Brand name: Razadyne
Drug class: Parasympathomimetic (Cholinergic) Agents
- Anticholinesterase Agents
VA class: CN900
Chemical name: (4aS,6R,8aS)-4a,5,9,10,11,12-hexahydro-3-methoxy-11-methyl-6H-benzofuro[3a,3,2-ef][2]benzazepin-6-ol hydrobromide
Molecular formula: C₁₇H₂₁N0₃.HBr
CAS number: 1953-04-4

Medically reviewed by Drugs.com on Oct 30, 2023. Written by ASHP.

Introduction

A centrally active, reversible acetylcholinesterase inhibitor.¹

Uses for Galantamine

Alzheimer’s Disease

Management of mild to moderate dementia of the Alzheimer’s type (Alzheimer’s disease).^{1 15}

Cholinesterase inhibitors (e.g., donepezil, galantamine, rivastigmine) are used for symptomatic management of dementia associated with Alzheimer's disease; however, these drugs shown to provide only modest benefits and do not alter the underlying dementing process.^{1 20 21 22 23 25 26} Because of the lack of established alternatives, experts generally recommend a trial with one of these agents in patients with Alzheimer's disease.^{20 21 22 23}

Mild Cognitive Impairment

Investigated in patients with mild cognitive impairment^{† [off-label]} who did not meet diagnostic criteria for Alzheimer’s disease, but was associated with increased mortality.¹ (See Mortality under Cautions.) Not approved by FDA for this use.¹²

In general, no evidence of benefit with cholinesterase inhibitors in patients with mild cognitive impairment who do not have dementia.²⁷

Galantamine Dosage and Administration

Administration

Oral Administration

Administer conventional tablets or oral solution orally twice daily, preferably with morning and evening meals.^{1 15 16}

Administer extended-release capsules orally once daily in the morning, preferably with food.^{1 14}

Administer oral solution using the dosing syringe provided by the manufacturer; refer to accompanying patient information for instructions.¹⁵ Dilute appropriate dose of oral solution in 100 mL of a nonalcoholic beverage just prior to administration and stir well; consume entire mixture immediately.¹⁵

Dosage

Available as galantamine hydrobromide; dosage is expressed in terms of galantamine.^{1 14 15 16}

Slow dosage escalation is recommended to minimize adverse effects; minimum of 4 weeks at prior dosage is recommended before dosage is increased.^{1 15}

If galantamine therapy interrupted for more than 3 days, resume therapy using the lowest dosage and titrate upward to prior dosage.¹

Adults

Alzheimer’s Disease

Oral

Initially, 4 mg twice daily (as conventional tablets or oral solution) or 8 mg once daily (as extended-release capsules).^{1 15} May increase dosage after a minimum of 4 weeks to 8 mg twice daily (as conventional tablets or oral solution) or 16 mg once daily (as extended-release capsules) based on patient response and tolerability.^{1 15}

May attempt further increases to 12 mg twice daily (as conventional tablets or oral solution) or 24 mg once daily (as extended-release capsules) after a minimum of 4 weeks of treatment at the previous dosage.^{1 15}

Maintenance dosage recommended by the manufacturer is 8–12 mg twice daily (as conventional tablets and oral solution) or 16–24 mg once daily (as extended-release capsules).^{1 15} Higher dosages (e.g., 16 mg twice daily) do not result in greater efficacy and are less well tolerated than lower dosages.^{1 15}

Special Populations

Hepatic Impairment

Alzheimer’s Disease

Oral

Dosage generally should not exceed 16 mg daily in patients with moderate hepatic impairment (Child-Pugh score of 7–9).¹ Use not recommended in patients with severe hepatic impairment (Child-Pugh score of 10–15).¹

Renal Impairment

Alzheimer’s Disease

Oral

Dosage generally should not exceed 16 mg daily in patients with Cl_cr of 9–59 mL/minute.¹ Use not recommended in patients with Cl_cr <9 mL/minute.¹

Cautions for Galantamine

Contraindications

• Known hypersensitivity to galantamine or any ingredient in the formulation.¹

Warnings/Precautions

Cardiovascular Effects

Potential bradycardia, AV block, or other vagotonic effects on the heart.¹

Patients with supraventricular cardiac conduction abnormalities and those receiving concomitant therapy with drugs that substantially decrease heart rate appear to be at particular risk.¹

Use with caution in patients with sick sinus syndrome or other conduction defects.²⁰

GI Effects

Possible diarrhea, nausea, vomiting, and weight loss; such effects are dose related and generally mild to moderate in severity.^{1 20} Manufacturer states to monitor patient's weight during therapy.¹

Peptic Ulcers/GI Bleeding

Cholinesterase inhibitors may increase gastric acid secretion.¹ Monitor closely for manifestations of active or occult GI bleeding, especially in patients with increased risk (e.g., history of ulcer disease, concomitant NSAIA therapy).¹

GU Effects

Although not reported in clinical studies with galantamine, cholinomimetic agents may cause bladder outflow obstruction.¹

Neurologic Effects

Drugs that increase cholinergic activity have the potential for causing seizures; seizures also may be a manifestation of Alzheimer’s disease.¹

Respiratory Effects

Use with caution in patients with a history of severe asthma or obstructive pulmonary disease because of increased cholinergic activity.¹

Mortality

Higher incidence of death reported in patients receiving galantamine than in those receiving placebo in 2 studies in patients with mild cognitive impairment^{† [off-label]} who did not meet diagnostic criteria for Alzheimer’s disease.¹ Deaths were due to various causes expected in a geriatric population; approximately half in galantamine-treated patients were due to vascular causes (i.e., MI, stroke, sudden death).¹ In addition, the incidence of mortality in placebo-treated patients in these 2 studies was substantially lower than that reported in placebo-treated patients in studies that evaluated galantamine in patients with Alzheimer’s disease.¹

