Pharmacodynamics and pharmacokinetics
The drug Exelon with the active ingredient rivastigmine is a cholinesterase inhibitor , namely, it selectively suppresses acetylcholinesterase and butyrylcholinesterase , thereby slowing down the destruction of acetylcholine secreted by functionally intact neurons and helping to improve synaptic transmission . In the hippocampus and cerebral cortex, rivastigmine selectively increases the content of acetylcholine , which leads to an increase in the quality of cholinergic transmission of nerve impulses. The drug has a positive effect on patients with observed decline in cognitive function acetylcholine deficiency , including manifestations of dementia in Parkinson's disease and Alzheimer's .
In addition to these effects, there is evidence that inhibition of these cholinesterases may lead to inhibition of the formation of the protein portions of the amyloid-beta responsible for the formation of amyloid plaques , which are the primary pathological manifestation of Alzheimer's disease . The effects of rivastigmine develop through its interaction with enzyme , followed by the formation of a covalent bond, leading to temporary deactivation of the corresponding enzyme .
When 3 mg of rivastigmine an approximately 40% acetylcholinesterase activity was observed in their cerebrospinal fluid (CSF) within the first hour and a half After approximately 9 hours after recording the maximum inhibitory effect of rivastigmine acetylcholinesterase activity returns to its original values. of butyrylcholinesterase in the CSF is also reversible, with the enzyme returning to its original level after 3.6 hours.
When rivastigmine by patients with Alzheimer's disease, there is a dose-dependent (in a daily dosage range of up to 12 mg) inhibition of acetylcholinesterase in the CSF, as well as butyrylcholinesterase , the level of which decreases by approximately 60% when using rivastigmine at a daily dose of 12 mg. This effectiveness of the drug remained throughout the entire studied period of its use, which was 12 months.
During 12 months of rivastigmine , a statistically significant relationship was proven between its inhibition of both enzymes in the CSF and positive changes in the cognitive functions of patients suffering from Alzheimer's disease . The studies carried out reliably associated the improvement in test results of attention , memory and reaction speed with inhibition of butyrylcholinesterase .
Administration of the Exelon patch to patients with mild/moderate dementia in Alzheimer 's disease (MMSE - 10-20 points) compared with placebo led to a significant improvement in their cognitive functionality (including improvement in speech , attention and memory ), an increase in functional status, and an increase in daily activities.
TTC Exelon is characterized by slow absorption of the active ingredient rivastigmine . The time for determining 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.
of rivastigmine was observed over approximately 40 minutes , until the processes of absorption of the active ingredient of fresh TTS predominated over the elimination of this drug. Over the next 8 hours, the plasma concentration of rivastigmine slowly increases and again reaches its maximum. The lowest concentration of rivastigmine at steady state was about 50% of the maximum, in contrast to oral forms of this drug, when using the next dose, the plasma concentration of the active ingredient was practically equal to zero. Similar time parameters of plasma rivastigmine were observed when using the Exelon patch in a daily dosage range of 4.6-13.3 mg.
Compared with oral administration of rivastigmine, its exposure (AUC and Cmax) with the use of the patch is obviously lower, but the increase in these values is proportional to the increase in the dose of TTC Exelon. When the daily dosage of TTC was increased from 4.6 mg to 9.5 mg, the AUC of rivastigmine increased by 2.6 times, and when the daily dose was increased to 13.3 mg by 4.9 times.
The relative differences in the parameters (variation index, IR) Cmax and Cmin of rivastigmine when using patches with different dosages, respectively, were 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 oral forms of the drug, where the IC was 3.96 for a daily dose of 6 mg and 4.15 for a daily dose dose 12 mg.
The mass fraction of rivastigmine , which is released over 24 hours from TTS Exelon, does not correspond to that after oral administration of a similar dose of this drug (as assessed by plasma exposure of rivastigmine over 24 hours). The daily dose of Exelon 9.5 mg patch is equivalent to the daily dose of rivastigmine 12 mg taken orally.
In a direct comparison between the use of a single dose of the patch and oral capsules, the interpopulation variability in the daily Cmax and AUC of rivastigmine was 43% and 49% for the patch and 74% and 103% for the capsules, respectively. In the case of repeated use of Exelon for the treatment of dementia in Alzheimer's disease and the drug reached a steady state, the observed interpopulation variability in daily Cmax and AUC of rivastigmine was also significantly lower for the patch compared to oral capsules and, respectively, was 45% and 43% versus 71% and 73% .
