Galantamine hydrobromide

Galantamine hydrobromide
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Disclaimer

WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.

Overview

Galantamine hydrobromide is a cholinergic muscarinic agonist that is FDA approved for the treatment of mild to moderate dementia of the Alzheimer's type. Common adverse reactions include dehydration, aggression, upper and lower GI bleeding, hypokalemia.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

• Galantamine hydrobromide is indicated for the treatment of mild to moderate dementia of the Alzheimer's type.
• The dosage of galantamine shown to be effective in controlled clinical trials is 16 to 32 mg/day given as twice daily dosing. As the dose of 32 mg/day is less well tolerated than lower doses and does not provide increased effectiveness, the recommended dose range is 16 to 24 mg/day given in a BID regimen.
• The dose of 24 mg/day did not provide a statistically significant greater clinical benefit than 16 mg/day. It is possible, however, that a daily dose of 24 mg of galantamine might provide additional benefit for some patients.
• The recommended starting dose of galantamine is 4 mg twice a day (8 mg/day). The dose should be increased to the initial maintenance dose of 8 mg twice a day (16 mg/day) after a minimum of 4 weeks. A further increase to 12 mg twice a day (24 mg/day) should be attempted after a minimum of 4 weeks at 8 mg twice a day (16 mg/day). Dose increases should be based upon assessment of clinical benefit and tolerability of the previous dose.
• Galantamine should be administered twice a day, preferably with morning and evening meals.
• Patients and caregivers should be advised to ensure adequate fluid intake during treatment. If therapy has been interrupted for several days or longer, the patient should be restarted at the lowest dose and the dose escalated to the current dose.
• The abrupt withdrawal of galantamine in those patients who had been receiving doses in the effective range was not associated with an increased frequency of adverse events in comparison with those continuing to receive the same doses of that drug. The beneficial effects of galantamine are lost, however, when the drug is discontinued.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Galantamine hydrobromide in adult patients.

Non–Guideline-Supported Use

• Alzheimer's disease
• Multi-infarct dementia

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Galantamine hydrobromide FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Galantamine hydrobromide in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Galantamine hydrobromide in pediatric patients.

Contraindications

It is contraindicated in patients with known hypersensitivity to galantamine hydrobromide or to any excipients used in the formulation

Warnings

Anesthesia

• Galantamine, as a cholinesterase inhibitor, is likely to exaggerate the neuromuscular blocking effects of succinylcholine-type and similar neuromuscular blocking agents during anesthesia.

Cardiovascular Conditions

• Because of their pharmacological action, cholinesterase inhibitors have vagotonic effects on the sinoatrial and atrioventricular nodes, leading to bradycardia and AV block. These actions may be particularly important to patients with supraventricular cardiac conduction disorders or to patients taking other drugs concomitantly that significantly slow heart rate. Postmarketing surveillance of marketed anticholinesterase inhibitors has shown, however, that bradycardia and all types of heart block have been reported in patients both with and without known underlying cardiac conduction abnormalities. Therefore all patients should be considered at risk for adverse effects on cardiac conduction.
• In randomized controlled trials, bradycardia was reported more frequently in galantamine-treated patients than in placebo-treated patients, but was rarely severe and rarely led to treatment discontinuation. The overall frequency of this event was 2 to 3% for galantamine doses up to 24 mg/day compared with <1% for placebo. No increased incidence of heart block was observed at the recommended doses.
• Patients treated with galantamine up to 24 mg/day using the recommended dosing schedule showed a dose-related increase in risk of syncope (placebo 0.7% [2/286]; 4 mg BID 0.4% [3/692]; 8 mg BID 1.3% [7/552]; 12 mg BID 2.2% [6/273]).

