Galantamine

Oral
Alzheimer's dementia

Patients taking potent CYP2D6 or CYP3A4 inhibitors: Reduced maintenance dose may be considered according to tolerability.

Pharmacogenomics:

Galantamine is primarily metabolised by CYP2D6 and CYP3A4 isoenzymes to inactive metabolites. Individuals with reduced CYP2D6 activity, known as CYP2D6 poor metabolisers, may experience an increased galantamine exposure. The prevalence of CYP2D6 poor metabolisers is estimated at approx 7% of the normal population.

CYP2D6 poor metabolisers
Patient may experience increased galantamine exposure. Although results of researches indicate an increased exposure, CYP2D6 poor metabolisers do not require dosage adjustments since the galantamine dose is titrated according to individual tolerability.

Pharmacogenetic testing prior to galantamine treatment initiation has not been addressed by currently available references.

CrCl (mL/min)	Dosage
<9	Contraindicated.

Moderate (Child-Pugh score 7-9): As conventional tab, oral susp: Initially, 4 mg once daily for at least 1 week, then increased to 4 mg bid for at least 4 weeks. Max: 8 mg bid. As modified-release cap: Initially, 8 mg every other day for 1 week, then increased to 8 mg once daily for 4 weeks. Max: 16 mg daily. Doses are given preferably in the morning. Severe (Child-Pugh score >9): Contraindicated.

Should be taken with food.

Severe renal and hepatic impairment.

Patient with CV disease (e.g. immediate post-MI period, new-onset atrial fibrillation, 2nd degree heart block or greater, unstable angina pectoris, CHF, sick sinus syndrome, bradycardia, or other supraventricular cardiac conduction abnormalities); uncorrected electrolyte disturbances (e.g. hyper- or hypokalaemia); history of seizure disorders; Parkinson’s disease; asthma, COPD, active pulmonary infections (e.g. pneumonia); bladder outlet obstruction or prostatic hyperplasia; gastrointestinal obstruction or recovering from gastrointestinal surgery; risk factors for ulcer disease (e.g. history of ulcer, concomitant NSAID use). Moderate renal and mild to moderate hepatic impairment. Elderly. Pregnancy and lactation. CYP2D6 poor metabolisers.

Significant: Serious skin reactions (e.g. Stevens-Johnson syndrome, acute generalised exanthematous pustulosis, erythema multiforme), CNS depression, vagotonic effects on heart rate (e.g. bradycardia, atrioventricular node block), weight loss, seizures, increase gastric acid secretion, bladder outflow obstruction, BPH symptoms exacerbation.
Cardiac disorders: Palpitations.
Ear and labyrinth disorders: Tinnitus.
Eye disorders: Blurred vision.
Gastrointestinal disorders: Nausea, vomiting, abdominal pain, diarrhoea, dyspepsia.
General disorders and admin site conditions: Fatigue, asthenia, malaise, lethargy.
Injury, poisoning and procedural complications: Fall, laceration.
Investigations: Increased hepatic enzymes.
Metabolism and nutrition disorders: Decreased appetite, dehydration.
Musculoskeletal and connective tissue disorders: Muscle spasms, muscle weakness.
Nervous system disorders: Headache, dizziness, somnolence, syncope, tremor.
Psychiatric disorders: Depression, hallucination.
Skin and subcutaneous tissue disorders: Hyperhidrosis.
Vascular disorders: Hypertension, flushing.

PO: C

This drug may cause dizziness and somnolence, if affected, do not drive or operate machinery. Drink adequate amount of fluids during your treatment with this medicine.

Monitor body weight; mental status; symptoms of active or occult gastrointestinal bleeding, gastrointestinal intolerance, and cholinergic crisis.

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.

Increased bioavailability and risk of cholinergic adverse effects with potent CYP2D6 inhibitors (e.g. quinidine, paroxetine, fluoxetine); and CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, erythromycin). Additive effects with other cholinomimetics (e.g. ambenonium, donepezil, neostigmine, pyridostigmine, rivastigmine, systemic pilocarpine). May antagonise anticholinergic effects of atropine.

Delay rate of absorption with food.

Description: Galantamine is a selective, competitive and reversible centrally-acting acetylcholinesterase inhibitor. It elevates acetylcholine in the cerebral cortex by slowing its degradation. It also increases acetylcholine from surviving presynaptic terminals by modulating the nicotinic acetylcholine receptors. Glutamate and serotonin levels may also be increased.
Pharmacokinetics:
Absorption: Well absorbed from the gastrointestinal tract. Food delays rate of absorption. Bioavailability: Approx 90%. Time to peak plasma concentration: Approx 1 hour (immediate-release); approx 4.5-5 hours (modified-release).
Distribution: Volume of distribution: 175 L. Plasma protein binding: 18%.
Metabolism: Metabolised in the liver mainly by CYP2D6 isoenzyme and CYP3A4 isoenzyme to O-desmethyl-galantamine, and galantamine-N-oxide metabolites, respectively.
Excretion: Via urine (approx 20-30% as unchanged drug); faeces (approx 6%). Elimination half-life: Approx 7 hours.

Source: National Center for Biotechnology Information. PubChem Database. Galantamine, CID=9651, https://pubchem.ncbi.nlm.nih.gov/compound/Galantamine (accessed on Jan. 22, 2020)

Tab/cap: Store at 25°C. Oral solution: Store between 20-25°C.

Neurodegenerative Disease Drugs

N06DA04 - galantamine ; Belongs to the class of anticholinesterases. Used in the management of dementia.

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