Galantamine
Galantamine
Definition
Galantamine belongs to a class of drugs called acetylcholinesterase inhibitors. In the United States, galantamine is sold under the brand name Razadyne (formerly Reminyl).
Purpose
Galantamine is used to treat the symptoms of Alzheimer’s disease. Galantamine is also being evaluated for the treatment of respiratory depression , mania, vascular dementia due to stroke or cardiac arrest that causes brain lesions, and reversal of side effects (e.g., blurred vision and mental changes) caused by medications such as scopolamine, as well as for other mental disorders.
Description
Alzheimer’s disease develops when brain cells, called neurons, undergo an early and selective death. It is believed that the premature death of these neurons may be prevented if stimulated by a brain chemical called acetylcholine. Acetylcholine is recycled by an enzyme called acetylcholinesterase. Galantamine works by inhibiting this enzyme. The inhibition of acetylcholinesterase increases the concentration of available acetylcholine.
Galantamine has only been studied, and is only used, in patients with mild-to-moderate Alzheimer’s disease according to the Alzheimer’s Disease Assessment Scale.
Galantamine is available in 4-mg, 8-mg, and 12-mg tablets.
Recommended dosage
The recommended initial dose of galantamine in adults is 4 mg twice daily. After a minimum of four weeks of treatment with galantamine, the dosage may be increased to 8 mg twice daily. Further increases to 12 mg twice daily should be initiated only after a minimum of four weeks at the previous dose.
Increased side effects associated with higher doses may prevent the increase in dose in some patients. Patients with moderate liver or kidney problems should not exceed 16 mg of galantamine daily.
Precautions
Galantamine should not be used in patients with severe liver or kidney problems. Since there are no well-controlled studies for the use of galantamine in pregnancy, galantamine should only be used if the potential benefits justify the potential risks to the fetus.
Patients who are undergoing anesthesia or bladder or gastrointestinal surgery should take galantamine only after a discussion with their physician. Patients with gastrointestinal problems should be closely monitored if it is decided that they should take galantamine. Galantamine should be used under close physician supervision in patients who have Parkinson’s disease, severe asthma, or obstructive pulmonary disease. Because galantamine may slow down the heart, patients with any heart conditions, and especially patients taking other medications that slow down the heart, should be evaluated before starting galantamine.
Side effects
The most common side effects reported with the use of galantamine are nausea, vomiting, diarrhea, anorexia, and abdominal pain. These occur most often at dosage-escalation periods. The average duration of nausea is five to seven days. These side effects tend to be less frequent if the patient is taking a total daily dosage of 16 mg. Eleven percent of patients receiving 24 mg daily lose weight, while 6% of patients receiving 16 mg daily experience weight loss.
KEY TERMS
Acetylcholine —A naturally occurring chemical in the body that transmits nerve impulses from cell to cell. Generally, acetylcholine has opposite effects from dopamine and norepinephrine; it causes blood vessels to dilate, lowers blood pressure, and slows the heartbeat. Central nervous system well-being is dependent on a balance among acetylcho-line, dopamine, serotonin, and norepinephrine.
Acetylcholinesterase —The chemical responsible for the breakdown of acetylcholine.
Parkinson’s disease —A disease of the nervous system most common in people over age 60, characterized by a shuffling gait, trembling of the fingers and hands, and muscle stiffness.
Other common side effects include dizziness, headache, tremors, fatigue , depression, agitation, irritation, and insomnia. These side effects have a higher incidence and severity if higher doses are used. If side effects become severe, the dosage should be adjusted downward under physician supervision.
Interactions
There is currently little data regarding potential drug interactions with galantamine. Medications that are known to increase levels of galantamine in the body include cimetidine, erythromycin, ketoconazole, and paroxetine.
Resources
PERIODICALS
Ancoli-Israel, Sonia, and others. “Effects of Galantamine Versus Donepezil on Sleep in Patients with Mild to Moderate Alzheimer Disease and Their Caregivers: A Double-Blind, Head-To-Head, Randomized Pilot Study.” Alzheimer Disease & Associated Disorders 19.4 (October-December 2005): 240–45.
Biederman, Joseph, and others. “A Double-Blind Comparison of Galantamine Hydrogen Bromide and Placebo in Adults with Attention-Deficit/Hyperactivity Disorder: A Pilot Study.” Journal of Clinical Psychopharmacology 26.2 (April 2006): 163–66.
Brodaty, Henry, and others. “Galantamine Prolonged-Release Formulation in the Treatment of Mild to Moderate Alzheimer’s Disease.” Dementia and Geriatric Cognitive Disorders 20.2-3 (August 2005): 120–32.
Harry, Robin D. J., and Konstantine K. Zakzanis. “A Comparison of Donepezil and Galantamine in the treatment of Cognitive Symptoms of Alzheimer’s Disease: A Meta-Analysis.” Human Psychopharmacology: Clinical and Experimental 20.3 (April 2005): 183–87.
Koontz, Jennifer, and Andrius Baskys. “Effects of Galantamine on Working Memory and Global Functioning in Patients with Mild Cognitive Impairment: A Double-Blind Placebo-Controlled Study.” American Journal of Alzheimer’s Disease and Other Dementias 20.5 (September-October 2005): 295–302.
