe extrapyramidal symptoms have occurred in some patients. Risk C: Monitor therapy
Beta-Blockers: Acetylcholinesterase Inhibitors may enhance the bradycardic effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy
Cholinergic Agonists: Acetylcholinesterase Inhibitors may enhance the adverse/toxic effect of Cholinergic Agonists. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Risk C: Monitor therapy
Ginkgo Biloba: May enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Neuromuscular-Blocking Agents (Nondepolarizing): Acetylcholinesterase Inhibitors may diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May decrease the metabolism of Galantamine. Exceptions: Citalopram; Escitalopram; Fluvoxamine. Risk C: Monitor therapy
Succinylcholine: Acetylcholinesterase Inhibitors may enhance the neuromuscular-blocking effect of Succinylcholine. Risk C: Monitor therapy
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.
Storage
Store at 15°C to 30°C (59°F to 86°F). Do not freeze oral solution; protect from light.
Mechanism of Action
Centrally-acting cholinesterase inhibitor (competitive and reversible). It elevates acetylcholine in cerebral cortex by slowing the degradation of acetylcholine. Modulates nicotinic acetylcholine receptor to increase acetylcholine from surviving presynaptic nerve terminals. May increase glutamate and serotonin levels.
Pharmacodynamics/Kinetics
Duration: 3 hours; maximum inhibition of erythrocyte acetylcholinesterase ~40% at 1 hour post 8 mg oral dose; levels return to baseline at 30 hours
Absorption: Rapid and complete
Distribution: 175 L; 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: ~90%
Half-life elimination: 7 hours
Time to peak: Immediate release: 1 hour (2.5 hours with food); extended release: 4.5-5 hours
Excretion: Urine (25%)
Dosage
Oral: Adults:
Note: Oral solution and tablet should be taken with breakfast and dinner; capsule should be taken with breakfast. If therapy is interrupted for ?3 days, restart at the lowest dose and increase to current dose.
Immediate release tablet or solution: Mild-to-moderate dementia of Alzheimer's: Initial: 4 mg twice a day for 4 weeks; if tolerated, increase to 8 mg twice daily for ?4 weeks; if tolerated, increase to 12 mg twice daily
Range: 16-24 mg/day in 2 divided doses
Extended-release capsule: Initial: 8 mg once daily for 4 weeks; if tolerated, increase to 16 mg once daily for ?4 weeks; if tolerated, increase to 24 mg once daily
Range: 16-24 mg once daily
Conversion to galantamine from other cholinesterase inhibitors: Patients experiencing poor tolerability with donepezil or rivastigmine should wait until side effects subside or allow a 7-day washout period prior to beginning galantamine. Patients not experiencing side effects with donepezil or rivastigmine may begin galantamine therapy the day immediately following discontinuation of previous therapy (Morris, 2001).
Elderly: No dosage adjustment needed
Dosage adjustment in renal impairment:
Moderate renal impairment: Maximum dose: 16 mg/day.
Severe renal dysfunction (Clcr <9 mL/minute): Use is not recommended
Dosage adjustment in hepatic impairment:
Moderate liver dysfunction (Child-Pugh score 7-9): Maximum dose: 16 mg/day
Severe liver dysfunction (Child-Pugh score 10-15): Use is not recommended
Administration: Oral
Administer oral solution or tablet with breakfast and dinner; administer extended release capsule with breakfast. If therapy is interrupted for ?3 days, restart at the lowest dose and increase to current dose. If using oral solution, mix dose with 3-4 ounces of any nonalcoholic beverage; mix well and drink immediately.
Monitoring Parameters
Mental status
Dietary Considerations
Administration with food is preferred, but not required; should be taken with breakfast and dinner (tablet or solution) or with breakfast (capsule).
Patient Education
This medication will not cure Alzheimer's disease, but may help reduce symptoms. Use exactly as directed; do not increase dose or discontinue without consulting prescriber. Maintain adequate hydration unless instructed to restrict fluid intake. May cause dizziness, sedation, hypotension, or tremor (use caution when driving or engaging in hazardous tasks, rise slowly from sitting or lying position, and use caution when climbing stairs until response to drug is known); diarrhea; or nausea or vomiting (small frequent meals, good mouth care, sucking lozenges, or chewing gum may help). Report persistent GI disturbances; significantly increased salivation, sweating, or tearing; excessive fatigue, insomnia, dizziness, or depression; increased muscle, joint, or body pain or spasms; vision changes; respiratory changes, wheezing, or signs of dyspnea; chest pain or palpitations; or other adverse reactions. Breast-feeding precaution: Breast-feeding is not recommended.
Geriatric Considerations
No dosage adjustment needed.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Nursing: Physical Assessment/Monitoring
Assess bladder and sphincter adequacy prior to starting therapy. Assess other medications patient may be taking for effectiveness and interactions (especially those dependent on cytochrome P450 metabolism). Monitor therapeutic effectiveness and adverse reactions at beginning of therapy and periodically throughout therapy (eg, cholinergic crisis). Assess knowledge/teach appropriate use, interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release, oral, as hydrobromide: 8 mg, 16 mg, 24 mg
Razadyne® ER: 8 mg, 16 mg, 24 mg [contains gelatin]
Solution, oral, as hydrobromide: 4 mg/mL (100 mL)
Razadyne®: 4 mg/mL (100 mL) [with calibrated pipette]
Tablet, as hydrobromide: 4 mg, 8 mg, 12 mg
Razadyne®: 4 mg, 8 mg, 12 mg
Pricing: U.S. (www.drugstore.com)
Capsule, 24-hour (Razadyne ER)
8 mg (30): $203.10
16 mg (30): $203.67
24 mg (30): $203.63
Tablets (Razadyne)
4 mg (30): $97.01
8 mg (30): $103.89
12 mg (30): $103.89
References
Morris JC, Farlow MR, Ferris SH, et al, “Therapeutic Continuity in Alzheimer's Disease: Switching Patients to Galantamine. Panel Discussion: Recommendations for Prescribers,” Clin Ther, 2001, 23 (Suppl A):31-9.
Rabins PV, Blacker D, Rovner BW, et al, “Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias,” October, 2007. Available at http://www.psych.org/psych_pract/treatg/pg/prac_guide.cfm
Raskind MA, Peskind ER, Wessel T, et al, “Galantamine in AD: A 6-month Randomized, Placebo-Controlled Trial With a 6-month Extension. The Galantamine USA-1 Study Group,” Neurology, 2000, 54:2261-8.
Tariot PN, Solomon PR, Morris JC, et al, “A 5-month, Randomized, Placebo-controlled Trial of Galantamine in AD. The Galantamine USA-10 Study Group,” Neurology, 2000, 54:2269-76.
International Brand Names
Lexi-Comp.com
Last full review/revision November 2009
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