Gastrointestinal Conditions

• Through their primary action, cholinomimetics may be expected to increase gastric acid secretion due to increased cholinergic activity. Therefore, patients should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those with an increased risk for developing ulcers, e.g., those with a history of ulcer disease or patients using concurrent nonsteroidal anti-inflammatory drugs (NSAIDS). Clinical studies of galantamine have shown no increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding.
• Galantamine, as a predictable consequence of its pharmacological properties, has been shown to produce nausea, vomiting, diarrhea, anorexia, and weight loss.

Genitourinary

• Although this was not observed in clinical trials with galantamine, cholinomimetics may cause bladder outflow obstruction.

Neurological Conditions

Seizures

• Cholinesterase inhibitors are believed to have some potential to cause generalized convulsions. However, seizure activity may also be a manifestation of Alzheimer's disease. In clinical trials, there was no increase in the incidence of convulsions with galantamine, compared to placebo.

Pulmonary Conditions

• Because of its cholinomimetic action, galantamine should be prescribed with care to patients with a history of severe asthma or obstructive pulmonary disease.

Adverse Reactions

Clinical Trials Experience

Pre-Marketing Clinical Trial Experience

• The specific adverse event data described in this section are based on studies of the immediate release tablet formulation.

Adverse Events Leading to Discontinuation

• In two large scale, placebo-controlled trials of 6 months duration in which patients were titrated weekly from 8 to 16 to 24, and to 32 mg/day, the risk of discontinuation because of an adverse event in the galantamine group exceeded that in the placebo group by about threefold. In contrast, in a 5-month trial with escalation of the dose by 8 mg/day every 4 weeks, the overall risk of discontinuation because of an adverse event was 7%, 7%, and 10% for the placebo, galantamine 16 mg/day, and galantamine 24 mg/day groups, respectively, with gastrointestinal adverse effects the principle reason for discontinuing galantamine. Table 1 shows the most frequent adverse events leading to discontinuation in this study.

This image is provided by the National Library of Medicine.

Adverse Events Reported in Controlled Trials

• The reported adverse events in trials using galantamine reflect experience gained under closely monitored conditions in a highly selected patient population. In actual practice or in other clinical trials, these frequency estimates may not apply, as the conditions of use, reporting behavior and the types of patients treated may differ.
• The majority of these adverse events occurred during the dose-escalation period. In those patients who experienced the most frequent adverse event, nausea, the median duration of the nausea was 5 to 7 days.
• Administration of galantamine with food, the use of anti-emetic medication, and ensuring adequate fluid intake may reduce the impact of these events.
• The most frequent adverse events, defined as those occurring at a frequency of at least 5% and at least twice the rate on placebo with the recommended maintenance dose of either 16 or 24 mg/day of galantamine under conditions of every 4 week dose-escalation for each dose increment of 8 mg/day, are shown in Table 2. These events were primarily gastrointestinal and tended to be less frequent with the 16 mg/day recommended initial maintenance dose.

This image is provided by the National Library of Medicine.

• Adverse events occurring with an incidence of at least 2% in placebo-treated patients that was either equal to or greater than with galantamine treatment were constipation, agitation, confusion, anxiety, hallucination, injury, back pain, peripheral edema, asthenia, chest pain, urinary incontinence, upper respiratory tract infection, bronchitis, coughing, hypertension, fall, and purpura.
• There were no important differences in adverse event rates related to dose or sex. There were too few non-Caucasian patients to assess the effects of race on adverse event rates.
• No clinically relevant abnormalities in laboratory values were observed.
• Other Adverse Events Observed During Clinical Trials
• Galantamine was administered to 3055 patients with Alzheimer's disease. A total of 2357 patients received galantamine in placebo-controlled trials and 761 patients with Alzheimer's disease received galantamine 24 mg/day, the maximum recommended maintenance dose. About 1000 patients received galantamine for at least one year and approximately 200 patients received galantamine for two years.
• To establish the rate of adverse events, data from all patients receiving any dose of galantamine in 8 placebo-controlled trials and 6 open-label extension trials were pooled. The methodology to gather and codify these adverse events was standardized across trials, using WHO terminology. All adverse events occurring in approximately 0.1% are included, except for those already listed elsewhere in labeling, WHO terms too general to be informative, or events unlikely to be drug caused. Events are classified by body system and listed using the following definitions: frequent adverse events - those occurring in at least 1/100 patients; infrequent adverse events - those occurring in 1/100 to 1/1000 patients; rare adverse events - those occuring in fewer than 1/1000 patients. These adverse events are not necessarily related to galantamine treatment and in most cases were observed at a similar frequency in placebo-treated patients in the controlled studies. Additional adverse events observed in other clinical trials are also included below.

