Galantamine

Galantamine is a Drug for neurodegenerative disease (Dementia) belonging to Acetylcholinesterase Inhibitor class.

Galantamine is a cholinesterase inhibitor used to manage mild to moderate dementia associated with Alzheimer's Disease.

Galantamine is absorbed well from the gastrointestinal tract. It has Bioavailability of Approximately 90%. Time taken to reach peak plasma concentration is Approximately 1 hour for immediate-release and approximately 4.5-5 hours modified-release. Galantamine is having Volume of distribution of about 175 L. It is 18% bound to plasma protein. Galantamine is mainly metabolized in the liver by CYP2D6 isoenzyme and CYP3A4 isoenzyme to O-desmethyl-galantamine, and galantamine-N-oxide metabolites, respectively. It is primarily excreted Via urine (approximately 20-30% as unchanged drug) and about 6% in faeces.

Galantamine shows side effects like Nausea, vomiting, diarrhea, loss of appetite, stomach pain, heartburn, weight loss, extreme tiredness, etc.

Galantamine is available as Oral Tablet, Oral capsule and Oral solution.

Galantamine is available in India, US, European, Japan, Sweden and Canada.

Galantamine belongs to Acetylcholinesterase Inhibitor class and acts as Drug for neurodegenerative disease (Dementia).

Galantamine centrally acting cholinesterase inhibitor (competitive and reversible). It elevates acetylcholine in cerebral cortex by slowing the degradation of acetylcholine. Modulates nicotinic acetylcholine receptor to increase acetylcholine from surviving presynaptic nerve terminals. May increase glutamate and serotonin levels.

The Onset and Duration of action of Galantamine is not clinically established.

The Time to peak plasma concentration of Galantamine is approximately 1 hour (2.5 hours with food) by immediate release and 4.5-5 hours by extended release.

Galantamine is available in the form of Oral Tablet, Oral capsule, and Oral solution.

Galantamine Tablet, capsule, and solution are taken orally usually once or twice daily.

Galantamine is used to treat mild-to-moderate dementia associated with Alzheimer's disease. Galantamine does not cure Alzheimer's but it may slow the loss of or improve the patient's awareness of surroundings, ability to perform daily functions, and ability to think and remember.

Galantamine is a Drug for neurodegenerative disease (Dementia) belonging to Acetylcholinesterase Inhibitor class.

Galantamine centrally acting cholinesterase inhibitor (competitive and reversible). It elevates acetylcholine in cerebral cortex by slowing the degradation of acetylcholine. Modulates nicotinic acetylcholine receptor to increase acetylcholine from surviving presynaptic nerve terminals. May increase glutamate and serotonin levels.

Galantamine is approved for use in the following clinical indications

• Alzheimer disease
• Dementia with Lewy bodies and Parkinson disease dementia
• Vascular dementia, comorbid

• Alzheimer disease

Immediate-release tablet or solution:

Oral: Initial: 4 mg twice daily for 4 weeks; if tolerated, increase to 8 mg twice daily for ≥4 weeks; if tolerated, increase to 12 mg twice daily. Range: 16 to 24 mg daily in 2 divided doses.

Extended-release capsule:

Oral: Initial: 8 mg once daily for 4 weeks; if tolerated, increase to 16 mg once daily for ≥4 weeks; if tolerated, increase to 24 mg once daily. Range: 16 to 24 mg once daily.

• Dementia with Lewy bodies and Parkinson disease dementia
• Vascular dementia, comorbid

Oral: Initial: 4 mg twice daily for 4 weeks; increase to 8 mg twice daily for 4 weeks; if tolerated, increase to 12 mg twice daily. Range: 16 to 24 mg/day in 2 divided doses.

Galantamine is available in various strengths as 4 mg; 8 mg; 12 mg; 4 mg/mL; 16 mg; 24 mg.

Galantamine is available in the form of Oral Tablet, Oral capsule, and Oral solution.

• Dosage Adjustment in Kidney Patient

Mild impairment: There are no dosage adjustments provided in the manufacturer’s labeling.

Moderate impairment (CrCl 9 to 59 mL/minute): Maximum dose: 16 mg/day.

Severe impairment (CrCl <9 mL/minute): Use is not recommended.

• Dosage Adjustment in Hepatic impairment Patient

Mild impairment (Child-Pugh class A): There are no dosage adjustments provided in the manufacturer’s labeling; however, single-dose galantamine pharmacokinetics were like that observed in healthy subjects.

Moderate impairment (Child-Pugh class B): Maximum dose: 16 mg/day.

Severe impairment (Child-Pugh class C): Use is not recommended.

Galantamine is contraindicated in patients with known hypersensitivity to galantamine hydrobromide or to any excipients used in the formulation.

• CNS depression

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Extrapyramidal effects

May exacerbate extrapyramidal symptoms due to an increase in cholinergic tone.

• Skin reactions

Skin reactions including Stevens-Johnson syndrome, acute generalized exanthematous pustulosis and erythema multiforme have been reported. Treatment discontinuation may be necessary if skin reaction occurs; if rash is suspected to be drug related, do not resume galantamine and consider alternative therapy.

• Vagotonic effects

Cholinesterase inhibitors may have vagotonic effects which may cause bradycardia and/or heart block with or without a history of cardiac disease.

• Weight loss

Weight loss has been observed, monitor body weight.

• Cardiac conduction abnormalities

Use with caution in patients with sick-sinus syndrome, bradycardia, or conduction abnormalities.

