Exelon, 3mg capsules, 28pcs

Composition

1 capsule contains:

Active ingredient:

rivastigmine (in the form of hydrotartrate) 3 mg.

Auxiliary substances:

magnesium stearate,

methylhydroxypropylcellulose (hypromellose),

microcrystalline cellulose,

colloidal anhydrous silicon dioxide,

titanium dioxide (E 171),

gelatin,

iron oxide yellow (E 172),

iron oxide red (E 172).

Pharmacological action

Exelon 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 Exelon 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 enzyme activity returns to its original level after about 9 hours. It was shown that butyrylcholinesterase activity in CSF in young healthy volunteers is reversibly inhibited and restored to the initial one 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 rivastigmine inhibition of both CSF enzymes and changes in cognitive function in patients with Alzheimer’s disease; however, it is the inhibition of butyrylcholinesterase in CSF that significantly and stably correlates with improvements in memory, attention, and reaction time tests.

The effectiveness of Exelon therapy in Alzheimer’s disease was shown in patients with mild to moderate dementia (10-24 points on the Mini Mental State Examination (MMSE)). According to clinical studies, Exelon therapy leads to a significant improvement in cognitive functions (attention, memory, speech, etc. ), functional status and activity in everyday life, as well as to a decrease in the severity of the disease and the severity of mental and behavioral manifestations (such as agitation, tearfulness, illusions, hallucinations, etc. ).

Studies have shown that the effect of Exelon therapy is observed at approximately the 12th week and persists for 6 months of therapy, while during the control period of time in the group of patients receiving placebo, a deterioration in the corresponding indicators was observed.

For dementia associated with Parkinson’s disease, the efficacy of Exelon was demonstrated in a placebo-controlled study lasting 24 weeks in patients with mild to moderate dementia (10-24 MMSE points). Patients treated with Exelon showed statistically significant improvement in cognitive functions (attention, memory, speech, etc. ), while patients treated with placebo, similar indicators worsened.

Indications

-Mild or moderate Alzheimer’s type dementia: probable Alzheimer’s disease, Alzheimer’s disease.

– Mild to moderate dementia in Parkinson’s disease.

Use during pregnancy and lactation

The safety of using Exelon during pregnancy in humans has not yet been established, so the drug can be prescribed during pregnancy only in cases where the expected success of treatment exceeds the potential risk to the fetus.

It is not known whether rivastigmine is excreted in breast milk.

Therefore, during the use of the drug, you should stop breastfeeding. Experimental studies have shown that rivastigmine has no teratogenic properties.

Contraindications

-Hypersensitivity to rivastigmine, other carbamate derivatives or other ingredients that make up the drug. – Exelon is contraindicated in patients with severe hepatic impairment, as its use in this population has not been studied. With caution: – Exelon, as well as other cholinomimetic agents, should be used with caution in patients with sinus node weakness syndrome or conduction disorders 6 sino-artrial 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 selection period, as well as when using 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 overall incidence of adverse events associated with Exelon 9.5/24 h TTS therapy (50.5%) was lower compared to oral therapy with capsules at a daily dose of 3-12 mg (63.3%) (for comparison, in the placebo group, this indicator was 46%).

The most frequent reactions were observed from the digestive system. Nausea (7.2%) and vomiting (6.2%) were significantly less when using TTS Exelon 9.5 mg/24 h compared with the capsules for oral use,23.1% and 17.0%, respectively (in the placebo group the same values were 5.0% and 3.3%).

The incidence of adverse reactions in patients (291 people) with dementia of Alzheimer’s type, treated TTS Exelon (all dosages), is defined as follows: very often (≥1/10), often (≥ 1/100, less than 1/10), infrequently (≥1/1000, less than 1/100), rare (≥1/10 000, less than 1/1000), very rare (less than 1/10 000), separately presented adverse reactions, the frequency of which is uncertain.

Infectious and parasitic diseases: often-urinary tract infections.

From the side of metabolism: often – anorexia.

From the nervous system: often-anxiety, depression, delirium, headache, fainting; very rarely-extrapyramidal disorders; frequency unknown-hallucinations.

From the cardiovascular system: infrequently-bradycardia, cerebral circulatory disorders.

From the digestive system: often – nausea, vomiting, diarrhea, dyspepsia, abdominal pain; infrequently-gastric ulcer.

Dermatological reactions: often-rash.

On the part of the body as a whole and reactions at the site of TTS attachment: often – erythema, edema and itching, irritation, inflammation at the site of application, increased fatigue, asthenia, fever, weight loss.

In clinical trials, the following adverse reactions were observed significantly more frequently when using the drug at doses greater than 9.5 mg/24 h than in the TTS Exelon 9.5 mg/24 h and placebo groups: dizziness, insomnia, agitation, decreased appetite, atrial fibrillation, heart failure (possibly related to an increase in the dose). The frequency of these adverse reactions during Exelon 9.5 mg/24 h TTS therapy was similar to that in the placebo group.

The following adverse reactions were observed only when treated with Exelon capsules or oral solution and were not reported with Exelon TTC 9.5 mg/24 h: dizziness (very common), agitation, drowsiness, general malaise, tremor, confusion, increased sweating (common), insomnia, accidental falls, increased liver activity (sometimes), convulsions, duodenal ulceration, angina pectoris, myocardial infarction (rare), arrhythmias (for example, AV block, atrial fibrillation, tachycardia), increased blood pressure, pancreatitis, gastrointestinal bleeding, hallucinations (very rare); in some cases-severe vomiting leading to esophageal rupture (frequency unknown).

Dermatological reactions

When using TTS Exelon, redness of the skin (erythema) at the application site was most often noted, usually disappearing in most patients within 24 hours. In clinical studies, the use of TTS Exelon 9.5 mg/24 h showed mild (21.8%), moderate (12.5%), severe (6.5%) redness of the skin, mild (11.9%), moderate (7.3%) and severe (5%) itching.

Pruritus and erythema were observed in 1.7% and 1.1% of patients treated with Exelon 9.5 mg/24 h TTS, respectively. Most skin reactions developed only in the area of TTC application. When using TTS Exelon 9.5 mg/24 h, discontinuation of treatment with the drug due to the development of dermatological reactions was noted only in 2.4% of cases.

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, antidiabetic agents, central-acting antihypertensive agents, beta-blockers, calcium channel blockers, drugs that have a positive inotropic effect, antianginal agents, nonsteroidal anti-inflammatory drugs, estrogens, analgesics, benzodiazepines and antihistamines was not accompanied by any changes in the kinetics of the drug. treatment with 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 (muscle relaxants of the succinylcholine type).

How to take, course of use and dosage

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

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 a day.

The initial recommended dose is 1.5 mg (0.75 ml of solution) 2 times a day. If this dose is well tolerated after at least two weeks of treatment, it can be increased to 3.0 mg 2 times a 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 a day and then up to 6 mg 2 times a day – with a time interval of at least 2 weeks after each dose increase.

Adverse events such as nausea, vomiting, abdominal pain, decreased appetite, or weight loss observed during treatment may decrease after skipping one 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 mg to 6.0 mg 2 times a day. In order to achieve the best therapeutic effect, the dose of the drug should be kept at the maximum well-tolerated level.

Maximum daily dose: 6.0 mg 2 times a day.

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. Equal doses of Exelon, used as capsules or as 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.

Form of production

Capsules

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

5 years

Active ingredient

Rivastigmine

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

For adults as directed by your doctor

Indications

Acquired Dementia, Alzheimer’s Disease, Parkinson ‘s Disease