Galantamine HBr - Uses, Dosage, Warnings, Side Effects, and Pharmacological Aspects

Overview

Galantamine HBr is a drug that belongs to the class of acetylcholinesterase inhibitors. It is used to manage the symptoms of Alzheimer's disease and other memory impairments. Galantamine HBr refers to Galantamine hydrobromide, the hydrobromide salt form of Galantamine. Galantamine is a tertiary alkaloid derived synthetically or naturally from the bulbs and flowers of the Amaryllidaceae family. It can inhibit acetylcholinesterase and enhance the neurocognitive function in Alzheimer's disease.

The usage of Galantamine began in the 1950s in the Soviet Union. It was first isolated from bulbs of Galanthus nivalis in 1956 by D. Paskov, a Bulgarian chemist. The active ingredient was found to have acetylcholinesterase-inhibiting properties. This drug began in 1959, but full-scale manufacturing was optimized in the 1990s. FDA (The Food and Drug Administration) approved the medical use of Galantamine HBr in 2004.

How Does Galantamine HBr Work?

The exact reason behind the cognitive impairment in Alzheimer's disease has not been established. The loss of cholinergic function characterizes it. It has been studied that the acetylcholine-producing neurons undergo degeneration in the brain of Alzheimer's patients. The degree of cognitive impairment and density of amyloid plaques depends on cholinergic loss.

Galantamine HBr is a competitive and reversible acetylcholinesterase inhibitor (an enzyme). The exact mechanism of action of Galantamine has yet to be established. It was observed that Galantamine reversibly inhibits the hydrolysis of acetylcholine by cholinesterase. This inhibition increases the concentration of acetylcholine, thereby enhancing the cholinergic function. This mechanism prevents cholinergic loss by maintaining the cholinergic neurons intact. However, Galantamine does not alter the course of underlying dementia.

Uses

1. Galantamine HBr is used to treat mild to moderate dementia in Alzheimer's disease.

2. Galantamine is also used to treat memory impairments like dementia associated with Parkinson's disease, Down's syndrome, multiple sclerosis, and frontotemporal dementia.

3. It also treats cognitive impairment associated with Lewy body disease, traumatic brain injury, electroconvulsive therapy, schizophrenia, and bipolar disorder.

4. It is used to treat post-traumatic nerve palsy of oculomotor and trochlear nerves.

5. It is also used to manage acute Scopolamine toxicity and organophosphorus poisoning.

Dosage:

Galantamine HBr is a prescription drug for tablets, extended-release capsules, and oral solutions.

The recommended initial dose of Galantamine tablets is 4 mg (milligram) twice a day which is 8 mg daily. After four weeks, the dosage is increased to 8 mg twice daily (16 mg/day). After that, it is increased to 12 mg twice daily (24 mg/day) after four weeks of 16 mg daily dosage.

Warnings:

1) Skin Reactions: Galantamine can cause serious skin reactions like Steven-Johnson syndrome and acute generalized exanthematous pustulosis. If such skin reactions are seen, the drug should be discontinued.

2) Cardiovascular Conditions: Galantamine can cause bradycardia and AV (atrioventricular) node block. It can occur in patients with or without underlying cardiac conduction abnormalities. Hence, Galantamine can cause adverse effects on cardiac function.

3) Gastrointestinal Conditions: Galantamine should be used cautiously in patients with ulcer disease. It increases the risk of gastrointestinal bleeding and causes nausea, vomiting, diarrhea, anorexia, and weight loss.

4) Genitourinary Conditions: Galantamine may cause bladder outflow obstruction.

5) Neurological Conditions: Galantamine may cause seizures. Patients taking this drug should be monitored for seizures.

6) Respiratory Conditions: It should be cautiously used in asthma or obstructive pulmonary disease patients to prevent adverse effects.

For Patients

What Is Alzheimer?

Alzheimer's is a neurological disorder that causes a progressive decline in behavioral and social skills. It causes the brain to shrink. This disease remains the common cause of dementia in older adults. It starts slowly and progressively worsens dementia. It affects memory and thinking ability and interferes with the individual's daily activities. It deteriorates over time and ultimately results in the death of the individual. It is usually seen in individuals above 65 but can also begin at 30.