In patients weighing 65 kg with Alzheimer's disease the Css of rivastigmine increased approximately twice as compared to patients weighing 35 kg and, on the contrary, decreased by 2 times for patients weighing 100 kg. rivastigmine exposure when Exelon dosages are increased is particularly significant for patients with very low body weight.
Over the course of 24 hours, rivastigmine was released quite well from the Exelon patch, penetrating into the skin by approximately 50% of the full dosage. The highest AUC∞ coefficient of rivastigmine , as well as its metabolic , NAP 266-90, was recorded when the patch was applied to the shoulder, upper chest or back. If it is impossible to use TTC in these areas of the body, a patch can be applied to the thigh and abdomen, adjusted to reduce the AUC dose by approximately 20-30%.
Significant plasma accumulation of rivastigmine itself , as well as its metabolite , was not observed, however, with repeated use, the serum content of rivastigmine was higher than in the first 24 hours.
The binding of rivastigmine to plasma proteins is at the level of 40%. The drug easily penetrates the BBB . Apparent Vd values vary between 1.8-2.7 l/kg
The metabolic transformation of rivastigmine is significant and rapid with a plasma T1/2 of approximately 3.4 hours after patch removal. 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 administration (1.4 and 1.7 hours, respectively). The main route of metabolism of rivastigmine is its hydrolysis by 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 experimental studies and in vitro testing of the drug, the cytochrome P450 takes minimal part in the metabolism of rivastigmine . The total serum clearance of rivastigmine is approximately 130 l/h with an intravenous injection of the drug at a dose of 0.2 mg, decreases to 70 l/h with an intravenous injection of 2.7 mg of rivastigmine and is consistent with the inversely proportional, nonlinear nature of its parameters pharmacokinetics, due to the elimination of the drug as the body becomes saturated with it.
The ratio of AUC∞ NAP 226-90 metabolite to the original substance was 0.7 for the patch and 3.5 for capsules, which gives the right to note a reduced intensity of metabolic transformation processes during cutaneous use of Exelon. The release of a smaller amount of NAP 226-90 metabolite is dictated by the absence of first-pass metabolism processes (“first pass” through the liver).
Rivastigmine excreted primarily by the kidneys in the form of metabolic products. In unchanged form, the drug is practically undetectable in urine. After 24 hours, virtually 90% of the dose used is excreted by the kidneys, less than 1% of the drug is excreted by the intestines.
In elderly patients suffering from Alzheimer's disease , the use of TTC Exelon did not lead to changes in the bioavailability of rivastigmine due to age-related changes.
For liver / kidney , the specifics of using the Exelon patch have not been studied.
It is known that after oral administration of rivastigmine to patients with mild and moderately severe hepatic impairment , there was an increase in Cmax of the drug by 60%, and its AUC by more than 100%, compared with patients without hepatic pathologies.
In patients with Alzheimer's disease and parallel moderate pathologies of renal function, an increase in Cmax and AUC values was noted by more than twice as compared to patients without renal pathologies. However, in cases of severe impairment of renal function, no changes in these parameters occurred.
Why does this work?
In the instructions for Exelon, the manufacturer specifies that rivastigmine is capable of selectively blocking the activity of acetyl esterase and butyrylcholinesterase. If the patient receives such treatment, acetylcholine is destroyed more slowly in his body. This substance is responsible for the normal functionality and generation of neurons. Proper use of shepherd helps improve the quality of neurotransmission. The ability to selectively increase the concentration of acetylcholine in the cerebral cortex and hippocampus has been established. All this leads to an increase in the quality of cholinergic transmission.
Cognitive function becomes better - it is greatly reduced precisely because of the lack of acetylcholine. This process always accompanies Parkinson's and Alzheimer's diseases. Inhibition of acetylcholinase is accompanied by the slow generation of beta-amyloid elements, the accumulation of which provokes one of the main pathological signs of Alzheimer's disease - amyloid plaques. It has been established that the degree of influence on the spinal cord fluid is determined by the dosage of the drug received by the patient.
Contraindications
The use of the Exelon patch is absolutely contraindicated for:
- personal hypersensitivity to rivastigmine and/or other components of the drug, as well as to other carbamate ;
- pregnancy;
- previously diagnosed (in history) contact allergic dermatitis , which developed due to the use of the patch;
- breastfeeding;
- under the age of 18 years.
