Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/3229
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Galantamine (Tablet)
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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.<br/>Doses in Special Populations: 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. 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.
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Galantamine hydrobromide is a reversible, competitive acetylcholinesterase inhibitor. Galantamine hydrobromide is known chemically as (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. It has an empirical formula of CHNOHBr and a molecular weight of 368.27. Galantamine hydrobromide is a white to almost white powder and is sparingly soluble in water. The structural formula for galantamine hydrobromide is: Galantamine hydrobromide for oral use is available in round, white film-coated tablets of 4 mg, 8 mg, and 12 mg. Each 4, 8, and 12 mg (base equivalent) tablet contains 5.128, 10.256, and 15.384 mg of galantamine hydrobromide USP, respectively. Inactive ingredients are colloidal silicon dioxide, crospovidone, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol and titanium dioxide.
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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.<br/>Pharmacokinetics: Galantamine is well absorbed with absolute oral bioavailability of about 90%. It has a terminal elimination half-life of about 7 hours and pharmacokinetics are linear over the range of 8 to 32 mg/day. The maximum inhibition of acetylcholinesterase activity of about 40% was achieved about one hour after a single oral dose of 8 mg galantamine in healthy male subjects.<br/>Absorption and Distribution: Galantamine is rapidly and completely absorbed with time to peak concentration about 1 hour. Bioavailability of the tablet was the same as the bioavailability of an oral solution. Food did not affect the AUC of galantamine but Cdecreased by 25% and Twas delayed by 1.5 hours. The mean volume of distribution of galantamine is 175 L. The plasma protein binding of galantamine is 18% at therapeutically relevant concentrations. In whole blood, galantamine is mainly distributed to blood cells (52.7%). The blood to plasma concentration ratio of galantamine is 1.2.<br/>Metabolism and Elimination: Galantamine is metabolized by hepatic cytochrome P450 enzymes, glucuronidated, and excreted unchanged in the urine. In vitro studies indicate that cytochrome CYP2D6 and CYP3A4 were the major cytochrome P450 isoenzymes involved in the metabolism of galantamine, and inhibitors of both pathways increase oral bioavailability of galantamine modestly (see PRECAUTIONS, Drug-Drug Interactions). O-demethylation, mediated by CYP2D6 was greater in extensive metabolizers of CYP2D6 than in poor metabolizers. In plasma from both poor and extensive metabolizers, however, unchanged galantamine and its glucuronide accounted for most of the sample radioactivity. In studies of oralH-galantamine, unchanged galantamine and its glucuronide, accounted for most plasma radioactivity in poor and extensive CYP2D6 metabolizers. Up to 8 hours post-dose, unchanged galantamine accounted for 39 to 77% of the total radioactivity in the plasma, and galantamine glucuronide for 14 to 24%. By 7 days, 93 to 99% of the radioactivity had been recovered, with about 95% in urine and about 5% in the feces. Total urinary recovery of unchanged galantamine accounted for, on average, 32% of the dose and that of galantamine glucuronide for another 12% on average. After i.v. or oral administration, about 20% of the dose was excreted as unchanged galantamine in the urine in 24 hours, representing a renal clearance of about 65 mL/min, about 20 to 25% of the total plasma clearance of about 300 mL/min.<br/>Special Populations:<br/>CYP2D6 Poor Metabolizers: Approximately 7% of the normal population has a genetic variation that leads to reduced levels of activity of CYP2D6 isozyme. Such individuals have been referred to as poor metabolizers. After a single oral dose of 4 mg or 8 mg galantamine, CYP2D6 poor metabolizers demonstrated a similar Cand about 35% AUC���increase of unchanged galantamine compared to extensive metabolizers. A total of 356 patients with Alzheimer's disease enrolled in two Phase 3 studies were genotyped with respect to CYP2D6 (n=210 heteroextensive metabolizers, 126 homoextensive metabolizers, and 20 poor metabolizers). Population pharmacokinetic analysis indicated that there was a 25% decrease in median clearance in poor metabolizers compared to extensive metabolizers. Dosage adjustment is not necessary in patients identified as poor metabolizers as the dose of drug is individually titrated to tolerability.