Exelon TTS 9.5mg #30
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Exelon instructionYou can buy Exelon hereComposition1 transdermal therapeutic system (patch, TTS) may include rivastigmine in dosages: 9 mg (4.6 mg / day); 18 mg (9.5 mg / day); or 27 mg (13.3 mg / day).Optional: acrylic acid copo..
You can buy Exelon here
1 transdermal therapeutic system (patch, TTS) may include rivastigmine in dosages: 9 mg (4.6 mg / day); 18 mg (9.5 mg / day); or 27 mg (13.3 mg / day).
Optional: acrylic acid copolymer, D, L-α-tocopherol, butyl methacrylate and methyl methacrylate copolymer.
Adhesive layer: D, L-α-tocopherol, dimethicone, silicone copolymer.
Novartis Pharma produces Exelon in the form of a transdermal therapeutic system (patch) with an adhesive adhesive surface of 5 cm2 for 9 mg; 10 cm2 for 18 mg; 15 cm2 for 27 mg.
Pharmacodynamics and pharmacokinetics
Exelon with the active ingredient rivastigmine is an inhibitor of cholinesterase, namely, it selectively inhibits acetylcholinesterase and butyrylcholinesterase of the carbamate type in the brain, thereby slowing down the destruction of acetylcholine secreted by functionally conserved neurons and contributing to the synthesis. In the hippocampus and cerebral cortex, rivastigmine selectively increases acetylcholine content, which leads to an increase in the quality of cholinergic transmission of nerve impulses. The drug has a positive effect on patients with the observed decrease in cognitive functions caused by acetylcholine deficiency, including the manifestations of dementia in Parkinson's and Alzheimer's disease.
In addition to these effects, there is evidence that the suppression of these cholinesterases can lead to inhibition of the formation of the protein portions of the beta-amyloid precursor responsible for the formation of amyloid plaques, which are the primary pathological manifestation of Alzheimer's disease. The effects of rivastigmine develop due to its interaction with the target enzyme, followed by the formation of a covalent bond, resulting in a temporary deactivation of the corresponding enzyme.
When prescribing 3 mg of rivastigmine to healthy young men, during the first one and a half hours in their cerebrospinal fluid (CSF), a decrease in the activity of acetylcholinesterase was observed by about 40%. After about 9 hours after fixing the maximum inhibitory effect of rivastigmine, the acetylcholinesterase activity returns to its original values. The process of suppression in butyrylcholinesterase in CSF is also reversible with the return of the initial level of the enzyme after 3.6 hours.
In the case of rivastigmine in patients with Alzheimer's disease, dose-dependent (in the daily dosage range up to 12 mg) inhibition of acetylcholinesterase in CSF, as well as butyrylcholinesterase is noted, the level of which decreases by about 60% when using rivastigmine in a daily dose of 12 mg. This efficacy of the drug was maintained throughout the study period of its use, which is 12 months.
During the 12-month treatment with rivastigmine, a statistically significant relationship was found between the indicators of its inhibition in the CSF of both enzymes and positive changes in the cognitive functions of Alzheimer's patients. Studies have reliably associated improvements in the test results of attention, memory, and responsiveness specifically with inhibition of butyrylcholinesterase in the CSF.
The administration of Exelon patch to patients with mild / moderate dementia in Alzheimer's disease (MMSE - 10-20 points) compared with placebo resulted in a significant improvement in their cognitive functionality (including improved speech, attention and memory), increased functional status, and increased daily activity.
TTS Exelon is characterized by slow absorption of the active ingredient rivastigmine. The time of determination of rivastigmine in the blood, after using the first dose of the patch, was 30-60 minutes. TCmax ranged from 10-16 hours, after which the serum content of the drug gradually decreased over 24 hours.
After changing the used patch to a new one, for about 40 minutes a slow decrease in Css rivastigmine was observed, up to the moment when the absorption of the active ingredient with fresh TTS prevailed over the elimination of this drug. In the next 8 hours, the plasma content of rivastigmine slowly rises and again reaches its maximum. The lowest concentration of rivastigmine in the equilibrium state was about 50% of the maximum, in contrast to the oral forms of this drug, when using the next dose of which the plasma concentration of the active ingredient was almost zero. Similar time parameters of the plasma content of rivastigmine were noted when using the Exelon patch in the daily dosage range of 4.6-13.3 mg.
