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AURO-GALANTAMINE ER is a brand name for Galantamine, supplied as a capsule (extended release). The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: AND CLINICAL USE ........................................................................... 3 CONTRAINDICATIONS ................................................................................................. 3 WARNINGS AND PRECAUTIONS ............................................................................... 4…
Verbatim from this product's HC label. Tap a section to expand.
AURO-GALANTAMINE ER (galantamine hydrobromide) is not indicated for use in patients with mild cognitive impairment (see WARNINGS AND PRECAUTIONS, Special Populations, Patients with Mild Cognitive Impairment (MCI): Mortality in Investigational Trials in MCI).
AURO-GALANTAMINE ER should only be prescribed by (or following consultation with) clinicians who are experienced in the diagnosis and management of Alzheimer’s disease. AURO-GALANTAMINE ER extended release capsules should be administered once daily in the morning, preferably with food.
Patients and caregivers should be advised to ensure adequate fluid intake during treatment.
Dosing Considerations Concomitant Treatment:
In patients treated with potent CYP2D6 or CYP3A4 inhibitors, dose reductions can be considered. Special Populations: Dosage adjustments may be required for elderly patients (>85 years old) with low body weight (especially females), and patients with hepatic and/or renal impairment.
Missed Dose: The missed dose should be taken at the next scheduled dose. Doses should not be doubled. 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.
Recommended Dose and Dosage Adjustment The dosage of galantamine (as galantamine ER) shown to be effective in controlled clinical trials is 16–32 mg/day. 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 16–24 mg/day.
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 is 8 mg once daily for 4 weeks.
The dose should be increased to the initial maintenance dose of 16 mg once daily after 4 weeks. If this initial maintenance dose is well tolerated, a further increase to 24 mg once daily may be considered only after a minimum of 4 weeks at mg once daily.
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.
Clinical Trial Adverse Drug Reactions Because clinical trials are conducted under very specific conditions, the adverse drug reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. A total of 2287 patients with mild to moderate Alzheimer’s disease were treated with galantamine in Phase III controlled clinical studies using either a 1-week or 4-week dose- escalation period, and 761 patients received galantamine 24 mg/day, the maximum recommended maintenance dose.
The number of patients who completed the studies was 1686 (72%). The mean duration of treatment for all galantamine groups was 130 days (range 1–214 days). Adverse Events Leading to Discontinuation Overall, 19% (441/2287) of patients treated with galantamine discontinued from Phase III controlled clinical trials due to adverse events compared to 8% (98/1159) in the placebo group.
For patients treated with galantamine, the rate of discontinuation due to adverse events was 14% for males and 22% for females. In the 4-week dose-escalation fixed-dose study (GAL-USA-10), 8% (55/692) of patients treated with galantamine withdrew due to adverse events compared to 7% (20/286) in the placebo group.
During the dose-escalation phase of this study the incidence of discontinuations due to adverse events was 4% for placebo, 5% for galantamine 16 mg/day and 6% for galantamine 24 mg/day. During the maintenance phase, 4% of patients who received placebo, 3% of patients who received galantamine 16 mg/day and 4% of patients who received galantamine 24 mg/day withdrew from this study due to adverse events.
1 shows the most frequent adverse events leading to discontinuation for study GAL- USA-10, in which the recommended 4-week dose-escalation schedule was used. 2. These events were primarily gastrointestinal and tended to occur at a lower rate with 16 mg/day, the initial recommended maintenance dose.
Carcinogenesis and Mutagenesis See Product Monograph Part II:
TOXICOLOGY, Mutagenicity and Carcinogenicity for discussion on animal data. Cardiovascular Because of their pharmacological action, cholinesterase inhibitors have vagotonic effects on the sinoatrial and atrioventricular nodes, leading to bradycardia and all types of atrioventricular node block (see ADVERSE REACTIONS).
These actions may be particularly important to patients with “sick sinus syndrome” or other supraventricular cardiac conduction disorders, or to patients taking other drugs concomitantly which significantly slow heart rate. In clinical trials, patients with serious cardiovascular disease were excluded.
Caution should be exercised in treating patients with active coronary artery disease or congestive heart failure. It is recommended that AURO-GALANTAMINE ER not be used in patients with cardiac conduction abnormalities (except for right bundle branch block) including “sick sinus syndrome” and those with unexplained syncopal episodes.
In randomized controlled trials, bradycardia was reported at 2–3% for galantamine doses up to 24 mg/day compared with <1% for placebo, but was rarely severe and rarely led to treatment discontinuation. No increased incidence of heart block was observed at the recommended doses.