<br/>Drug-Drug Interactions (see also PRECAUTIONS, Drug-Drug Interactions): Multiple metabolic pathways and renal excretion are involved in the elimination of galantamine so no single pathway appears predominant. Based on in vitro studies, CYP2D6 and CYP3A4 were the major enzymes involved in the metabolism of galantamine. CYP2D6 was involved in the formation of O-desmethyl-galantamine, whereas CYP3A4 mediated the formation of galantamine-N-oxide. Galantamine is also glucuronidated and excreted unchanged in urine.<br/>(A) Effect of Other Drugs on the Metabolism of Galantamine:: Drugs that are potent inhibitors for CYP2D6 or CYP3A4 may increase the AUC of galantamine. Multiple dose pharmacokinetic studies demonstrated that the AUC of galantamine increased 30% and 40%, respectively, during coadministration of ketoconazole and paroxetine. As coadministered with erythromycin, another CYP3A4 inhibitor, the galantamine AUC increasedonly 10%. Population PK analysis with a database of 852 patients with Alzheimer's disease showed that the clearance of galantamine was decreased about 25 to 33% by concurrent administration of amitriptyline (n=17), fluoxetine (n=48), fluvoxamine (n=14), and quinidine (n=7), known inhibitors of CYP2D6. Concurrent administration of H-antagonists demonstrated that ranitidine did not affect the pharmacokinetics of galantamine, and cimetidine increased the galantamine AUC by approximately 16%. A multiple dose pharmacokinetic study with concurrent administration of memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, demonstrated that co-administration of memantine in a dose of 10 mg BID did not affect the pharmacokinetic profile of galantamine (16 mg daily) at steady state.<br/>(B) Effect of Galantamine on the Metabolism of Other Drugs:: In vitro studies show that galantamine did not inhibit the metabolic pathways catalyzed by CYP1A2, CYP2A6, CYP3A4, CYP4A, CYP2C, CYP2D6 and CYP2E1. This indicated that the inhibitory potential of galantamine towards the major forms of cytochrome P450 is very low. Multiple doses of galantamine (24 mg/day) had no effect on the pharmacokinetics of digoxin and warfarin (R- and S- forms). Galantamine had no effect on the increased prothrombin time induced by warfarin.
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Galantamine Tablets, USP are contraindicated in patients with known hypersensitivity to galantamine hydrobromide or to any excipients used in the formulation.
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Galantamine Tablets, USP are available as follows: 4 mgtablet: 5 mm, normal convex, white film coated tablet debossed "GT over 4" on one side and "G" on the other. Bottles of 60 NDC 57315-108-01 Bottles of 1000 NDC 57315-108-02 8 mgtablet: 6.55 mm, normal convex, white film coated tablet debossed "GT over 8" on one side and "G" on the other. Bottles of 60 NDC 57315-109-01 Bottles of 1000 NDC 57315-109-02 12 mgtablet: 8 mm, normal convex, white film coated tablet debossed "GT over 12" on one side and "G" on the other. Bottles of 60 NDC 57315-110-01 Bottles of 1000 NDC 57315-110-02 Galantamine base equivalent. Store at 20��to 25��C (68��to 77��F) [see USP Controlled Room Temperature]. Dispense in a tight light-resistant container as described in the USP. Keep out of reach of children. MANUFACTURED BY ALPHAPHARM PTY LTD 15 Garnet Street Carole Park QLD 4300 Australia PM No: 1753/4 Revised September 2008
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Information for patients and Caregivers: Caregivers should be instructed about the recommended dosage and administration of galantamine hydrobromide. Galantamine hydrobromide tablets should be administered twice per day, preferably with the morning and evening meals. Dose escalation (dose increases) should follow minimum of four weeks at prior dose. Patients and caregivers should be advised that the most frequent adverse events associated with use of the drug can be minimized by following the recommended dosage and administration. 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.