Exelon

Exelon is a brand name for rivastigmine, a cholinesterase inhibitor used in the treatment of mild to moderate Alzheimer's disease dementia and dementia associated with Parkinson's disease. Available as oral capsules, an oral solution, and a transdermal patch, Exelon works by enhancing the activity of acetylcholine, the principal neurotransmitter involved in memory and cognition, in the brain. It is one of a small number of medicines licensed for dementia that provide meaningful, though modest, symptomatic improvement in cognitive function and daily living activities.

Mechanism of Action

Rivastigmine inhibits two enzymes responsible for breaking down acetylcholine in the brain: acetylcholinesterase and butyrylcholinesterase. By blocking this degradation, rivastigmine increases the concentration and duration of action of acetylcholine at cholinergic synapses. This enhances neuronal signalling in the areas of the brain most affected by the neurodegeneration underlying Alzheimer's and Parkinson's dementia, primarily the hippocampus and cortex, which are critical for memory encoding and higher cognitive processing.

Patch vs. Oral Formulations

Exelon is unique among UK-licensed cholinesterase inhibitors in being available as a transdermal patch as well as oral preparations. The patch, applied once daily to the skin, provides steady-state drug delivery without the peaks that follow oral dosing, which are associated with the nausea and vomiting commonly reported with oral rivastigmine. Clinical trials and post-marketing experience confirm that the Exelon patch causes significantly fewer gastrointestinal side effects than capsules at equivalent therapeutic doses. For patients with swallowing difficulties, caregiver-administered drug regimens, or a history of nausea on oral cholinesterase inhibitors, the patch is frequently the preferred formulation.

Exelon capsules are taken twice daily with morning and evening meals to reduce the risk of nausea. The Exelon patch is applied once daily to clean, dry, hairless skin on the upper or lower back, upper arm, or chest, and removed after 24 hours.

Starting Treatment and Titration

Treatment with Exelon requires a gradual dose escalation to minimise the cholinergic side effects, particularly nausea, vomiting, and dizziness, that occur when the dose is increased too quickly. For capsules, treatment begins at 1.5mg twice daily and is increased by 1.5mg per dose no more frequently than every four weeks, up to a maximum of 6mg twice daily. For the patch, treatment begins at the 4.6mg per 24 hours strength and is increased to 9.5mg per 24 hours after a minimum of four weeks if the initial dose is well tolerated.

Patch Application Technique

Select a different skin site each day, rotating through available locations to avoid skin irritation. Remove the previous day's patch before applying the new one. Press the patch firmly in place for at least 30 seconds. The patch should remain in place during bathing, swimming, and light exercise. Avoid exposing the patch to prolonged heat (such as electric blankets or saunas), which increases drug absorption. Used patches still contain active drug and should be folded and disposed of carefully, out of reach of children.

For Exelon capsules, the starting dose is 1.5mg twice daily with food. The dose is increased in steps of 1.5mg twice daily every four weeks, as tolerated, to a maintenance dose of 3-6mg twice daily. The maximum dose is 6mg twice daily (12mg total daily dose).

For the Exelon transdermal patch: begin with the 4.6mg/24h patch once daily for at least four weeks. If well tolerated and further benefit is sought, increase to the 9.5mg/24h patch. The 13.3mg/24h patch may be considered for patients with Alzheimer's disease who show continued deterioration despite four months on the 9.5mg patch, under specialist review.

Dose escalation should be paused or reversed if side effects, including nausea, vomiting, anorexia, or weight loss, develop. Exelon is used with caution in patients with significant renal or hepatic impairment; in mild to moderate impairment, careful titration is sufficient, but the drug is not recommended in severe impairment. No specific dose adjustment is required for age alone.

Common Side Effects

• Nausea and vomiting (more common with capsules than patch)
• Loss of appetite and weight loss
• Diarrhoea or abdominal discomfort
• Dizziness or headache
• Fatigue and weakness (asthenia)
• Skin irritation, redness, or itching at the patch site
• Tremor or worsening of Parkinson's symptoms at higher doses

Serious Side Effects

• Severe vomiting leading to aspiration or significant dehydration, particularly in frail elderly patients, may require hospitalisation
• Peptic ulceration or gastrointestinal bleeding, as cholinesterase inhibitors increase gastric acid secretion
• Seizures (rare), related to cholinergic activity in susceptible patients
• Severe allergic skin reactions at the patch site (allergic contact dermatitis), distinguish from local irritation; patch should be stopped and medical advice sought

Gastrointestinal and Cardiac Monitoring

Rivastigmine can cause significant gastrointestinal side effects, particularly during dose titration. Persistent nausea, vomiting, or significant weight loss during dose escalation should prompt a reduction back to the previously tolerated dose before attempting re-escalation. Rapid dose escalation is the most common cause of treatment failure and patient dropout. Exelon should be used with caution in patients with a history of peptic ulceration or concurrent NSAID or aspirin use, which together with the increased acid secretion driven by cholinergic activity raises the risk of gastrointestinal bleeding.

Rivastigmine can slow the heart rate (bradycardia) and affect cardiac conduction, making it necessary to exercise caution in patients with sick sinus syndrome or other supraventricular conduction abnormalities. Patients with asthma, COPD, or obstructive lung disease should be monitored for bronchospasm, as cholinergic stimulation can increase airway secretions and bronchial constriction.

Caregiver Involvement and Safe Prescribing

Dementia management involves caregivers closely. Clear instructions about the correct patch size, daily rotation, and removal of the old patch are essential to prevent accidental double-dosing. A known medication error with the Exelon patch involves applying a new patch without removing the previous one, resulting in double the intended dose and significant cholinergic toxicity. Written and verbal instructions should be provided to both the patient (where appropriate) and their caregiver at each review.

• Known hypersensitivity to rivastigmine, carbamate derivatives, or any excipient
• Severe hepatic impairment
• Previous severe skin reactions to the Exelon patch (allergic contact dermatitis)
• Use of other cholinergic drugs concurrently without specialist advice
• Severe renal impairment (use with caution and under specialist supervision)
• History of severe gastrointestinal side effects with other cholinesterase inhibitors without dose management plan
• Active peptic ulceration or recent gastrointestinal bleeding without concurrent gastroprotective treatment