galantamine hbr 12 mg tablet generic razadyne

Uses

Alzheimer's Disease

Galantamine hydrobromide is used for the palliative treatment of mild to moderate dementia of the Alzheimer's type (Alzheimer's disease). Efficacy has been demonstrated in 5 randomized, placebo-controlled studies of 3-6 months' duration in patients diagnosed with probable Alzheimer's disease utilizing a dual outcome assessment strategy; 4 of these studies utilized conventional tablets, and 1 study utilized extended-release capsules. Changes in cognitive performance were assessed by various instruments, including the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS cog), and changes in overall clinical effects were assessed using the Clinician's Interview Based Impression of Change that required the use of caregiver information (CIBIC plus). (For additional information on ADAS cog and CIBIC plus, see Uses: Alzheimer's Disease in Donepezil Hydrochloride 12:04.) Overall, galantamine 8-16 mg twice daily (as conventional tablets) was found to be more effective than placebo for improvements in cognitive function and overall clinical status as assessed by the ADAS cog and CIBIC plus scales. In a 6-month study, galantamine 16-24 mg once daily (as extended-release capsules) was as effective as galantamine 8-12 mg twice daily (as conventional tablets) and more effective than placebo in improving cognitive function and overall daily function as assessed by the ADAS cog and Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scales, respectively; however, galantamine extended-release capsules were not more effective than placebo in improving overall clinical status (as assessed by the CIBIC plus scale). In a 6-month extension of a randomized, placebo-controlled study utilizing galantamine conventional tablets, clinical improvements were maintained over a 12-month study period in patients who continued to receive galantamine therapy. However, as with other anticholinesterase inhibitors (e.g., donepezil, tacrine), improvement associated with galantamine therapy was not maintained following discontinuance of the drug, suggesting that galantamine does not alter the underlying disease process of dementia.

For additional information on the management of Alzheimer's disease, .

Mild Cognitive Impairment

Galantamine has been investigated in patients with mild cognitive impairment who did not meet diagnostic criteria for Alzheimer's disease. However, the incidence of death in patients receiving galantamine was higher than the incidence in those receiving placebo in 2 randomized controlled studies in patients with mild cognitive impairment. (See Mortality under Warning/Precautions: Warnings, in Cautions.) Galantamine is not approved by the US Food and Drug Administration (FDA) for use in patients with mild cognitive impairment who do not have Alzheimer's disease; the manufacturer of galantamine does not intend to seek FDA approval for this indication.

Dosage and Administration

Administration

Galantamine hydrobromide conventional tablets and oral solution are administered orally twice daily, preferably with morning and evening meals. Galantamine hydrobromide extended-release capsules are administered orally once daily in the morning, preferably with food. Administration of galantamine with food and use of a slow, 4-week interval escalation of dosages may reduce the incidence of adverse GI effects (e.g., nausea, vomiting).

The oral solution should be administered using the graduated pipette provided by the manufacturer, referring to the accompanying patient information for instructions. The appropriate dose should be diluted in 100 mL of a nonalcoholic beverage just prior to administration, stirring well and then consuming the entire mixture.

Dispensing and Administration Precautions

Because similarity in spelling between Reminyl (the former trade name for galantamine hydrobromide) and Amaryl (the trade name for glimepiride, a sulfonylurea antidiabetic agent) previously has resulted in dispensing errors, the manufacturer of Reminyl announced in April 2005 that the trade name for galantamine hydrobromide would be changed from Reminyl to Razadyne to avoid future dispensing errors. (See Dispensing and Administration Precautions under Warnings/Precautions: General Precautions, in Cautions.)

Dosage

Dosage of galantamine hydrobromide is expressed in terms of galantamine. The recommended initial adult dosage of galantamine is 4 mg twice daily (as conventional tablets or oral solution) or 8 mg once daily (as extended-release capsules). The dosage may be increased 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). Subsequent increases to 12 mg twice daily (as conventional tablets or oral solution) or 24 mg once daily (as extended-release capsules) should be attempted after a minimum of 4 weeks of treatment at the previous dosage. Dosage increments should be based on clinical assessment of benefit and tolerance of the previous dosage. The recommended dosage of galantamine is 8-12 mg twice daily (as conventional tablets or oral solution); a dosage of 16-24 mg once daily (as extended-release capsules) was effective in clinical studies. Use of higher dosages (e.g., 16 mg twice daily) does not result in greater efficacy and is less well tolerated than lower dosages. If galantamine therapy has been interrupted for more than a few days for any reason and reinitiation of the drug is not contraindicated, therapy should be restarted using the lowest dosage and titrated upward to prior dosages.

Special Populations

Use with caution in patients with mild to moderate hepatic or renal impairment. Dosage generally should not exceed 16 mg daily in patients with moderate hepatic (Child-Pugh score of 7-9) or moderate renal impairment. Use not recommended in patients with severe hepatic (Child-Pugh score of 10-15) or severe renal (creatinine clearance less than 9 mL/minute) impairment.

Cautions

Contraindications

Known hypersensitivity to galantamine hydrobromide or any ingredient in the formulation.