Body As a Whole

• General Disorders

• Frequent: chest pain, asthenia, fever, malaise

• Cardiovascular System Disorders

• Postural hypotension, hypotension, dependent edema, cardiac failure, myocardial ischemia or infarction

• Central & Peripheral Nervous System Disorders

• Vertigo, hypertonia, convulsions, involuntary muscle contractions, paresthesia, ataxia, hypokinesia, hyperkinesia, apraxia, aphasia, leg cramps, tinnitus, transient ischemic attack or cerebrovascular accident

Gastrointestinal System Disorders

Frequent

• Flatulence; Infrequent: gastritis, melena, dysphagia, rectal hemorrhage, dry mouth, saliva increased, diverticulitis, gastroenteritis, hiccup; Rare: esophageal perforation

Heart Rate & Rhythm Disorders

• Infrequent

• AV block, palpitation, atrial arrhythmias including atrial fibrillation and supraventricular tachycardia, QT prolonged, bundle branch block, T-wave inversion, ventricular tachycardia; Rare: severe bradycardia

Metabolic & Nutritional Disorders

• Infrequent

• Hyperglycemia, alkaline phosphatase increased

Platelet, Bleeding & Clotting Disorders

• Infrequent

• Purpura, epistaxis, thrombocytopenia

Psychiatric Disorders

• Infrequent

• Apathy, paroniria, paranoid reaction, libido increased, delirium.

• Rare

• Suicidal ideation, suicide

Urinary System Disorders

• Frequent

• Incontinence

• Infrequent

• Hematuria, micturition frequency, cystitis, urinary retention, nocturia, renal calculi

Postmarketing Experience

• Other adverse events from post-approval controlled and uncontrolled clinical trials and post-marketing experience observed in patients treated with galantamine include:

Body as a Whole

General Disorders

• Dehydration (including rare, severe cases leading to renal insufficiency and renal failure)

Psychiatric Disorders

• Aggression

Gastrointestinal System Disorders

• Upper and lower GI bleeding

Metabolic & Nutritional Disorders

• Hypokalemia
• These adverse events may or may not be causally related to the drug.

Drug Interactions

There is limited information regarding Galantamine hydrobromide Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Galantamine hydrobromide in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Galantamine hydrobromide in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Galantamine hydrobromide during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Galantamine hydrobromide in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Galantamine hydrobromide in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Galantamine hydrobromide in geriatric settings.

Gender

There is no FDA guidance on the use of Galantamine hydrobromide with respect to specific gender populations.

Race

There is no FDA guidance on the use of Galantamine hydrobromide with respect to specific racial populations.

Renal Impairment

• For patients with moderate renal impairment the dose should generally not exceed 16 mg/day. In patients with severe renal impairment (creatinine clearance <9 mL/min), the use of galantamine is not recommended.

Hepatic Impairment

• Galantamine plasma concentrations may be increased in patients with moderate to severe hepatic impairment. In patients with moderately impaired hepatic function (Child-Pugh score of 7 to 9), the total daily dose should generally not exceed 16 mg/day. The use of galantamine in patients with severe hepatic impairment (Child-Pugh score of 10 to 15) is not recommended.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Galantamine hydrobromide in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Galantamine hydrobromide in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

Monitoring

• Patients should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those with an increased risk for developing ulcers, e.g., those with a history of ulcer disease or patients using concurrent nonsteroidal anti-inflammatory drugs (NSAIDS).
• The reported adverse events in trials using galantamine reflect experience gained under closely monitored conditions in a highly selected patient population.