What Causes Alzheimer?

The abnormal build-up of proteins in the brain cells causes Alzheimer's disease. One of the proteins called amyloid deposits around the cells in the form of plaques. Another protein, called tau, deposits in the form of tangles in the brain cells. The brain shrinks, and the chemical messengers responsible for sending messages or signals between the brain cells are affected. This process begins many years before the symptoms develop.

What Happens in Alzheimer?

Alzheimer's disease is the main reason for dementia in 60 to 70 percent of patients. The early symptom of this disease is difficulty in remembering recent events. It causes symptoms like mood swings, behavioral problems, self-neglect, loss of motivation, and communication difficulties.

How Is Alzheimer Different From Schizophrenia?

In both conditions, neurochemical changes affect the dopaminergic or cholinergic axis. Both disorders have similar symptoms and similarities in the pattern of brain dysfunction and biochemical dysfunction. However, Alzheimer's and schizophrenia are different; memory impairment and thinking difficulties are seen in Alzheimer's, whereas hallucinations and delusions are seen in schizophrenia.

Learn More About Galantamine HBr

Facts to Know Before Starting Galantamine HBr:

When and Why Switch to Galantamine HBr?

Various medications are prescribed for treating Alzheimer's disease. Acetylcholinesterase inhibitors such as Donepezil, Galantamine, and Rivastigmine are commonly prescribed for Alzheimer's. All three drugs work in the same way. However, each individual responds differently, and some may have fewer side effects from one of these drugs. These drugs prevent cholinergic loss by keeping the cholinergic neurons intact.

How Effective Is Galantamine HBr?

It has been reported that Galantamine HBr effectively prevents the progression of the disease by keeping the functioning neurons intact. It prevents the worsening of dementia in mild to moderate types of Alzheimer's disease. However, the underlying course of dementia remains unaltered.

Things to Inform the Doctor Before Galantamine HBr Is Prescribed:

1. Galantamine should not be used if the patient is allergic to it.

2. It is not known if Galantamine can harm an unborn baby. It should not be used if the patient is pregnant or planning to become pregnant.

3. The presence of Galantamine in breast milk is not known. However, breastfeeding should be avoided while taking this drug.

4. The presence of heart diseases, kidney diseases, liver diseases, stomach ulcers, asthma or chronic obstructive pulmonary disease (COPD), seizures, and urinary problems should be informed.

Starting Galantamine HBr:

How to Take Galantamine HBr?

Galantamine HBr should be taken as prescribed by the doctor. The extended-release capsules work better with food. It should be taken with food. Galantamine capsules should be swallowed as a whole. It should not be chewed, broken, or opened. The oral solution should be measured with a spoon or cup before consumption. All the instructions should be carefully followed while taking Galantamine.

Things to Be Followed While Under Galantamine HBr:

1. It is important to follow all the instructions given by the doctor and visit the doctor regularly to check the progress and unwanted effects.

2. Galantamine may harm the unborn baby. If pregnancy occurs during the treatment, they should be informed to the doctor.

3. Breastfeeding is not advisable, and it should be avoided while taking Galantamine.

4. Galantamine can cause cardiac disorders. If symptoms like chest pain, breathing difficulty, and swelling of hands and feet occur, they should be informed to the doctor.

5. Galantamine can cause allergic reactions like rashes, hives, breathing difficulties, and swelling of the face, hands, and feet. If such reactions develop, they should be informed to the doctor.

6. Galantamine HBr should be stopped before undergoing surgery. So, informing the surgeon about this drug's consumption is important.

7. If this drug is stopped or the dosage is missed, it should be consulted with the doctor before starting it again.

8. It can cause various adverse effects. The occurrence of any unwanted effects or abnormalities should be informed to the doctor.

Advice for Caregivers:

The caregivers should inform the doctor if the patient develops allergic reactions like rashes, hives, breathing difficulties, or other symptoms like chest pain or other abnormalities, including seizures.

Things to Do After Taking Galantamine HBr:

If any noticeable symptoms or unwanted effects are present after taking Galantamine HBr, they should be informed the doctor. If allergic reactions or symptoms like chest pain, breathing difficulties, or seizures develop, they should be immediately informed to the doctor.

