Exelon, vial 100mg, 50ml

$107.00

Active ingredient:	Rivastigmine
Dosage form:	Solution for oral use
Indications for use:	Alzheimer's disease, Dementia, Parkinson's disease

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Categories: Alzheimer's, Medication, Neurology, psychiatry

Indications

Mild to moderate Alzheimer’s dementia (probable Alzheimer’s disease, Alzheimer’s disease)

Mild to moderate dementia in Parkinson’s disease

Contraindications

Hypersensitivity to rivastigmine, other carbamate derivatives, or other Excelon ingredients.
Exelon is contraindicated in patients with severe hepatic impairment, as its use in this population has not been studied.
Under 18 years of age

With caution
Exelon, like other cholinomimetic agents, should be used with caution in patients with sinus node weakness syndrome or conduction disorders (sino-atrial block, atrioventricular block).
Cholinergic stimulation can increase the secretion of hydrochloric acid in the stomach, lead to increased urinary tract obstruction and exacerbation of convulsive syndrome, so caution should be exercised when prescribing Exelon to patients predisposed to these conditions.
Exelon, as well as other cholinomimetics, should be used with caution in patients with a history of bronchial asthma or obstructive airway diseases.
Taking into account the pharmacodynamic properties of Exelon, it should not be administered simultaneously with other cholinomimetic drugs.
During the dose adjustment period, as with other cholinomimetics, adverse events were observed for a short period after increasing the dose. The severity of adverse events may decrease in response to a reduction in the dose of the drug. Otherwise, you should cancel Exelon.

Composition

of 1 ml of the oral solution contains:

active ingredient:

rivastigmine (in the form of tartrate) 2 mg,

excipients:

sodium benzoate,

citric acid anhydrous,

sodium citrate,

dihydrate powder,

yellow quinoline WS (E 104),

purified water.

Composition

1 ml of the oral solution contains:

Active ingredient:

rivastigmine (in the form of tartrate) 2 mg,

excipients:

sodium benzoate,

citric acid anhydrous,

sodium citrate,

dihydrate powder,

yellow quinoline WS (E 104),

purified water.

Pharmacological action

Pharmacodynamics

Rivastigmine is a selective inhibitor of brain acetyl-and butyrylcholinesterase used for the treatment of Alzheimer’s disease and dementia in Parkinson’s disease. Rivastigmine slows down the breakdown of the neurotransmitter acetylcholine produced by functionally intact neurons.

At the same time, rivastigmine selectively increases the content of acetylcholine in the cerebral cortex and hippocampus, and thus contributes to the improvement of cholinergic nervous transmission. Exelon may have a positive effect in reducing cognitive functions associated with acetylcholine deficiency, in particular, in dementia associated with Alzheimer’s disease and Parkinson’s disease. In addition, there is evidence that inhibition of cholinesterases can slow the formation of fragments of the protein precursor beta-amyloid, which is involved in amyloidogenesis, and thus slow the formation of amyloid plaques, which are one of the main pathological signs of Alzheimer’s disease.

Rivastigmine interacts with the target enzyme to form a covalent bond, which leads to temporary inactivation of the enzyme. It was shown that in young healthy men, after taking the drug at a dose of 3 mg, the activity of acetylcholinesterase in the cerebrospinal fluid (CSF) decreases by approximately 40% during the first 1.5 hours. After reaching the maximum inhibitory effect, the activity of the enzyme returns to its original value in about 9 hours. It was shown that butyrylcholinesterase activity in CSF in young healthy volunteers is reversibly inhibited and restored to its initial state after 3-6 hours. In patients with Alzheimer’s disease, rivastigmine inhibition of CSF acetylcholinesterase activity is dose-dependent in the studied dose range (up to the highest dose of 6 mg twice daily).