2% [6/273]). A 6-week cardiovascular safety clinical trial (GAL-USA-16; n=139) was performed to investigate the effect of galantamine at doses up to 32 mg/day. This dosing regimen was: 8 mg/day in Week 1, 16 mg/day in Week 2, 24 mg/day in Weeks 3 and 4, and 32 mg/day in Weeks 5 and 6.
Heart block/pauses greater than two seconds were more common in galantamine-treated patients than in placebo-treated patients. It should be noted that a forced one-week dose escalation was used in this study, which is not recommended.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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The beneficial effects of galantamine are lost, however, when the drug is discontinued. Geriatrics Dose escalation for elderly patients (>85 years old) with low body weight (especially females) or serious comorbid diseases should be undertaken with particular caution.
Page 18 of 54 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 7–9), based on pharmacokinetic modelling, dosing with galantamine extended release capsules should begin with 8 mg every other day in the morning, preferably with food, for at least 1 week.
Then the dosage should be increased to 8 mg once daily for at least 4 weeks. In these patients, daily doses should not exceed a total of 16 mg once daily. Since no data are available on the use of galantamine in patients with severe hepatic impairment (Child-Pugh score of 10–15), AURO- GALANTAMINE ER is not recommended for this population (see WARNINGS AND PRECAUTIONS).
Renal Impairment For patients with renal impairment (creatinine clearance of 9 to 60 mL/min), dose escalation should proceed cautiously and the maintenance dose should generally not exceed 16 mg once daily. Since no data are available on the use of galantamine in patients with a creatinine clearance less than 9 mL/min, AURO-GALANTAMINE ER is not recommended for this population (see WARNINGS AND PRECAUTIONS).
In a population of cognitively-impaired individuals, safe use of this and all other medications may require supervision. OVERDOSAGE Symptoms Overdosage with cholinesterase inhibitors can result in cholinergic crisis characterized by severe nausea, vomiting, gastro-intestinal cramping, salivation, lacrimation, urination, defecation, sweating, bradycardia, hypotension, respiratory depression, collapse and convulsions.
Increasing muscle weakness together with tracheal hypersecretion and bronchospasm, may lead to vital airway compromise. There have been post-marketing reports of torsade de pointes, QT prolongation, bradycardia, ventricular tachycardia and brief loss of consciousness in association with inadvertent overdoses of galantamine.
In one case where the dose was known, eight 4 mg tablets (32 mg total) were ingested on a single day. 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. Another patient, who was prescribed 16 mg/day, inadvertently ingested 160 mg and experienced sweating, vomiting, bradycardia, and near-syncope one hour later, which necessitated hospital treatment.
His symptoms resolved within 24 hours. Page 19 of 54 Treatment Galantamine has a plasma half-life of approximately 7–8 hours. It is recommended that, in case of asymptomatic overdose, no further dose of AURO-GALANTAMINE ER should be administered and the patient should be monitored.
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 […]
Administration of galantamine with food, the use of anti-emetic medication and ensuring adequate fluid intake may reduce the impact of these events. 2: Most frequent adverse events in a randomized placebo-controlled clinical trial with a 4-week dose increment during dose-escalation and maintenance phases (GAL-USA- 10) Week 1–12† Week 13–21 Adverse Events Placebo n=286 % 16 mg/day n=279 % 24 mg/day n=273 % Placebo n=259 % 16 mg/day n=243 % 24 mg/day n=241 % Nausea 5 11 13 <1 4 6 Vomiting <1 5 6 <1 2 6 Diarrhea 5 9 4 2 5 2 Anorexia 2 5 5 1 2 5 †Dose escalation occurred with 4 weeks per dose increment.
The majority of these adverse events occurred during the dose-escalation period. Nausea and vomiting, the most frequent adverse events, occurred more frequently at higher doses, lasted 5–7 days in most cases, and the majority of patients had one episode.
The incidence of weight loss in this study was, during dose escalation (Weeks 1–12): placebo, 1%; 16 mg/day, 3%; 24 mg/day, 2%; and during the maintenance phase (Weeks 13–21): placebo, <1%; 16 mg/day, 3%; 24 mg/day, 3%. Dose-escalation should be cautious and maintenance dosing should remain flexible and be adjusted according to individual needs.
Adverse Events Reported in Controlled Trials The reported adverse events in trials of 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 behaviour and the types of patients treated may differ.
3 lists the most common adverse events (adverse events occurring with an incidence of 2% with galantamine treatment and in which the incidence was greater than with placebo treatment) for four placebo-controlled trials for patients treated with 16 or 24 mg/day of galantamine.