<br/>Deaths in Subjects with Mild Cognitive Impairment (MCI): In two randomized placebo controlled trials of 2 years duration in subjects with mild cognitive impairment (MCI), a total of 13 subjects on galantamine (n=1026) and 1 subject on placebo (n=1022) died. The deaths were due to various causes which could be expected in an elderly population; about half of the galantamine deaths appeared to result from various vascular causes (myocardial infarction, stroke, and sudden death). Although the difference in mortality between galantamine and placebo-treated groups in these two studies was significant, the results are highly discrepant with other studies of galantamine. Specifically, in these two MCI studies, the mortality rate in the placebo-treated subjects was markedly lower than the rate in placebo-treated patients in trials of galantamine in Alzheimer's disease or other dementias (0.7 per 1000 person years compared to 22 to 61 per 1000 person years, respectively). Although the mortality rate in the galantamine-treated MCI subjects was also lower than that observed in galantamine-treated patients in Alzheimer's disease and other dementia trials(10.2 per 1000 person years compared to 23 to 31 per 1000 person years, respectively), the relative difference was much less. When the Alzheimer's disease and other dementia studies were pooled (n=6000), the mortality rate in the placebo group numerically exceeded that in the galantamine group. Furthermore, in the MCI studies, no subjects in the placebo group died after 6 months, a highly unexpected finding in this population. Individuals with mild cognitive impairment demonstrate isolated memory impairment greater than expected for their age and education, but do not meet current diagnostic criteria for Alzheimer's disease.<br/>Special Populations:<br/>Hepatic Impairment: In patients with moderately impaired hepatic function, dose titration should proceed cautiously (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION). The use of galantamine in patients with severe hepatic impairment is not recommended.<br/>Renal Impairment: In patients with moderately impaired renal function, dose titration should proceed cautiously (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION). In patients with severely impaired renal function (CL<9 mL/min) the use of galantamine is not recommended.<br/>Drug-Drug Interactions (see also CLINICAL PHARMACOLOGY, Drug-Drug Interactions):<br/>Use With Anticholinergics: Galantamine has the potential to interfere with the activity of anticholinergic medications.<br/>Use With Cholinomimetics and Other Cholinesterase Inhibitors: A synergistic effect is expected when cholinesterase inhibitors are given concurrently with succinylcholine, other cholinesterase inhibitors, similar neuromuscular blocking agents or cholinergic agonists such as bethanechol.<br/>A) Effect of Other Drugs on Galantamine:<br/>In vitro: CYP3A4 and CYP2D6 are the major enzymes involved in the metabolism of galantamine. CYP3A4 mediates the formation of galantamine-N-oxide; CYP2D6 leads to the formation of O-desmethyl-galantamine. Because galantamine is also glucuronidated and excreted unchanged, no single pathway appears predominant.<br/>In vivo: Cimetidine and Ranitidine: Galantamine was administered as a single dose of 4 mg on day 2 of a 3-day treatment with either cimetidine (800 mg daily) or ranitidine (300 mg daily). Cimetidine increased the bioavailability of galantamine by approximately 16%. Ranitidine had no effect on the PK of galantamine. Ketoconazole: Ketoconazole, a strong inhibitor of CYP3A4 and an inhibitor of CYP2D6, at a dose of 200 mg BID for 4 days, increased the AUC of galantamine by 30%. Erythromycin: Erythromycin, a moderate inhibitor of CYP3A4 at a dose of 500 mg QID for 4 days, affected the AUC of galantamine minimally (10% increase). Paroxetine: Paroxetine, a strong inhibitor of CYP2D6, at 20 mg/day for 16 days, increased the oral bioavailability of galantamine by about 40%. Memantine: Memantine, an N-methyl-D-aspartate receptor antagonist, at a dose of 10 mg BID had no effect on the pharmacokinetics of galantamine (16 mg/day) at steady state.<br/>B) Effect of Galantamine on Other Drugs:<br/>In vitro: Galantamine did not inhibit the metabolic pathways catalyzed by CYP1A2, CYP2A6, CYP3A4, CYP4A, CYP2C, CYP2D6 or CYP2E1. This indicates that the inhibitory potential of galantamine towards the major forms of cytochrome P450 is very low.<br/>In vivo: Warfarin: Galantamine at 24 mg/day had no effect on the pharmacokinetics of R-and-S-warfarin (25 mg single dose) or on the prothrombin time. The protein binding of warfarin was unaffected by galantamine. Digoxin: Galantamine at 24 mg/day had no effect on the steady-state pharmacokinetics of digoxin (0.375 mg once daily) when they were coadministered. In this study, however, one healthy subject was hospitalized for 2and 3degree heart block and bradycardia.