Inhibition of butyrylcholinesterase is also dose-dependent; a dose of 6 mg 2 times a day causes a decrease in the activity of the enzyme by more than 60% compared to the initial one. This effect of Exelon was maintained for 12 months of therapy (the maximum studied period). Statistically significant correlations were shown between the degree of inhibition of both CSF enzymes by rivastigmine and changes in cognitive functions in patients with Alzheimer’s disease; however, it is the inhibition of butyrylcholinesterase in CSF that significantly and stably correlates with improved results of memory, attention, and reaction speed tests.

Exelon therapy for Alzheimer’s disease and dementia associated with Parkinson’s disease leads to a significant improvement in cognitive functions (attention, memory, speech, etc. ). In addition, during therapy for Alzheimer’s disease, there is an improvement in functional status and activity in everyday life, as well as a decrease in the severity of the disease and the severity of mental and behavioral manifestations.

Pharmacokinetics

Absorption Vivastigmine is rapidly and completely absorbed. The maximum plasma concentration (cmax) is reached after approximately 1 hour. Due to the interaction of rivastigmine with the target enzyme, when the dose of the drug is increased, the increase in its bioavailability is 1.5 times higher than expected (for this dose increase). After taking a dose of 3 mg, the absolute bioavailability is about 36%. When rivastigmine is taken together with food, rivastigmine absorption slows down (the time to reach_cmax increases by 74 minutes);_{the cmax value} decreases by 43%, while the area under the concentration-time curve AUC increases by approximately 9%.

Distribution Vivastigmine binds to plasma proteins to a weak extent (approximately 40%). Easily penetrates the blood-brain barrier. The apparent volume of distribution is 1.8-2.7 l / kg.

Metabolism Vivastigmine is rapidly metabolized (plasma half-life (Ti2) is about 1 hour), mainly by hydrolysis by cholinesterase to form a de-carbamylated metabolite. In vitro, this metabolite has shown minimal ability to inhibit acetylcholinesterase (

Excretion Vivastigmine is mainly excreted by the kidneys as metabolites; it is not detected unchanged in the urine. 24 hours after use, more than 90% of the dose is eliminated. Less than 1% of the dose is excreted in the faeces. No accumulation of rivastigmine or its decarbamylated metabolite is observed in patients with Alzheimer’s disease.

Pharmacokinetics in elderly patients Although the bioavailability of rivastigmine in the elderly is higher than in healthy young volunteers, however, in patients with Alzheimer’s disease aged 50 to 92 years, no age-related changes in bioavailability were detected in clinical studies.

Indications

Mild to moderate Alzheimer’s dementia (probable Alzheimer’s disease, Alzheimer’s disease)

Mild to moderate dementia in Parkinson’s disease

Use during pregnancy and lactation

Experimental data have shown that rivastigmine has no teratogenic properties.

However, the safety of using Exelon during human pregnancy has not yet been established, so the drug can be prescribed to pregnant women only in cases where the expected benefit of treatment exceeds the potential risk to the fetus.

It is not known whether Exelon passes into breast milk. Therefore, during the use of the drug, you should stop breastfeeding.

Contraindications

Hypersensitivity to rivastigmine, other carbamate derivatives, or other Excelon ingredients.
Exelon is contraindicated in patients with severe hepatic impairment, as its use in this population has not been studied.
Under 18 years of age

Exelon, like other cholinomimetic agents, should be used with caution in patients with sinus node weakness syndrome or conduction disorders (sino-atrial block, atrioventricular block). Cholinergic stimulation can increase the secretion of hydrochloric acid in the stomach, lead to increased urinary tract obstruction and exacerbation of convulsive syndrome, so caution should be exercised when prescribing Exelon to patients predisposed to these conditions. Exelon, as well as other cholinomimetics, should be used with caution in patients with a history of bronchial asthma or obstructive airway diseases. Taking into account the pharmacodynamic properties of Exelon, it should not be administered simultaneously with other cholinomimetic drugs. During the dose adjustment period, as with other cholinomimetics, adverse events were observed for a short period after increasing the dose. The severity of adverse events may decrease in response to a reduction in the dose of the drug. Otherwise, you should cancel Exelon.