• Hepatic impairment

Use with caution in patients with mild to moderate liver impairment; not recommended in severe impairment. Dose adjustment recommended in moderate impairment.

• Peptic ulcer disease

Use with caution in patients at risk of ulcer disease (eg, previous history or NSAID use); may increase gastric acid secretion. Monitor for symptoms of bleeding.

• Renal impairment

Use with caution in patients with moderate renal impairment; not recommended in severe impairment (CrCl <9 mL/minute).

• Respiratory disease

Use with caution in patients with COPD and/or asthma.

• Seizure disorder

Use with caution in patients with a history of seizure disorder.

• Urinary tract obstruction

Use with caution in patients with bladder outlet obstruction; cholinomimetics may cause or worsen outflow obstructions.

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Galantamine ER and Galantamine is administered to a nursing woman.

There are no adequate and well-controlled studies in pregnant women. In studies conducted in animals, administration of galantamine during pregnancy resulted in developmental toxicity (increased incidence of morphological abnormalities and decreased growth in offspring) at doses like or greater than those used clinically. Galantamine ER and Galantamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Common

Nausea, vomiting, Bradycardia, syncope Weight loss, Abdominal distress, abdominal pain, decreased appetite, diarrhea, dyspepsia, Depression, dizziness, drowsiness, falling, fatigue, headache, lethargy, malaise, Muscle spasm, tremor, Laceration, First degree atrioventricular block, flushing, hypotension, palpitations, sinus bradycardia, supraventricular extrasystole, Hyperhidrosis, Dehydration, Dysgeusia, retching, Hypersomnia, myasthenia, paresthesia, Blurred vision.

Rare

Complete atrioventricular block, hypertension, Acute generalized exanthematous pustulosis, erythema multiforme, skin rash, Stevens-Johnson syndrome, Hepatitis, increased liver enzymes, Hypersensitivity reaction, Drug-induced extrapyramidal reaction, hallucination, seizure, Tinnitus.

• Use with Anticholinergics

Galantamine has the potential to interfere with the activity of anticholinergic medications

• 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.

The common side effects of Galantamine include the following

Common side effects

Nausea, vomiting, diarrhea, loss of appetite, stomach pain, heartburn, weight loss, extreme tiredness, dizziness, pale skin, headache, shaking of a part of your body that you cannot control, depression, difficulty falling asleep or staying asleep, runny nose.

Rare side effects

Difficulty urinating, blood in the urine, pain or burning while urinating, seizures, slowed heartbeat, fainting, shortness of breath, black and tarry stools, red blood in the stools, bloody vomit, vomit that looks like coffee grounds.

• Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. In studies conducted in animals, administration of galantamine during pregnancy resulted in developmental toxicity (increased incidence of morphological abnormalities and decreased growth in offspring) at doses like or greater than those used clinically. Galantamine ER and Galantamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Galantamine ER and Galantamine is administered to a nursing woman.

• Pediatric Use

The safety and effectiveness in pediatric patients have not been established.

• Geriatric Use

Eight double-blind, placebo-controlled clinical trials and 5 open-label trials in a total of 6519 patients have investigated Galantamine ER and Galantamine in the treatment of mild to moderate dementia of the Alzheimer’s type. The mean age of patients enrolled in these clinical studies was 75 years; 78% of these patients were between 65 and 84 years of age, and 10% of patients were 85 years of age or older.

Symptoms: Muscle weakness or fasciculations, severe nausea, vomiting, gastrointestinal cramping, salivation, lacrimation, urination, defaecation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness with tracheal hypersecretion and bronchospasms may lead to compromised vital airways.

Management: Symptomatic and supportive treatment. May administer atropine for severe cases at initial dose of 0.5-1 mg via IV inj, then adjust subsequent doses according to response.

• Pharmacodynamic

Galantamine is a competitive and reversible inhibitor of acetylcholinesterase that works to increase acetylcholine levels. Galantamine acts both centrally and peripherally to inhibit both muscle and brain acetylcholinesterase, thereby increasing cholinergic tone.Galantamine is also a positive allosteric modulator of neuronal nicotinic acetylcholine receptors. As dementia is a progressive neurodegenerative disease, galatamine has a negligible effect in altering the course of the underlying process of dementia and may exert its therapeutic effectiveness for a short period of time. However, galantamine promoted improvements in cognition, global function, activities of daily living, and behavioural symptoms in clinical studies of Alzheimer’s disease. Galantamine exhibited therapeutic efficacy in studies of vascular dementia and Alzheimer’s disease with cerebrovascular disease.

• Pharmacokinetics

Absorption

Galantamine is absorbed well from the gastrointestinal tract. It is having Bioavailability of Approximately 90%. Time taken to reach peak plasma concentration is Approximately 1 hour for immediate-release and approximately 4.5-5 hours modified-release.

Distribution

Galantamine is having Volume of distribution of about 175 L. It is 18% bound to plasma protein.

Metabolism and Excretion

Galantamine is mainly metabolized in the liver mainly by CYP2D6 isoenzyme and CYP3A4 isoenzyme to O-desmethyl-galantamine, and galantamine-N-oxide metabolites, respectively. It is mainly excreted Via urine (approximately 20-30% as unchanged drug) and approximately 6% in faeces.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021169Orig1s032,021224Orig1s030,021615Orig1s023lbl.pdf
• https://www.drugs.com/mtm/galantamine.html
• https://go.drugbank.com/drugs/DB00674
• https://medlineplus.gov/druginfo/meds/a699058.html