IV Compatibility

There is limited information regarding the compatibility of Galantamine hydrobromide and IV administrations.

Overdosage

• Because strategies for the management of overdose are continually evolving, it is advisable to contact a poison control center to determine the latest recommendations for the management of an overdose of any drug.
• As in any case of overdose, general supportive measures should be utilized. Signs and symptoms of significant overdosing of galantamine are predicted to be similar to those of overdosing of other cholinomimetics. These effects generally involve the central nervous system, the parasympathetic nervous system, and the neuromuscular junction. In addition to muscle weakness or fasciculations, some or all of the following signs of cholinergic crisis may develop: severe nausea, vomiting, gastrointestinal cramping, salivation, lacrimation, urination, defecation, sweating, bradycardia, hypotension, respiratory depression, collapse and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved.
• Tertiary anticholinergics such as atropine may be used as an antidote for galantamine overdosage. Intravenous atropine sulfate titrated to effect is recommended at an initial dose of 0.5 to 1.0 mg i.v. with subsequent doses based upon clinical response. Atypical responses in blood pressure and heart rate have been reported with other cholinomimetics when coadministered with quaternary anticholinergics. It is not known whether galantamine and/or its metabolites can be removed by dialysis (hemodialysis, peritoneal dialysis, or hemofiltration). Dose-related signs of toxicity in animals included hypoactivity, tremors, clonic convulsions, salivation, lacrimation, chromodacryorrhea, mucoid feces, and dyspnea.
• In a postmarketing report, one patient who had been taking 4 mg of galantamine daily for a week inadvertently ingested eight 4 mg tablets (32 mg total) on a single day. Subsequently, she developed bradycardia, QT prolongation, ventricular tachycardia and torsades de pointes accompanied by a brief loss of consciousness for which she required hospital treatment. Two additional cases of accidental ingestion of 32 mg (nausea, vomiting, and dry mouth; nausea, vomiting, and substernal chest pain) and one of 40 mg (vomiting), resulted in brief hospitalizations for observation with full recovery. One patient who was prescribed 24 mg/day and had a history of hallucinations over the previous two years, mistakenly received 24 mg twice daily for 34 days and developed hallucinations requiring hospitalization.

Pharmacology

There is limited information regarding Galantamine hydrobromide Pharmacology in the drug label.

Mechanism of Action

• Although the etiology of cognitive impairment in Alzheimer's disease (AD) is not fully understood, it has been reported that acetylcholine-producing neurons degenerate in the brains of patients with Alzheimer's disease. The degree of this cholinergic loss has been correlated with degree of cognitive impairment and density of amyloid plaques (a neuropathological hallmark of Alzheimer's disease).
• Galantamine, a tertiary alkaloid, is a competitive and reversible inhibitor of acetylcholinesterase. While the precise mechanism of galantamine's action is unknown, it is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by cholinesterase. If this mechanism is correct, galantamine's effect may lessen as the disease process advances and fewer cholinergic neurons remain functionally intact. There is no evidence that galantamine alters the course of the underlying dementing process.

Structure

There is limited information regarding Galantamine hydrobromide Structure in the drug label.

Pharmacodynamics

There is limited information regarding Galantamine hydrobromide Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Galantamine hydrobromide Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Galantamine hydrobromide Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Galantamine hydrobromide Clinical Studies in the drug label.

How Supplied

There is limited information regarding Galantamine hydrobromide How Supplied in the drug label.

Storage

There is limited information regarding Galantamine hydrobromide Storage in the drug label.

Images

Drug Images

{{#ask: Page Name::Galantamine hydrobromide |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

{{#ask: Label Page::Galantamine hydrobromide |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Galantamine hydrobromide Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Galantamine hydrobromide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Galantamine hydrobromide Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Galantamine hydrobromide Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.