Rivastigmine (Exelon)

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

Acetylcholinesterase inhibitors are indicated in:

Rivastigmine is also indicated for the treatment of Lewy Body Dementia. Rivastigmine also shows some promising results in patients with traumatic brain injury with moderate to severe memory deficits.[2]

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.

  • Start rivastigmine at 1.5 mg PO BID
  • Depending on clinical response and tolerability, subsequently can increase by 1.5mg q4weeks (3mg PO BID, 4.5mg PO BID, and finally to 6 mg PO BID)
    • Max PO dose is 6 mg PO BID
    • Wait at least 2 weeks between every dose increase
  • On the patch formulation, start at 4.6 mg per 24-hour patch (remain on for minimum of 4 weeks before increasing)
  • The dose can then be increased to 9.5 mg per 24-hour patch (remain on for minimum of 4 weeks before increasing)
  • The maximum dose is 13.3 mg per 24-hour patch
  • Don't forget to rotate the patch site daily to minimize skin irritation, and remember to change the patch every 24 hours.

If switching from oral rivastigmine to the patch:

  • If on 6 mg daily, should start with the 4.6 mg per 24-hour patch
  • If on 6–12 mg daily, should start with the 9.5-mg per 24-hour patch
  • Wait at least 4 weeks before making a dose increase
  • 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
    • Acetylcholine is the key neurotransmitter involved in autonomic regulation of the airways, and is responsible for bronchoconstriction, mucus secretion, and inflammation in diseases like asthma and COPD.
      • Inhaled anticholinergics (e.g. - ipratropium) are thus frequently used as bronchodilators in the management of asthma/COPD (i.e. - reducing acetylcholine activity reduces bronchoconstriction and inflammation).
    • Thus, those with a history of severe COPD also taking acetylcholinesterase inhibitors are at risk for worsening respiratory symptoms and exacerbation caused by the excess acetylcholine in the lungs.[3]
  • 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, and increase risk of seizures
  • Night-time administration of donepezil can cause night-time disturbances, including insomnia, nightmares, and vivid dreams.[4]
    • Thus, daytime administration may be warranted if patients are experiencing night-time disturbances.[5]
  • 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.