In comparison with oral administration of rivastigmine, its exposure (AUC and Cmax) when applying the patch is obviously less, but an increase in these values is proportional to an increase in the dose of TTS Exelon. In the case of an increase in daily dosages of TTS from 4.6 mg to 9.5 mg, the AUC of rivastigmine increased 2.6 times, and with an increase in the daily dose to 13.3 mg, 4.9 times.
The relative differences in the parameters (vibration index, IR) Cmax and Cmin of rivastigmine using patches with different dosages, respectively, was 0.58 for a daily dose of 4.6 mg; 0.77 for a daily dose of 9.5 mg and 0.72 for a daily dose of 13.3 mg, which is noticeably lower than when taking the oral form of the drug, where the IR was 3.96 for a daily dose of 6 mg and 4.15 for a daily dose doses of 12 mg.
The mass part of rivastigmine, which is released within 24 hours from TTS Exelon, does not correspond to that when taken orally with a similar dose of this drug (according to the plasma exposure of rivastigmine for 24 hours). The use of the daily dosage of Exelon 9.5 mg patch is equivalent to the oral administration of a daily dose of rivastigmine 12 mg.
When directly comparing the use of a single dose of the patch and oral capsules, the interpopulation variability of diurnal Cmax and AUC of rivastigmine was 43% and 49% for the patch and 74% and 103% respectively for the capsules. In the case of Exelon's repeated use for treating dementia in Alzheimer's disease and when the drug reaches an equilibrium state, the observed interpopulation variability of diurnal Cmax and AUC rivastigmine was also significantly lower for the patch compared to oral capsules and was 45% and 43% versus 71% and 73% .
In patients with a body weight of 65 kg with Alzheimer's disease, Css rivastigmine increased approximately twice as compared with patients with a body weight of 35 kg and, on the contrary, decreased by 2 times with a weight for patients of 100 kg. The effect of the patient's weight on the exposure of rivastigmine in case of an increase in dosages of Exelon is especially significant for patients with very low body mass.
During the day, rivastigmine was released quite well from the patch of Ecelon, penetrating the skin approximately 50% of the total dosage. The highest coefficient of AUC∞ of rivastigmine, as well as the product of its metabolism, NAP 266-90 was recorded when the patch was applied to the shoulder, upper chest or back. If it is impossible to use TTS in these areas of the body, sticking the patch on the thigh and abdomen is allowed, with the amendment of reducing the AUC dose by about 20-30%.
No significant plasma cumulation of rivastigmine itself, as well as its metabolite, was observed, however, with repeated use, the serum content of rivastigmine was higher than in the first 24 hours.
Rivastigmine binding to plasma proteins is at 40%. The drug easily penetrates the BBB. Indicators of apparent Vd vary in the range of 1.8-2.7 l / kg
Rivastigmine's metabolic transformations are significant and rapid, with plasma T1 / 2 of about 3.4 hours after removing the patch. The degree of elimination of rivastigmine was limited by the level of its absorption, which explains the increase in T1 / 2 after using the patch (3.4 hours) compared with oral administration of the drug or its intravenous injection (1.4 and 1.7 hours respectively). The main route of metabolism of rivastigmine is its hydrolysis with cholinesterase with the release of a decarbamylated metabolic product, NAP 226-90, which demonstrates in vitro minimal (less than 10%) ability to inhibit acetylcholinesterase.
According to the experimental studies and testing of the drug in vitro, the cytochrome P450 system takes minimal part in the metabolism of rivastigmine. The total serum clearance of rivastigmine is approximately 130 l / h, with iv injection of the drug at a dose of 0.2 mg, decreases to 70 l / h with iv administration of 2.7 mg of rivastigmine and is consistent with its inversely proportional, non-linear character. pharmacokinetics, due to the excretion of the drug as it saturates the body.
The ratio of AUC∞ NAP 226-90 metabolite to the original substance was 0.7 for a patch at 3.5 for capsules, which gives the right to note the reduced intensity of metabolic transformation processes in the skin use of Exelon. Isolation of a smaller amount of NAP 226-90 metabolite is dictated by the absence of processes of first-pass metabolism (“first pass” through the liver).
Rivastigmine is eliminated mainly by the kidneys in the form of its metabolic products. In unchanged form of the drug in the urine is practically undetectable. After 24 hours, the kidneys excreted virtually 90% of the used dose, less than 1% of the drug is excreted by the intestine.