López-Pousa, S., and others. “Differential Efficacy of Treatment with Acetylcholinesterase Inhibitors in Patients with Mild and Moderate Alzheimer’s Disease Over a 6-Month Period.” Dementia and Geriatric Cognitive Disorders 19.4 (March 2005): 189–95.
Ochoa, Enrique L. M. “Galantamine May Improve Attention and Speech in Schizophrenia.” Human Psychopharmacology: Clinical and Experimental 21.2 (March 2006): 127–28.
Robinson, Dean M., and Greg L. Plosker. “Galantamine Extended Release in Alzheimer’s Disease: Profile Report.” Drugs and Aging 23.10 (2006): 839–42.
Rockwood, Kenneth, and others. “Attainment of Treatment Goals by People with Alzheimer’s Disease Receiving Galantamine: A Randomized Controlled Trial.” Canadian Medical Association Journal 174.8 (April 2006): 1099–1105.
Schubert, Max H., Keith A. Young, and Paul B. Hicks. “Galantamine Improves Cognition in Schizophrenic Patients Stabilized on Risperidone.” Biological Psychiatry 60.6 (September 2006): 530–33.
Takeda, A., and others. “A Systematic Review of the Clinical Effectiveness of Donepezil, Rivastigmine and Galantamine on Cognition, Quality of Life and Adverse Events in Alzheimer’s Disease.” International Journal of Geriatric Psychiatry 21.1 (January 2006): 17–28.
OTHER
Ortho-McNeil Neurologics, Inc. “Full U.S. Prescribing Information for Razadyne.” Available online at <http://www.razadyneer.com/active/janus/en_US/assets/common/company/pi/razadyne.pdf>. Revised May 2006.
Ajna Hamidovic, Pharm.D.
Ruth A. Wienclaw, PhD
Galantamine
Galantamine
Definition
Galantamine belongs to a class of drugs called acetylcholinesterase inhibitors. In the United States galantamine is sold under brand name Reminyl.
Purpose
Galantamine is used to treat the symptoms of Alzheimer's disease . Galantamine is also being evaluated for the treatment of respiratory depression, mania, vascular dementia due to stroke or cardiac arrest that causes brain lesions, and reversal of side effects, such as blurred vision and mental changes caused by medications such as scopolamine.
Description
Alzheimer's disease develops when brain cells, called neurons, undergo an early, and selective death. It is believed that the premature death of these neurons may be prevented if stimulated by a brain chemical called acetylcholine. Acetylcholine is recycled by an enzyme called acetylcholinesterase. Galantamine works by inhibiting this enzyme. The inhibition of acetylcholinesterase increases the concentration of available acetylcholine.
Galantamine has only been studied, and is only used, in patients with mild-to-moderate Alzheimer's disease according to the Alzheimer's Disease Assessment Scale.
Galantamine is available in 4-mg, 8-mg, and 12-mg tablets.
Recommended dosage
The recommended initial dose of galantamine in adults is 4 mg twice daily. After a minimum of four weeks of treatment with galantamine, it may be increased to 8 mg twice daily. Further increases to 12 mg twice daily should be initiated only after a minimum of four weeks at the previous dose.
Increased side effects associated with higher doses may prevent the increase in dose in some patients. Patients with moderate liver or kidney problems should not exceed 16 mg of galantamine daily.
Precautions
Galantamine should not be used in patients with severe liver or kidney problems. Since there are no well-controlled studies for the use of galantamine in pregnancy, galantamine should only be used if the potential benefits justify the potential risks to the fetus.
Patients who are undergoing anesthesia or bladder or gastrointestinal surgery should take galantamine only after a discussion with their physician. Patients with gastrointestinal problems should be closely monitored if it is decided that they should take galantamine. Galantamine should be used under close physician supervision in patients who have Parkinson's disease, severe asthma, or obstructive pulmonary disease. Because galantamine may slow down the heart, patients with any heart condition, and especially patients taking other medications that slow down the heart, should be evaluated before starting galantamine.
Side effects
The most common side effects reported with the use of galantamine are nausea, vomiting, diarrhea, anorexia, and abdominal pain. These occur most often at dosage-escalation periods. The average duration of nausea is five to seven days. These side effects tend to be less frequent if the patient is taking a total daily dosage of 16 mg. Eleven percent of patients receiving 24 mg daily lose weight, while 6% of patients receiving 16 mg daily experience weight loss.
Other common side effects include dizziness, headache, tremor, fatigue , depression, agitation, irritation, and insomnia . These side effects have a higher incidence and severity if higher doses are used. If side effects become severe, the dosage should be adjusted downward under physician supervision.
Interactions
There is currently little data regarding potential drug interactions with galantamine. Medications that are known to increase levels of galantamine in the body include cimetidine, erythromycin, ketoconazole, and paroxetine .
Resources
BOOKS
Janssen Inc. Staff. Product Information Reminyl-Galantamine. Titusville, NJ: Janssen Inc., Reviewed 10/2001.
PERIODICALS
Davidsson, Pia. "Differential Increase in Cerebrospinal Fluid-Acetylcholinesterase After Treatment With Acetylcholinesterase Inhibitors in Patients With Alzheimer's Disease." Neuroscience Letters 300 (2001): 157-160.
Wilcock, Gordon. "Efficacy and Safety of Galantamine In Patients With Mild to Moderate Alzheimer's Disease: Multicentre Randomised Controlled Trial." British Medical Journal 321 (2000): 1445-1449.
Ajna Hamidovic, Pharm.D.