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| Trade names | Exelon, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a602009 |
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| Routes of administration | By mouth,transdermal patch |
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| Pharmacokinetic data | |
| Bioavailability | 60 to 72% |
| Protein binding | 40% |
| Metabolism | Liver, viapseudocholinesterase |
| Eliminationhalf-life | 1.5 hours |
| Excretion | 97% in urine |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.120.679 |
| Chemical and physical data | |
| Formula | C14H22N2O2 |
| Molar mass | 250.342 g·mol−1 |
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Rivastigmine, sold under the brand nameExelon among others, is anacetylcholinesterase inhibitor used for the treatment of dementia associated withAlzheimer's disease and withParkinson's disease.[4][6][7] Rivastigmine can be administered orally or via atransdermal patch; the latter form reduces the prevalence of side effects,[8] which typically include nausea and vomiting.[9]
Rivastigmine is eliminated through the urine, and appears to have relatively few drug-drug interactions.[9]
It was patented in 1985 and came into medical use in 1997.[10]
Rivastigmine isindicated for the treatment of dementia of the Alzheimer's type;[4] and for the treatment of dementia associated with Parkinson's disease.[4]
Rivastigmine capsules, liquid solution and patches are used for the treatment of mild to moderate dementia of theAlzheimer's type, and for mild to moderateParkinson's disease dementia.[11]
Rivastigmine has demonstrated treatment effects on the cognitive (thinking and memory), functional (activities of daily living) and behavioural problems commonly associated with Alzheimer's.[12][13][14][15]
In people with either type of dementia, rivastigmine has been shown to provide meaningful symptomatic effects that may allow patients to remain independent and 'be themselves' for longer. In particular, it appears to show marked treatment effects in patients showing a more aggressive course of disease, such as those with younger onset ages, poor nutritional status, or those experiencing symptoms such as delusions or hallucinations.[16] For example, the presence of hallucinations appears to be a predictor of especially strong responses to rivastigmine, both in Alzheimer's and Parkinson's patients.[17][18] These effects might reflect the additional inhibition of butyrylcholinesterase, which is implicated in symptom progression and might provide added benefits over acetylcholinesterase-selective drugs in some patients.[16][17] Multiple-infarct dementia patients may show slight improvement in executive functions and behaviour. No firm evidence supports usage in schizophrenia patients.
Its efficacy is similar todonepezil andtacrine. Doses below 6 mg/d may be ineffective. The effects of this kind of drug in different kinds of dementia (including Alzheimer's dementia) are modest, and it is still unclear which AChE (BChE) esterase inhibitor is better in Parkinson's dementia, though rivastigmine is well-studied.
Side effects may include nausea and vomiting, decreased appetite and weight loss.[9]
The strong potency of rivastigmine, provided by its dual inhibitory mechanism, has been postulated to lead to more nausea and vomiting during the titration phase of oral rivastigmine treatment.[9]
In a large clinical trial of the rivastigmine patch in 1,195 patients with Alzheimer's disease, the target dose of 9.5 mg/24-hour patch provided similar clinical effects (e.g. memory and thinking, activities of daily living, concentration) as the highest doses of rivastigmine capsules, but with one-third fewer reports of nausea and vomiting.[8]
Usage of rivastigmine was associated with a higher frequency of reports of death as an adverse event in the Food and Drug Administration Adverse Event Reporting System database compared to the other acetylcholinesterase inhibiting drugs donepezil and galantamine; this increase could be related to improper application of the transdermal patch, or because rivastigmine is more often used during advanced illness.[19]
Rivastigmine can increase gastric acid; it is discontinued if there are signs of gastrointestinal bleeding, particularly in individuals usingnonsteroidal anti-inflammatory drugs (NSAIDs) or who have a history ofpeptic ulcer disease.[20]
Rivastigminetartrate is a white to off-white, fine crystalline powder that is both lipophilic (soluble in fats) and hydrophilic (soluble in water). It comes in a variety of administrations including a capsule, solution and atransdermal patch. Like othercholinesterase inhibitors, it requires doses to be increased gradually over several weeks; this is usually referred to as the titration phase.[9]
Rivastigmine, acholinesterase inhibitor, inhibits bothbutyrylcholinesterase andacetylcholinesterase (unlikedonepezil, which selectively inhibits acetylcholinesterase). It is thought to work by inhibiting these cholinesterase enzymes, which would otherwise break down the brainneurotransmitter acetylcholine.[21]
When given orally, rivastigmine is well absorbed, with a bioavailability of about 40% in the 3-mg dose. Pharmacokinetics are linear up to 3 mg twice daily, but nonlinear at higher doses. Elimination is through the urine. Peak plasma concentrations are seen in about one hour, with peak cerebrospinal fluid concentrations at 1.4–3.8 hours. When given by once-daily transdermal patch, the pharmacokinetic profile of rivastigmine is much smoother, compared with capsules, with lower peak plasma concentrations and reduced fluctuations.[22] The 9.5 mg/24 h rivastigmine patch provides comparable exposure to 12 mg/day capsules (the highest recommended oral dose).[22]
The compound does cross theblood–brain barrier. Plasma protein binding is 40%.[23] The major route of metabolism is by its target enzymes via cholinesterase-mediated hydrolysis. Elimination bypasses the hepatic system, so hepatic cytochrome P450 (CYP) isoenzymes are not involved.[24] The low potential for drug-drug interactions (which could lead to adverse effects) has been suggested as due to this pathway compared to the many common drugs that use the cytochrome P450 metabolic pathway.[9]
A QbD driven HPLC method was developed for the quantification of rivastigmine in rat plasma and brain for its pharmacokinetics study.[25]].
Rivastigmine was developed byMarta Weinstock-Rosin of the Department of Pharmacology at theHebrew University of Jerusalem[26] and sold toNovartis byYissum for commercial development. It is a semi-synthetic derivative ofphysostigmine.[27]
