Pharmacological action of Exelon 

Selective inhibitor of cerebral acetylcholinesterase. Enzyme inactivation is due to the temporary formation of a complex with a covalent bond.

Slowing down the breakdown of acetylcholine, which is released by functionally intact cholinergic neurons, leads to facilitation of cholinergic neurotransmission.

Experimental studies have shown that rivastigmine selectively increases the content of acetylcholine in the cerebral cortex and hippocampus.

Rivastigmine has a positive effect on the inherent cholinergic-mediated cognitive deficits in Alzheimer's disease. In addition, there are indications that inhibition of cholinesterase may slow down the formation of fragments of the beta-amiloid-precurcor protein (APP) involved in amyloidogenesis and, therefore, the formation of amyloid plaques, which are one of the main pathological signs of the disease. Alzheimer's.

Improves indicators of cognitive function, general physical activity and activity in daily life, and also reduces the severity of manifestations of the disease.

Pharmacokinetics

Rivastigmine binds to plasma proteins to a weak degree (about 40%), easily penetrates the BBB.

Metabolism of rivastigmine occurs mainly by hydrolysis with cholinesterase to form a decarbamylated metabolite, which in vitro has demonstrated minimal ability to inhibit acetylcholinesterase (<10%). In accordance with the data obtained in vitro and in experimental studies, the main isozymes of cytochrome P450 are minimally involved in the metabolism of rivastigmine. The total plasma clearance of rivastigmine is about 130 l / h after i.v. administration at a dose of 0.2 mg and decreases to 70 l / h after i.v. administration of 2.7 mg, which is consistent with the nonlinear, inversely proportional nature of the pharmacokinetics of rivastigmine due to its elimination with saturation ...

In patients with mild and moderate hepatic impairment after oral administration of rivastigmine, an increase in Cobserved bymax by about 60% and AUC wasmore than 2 times compared with healthy individuals.

In patients with Alzheimer's disease and moderately severe renal impairment after oral administration of rivastigmine, an increase in Cobserved bymax and AUC wasmore than 2 times compared with healthy individuals; however, in patients with Alzheimer's disease and severely impaired renal function, no changes in Cmax and AUC were observed.

Indications for the active substances of Exelon®

Mild and moderate dementia of the Alzheimer's type (in the case of suspected or established Alzheimer's disease).

Dosage regimen of Exelon 

The initial dose is 1-1.5 mg 2 times / day. With good tolerance, a single dose can be increased to 3 mg, then to 4.5 and to 6 mg; reception frequency - 2 times / day; the interval between each dose increase should be at least 2 weeks. In order to achieve the best therapeutic effect, the dose of rivastigmine should be kept at the maximum well-tolerated level.

Side effects from the gastrointestinal tract or weight loss observed during treatment can be reduced by skipping one or more doses. If the side effect persists, then the daily dose should be reduced to the previous, well-tolerated level.

Contraindications for use

Hypersensitivity to rivastigmine, other carbamate derivatives.

Application during pregnancy and lactation 

The safety of the use of rivastigmine during pregnancy in humans has not yet been established. Application is possible only in cases where the expected benefit of treatment for the mother outweighs the potential risk to the fetus.

It is not known whether rivastigmine is excreted in human breast milk, therefore, if necessary, use during lactation should stop breastfeeding.

Special instructions

Use with caution in patients with SSS or severe arrhythmias, an increased risk of erosive and ulcerative lesions of the gastrointestinal tract, respiratory diseases (including a history), with obstruction of the urinary tract, convulsions. There is no experience of using rivastigmine in patients with bronchial asthma in the acute phase.

Influence on the ability to drive vehicles and control mechanisms

Use with caution in patients whose activities require concentration of attention and high speed of psychomotor reactions.

Drug Interactions

Rivastigmine is metabolized primarily by hydrolysis with the participation of esterases. Metabolism with the participation of the main isoenzymes of the cytochrome P450 system occurs to a minimum extent. Therefore, pharmacokinetic interaction with other drugs metabolized with the participation of these enzymes is unlikely.

With simultaneous use with anticholinergic drugs, a change in the activity of anticholinergic drugs is possible.

With simultaneous use, it is possible to enhance the action of depolarizing muscle relaxants during anesthesia.

Side effect

From the side of the central nervous system: increased fatigue, asthenia, dizziness, headache, agitation, insomnia, disorientation, depression, drowsiness.

From the digestive system: nausea, vomiting, diarrhea, abdominal pain, loss of appetite.

Others: Accidental injury, upper respiratory tract infections, urinary tract infections, increased sweating, feeling unwell, weight loss, and tremors.

Nausea, vomiting, loss of appetite and weight loss were more common in women.