Side effects

The most frequently reported adverse events (AES) from the digestive system: nausea (38%), vomiting (23%), mainly during the period of increasing the dose. According to clinical studies, adverse reactions from the digestive system and weight loss were more common in women. In patients with Alzheimer’s type dementia treated with Exelon, the AES listed in Table 1 were observed.

Table 1

Infections and infestations
Urinary tract infections	Very rare
Mental disorders
Anorexia	Very often
Agitation	Often
Confusion	Is common
Insomnia	Sometimes
Depression	Sometimes
Hallucinations	Very rare
Central nervous system disorders
Vertigo	Very often
Headache	Often
Drowsiness	Often
Tremor	Often
Fainting	Sometimes
Convulsive attacks	Rarely
Extrapyramidal disorders (worsening of Parkinson’s disease)	Very rare
Disorders of the cardiovascular system
Angina, myocardial infarction	Rarely
Arrhythmia (bradycardia, atrioventricular block, atrial fibrillation, tachycardia)	Very rare
Marked increase in blood pressure (BP)	Very rare
Disorders of the digestive system
Nausea	Very often
Vomiting	Very often
Diarrhea	Very often
Reduced appetite	Very often
Abdominal pain and dyspepsia	are Common
Stomach and duodenal ulcers	Rarely
Violations of laboratory parameters of liver function	Sometimes
Bleeding from the gastrointestinal tract(GIT)	Very rare
Pancreatitis	Very rare
Severe vomiting leading to rupture of the esophagus	Very rare
Skin and subcutaneous tissue disorders
Excessive sweating	Often
Rash, itching	Rarely
On the part of the body as a whole-general disorders
Increased fatigue and asthenia	Often
General malaise	Often
Random drops	Sometimes
Other things
Weight	loss Is Common

In patients with dementia in Parkinson’s disease treated with Exelon, AES were noted, indicated in Table 2. The frequency of adverse reactions was estimated as follows: occurring “very often” – ≥10%, “often” – ≥1% –

Table 2

Mental disorders
Insomnia	Sometimes
Alarm	Sometimes
Excited state	Sometimes
Central nervous system disorders
Tremor	Very often
Vertigo	Is Common
Drowsiness	Often
Headache	Often
Drowsiness	Often
Worsening of the course of Parkinson	‘s disease is common
Bradykinesia	Often
Dyskinesia	Often
Dystonia	Sometimes
Disorders of the cardiovascular system
Bradycardia	Often
Atrial Fibrillation	Sometimes
Atrioventricular block	Sometimes
Disorders of the digestive system
Nausea	Very often
Vomiting	Very often
Diarrhea	Is Common
Abdominal pain and dyspepsia	are Common
Increased salivation	Often
Musculoskeletal system disorders
Muscle rigidity	Is Common
Skin and subcutaneous tissue disorders
Excessive sweating	Often
On the part of the body as a whole-general disorders
Dehydration	Is Common
Increased fatigue and asthenia	Often
Gait Disorders	Are Common

When using Exelon in patients with dementia in Parkinson’s disease, the following adverse events were observed, possibly indicating a worsening of the course of Parkinson’s disease: tremor, falls, increased salivation, dyskinesia, Parkinsonism, hypokinesia, ataxia, bradykinesia, dystonia, gait disorders, muscle rigidity, balance disorders, muscle stiffness, trembling, and other motor disorders.

Interaction

Rivastigmine is mainly metabolized by hydrolysis with the participation of esterases. The metabolism of rivastigmine with the participation of the main cytochrome P 450 isoenzymes occurs to a minimal extent. Thus, pharmacokinetic interactions of rivastigmine with other drugs metabolized with the participation of these enzymes are unlikely. There was no pharmacokinetic interaction between rivastigmine and digoxin, warfarin, diazepam, or fluoxetine in healthy volunteers. The warfarin-induced increase in prothrombin time did not change when rivastigmine was administered. No adverse effects on intracardiac conduction were observed when rivastigmine and digoxin were co-administered.