Warnings/Precautions

Warnings

Cardiovascular Effects

Cholinesterase inhibitors such as galantamine may produce bradycardia, AV block, or other vagotonic effects on the heart. Although patients with supraventricular cardiac conduction abnormalities and those receiving concomitant therapy with drugs that substantially decrease heart rate appear to be at particular risk, these adverse cardiovascular effects may occur in any patient. In clinical studies, bradycardia or syncope was reported in 2-3 or 0.4-2.2%, respectively, of patients receiving up to 24 mg daily of galantamine compared with fewer than 1% of those receiving placebo.

Peptic Ulcers/GI Bleeding

Cholinesterase inhibitors such as galantamine may increase gastric acid secretion. Monitor closely for manifestations of active or occult GI bleeding, especially in patients at increased risk (e.g., history of ulcer disease, concomitant nonsteroidal anti-inflammatory agent [NSAIA] therapy).

Genitourinary Effects

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

Nervous System Effects

Potential for increased risk of seizures secondary to cholinergic activity (seizures also may be a manifestation of Alzheimer's disease).

Respiratory Effects

Like other drugs that increase cholinergic activity, use with caution in patients with a history of severe asthma or obstructive pulmonary disease.

Mortality

In 2 controlled studies of 2 years' duration in patients with mild cognitive impairment who did not meet diagnostic criteria for Alzheimer's disease, the incidence of death in those randomized to receive galantamine was higher than in those randomized to receive placebo (10.2 per 1000 person-years compared with 0.7 per 1000 person-years, respectively). The deaths were attributed to various causes that would be expected in a geriatric population; approximately half of the deaths in patients receiving galantamine were attributed to vascular causes (i.e., myocardial infarction, stroke, sudden death). Although the difference in mortality was significant, it should be noted that the incidence of mortality in these 2 studies differs from the incidence observed in other placebo-controlled studies that evaluated galantamine. The incidence of death in placebo-treated patients with mild cognitive impairment was substantially lower than the incidence observed in clinical studies in placebo-treated patients with Alzheimer's disease (0.7 per 1000 person-years compared with 21-61 per 1000 person-years, respectively). In addition, the incidence of death in galantamine-treated patients with mild cognitive impairment was lower than the incidence observed in clinical studies in galantamine-treated patients with Alzheimer's disease (10.2 per 1000 person-years compared with 23-31 per 1000 person-years, respectively). In the studies in patients with mild cognitive impairment, no placebo-treated patient died after 6 months, an unexpected finding in this age group.

General Precautions

Dispensing and Administration Precautions

Because of similarity in spelling between Reminyl (the former trade name for galantamine) and Amaryl (the trade name for glimepiride, a sulfonylurea antidiabetic agent), dispensing errors resulting in serious adverse events (e.g., severe hypoglycemia, death) have been reported. Therefore, in April 2005, the manufacturer of Reminyl announced that the trade name for galantamine hydrobromide would be changed from Reminyl to Razadyne to avoid future dispensing errors.

Specific Populations

Pregnancy

Category B. (.)

Lactation

Not known whether galantamine is distributed into milk; use in nursing women is not currently indicated.

Pediatric Use

Use not recommended.

Hepatic Impairment

Use not recommended in patients with severe hepatic impairment (Child-Pugh score of 10-15). Caution in patients with moderate hepatic impairment. (See Dosage and Administration: Special Populations.)

Renal Impairment

Use not recommended in patients with severe renal impairment (creatinine clearance less than 9 mL/minute). Caution in patients with moderate renal impairment. (See Dosage and Administration: Special Populations.)

Common Adverse Effects

Adverse effects reported in 5% or more of patients receiving galantamine hydrobromide (as conventional tablets) and with an incidence of at least twice that of placebo include nausea, vomiting, diarrhea, anorexia, and weight decrease; adverse effects associated with galantamine hydrobromide extended-release capsules were similar to those reported with the conventional tablets. Most adverse effects associated with galantamine occurred during the upward titration of dosages. Administration of galantamine with food, use of antiemetic agents, and ensuring adequate fluid intake may reduce the impact of these adverse events.

Drug Interactions

Drugs Affecting or Metabolized by Hepatic Microsomal (Cytochrome P-450) Enzymes

Inhibitors or inducers of cytochrome P-450 (CYP) isoenzymes 3A4 or 2D6; potential pharmacokinetic interaction (altered galantamine metabolism).

Amitriptyline, Fluoxetine, Fluvoxamine, Quinidine

Pharmacokinetic interaction (decreased galantamine clearance).

Cimetidine, Paroxetine

Pharmacokinetic interaction (increased galantamine bioavailability).

Erythromycin, Ketoconazole

Pharmacokinetic interaction (increased area under the plasma galantamine concentration-time curve).

Digoxin, Ranitidine, Warfarin

Pharmacokinetic interaction unlikely.

Anesthesia

Potential pharmacologic interaction (exaggerated response to succinylcholine-type muscle relaxants during surgery).

Anticholinergics

Potential pharmacologic interaction (antagonistic effects).

Cholinomimetics and Other Cholinesterase Inhibitors

Potential pharmacologic interaction (additive effects).