TTS Exelon should be used with extreme caution when:
- organic sinus node dysfunction or conduction disorders (including AV block and sinoatrial block );
- peptic ulcer disease during the period of exacerbation or the patient’s predisposition to the formation of gastrointestinal ulcers ;
- tendency to develop convulsive syndrome and urinary tract obstruction ;
- bronchial asthma or frequent obstructive respiratory diseases observed in the past.
Side effects
The cumulative incidence of adverse effects when using the Exelon patch was 50.5%, which is slightly less than the incidence of similar events observed when taking capsules - 63.3% (in the placebo this figure was 46%).
Most often, when using a daily dose of 9.5 mg patch, side effects from the gastrointestinal tract , expressed as a percentage of 7.2% - nausea ; 6.2% - vomiting , with identical negative manifestations when taking capsules, 23.1% and 17.0%, respectively (in the placebo , these figures were 5.0% and 3.3%). Other side effects of the drug were less common.
Urinary system:
- infectious pathologies of the urinary tract .
Nervous system:
- fainting;
- depression;
- feeling of anxiety;
- delirium;
- headache;
- extrapyramidal disorders (very rare).
Metabolism:
- anorexia.
The cardiovascular system:
- cerebral circulatory disorders;
- bradycardia.
Digestive system:
- pain in the abdomen;
- nausea, vomiting;
- dyspeptic symptoms;
- diarrhea;
- ulcerative lesions of the gastrointestinal tract (occasionally).
Skin:
- skin rash;
- swelling;
- erythema;
- irritation;
- inflammation in the area of application.
Other:
- increased fatigue;
- temperature increase;
- asthenia;
- weight loss.
In clinical studies, when using a patch with a daily dosage of more than 9.5 mg, the following negative effects were observed much more often than when using TTC with a daily dose of 9.5 mg and in the placebo : atrial fibrillation , insomnia , agitation, decreased appetite , dizziness , heart failure . Presumably this is due to an increase in dosages of rivastigmine , since the frequency of similar adverse events in the group using the Exelon patch at a daily dose of 9.5 mg and the placebo was almost identical.
On the skin , the most common manifestations were: erythema at the application site, usually disappearing within 24 hours. In clinical studies, the use of TTS Exelon in a daily dose of 9.5 mg led to mild (21.8%), moderate (12.5%) and severe (6.5%) redness ( erythema ) of the skin, as well as mild (11.9%), moderate (7.3%) and severe (5%) skin itching .
When treated with a daily dosage of Exelon patch 9.5 mg, the appearance of itching and erythema was observed in 1.7% and 1.1% of patients, respectively. The overwhelming majority of skin adverse events occurred exclusively in the area of application. Interruption of therapy due to the development of skin manifestations was observed only in 2.4% of cases.
Exelon patch, instructions for use
Instructions for use of Exelon allow the use of the patch only under the supervision of medical personnel with clinical experience in the treatment of dementia of the Alzheimer's type .
of rivastigmine contained in the patch and released from it within 24 hours corresponds to: 9 mg: 4.6 mg; 18 mg:9.5 mg; 27 mg:13.3 mg.
For maximum effectiveness of therapy, the patch should be applied at the same time of day, after first removing the used dosage form. If the constant time for gluing the TTC is missed, the patch must be replaced as quickly as possible.
Treatment with TTC Exelon should begin with the use of a patch with a daily release of 4.6 mg.
If the patient tolerates 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 if there is adequate therapeutic efficacy.
In some cases, it may be necessary to increase the dosage of TTC Exelon to a maximum daily dose corresponding to 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. If the drug's tolerability deteriorates when its dose is increased, it is necessary to return to the last well-tolerated dosage.
Temporary cessation of therapy is required by situations that occur with the development of negative effects from the gastrointestinal tract and/or worsening of the observed extrapyramidal symptoms (including tremor ) until their complete resolution.
In 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 resumption of negative effects (in particular, severe vomiting ).
Transferring patients who have previously received oral forms of Exelon to the use of TTC is possible while maintaining the following dosage proportions. When taking oral rivastigmine at a daily dose of up to and including 6 mg, patch therapy can be continued at a daily release dose of 4.6 mg. With a previous oral daily dose of 6-12 mg rivastigmine, subsequent treatment with TTC can be started immediately with a daily dose of 9.5 mg. It is recommended to transfer the patient from oral forms of the drug to the patch the next day after the internal administration of the last dose of Exelon.
