Rivastigmine was developed in the 1980s by Dr. Marta Weinstock-Rosin and her team at the Hebrew University of Jerusalem as a semi-synthetic derivative of physostigmine. The university’s technology transfer company, Yissum, later sold its commercial rights to Novartis, which introduced the drug under the brand name Exelon for Alzheimer’s disease and Parkinson’s disease–related dementia. It received its first FDA approval in 1997. Rivastigmine is a prescription drug used to manage mild to moderate dementia related to Alzheimer’s disease and Parkinson’s disease. While it does not cure these conditions, it can help reduce or slow the worsening of cognitive and functional symptoms.
BRAND NAMES
Exelon: The most widely recognized brand, offered in capsule form, oral solution, and transdermal patch formulations.
Prometax: Another marketed brand of rivastigmine.
Nimvastid: A brand name under which rivastigmine is also available.
Other brands: Additional names include Rivamer, Rivastigmine 1 A Pharma, and various region-specific formulations.
MECHANISM OF ACTION
Rivastigmine works by inhibiting the enzymes acetylcholinesterase and butyrylcholinesterase in the brain. These enzymes break down acetylcholine, a neurotransmitter essential for memory and cognition. By blocking them, rivastigmine increases acetylcholine levels and enhances neural communication. This helps improve cognitive function in dementia patients. Its dual-enzyme inhibition distinguishes it from some other cholinesterase inhibitors.
PHARMACOKINETICS
Absorption
Rivastigmine is well absorbed orally, with absorption enhanced when taken with food. Its bioavailability increases with higher doses. The transdermal patch provides slower, steady absorption over 24 hours. Peak plasma levels occur within 1 hour for oral forms and 8–16 hours for patches. Absorption variability is lower with the patch.
Distribution
Rivastigmine has moderate distribution throughout body tissues, including the brain. It has low plasma protein binding, allowing more free drug to act on target enzymes. The drug crosses the blood–brain barrier effectively. Distribution is consistent across age groups. Steady-state levels depend on dosing frequency and formulation.
Metabolism
Rivastigmine is primarily metabolized through cholinesterase-mediated hydrolysis rather than liver cytochrome P450 enzymes. This reduces the risk of drug–drug interactions. The main metabolite is inactive and rapidly formed. Because liver enzymes are not significantly involved, the drug is suitable for patients with mild hepatic impairment. Transdermal forms may produce slightly different metabolic patterns.
Excretion
Rivastigmine and its metabolites are mostly excreted through the kidneys. Elimination is relatively quick, preventing drug accumulation. Less than 1% is excreted unchanged. Impaired renal function may influence clearance and dosing. The patch form reduces peak concentrations, lowering adverse reaction risk.
PHARMACODYNAMICS
Rivastigmine enhances cholinergic neurotransmission by boosting acetylcholine availability in the brain. This action improves memory, learning, and cognitive processing. Its dual inhibition of key enzymes provides broader activity compared to single-enzyme inhibitors. Effects are dose-dependent and may take weeks to show significant improvement. Rivastigmine mainly targets central nervous system symptoms.
ADMINISTRATION
Rivastigmine is administered orally in capsules or solution, or via a transdermal patch. The patch is preferred due to fewer gastrointestinal side effects. Oral forms should be taken with food to improve tolerance. The patch must be applied to clean, dry skin and replaced every 24 hours. Dose adjustments depend on patient response and tolerability.
DOSAGE AND STRENGTH
Rivastigmine is available in 1.5 mg, 3 mg, 4.5 mg, and 6 mg capsules and oral solution. Patch strengths include 4.6 mg/24 hr, 9.5 mg/24 hr, and 13.3 mg/24 hr. Treatment usually starts at the lowest dose and gradually increases. Titration helps reduce side effects, especially gastrointestinal symptoms. Maximum tolerated dose depends on individual patient response.
DRUG INTERACTIONS
Rivastigmine has fewer interactions because it does not rely on liver CYP450 enzymes. Caution is needed with other cholinergic or anticholinergic drugs. Combining with beta-blockers may increase the risk of bradycardia. Muscle relaxants used in anesthesia may have enhanced effects. Always assess interactions before starting therapy.
FOOD INTERACTIONS
Taking rivastigmine with food improves absorption and reduces nausea. No significant food restrictions are required. Fatty meals may delay peak absorption slightly without affecting overall effectiveness. Hydration may help decrease gastrointestinal discomfort. The patch is unaffected by food intake.
CONTRAINDICATIONS
Rivastigmine is contraindicated in patients with known hypersensitivity to the drug or carbamate derivatives. It should not be used in individuals with severe skin reactions to the patch. Caution is necessary in patients with bradycardia or conduction abnormalities. Those with gastrointestinal ulcers or recent surgery require careful monitoring. Severe hepatic impairment may limit use.
SIDE EFFECTS
Nausea and vomiting
Loss of appetite and weight loss
Dizziness or fainting
Diarrhea or abdominal discomfort
Skin irritation with patch use
OVER DOSE
Overdose may lead to severe cholinergic symptoms due to excessive acetylcholine accumulation. Symptoms include vomiting, sweating, tremors, slow heart rate, and breathing difficulty. Immediate medical care is required. Atropine may be used as an antidote to counter cholinergic effects. Supportive treatment depends on severity.
TOXICITY
Rivastigmine toxicity is usually related to excessive cholinergic stimulation. High doses can cause profound nausea, bradycardia, muscle weakness, and respiratory problems. Patch misuse or multiple patch applications can increase toxicity risk. Toxicity is reversible with prompt treatment. Proper dosing and monitoring reduce risk significantly.