In elderly patients suffering from Alzheimer's disease, the use of TX Excelon did not lead to changes in the bioavailability of rivastigmine due to age-related changes.
In case of liver / kidney pathologies, the study of the peculiarities of using Exelon plaster was not conducted.
It is known that after oral administration of rivastigmine in patients with mild and moderately impaired hepatic function, the Cmax of the drug was increased by 60%, and its AUC was more than 100% higher than in patients without hepatic abnormalities.
In patients with Alzheimer's disease and parallel moderately pronounced pathologies of renal function, Cmax and AUC more than doubled in comparison with patients without renal pathologies. However, with severe impairment of renal function, changes in these parameters did not occur.
Indications for use
The administration of TTS Exelon is indicated for the treatment of mild or moderately severe dementia of Alzheimer's type and mild or moderately severe dementia in Parkinson’s disease.
Exelon plaster is absolutely contraindicated for:
personal hypersensitivity to rivastigmine and / or other components of the drug, as well as to other carbamate derivatives;
previously diagnosed (in history) contact allergic dermatitis, developed on the background of the use of the patch;
under the age of 18 years.
With the utmost care, TTS Exelon should be used when:
organic sinus dysfunction or conduction disorders (including AV block and sinoatrial block);
peptic ulcer in the period of exacerbation or predisposition of the patient to the formation of gastrointestinal ulcers;
propensity to develop convulsive syndrome and urinary tract obstruction;
bronchial asthma or frequent obstructive diseases of the respiratory tract observed in the past.
The cumulative incidence of negative effects when using Exelon plaster was 50.5%, which is slightly lower compared to the frequency of similar phenomena observed when taking capsules - 63.3% (in the placebo group, this figure was 46%).
When using a daily dose of 9.5 mg of the patch, side effects of the gastrointestinal tract were most often observed, with 7.2% of the indications being nausea; 6.2% - vomiting, with identical negative manifestations when taking capsules, respectively, 23.1% and 17.0% (in the placebo group, these figures were 5.0% and 3.3%). The remaining side effects of the drug were less common.
infectious pathology of the urinary tract.
extrapyramidal disorders (very rarely).
The cardiovascular system:
circulatory disorders of the brain;
soreness in the abdomen;
ulcerative lesion of the digestive tract (occasionally).
inflammation in the area of application.
In clinical studies using a patch with a daily dosage of more than 9.5 mg, the following negative effects were observed more often than when using TTS with a daily dose of 9.5 mg and in the placebo group: atrial fibrillation, insomnia, agitation, decreased appetite, dizziness, heart failure. Presumably this is due to an increase in the dosages of rivastigmine, since the frequency of similar adverse events in the Exelon patch group at a daily dose of 9.5 mg and the placebo group was almost identical.
On the part of the skin, the most frequent manifestations were: erythema at the site of application, usually disappearing within 24 hours. When conducting clinical trials, the use of TTS Exelon in a daily dose of 9.5 mg resulted in mild (21.8%), moderate (12.5%) and pronounced (6.5%) reddening (erythema) of the skin, as well as mild (11.9%), moderate (7.3%) and severe (5%) skin itching.
During treatment with the use of a daily dosage of Exelon 9.5 mg patch, itching and erythema were observed in 1.7% and 1.1% of patients, respectively. The overwhelming majority of skin adverse events occurred exclusively in the field of application. Interruption of therapy due to the development of skin manifestations was noted only in 2.4% of cases.
Plaster Exelon, instructions for use
Instructions for use of Exelon allows the use of the patch only under the supervision of medical personnel with clinical experience in the treatment of Alzheimer's-type dementia.
The mass portion contained in the patch and released from it within 24 hours of rivastigmine corresponds to: 9 mg: 4.6 mg; 18 mg: 9.5 mg; 27 mg: 13.3 mg.
For maximum effectiveness of therapy, sticking the patch should be carried out at the same time of the day, after removing the used dosage form. In the case of skipping a constant sticking time TTS, you need to replace the patch as soon as possible.
Treatment of TTS Exelon should begin with the use of a patch with a daily release of 4.6 mg.
If the patient is well tolerated by this dose of rivastigmine, after 4 weeks of therapy, the daily dose can be increased to 9.5 mg, which is the recommended maintenance dosage with adequate therapeutic efficacy.
In some cases, it may be necessary to increase the dosage of TTS Ekselona to a maximum daily dose of 13.3 mg, but not earlier than after 6 months.