Sensitivity Reactions

Serious Skin Reactions

Serious skin reactions such as Stevens-Johnson syndrome and acute generalized exanthematous pustulosis reported.¹ Discontinue drug at the first sign of a skin rash unless rash is clearly not drug related.¹ If rash is severe, do not resume therapy and consider alternative treatment.¹

Prescribing and Dispensing Precautions

Similarity in spelling of Reminyl (the former trade name of galantamine) and Amaryl (glimepiride) has resulted in errors.^{10 11} In April 2005, manufacturer of galantamine announced that trade name would be changed from Reminyl to Razadyne to avoid future dispensing errors.¹³

Specific Populations

Pregnancy

No adequate data to inform developmental risks associated with use of galantamine in pregnant women.¹ Animal reproduction studies revealed some evidence of developmental toxicity.¹

Lactation

Not known whether galantamine is distributed into milk or if the drug affects the nursing infant or milk production.¹ Consider known benefits of breast-feeding along with the mother's clinical need for galantamine and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.¹

Pediatric Use

Safety and efficacy not established.¹

Hepatic Impairment

Use not recommended in patients with severe hepatic impairment (Child-Pugh score of 10–15).¹ Dosage modification recommended in patients with moderate hepatic impairment.¹ (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Use not recommended in patients with severe renal impairment (Cl_cr <9 mL/minute).¹ Dosage modification recommended in patients with moderate renal impairment.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Nausea, vomiting, diarrhea, dizziness, headache, decreased appetite.^{1 15}

Drug Interactions

Metabolized by CYP enzymes, principally CYP2D6 and 3A4.¹

Does not inhibit CYP1A2, 2A6, 3A4, 2C, 2D6, or 2E1 in vitro.¹

Drugs Affecting Hepatic Enzymes

CYP3A4 inhibitors: Possible increased systemic exposure of galantamine.¹

CYP2D6 inhibitors: Possible decrease in galantamine clearance of about 25–33%.¹

Specific Drugs

Galantamine Pharmacokinetics

Absorption

Bioavailability

Absolute oral bioavailability about 90%.¹ Bioavailabilities of oral solution and tablets are equivalent.¹ Extended-release capsules (24 mg once daily) and conventional tablets (12 mg twice daily) are bioequivalent when administered under fasting conditions.¹

Peak plasma concentrations attained within 1 or 4.5–5 hours after administration of conventional tablets or extended-release capsules, respectively.¹

Food

Conventional tablets or oral solution: Food did not affect the AUC, but peak plasma concentrations were decreased by 25% and time to peak plasma concentrations was delayed by 1.5 hours.¹

Extended-release capsules: No appreciable differences in pharmacokinetic parameters following administration with food.¹

Onset

Maximum inhibition of acetylcholinesterase (about 40%) achieved about 1 hour after a single 8-mg oral dose.¹

Special Populations

Approximately 50% higher systemic exposure following administration of extended-release capsules in patients with reduced levels of CYP2D6 (also known as poor metabolizers); however, dosage adjustment is not necessary.¹

Distribution

Extent

In whole blood, galantamine is mainly distributed to blood cells (52.7%).¹ Blood to plasma concentration ratio is 1.2.¹

Plasma Protein Binding

18% at therapeutically relevant concentrations.¹

Elimination

Metabolism

Metabolized in the liver by CYP isoenzymes (principally CYP2D6 and 3A4).¹

Clearance decreased 25% in patients with reduced levels of CYP2D6 activity; however, dosage adjustment is not necessary.¹

Elimination Route

Principally in urine.¹

Half-life

Terminal elimination half-life of about 7 hours.¹

Special Populations

In patients with moderate hepatic impairment (Child-Pugh score of 7–9), clearance decreased by about 25% compared with healthy individuals.¹ Exposure to the drug would be expected to increase further with increasing degree of hepatic impairment.¹

In patients with moderate or severe renal impairment, AUC following a single 8-mg dose of galantamine (as conventional tablets) increased by 37% or 67%, respectively, compared with values in healthy individuals.¹

Stability

Storage

Oral

Conventional Tablets and Extended-release Capsules

25°C; may be exposed to 15–30°C.¹

Solution

20–25°C.¹⁵ Do not freeze.¹⁵

Actions

• Binds reversibly with and inactivates acetylcholinesterase, thus inhibiting hydrolysis of acetylcholine and increasing the concentration of acetylcholine at cholinergic synapses.^{1 2 7} Also binds allosterically with nicotinic acetylcholine receptors and may potentiate the action of agonists (e.g., acetylcholine) at these receptors.^{2 6 7}

• Deficiency of acetylcholine caused by selective loss of cholinergic neurons in the cerebral cortex, nucleus basalis, and hippocampus is a pathologic feature of Alzheimer's disease associated with cognitive deficits.^{2 7 22 28}

• Effects may diminish as the Alzheimer’s disease process advances and fewer cholinergic neurons remain functioning.¹

Advice to Patients

• Risk of adverse effects (e.g., nausea, vomiting, anorexia, weight loss).¹

• Importance of administering galantamine with food and ensuring adequate fluid intake.¹

• Importance of beginning therapy at lowest dosage and gradually increasing back to prior dosage range if therapy is interrupted for any reason.¹

• Importance of understanding the proper procedure for administering the oral solution, including review of the patient information provided by the manufacturer; advise patients to direct questions about administration to their pharmacist or clinician.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Frequently asked questions

• Is Razadyne (galantamine) used to treat Alzheimer’s?

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