3 were derived from trials using a 1- week or the recommended 4-week dose-escalation period. 3: Adverse events reported in at least 2% of patients with Alzheimer’s disease administered Galantamine and at a frequency greater than with placebo (combined 1-and 4-week dose-escalation data) Body System/Adverse Events Placebo (n=801) % Galantamine † (n=1040) % Body as a whole - general disorders Fatigue Syncope 3 1 5 2 Central and peripheral nervous system disorders Dizziness Headache Tremor 6 5 2 9 8 3 Gastrointestinal system disorders Nausea Vomiting Diarrhea Abdominal pain Dyspepsia 9 4 7 4 2 24 13 9 5 5 Heart rate and rhythm disorders Bradycardia 1 2 Metabolic and nutritional disorders Anorexia Weight decrease 3 2 9 7 Psychiatric disorders Depression Insomnia Somnolence 5 4 3 7 5 4 Red blood cell disorders Anemia 2 3 Respiratory system disorders Rhinitis 3 4 Urinary system disorders Urinary tract infection Hematuria 7 2 8 3 † Adverse events in patients treated with 16 or 24 mg/day of galantamine in three placebo-controlled trials with a 1-week dose-escalation period and a 26-week fixed-dose galantamine treatment, and one placebo-controlled trial with the recommended 4-week dose-escalation period and a 21-week fixed- dose […]
Whether these cardiac effects are attenuated by slower titration rates is not known. Particular caution is warranted during titration where the majority of pauses occurred in the above study. Metabolism Weight Monitoring Cholinesterase inhibitors as well as Alzheimer’s disease can be associated with significant weight loss.
In controlled clinical trials, the use of galantamine was associated with weight loss. Weight decrease occurred early during treatment and was related to dose. Weight loss of ≥7% occurred more frequently in patients treated with galantamine and in female patients than in patients receiving placebo.
Where weight loss may be of clinical concern, body weight should be monitored. Page 5 of 54 Gastrointestinal Through their primary action, cholinesterase inhibitors may be expected to increase gastric acid secretion due to increased cholinergic activity.
, those with a history of ulcer disease or patients using concurrent nonsteroidal anti-inflammatory drugs (NSAIDs). In controlled clinical studies with galantamine, patients with symptomatic peptic ulceration were excluded. Clinical studies of galantamine have shown no increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding (see ADVERSE REACTIONS).
Galantamine, as a predictable consequence of its pharmacological properties, has been shown to produce nausea, vomiting and diarrhea, anorexia and weight loss. These effects appeared more frequently at higher doses (see ADVERSE REACTIONS), with nausea and vomiting being more prevalent in women and patients with lower body weight and correspondingly higher plasma drug concentrations.
Females are more sensitive to the cholinergic adverse effects associated with cholinesterase inhibitors and in general are more likely to experience nausea and vomiting than are males. In most cases, these effects were of mild to moderate intensity and transient and have resolved during continued galantamine treatment or upon treatment discontinuation.
Genitourinary Although not observed in clinical trials of galantamine, cholinomimetics may cause bladder outflow obstruction.
Neurologic Seizures:
In placebo-controlled trials with galantamine, cases of seizure were reported; there was no increase in incidence compared with placebo. Convulsions have been reported with galantamine (see ADVERSE REACTIONS). Seizure activity may also be a manifestation of Alzheimer’s disease.
The risk/benefit of AURO-GALANTAMINE ER treatment for patients with a history of seizure disorder must therefore be carefully evaluated. Galantamine has not been studied in patients with moderately severe or severe Alzheimer’s disease, non-Alzheimer dementias or individuals with Parkinsonian features.
The efficacy and safety of galantamine in these patient populations is unknown.
Peri-Operative Considerations Anesthesia:
Galantamine, as a cholinesterase inhibitor, is likely to exaggerate succinylcholine- type muscle relaxation during anesthesia. Respiratory Like other cholinomimetic drugs, AURO-GALANTAMINE ER should be prescribed with care for patients with a history of asthma or obstructive pulmonary disease.
, erythema multiforme), have been reported Page 6 of 54 in patients receiving galantamine (see ADVERSE REACTIONS, Post-Market Adverse Drug Reactions). Patients or caregivers should be instructed to inform their health care provider of any skin reactions that occur during treatment with AURO-GALANTAMINE ER.
It is recommended that treatment should be discontinued at the first appearance of skin rash. Special Populations Hepatic Impairment: […]