Each subsequent increase in dosage is possible only with a good personal response to the previous dose. In case of deterioration of the tolerance of the drug with an increase in its dose, it is necessary to return to the last well-tolerated dosage.
Temporary cessation of therapy requires situations that develop with the development of negative effects on the gastrointestinal tract and / or worsening of the observed extrapyramidal symptoms (including tremor), up to their complete resolution.
In the case of a break in treatment of several days, further therapy should be started with a daily dose of 4.6 mg in order to reduce the risk of recurrence of adverse events (in particular, severe vomiting).
Transfer of patients in the past who received oral forms of Excelon to the use of TTS is possible while maintaining the following dosage proportions. When administered orally, rivastigmine at a daily dose of up to 6 mg, inclusive, plaster therapy can be continued at a daily release dose of 4.6 mg. With the previous daily oral intake of 6-12 mg rivastigmine, subsequent treatment using TTS can immediately begin with a daily dose of 9.5 mg. The transfer of the patient from the oral form of the drug to the patch is recommended for the next day after an internal dose of the last dose of Exelon.
In case of liver / kidney pathologies, adjustment of the dosage regimen is not required, however, the recommended maintenance dose of Exelon TTS for such patients is a daily dose of 4.6 mg.
Using Exelon Patch
The procedure of sticking the first and subsequent plasters of Exelon should be carried out using clean, dry and intact areas of the skin, with the minimum amount (if possible) of hair. The use of any cosmetic or therapeutic agents in this area of the skin is not recommended. In case of damage or hyperemia of the alleged skin area for sticking the patch, it is forbidden to install TTS Exelon on it.
One patch is intended to be used for only 24 hours, after which it must be replaced with a similar one.
The recommended choice of TTS Exelon application areas includes: shoulder parts, upper part (right or left) of the chest (avoiding gluing on the mammary glands), lower or upper part (right or left) of the back. To reduce the risk of possible irritation and / or skin manifestations, it is recommended to alternate the areas of application of the patch (optimally, in one area of the body a patch should be used for no more than 14 days).
Before applying the new TTS, you must completely remove the previous patch.
Proper use of the patch involves its prior removal from the packaging, for which the package should be cut along the lines applied to it. After that, it is necessary to remove the protective film from the patch, while not touching its adhesive surface, apply TTS on the previously selected skin surface and remove the opposite protective layer from the patch surface. Using the palms of your hands, press the plaster tightly to the skin and hold it in this state for at least 30 seconds, making sure that the TTS is completely adherent, especially at the edges.
You can write on the patch the exact time and date of its imposition (with a thin pen). Wearing TTS on the body, without removing, should be for 24 hours.
After a day, it is necessary to replace the used patch with a new one, for which you should gently bend the corner of the TTS and pull it until the patch is completely removed. Next, you need to erase the remnants of glue, using warm soapy water (you should not use alcohol or other solvents).
Used TTS is to be disposed of by folding it in half, connecting adhesive parts, placing it in a sealed bag and then destroying or throwing it out of the reach of children.
Any contact with the surfaces of the plaster requires subsequent thorough washing of the hands (in order to prevent plaster from getting into the eyes).
When contacting with water, the properly glued Exelon plaster with tight-fitting edges does not peel off, which is important for the implementation of water hygiene procedures (shower, bath). Unintended removal of the TTS can be facilitated by the patient’s long stay near the heat source.
In case of accidental peeling of the patch, a new one should be attached in its place and replaced with the next one at the usual time of the next day.
In the event of the simultaneous use of two or more TTCs, it is necessary to remove them all and consult a doctor.
Unintentional overdose with oral forms of rivastigmine, as a rule, was not accompanied by clinically significant adverse events requiring discontinuation of treatment. In general, symptoms of overdose were manifested by nausea / vomiting, an increase in blood pressure, diarrhea, and sometimes hallucinations. Taking into account the vagotonic effect of Exelon on the heart rate, the development of fainting states and / or bradycardia can be allowed. There is information about the simultaneous oral administration of 46 mg rivastigmine, after which conservative treatment was prescribed, leading to the patient's complete recovery after 24 hours.
Reliable data on cases of overdose with the use of the patch Exelon, which led to any negative consequences, does not exist.
