Galantamine

Galantamine (Tradename: Razadyne) is an acetylcholinesterase inhibitor and cognitive-enhancing medication. It is used in the treatment of dementias and neurodegenerative disorders.

Acetylcholinesterase inhibitors are indicated in:

Acetylcholinesterase inhibitors, including donepezil, rivastigmine, and galantamine all inhibit acetylcholinesterase. The break down of acetylcholine is prevented by the drug binding and reversibly inactivating cholinesterases. This inhibits the hydrolysis of acetylcholine. As a result, acetylcholine levels increase in the brain, which may optimize function of remaining intact cholinergic neurons. This is thought to improve memory and cognitive function. However, treatment does not alter the underlying course of the disease. The increase in acetylcholine also occurs in other organ systems innervated by cholinergic neurons, and leads to the side effects in this medication class as well.

A baseline ECG (to rule out any conduction abnormalities), heart rate, weight, and blood pressure should be obtained prior to starting an acetylcholinesterase inhibitor.

Galantamine is available in oral immediate- or extended-release tablets and solution.

  • Starting dose for galantamine immediate-release tablet (or solution) is 4 mg PO BID (should remain on this dose for a minimum of 4 weeks)
    • If well tolerated, can increase to 8 mg PO BID (should remain on this dose for a minimum of 4 weeks)
    • If well tolerated, can increase to 12 mg PO BID (maximum dose)
  • If galantamine is stopped and therapy interrupted for more than several days, the medication should be slowly retitrated

Acetylcholinesterase inhibitors should be discontinued if the dementia progresses to a stage where there would be no clinically meaningful benefit from continuing therapy. If discontinuing, the dose should always be slowly tapered, and the patient should be monitored for 1-3 months for any signs of cognitive/functional decline. If this decline is seen, then the medication should be restarted.

  • Weight loss
    • Lower-weight patients should be closely monitored for vomiting, diarrhea, and loss of appetite. This applies to especially frail, elderly women, who tend to be more frequently affected
  • Upcoming surgeries
    • Acetylcholinesterase inhibitors can interact with muscle-relaxing anesthesias such as succinylcholine
  • Anti-arrhythmic medications
    • Donepezil may increase the risk of bradycardia with concurrent use of beta-blockers such as carvedilol, metoprolol, atenolol, or propranolol
  • History of gastric ulcers or regular NSAID (aspirin, ibuprofen, and naproxen)
    • Should be monitored for signs and symptoms of ulcers and gastrointestinal bleeding
  • Significant alcohol use can induce depressant effects, reduce the efficacy, and intensify the side effects of acetylcholinesterase inhibitors
  • Bradycardia (<50bpm) or AV block
  • Severe asthma and COPD, because the increase in acetylcholine activity can cause worsening respiratory function. (Remember that anticholinergics are frequently used as bronchodilators in the management of asthma/COPD!)
  • Severe hepatic or renal failure
  • Obstructive urinary disease
  • Seizures

The most common side effects of cholinesterase inhibitors include:

  • At lower doses: GI side effects (nausea, diarrhea, vomiting), weight loss, decreased appetite, insomnia, fatigue, muscle cramps, myalgia
    • These side effects will usually resolve on its own, starting low and going slow with dosing may help
  • Can cause dizziness, drowsiness, or syncope, especially during initiation of therapy
  • Discontinue if bradycardia develops or there is a significant conduction abnormality (i.e. - more than a first degree heart block)
  • At higher doses: side effects include headaches, dizziness, drowsiness, blurred vision, urinary frequency and incontinence
  • Can aggravate asthma and other breathing problems, risk of seizures, and increase nightmares
  • Anticholinergic drugs (e.g. - atropine, benztropine) may be less effective when combined with an acetylcholinesterase inhibitor. The cholinergic action of acetylcholinesterase inhibitors (an agonist) opposes the anticholinergic action (antagonists) of these medications. Anticholinergic drugs can also decrease the cholinergic action of acetylcholinesterase inhibitor, reducing its efficacy.
  • Beta-blockers (e.g. - propranolol, atenolol, timolol) combined with acetylcholinesterase inhibitors can increase the risk of bradycardia, heart block, and syncope.