Diet Modifications:

Dietary restrictions or modifications are not essential unless recommended by the doctor. A healthy and balanced diet can be followed while taking Galantamine. However, the use of alcohol or tobacco is not recommended while taking this drug.

Look Out for the Side Effects:

The patients should familiarize themselves with the common and rare side effects of Galantamine HBr so that the symptoms can be easily identified. If side effects are present, they should be informed to the doctor. Galantamine may also cause some other side effects that are not listed here.

The common side effects include the following

• Serious skin reactions.

• Reduced heart rate and chest pain.

• Reduced urine output.

• Blood in the urine.

• Bloody stools.

• Yellowish discoloration of the skin or eyes.

• Dehydration.

• Lightheadedness.

• Fever and sore throat.

• Nausea, vomiting, and diarrhea.

• Headache.

• Dizziness.

• Weight loss.

Less common side effects include the following:

• Chest pain or discomfort.

• Shortness of breath.

• Confusion.

• Blurred vision.

• Dry mouth.

• Rapid breathing.

• Nervousness.

• Unusual tiredness.

Staying on Galantamine HBr

Tips to Stay on Track:

Improvement in the symptoms of Alzheimer's disease can be experienced after taking Galantamine. If any side effects occur while taking this drug, it is essential to inform the doctor. The dosage schedule should be carefully followed. It should be consulted with the doctor on missing a dose.

Things to remember,

1) Sticking to the dosage schedule of Galantamine is important because missing the dosage schedule will affect the treatment outcome.

2) It is essential to follow up regularly with the doctor and inform them about the improvement in the symptoms of Alzheimer's disease.

For Doctors

Indications:

Galantamine HBr is used to treat mild to moderate dementia in Alzheimer's disease. It is also used in other disorders associated with cognitive impairment.

Mechanism of Action:

The exact reason behind the cognitive impairment in Alzheimer's disease has not been established. The loss of cholinergic function characterizes it. It has been studied that the acetylcholine-producing neurons undergo degeneration in the brain of Alzheimer's patients. The degree of cognitive impairment and density of amyloid plaques depends on cholinergic loss.

Galantamine HBr is a competitive and reversible inhibitor of acetylcholinesterase. The exact mechanism of action of Galantamine has yet to be established. It was observed that Galantamine reversibly inhibits the hydrolysis of acetylcholine by cholinesterase. This inhibition increases the concentration of acetylcholine, thereby enhancing the cholinergic function. This mechanism prevents cholinergic loss by maintaining the cholinergic neurons intact. However, Galantamine does not alter the course of underlying dementia.

Pharmacodynamics:

Galantamine HBr is a competitive and reversible inhibitor of acetylcholinesterase. It works by inhibiting the hydrolysis of acetylcholine by cholinesterase to increase the concentration of acetylcholine, thereby enhancing the cholinergic function. It promotes improvements in cognition and behavioral symptoms of Alzheimer's disease.

Pharmacokinetics:

Absorption and Bioavailability

It has a high oral bioavailability of about 90 %. It is equivalent to oral solutions and tablets. Peak plasma concentrations are achieved within 1 to 4.5 hours after administration. Maximum inhibition of acetylcholinesterase activity was achieved 1 hour after a single oral dose of 8 mg.

Distribution

Galantamine is mainly distributed in the blood cells in the whole blood. The plasma protein binding of Galantamine is 18 % at therapeutic doses.

Elimination

Galantamine is metabolized in the liver by the cytochrome isoenzymes and eliminated in the urine. The elimination half-life of Galantamine is about seven hours.

Warnings and Precautions:

• Galantamine can cause skin reactions like Steven-Johnson syndrome and acute generalized exanthematous pustulosis. If such skin reactions develop, the drug should be discontinued.

• Galantamine can cause bradycardia and AV (atrioventricular) node block in patients with or without underlying cardiac conduction abnormalities.

• Galantamine should be used cautiously in patients with ulcer disease as it increases the risk of gastrointestinal bleeding and causes nausea, vomiting, diarrhea, anorexia, and weight loss.

• Galantamine may cause other disorders, such as bladder outflow obstruction and seizures. In addition, it should be cautiously used in patients with asthma or obstructive pulmonary disease to prevent adverse effects.

