Rivastigmine
Cholinesterase inhibitor in Alzheimer and Parkinson dementia
Rivastigmine is a centrally acting acetylcholinesterase and butyrylcholinesterase inhibitor introduced by Novartis in 1998 under the brand name Exelon. It is available in oral form (capsules and solution) and as a transdermal patch, with numerous generics on the market. Rivastigmine is approved for symptomatic treatment of mild to moderate Alzheimer type dementia and mild to moderate dementia in idiopathic Parkinson's disease.
The substance is one of the three cholinesterase inhibitors approved for Alzheimer therapy in Europe (together with donepezil and galantamine). A distinctive feature is the additional inhibition of butyrylcholinesterase, which gains importance as Alzheimer's disease progresses. The patch is often better tolerated than the oral form in case of gastrointestinal side effects or swallowing problems and markedly improves adherence.
Mechanism of Action
In Alzheimer's disease, cholinergic neurons of the basal forebrain that project to the cortex degenerate. The resulting acetylcholine deficit contributes to cognitive decline. Rivastigmine reversibly but long lastingly (so called pseudoirreversibility) inhibits acetylcholinesterase and butyrylcholinesterase, raising synaptic acetylcholine concentration at cholinergic synapses.
Unlike donepezil, which inhibits only acetylcholinesterase, rivastigmine also acts on butyrylcholinesterase. In healthy people only about 10 percent of cerebral acetylcholine is broken down by butyrylcholinesterase, but this share rises substantially in Alzheimer patients as the disease advances and acetylcholinesterase activity falls. Dual inhibition may therefore offer advantages in later stages.
Cognitive effects are symptomatic and do not halt disease progression in a biological sense. In clinical trials rivastigmine measurably delays cognitive decline over 6 to 12 months, which positively affects daily function and care needs. In vascular dementia and other dementia types the evidence is weaker.
Indications
- Mild to moderate Alzheimer dementia as symptomatic long term therapy
- Mild to moderate dementia in Parkinson's disease, well documented; rivastigmine is the only cholinesterase inhibitor approved for this indication in Germany
- Lewy body dementia off label, scientifically plausible and clinically frequently used
- Early Alzheimer dementia with behavioural symptoms to stabilise everyday competencies
In severe dementia, use is debated. Memantine is approved there, and the combination of memantine and a cholinesterase inhibitor in moderate to severe stages is preferred by some experts.
Dosage and Administration
Capsules (oral): start with 1.5 mg twice daily, increase weekly to 3 mg, 4.5 mg and 6 mg twice daily. Target range 3 to 6 mg twice daily. Take in the morning and evening with meals to reduce gastrointestinal side effects.
Transdermal patch: start with 4.6 mg per 24 hours for 4 weeks, then 9.5 mg per 24 hours as target dose. If well tolerated and efficacy is insufficient, further up titration to 13.3 mg per 24 hours is possible. Change the patch daily at the same time and rotate the site (back, upper arm, chest, abdomen) daily; use the same site no earlier than after 14 days.
Therapy interruption: after a pause of more than 3 days, restart with the lowest dose and titrate again to avoid gastrointestinal side effects. Renal impairment: no formal dose adjustment, titrate cautiously. Hepatic impairment: in mild to moderate impairment dose as tolerated, in severe impairment use is not recommended.
Side Effects
Very common: nausea, vomiting (especially during titration), loss of appetite and weight loss, diarrhoea. In this respect the patch is considerably better tolerated than the oral form.
Common: headache, dizziness, fatigue, agitation, sleep disturbance, confusion, depression, abdominal pain, increased salivation, skin reactions at the patch (redness, itching).
Uncommon to rare: bradycardia, AV block, syncope, urinary incontinence, ulcers and gastrointestinal bleeding, pancreatitis, seizures, severe skin reactions at the patch, neuroleptic malignant syndrome after abrupt discontinuation together with antipsychotics.
Patch overdose: in several reported cases more than one patch was applied simultaneously or the old patch was not removed. The consequences were severe nausea, bradycardia and circulatory collapse. In case of misuse, remove all patches immediately and seek medical care.
Interactions
- Anticholinergics (biperiden, tricyclic antidepressants, promethazine): mutual loss of effect, avoid combination
- Parasympathomimetics (pilocarpine, bethanechol): additive effect, combine only on a clear indication
- β blockers (metoprolol, bisoprolol): enhanced bradycardia, caution especially in sick sinus syndrome
- Succinylcholine type muscle relaxants: enhanced neuromuscular block during anaesthesia
- Antipsychotics: additive circulatory effects, risk of neuroleptic malignant syndrome upon abrupt discontinuation
- NSAIDs: increased risk of gastrointestinal ulcers through additive acid secretion
Special Notes
Contraindications: known hypersensitivity, severe hepatic dysfunction, severe circulatory problems with low heart rate (sick sinus syndrome, AV block grade II or III), active gastrointestinal ulcers.
Discontinuation and end of therapy: in case of insufficient efficacy or poor tolerability, taper gradually. Abrupt discontinuation after long term therapy can cause rapid cognitive decline. The decision to end therapy is made jointly with patient, family and the GP or neurologist.
Pregnancy and breastfeeding: rivastigmine is not indicated for women of childbearing potential. Use during breastfeeding is not recommended, data on passage into breast milk are lacking. Children: no indication.
Patch handling: education of caregivers and relatives is critical. Always remove the old patch before applying a new one, rotate the application site daily and do not cut the patch. Contact with heat (sauna, heating blankets, hot baths, direct sun) can increase release. A memo system helps document patch changes.
Monitoring: cognitive testing (MMSE, MoCA, DemTect) every 6 months, weight, blood pressure, pulse and liver values. Review benefit risk at least yearly.
You might also be interested in
- Donepezil, selective cholinesterase inhibitor in Alzheimer's
- Levodopa, dopaminergic basic therapy in Parkinson's disease
- Entacapone, COMT inhibitor in Parkinson's
- Agomelatine, antidepressant with sleep regulating effect
- Aripiprazole, antipsychotic for behavioural symptoms in dementia
Frequently Asked Questions
Does rivastigmine cure Alzheimer's disease?
No. Rivastigmine eases cognitive symptoms by partially compensating for the acetylcholine deficit in the brain. The underlying neurodegeneration is not halted. Therapy aims to preserve everyday function and independence as long as possible and delay care dependence.
What is the advantage of the patch?
The patch releases rivastigmine smoothly over 24 hours and bypasses the gastrointestinal tract, which markedly reduces nausea and vomiting. Once daily use eases caregiving and adherence, especially for patients with swallowing difficulties or cognitive decline. Efficacy is comparable to the oral form.
What do I need to watch when changing the patch?
Always remove the old patch first, then apply the new one. Rotate sites daily (back, upper arm, chest, abdomen) and use the same site no sooner than after 14 days. Do not cut the patch; if skin irritation is marked, move to another area. Avoid heat sources directly on the patch.
When should therapy be ended?
Ending is sensible when the patient no longer communicates meaningfully, independence is largely lost despite therapy or side effects outweigh quality of life. Discontinuation is gradual, not abrupt. The decision is made as a team with family, GP and neurologist.
Sources
- EMA, Exelon (Rivastigmine) EPAR
- AWMF, S3 Guideline on Dementia
- Gelbe Liste, Rivastigmine active substance profile
- BfArM, Federal Institute for Drugs and Medical Devices
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