A possible treatment for an asymptomatic overdose should be to stop Exelon for the next 24 hours because of plasma T1 / 2 rivastigmine, which is 3.4 hours and the duration of acetylcholinesterase inhibition for 9 hours. In the case of manifestations of severe nausea with subsequent vomiting, it is necessary to consider the appointment of antiemetic drugs. Other possible negative effects require treatment consistent with the observed symptoms. In severe cases, you can assign in / in the introduction of Atropine sulfate in the initial dosage of 0.03 mg / kg, the further introduction of Atropine is carried out, if necessary, and in doses corresponding to the produced clinical effect. It is not recommended to use Scopolamine as an antidote.
Specialized research on the interaction of the drug Exelon in the form of a patch with other therapeutic agents was not carried out.
Due to the fact that the metabolic transformations of rivastigmine mainly take place with the participation of esterases by hydrolysis and with minimal influence of the cytochrome P450 system, its pharmacokinetic interactions with other drugs whose metabolism depends on the cytochrome P450 system are unlikely.
When conducting studies of rivastigmine with the participation of healthy volunteers, its pharmacokinetic interaction with Diazepam, Digoxin, Fluoxetine and Warfarin was not detected. The increase in prothrombin time caused by taking warfarin with parallel application of rivastigmine remained unchanged. The combined administration of rivastigmine with digoxin did not lead to an adverse effect of this combination on intracardiac conductivity.
Co-administration of rivastigmine with oral hypoglycemic drugs, antacids, antianginal drugs, antihistamines, antiemetics, estrogens, centrally acting antihypertensive drugs, analgesics (including NSAIDs), beta-adrenergic blockers, benzodiazepines, calcium channel blockers, and women, i'm using ipods, heart control drugs, including anti-inflammatory drugs changes in the pharmacokinetic parameters of rivastigmine or an increase in the risk of serious negative effects.
Due to the effect of rivastigmine on cholinergic structures, its simultaneous use with cholinomimetic drugs should be avoided.
In the case of parallel administration of anticholinergic drugs, it is necessary to take into account the multidirectionality of the effects of these drugs with the action of Excelon.
If during the course of treatment with Exelon there is a need for anesthesia, it should be remembered that the effects of rivastigmine are designed to inhibit cholinesterase, which can lead to an increase in the action of depolarizing muscle relaxants.
Terms of sale
The prescription is not required to buy Exelon TTS.
TTS Exelon can be stored at a maximum ambient temperature of 25 ° C, away from children.
The patch can be stored for 24 months, starting from the date stamped on the secondary packaging.
When raising dosages of rivastigmine, a possible increase in the incidence and severity of side effects should be considered.
The severity of rivastigmine from the gastrointestinal tract, including nausea / vomiting, most often observed at the beginning of therapy and at the time of increasing dosages, may decrease with decreasing dose of Exelon.
In the case of an interruption in treatment with Exelon, which is forced for several days, the return to the use of the patch should begin with the appointment of its minimum daily dose of 4.6 mg.
Against the background of Exelon treatment of patients with Alzheimer's disease, there is the possibility of reducing their weight, and therefore it is necessary to constantly monitor this physical parameter.
Alzheimer's disease, as indeed, the therapy of this disease is often not compatible with the performance of accurate and dangerous work, as well as driving a car.
Since the diseases for which rivastigmine is used are already formed at a mature age, the effect of this drug on the children's body has not been studied, and therefore the use of TTS Exelon up to 18 years is not recommended.
During pregnancy (and lactation)
According to experimental data, teratogenic properties of rivastigmine have not been established. The drug does not affect the observed fertility, but can lead to an increase in the period of gestation. Full data on the safety of using Exelon plaster for the treatment of pregnant women does not currently exist, and therefore its use in pregnancy is contraindicated. The use of Exelon pregnant women is allowed in exceptional cases, with many times greater than the benefits of such treatment for the expectant mother in comparison with the possible risk of adverse events for the fetus.
The possibility of penetration of rivastigmine into the milk of a nursing mother has not been studied, which is the reason for refraining from treatment or refusal to breastfeed.
Reviews of Exelon plaster are quite rare, as a result of which it is very difficult to carry out any comparative analysis of the effectiveness of this drug. From the reviews available on the Internet about Ekselone, one can draw on the positive experience of using TTS, including its inhibitory effect on the development of Alzheimer's disease and improving the general condition of the patient, but unfortunately it is not necessary to talk about full recovery from this, of course, serious illness. In the case when, according to the doctor, the use of Exelon plaster is necessary, you should listen to his recommendations and follow the instructions for use of the drug exactly.