<br/>Carcinogenesis, mutagenesis, impairment of fertility: In a 24-month oral carcinogenicity study in rats, a slight increase in endometrial adenocarcinomas was observed at 10 mg/kg/day (4 times the Maximum Recommended Human Dose [MRHD] on a mg/mbasis or 6 times on an exposure [AUC] basis) and 30 mg/kg/day (12 times MRHD on a mg/mbasis or 19 times on an AUC basis). No increase in neoplastic changes was observed in females at 2.5 mg/kg/day (equivalent to the MRHD on a mg/mbasis or 2 times on an AUC basis) or in males up to the highest dose tested of 30 mg/kg/day (12 times the MRHD on a mg/mand AUC basis). Galantamine was not carcinogenic in a 6-month oral carcinogenicity study in transgenic (P 53-deficient) mice up to 20 mg/kg/day, or in a 24-month oral carcinogenicity study in male and female mice up to 10 mg/kg/day (2 times the MRHD on a mg/mbasis and equivalent on an AUC basis). Galantamine produced no evidence of genotoxic potential when evaluated in the in vitro Ames S. typhimurium or E. coli reverse mutation assay, in vitro mouse lymphoma assay, in vivo micronucleus test in mice, or in vitro chromosome aberration assay in Chinese hamster ovary cells. No impairment of fertility was seen in rats given up to 16 mg/kg/day (7 times the MRHD on a mg/mbasis) for 14 days prior to mating in females and for 60 days prior to mating in males.<br/>Pregnancy:<br/>Pregnancy Category B:: In a study in which rats were dosed from day 14 (females) or day 60 (males) prior to mating through the period of organogenesis, a slightly increased incidence of skeletal variations was observed at doses of 8 mg/kg/day (3 times the Maximum Recommended Human Dose [MRHD] on a mg/mbasis) and 16 mg/kg/day. In a study in which pregnant rats were dosed from the beginning of organogenesis through day 21 post-partum, pup weights were decreased at 8 and 16 mg/kg/day, but no adverse effects on other postnatal developmental parameters were seen. The doses causing the above effects in rats produced slight maternal toxicity. No major malformations were caused in rats given up to 16 mg/kg/day. No drug related teratogenic effects were observed in rabbits given up to 40 mg/kg/day (32 times the MRHD on a mg/mbasis) during the period of organogenesis. There are no adequate and well-controlled studies of galantamine in pregnant women. Galantamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.<br/>Nursing mothers: It is not known whether galantamine is excreted in human breast milk. Galantamine has no indication for use in nursing mothers.<br/>Pediatric use: There are no adequate and well-controlled trials documenting the safety and efficacy of galantamine in any illness occurring in children. Therefore, use of galantamine in children is not recommended.
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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. Inaddition 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.
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Galantamine Hydrobromide
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Galantamine (Tablet)
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Pre-Marketing Clinical Trial Experience:: The specific adverse event data described in this section are based on studies of the immediate release tablet formulation.<br/>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.<br/>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. Table 3: The most common adverse events (adverse events occurring with an incidence of at least 2% with galantamine treatment and in which the incidence was greater than with placebo treatment) are listed in Table 3 for four placebo-controlled trials for patients treated with 16 or 24 mg/day of galantamine. a: Adverse events in patients treated with 16 or 24 mg/day of galantamine in four placebo-controlled trials are included. 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.<br/>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: frequentadverse 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: Infrequent: postural hypotension, hypotension, dependent edema, cardiac failure, myocardial ischemia or infarction Central&Peripheral Nervous System Disorders: Infrequent: 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<br/>Post-Marketing 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.
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Anesthesia: Galantamine, as a cholinesterase inhibitor, is likely to exaggerate the neuromuscular blocking effects of succinylcholine-type and similar neuromuscular blocking agents during anesthesia.<br/>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]).<br/>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 (see ADVERSE REACTIONS).<br/>Genitourinary: Although this was not observed in clinical trials with galantamine, cholinomimetics may cause bladder outflow obstruction.<br/>Neurological Conditions:<br/>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.<br/>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.
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Galantamine hydrobromide is indicated for the treatment of mild to moderate dementia of the Alzheimer's type.
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Galantamine
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