Indications and Uses:

1. Galantamine HBr is used to treat mild to moderate dementia in Alzheimer's disease.

2. Galantamine is also used to treat memory impairments like dementia associated with Parkinson's disease, Down's syndrome, multiple sclerosis, and frontotemporal dementia.

3. It also treats cognitive impairment associated with Lewy body disease, traumatic brain injury, electroconvulsive therapy, schizophrenia, and bipolar disorder.

4. It is used to treat post-traumatic nerve palsy of oculomotor and trochlear nerves.

5. It is also used to manage acute Scopolamine toxicity and organophosphorus poisoning.

Dosage:

Galantamine HBr is a prescription drug for tablets, extended-release capsules, and oral solutions.

The recommended initial dose of Galantamine tablets is 4 mg (milligram) twice a day which is 8 mg daily. After four weeks, the dosage is increased to 8 mg twice daily (16 mg/day). After that, it is increased to 12 mg twice daily (24 mg/day) after four weeks of 16 mg daily dosage.

Considerations for Administration:

• Dosage should be increased depending on the improvements and tolerability of the previous dose.

• Galantamine tablets should be prescribed twice a day.

• If the therapy was interrupted for over three days, it should be restarted with the lowest dose and escalated to the usual dose.

Contraindications:

1. Galantamine may harm the unborn baby. It is contraindicated in pregnant women and those planning for pregnancy.

2. Breastfeeding is not advisable, and it should be avoided while taking Galantamine.

3. Galantamine can cause cardiac disorders. It should be used cautiously in patients with or without underlying cardiac disorders.

4. Galantamine can cause allergic reactions like rashes, hives, breathing difficulties, and swelling of the face, hands, and feet. It is contraindicated in patients with Galantamine allergy.

5. Galantamine HBr can alter the effects of anesthesia. So, it should be stopped before undergoing surgery.

Results from Clinical Trials:

Five randomized, double-blind, placebo-controlled studies demonstrated the effectiveness of Galantamine Hbr in Alzheimer's patients. Studies showed that Galantamine improves cognitive function significantly. Extended-release tablets are more effective in causing a significant improvement. Studies demonstrated that Galantamine works by inhibiting the hydrolysis of acetylcholine by cholinesterase to increase the concentration of acetylcholine, thereby enhancing the cholinergic function. It promotes improvements in cognition and behavioral symptoms of Alzheimer's disease.

Drug Interactions:

Interactions With Other Drugs:

• Galantamine interferes with the activity of anticholinergic medications.

• It interacts with succinylcholine and other cholinesterase inhibitors.

• It also interacts with other drugs such as Ketoconazole, Erythromycin, Paroxetine, H2 antagonists, Memantine, Digoxin, and Warfarin.

Other Specifications:

• Cardiovascular Conditions: Galantamine can cause bradycardia and AV (atrioventricular) node block. It can occur in patients with or without underlying cardiac conduction abnormalities.

• Gastrointestinal Conditions: Galantamine increases the risk of gastrointestinal bleeding and causes nausea, vomiting, diarrhea, anorexia, and weight loss.

• Genitourinary Conditions: Galantamine may cause bladder outflow obstruction.

• Neurological Conditions: Galantamine may cause seizures.

• Respiratory Conditions: To prevent adverse effects, Galantamine should be used cautiously in asthma or obstructive pulmonary disease patients.

• Pregnancy: Galantamine may harm the unborn baby. It should not be used in pregnant women or those planning to become pregnant.

• Lactation: The presence of Galantamine in breast milk has not been established. But, breastfeeding should not be done while taking this tablet.

• Pediatric Use: The safety and effectiveness of Galantamine in the pediatric population have not been established.

• Geriatric Use: Galantamine tablets are effectively used to treat mild to moderate dementia in Alzheimer's disease.

• Hepatic Impairment: Galantamine tablets are not recommended for patients with severe hepatic impairment. A dosage adjustment is required in patients with moderate impairment.

• Renal Impairment: Galantamine tablets are not recommended for patients with less than 9 mL per minute of creatinine clearance. A dosage adjustment is required in patients with a clearance rate of 59 mL per minute.