Concomitant use of rivastigmine with commonly used medications such as antacids, antiemetics, hypoglycemic agents, central-acting antihypertensive agents, beta-blockers, slow calcium channel blockers, drugs that have a positive inotropic effect, antianginal agents, estrogens, analgesics, including nonsteroidal anti-inflammatory drugs, benzodiazepines and antihistamines, was not accompanied by any adverse reactions. either changes in the kinetics of rivastigmine or an increased risk of clinically significant adverse events.

During anesthesia, rivastigmine, being a cholinesterase inhibitor, can enhance the effects of depolarizing muscle relaxants (for example, suxamethonium salts). Rivastigmine may affect the activity of holinoblockers and holinomimetics.

How to take, course of use and dosage

Exelon should be taken 2 times a day, during breakfast and dinner.

The initial dose is 1.5 mg 2 times / day. When using the drug in patients who are particularly sensitive to the effects of cholinergic drugs, treatment should begin with the use of the drug at a dose of 1 mg 2 times / day.

Dose selection

The initial recommended dose is 1.5 mg 2 times a day. If this dose is well tolerated after at least 2 weeks of treatment, it can be increased to 3 mg 2 times / day. In case of good tolerability of the dose taken by the patient, it is possible to further increase it – up to 4.5 mg 2 times/day and then up to 6 mg 2 times/day – with a time interval of at least 2 weeks after each dose increase.

Adverse events, such as nausea, abdominal pain, decreased appetite or weight loss, observed during treatment may decrease after skipping 1 or more doses of the drug. If adverse events persist, the daily dose of the drug should be reduced to the previous well-tolerated dose.

The maintenance dose is from 1.5 to 6 mg 2 times / day. In order to achieve the best therapeutic effect, the dose of the drug should be kept at the maximum well-tolerated level.

The maximum daily dose is 6 mg 2 times/day.

Resume taking the drug after a break. If there is a break in taking the drug for several days or more, treatment should be resumed from the initial dose to reduce the risk of recurrent adverse reactions (for example, severe vomiting). A gradual increase in the dose is carried out stepwise, as described above.

In patients with impaired renal or hepatic function, no dosage adjustment is required.

Method of application of the solution for oral use

The required amount of solution should be removed from the bottle using the dispenser attached to it. The solution can be taken directly from the dispenser.

Equal doses of the drug used in the form of capsules and in the form of an oral solution are interchangeable.

Overdose

Symptoms. Accidental overdose of the drug in most cases was not accompanied by any clinical manifestations; almost all patients continued treatment with Exelon. Overdose was associated with nausea, vomiting, diarrhea, a marked increase in blood pressure, and hallucinations. Taking into account the vagotonic effect of cholinesterase inhibitors on heart rate (HR), the occurrence of tachycardia and/or syncope cannot be excluded. In one case,46 mg of the drug was taken; after conservative treatment, complete recovery was observed in 24 hours.

Treatment. Since the plasma half-life of rivastigmine is about 1 hour and the duration of acetylcholinesterase inhibition is about 9 hours, in cases of asymptomatic overdose, it is recommended not to use Exelon for the next 24 hours. If an overdose is accompanied by severe nausea and vomiting, the use of antiemetics should be considered. If other adverse events occur, appropriate symptomatic treatment is carried out if necessary.

In case of a significant overdose, atropine can be used, the initial dose of which is 0.03 mg/kg intravenously; the subsequent dosage depends on the clinical effect. The use of scopolamine as an antidote is not recommended.

Special instructions

As with other cholinomimetics, extrapyramidal disorders may develop or increase their severity when taking rivastigmine. When using rivastigmine in patients with dementia in Parkinson’s disease, there was an increase in the severity of motor disorders (including bradykinesia, dyskinesia, gait disorders), as well as an increase in the frequency and severity of tremor (which in some cases required discontinuation of therapy with the drug). Patients should be monitored regularly for these adverse events.

Impact on the ability to drive vehicles and work with mechanisms

Patients treated with Exelon were not found to have any motor dysfunction. However, the ability of a patient with Alzheimer’s disease to drive vehicles and work with complex mechanisms should be regularly evaluated by the attending physician.