In case of liver / kidney , no adjustment of the dosage regimen is required, however, the recommended maintenance dose of Exelon TTC for such patients is a daily dose of 4.6 mg.
Using the Exelon patch
The procedure for gluing the first and subsequent Exelon patches should be done using clean, dry and undamaged areas of the skin , with a minimum amount of hair (if possible). The use of any cosmetic or medicinal products on this area of the skin is not recommended. In case of damage or hyperemia of the skin area supposedly selected for gluing the patch, it is prohibited to install TTC Exelon on it.
One patch is intended for use for only 24 hours, after which it must be replaced with a similar one.
The recommended selection of areas for application of TTC Exelon includes: shoulder parts , upper part (right or left) of the chest (avoiding gluing to the mammary glands ), lower or upper (right or left) part of the back . To reduce the risk of possible irritation and/or skin manifestations, it is recommended to alternate areas of application of the patch (optimally, the patch should be used on one area of the body for no more than 14 days).
Before applying a new TTC, the previous patch must be completely removed.
Correct use of the patch involves first removing it from the package, for which you should cut the package along the line marked on it. the protective film from the patch without touching its adhesive surface, apply TTC to a pre-selected skin surface and remove the opposite protective layer from the surface of the patch. Using the palms of your hands, press the patch tightly to the skin and hold it in this state for at least 30 seconds, making sure that the TTC is completely attached , especially at the edges.
You can write on the patch the exact time and date of its application (with a thin pen). The TTC should be worn on the body without removing it for 24 hours.
After 24 hours, it is necessary to replace the used patch with a new one, for which you should carefully bend the corner of the TTC and pull it until the patch is completely removed. Next, you need to wipe off the remaining glue using warm soapy water (do not use alcohol or other solvents ).
Used TTS must be disposed of by folding it in half, connecting the adhesive parts, placing it in a sealed bag and further destroying it or throwing it away out of the reach of children.
Any contact with the surfaces of the patch requires subsequent thorough hand washing (to prevent the ingredients of the patch from getting into the eyes).
When in contact with water, a properly applied Exelon patch with tight-fitting edges does not come off, which is important for water hygiene procedures (shower, bath). Unintended removal of the TTC can be facilitated by the patient staying near a heat source for a long time.
If the patch accidentally peels off, attach a new one in its place and replace it with the next one at the usual time of the next day.
If you accidentally use two or more TTCs at the same time, you must remove them all and seek medical advice.
Subtleties of use
The patch that delivers rivastigmine to the patient’s body should not be applied to the same point every day. It is advisable to select several suitable zones and alternate them. The patch is re-attached to the same area only 14 days after the previous use on this part. In general, according to doctors, the patient should develop the habit of using the product. This will greatly simplify the treatment process both for the patient and for the loved ones and caregivers helping him.
The patch should not be used if the patient is receiving other medications with a cholinomimic effect, anticholinergics. If the doctor prescribes the patch, you must inform him of all medications the patient is already using. If the person using the patch will soon undergo surgery, you need to inform your doctor about the fact of using the transdermal system. The compounds contained in the patch may enhance the effects of some muscle relaxants used for anesthesia.
Overdose
Unintentional overdose of oral forms of rivastigmine , as a rule, was not accompanied by clinically significant adverse events requiring discontinuation of treatment. In general, overdose symptoms included nausea / vomiting , enlargement , diarrhea , and sometimes hallucinations . Taking into account the vagotonic effect of Exelon on heart rate , the development of fainting states and/or bradycardia . There is information about the simultaneous oral administration of 46 mg of rivastigmine , after which conservative treatment was prescribed, which led to complete recovery of the patient after 24 hours.
There is no reliable data on cases of overdose when using the Exelon patch, which led to any negative consequences.
Possible treatment for asymptomatic overdose should be to discontinue use of Exelon for the next 24 hours due to the plasma T1/2 of rivastigmine being 3.4 hours and the duration of acetylcholinesterase for 9 hours. In case of severe nausea followed by vomiting , it is necessary to consider prescribing antiemetic drugs . Other possible negative effects require treatment appropriate to the observed symptoms. In severe cases, intravenous administration of Atropine sulfate at an initial dosage of 0.03 mg/kg; further administration of Atropine is carried out if necessary and in doses corresponding to the clinical effect produced. of Scopolamine as an antidote .
Technical points
Recently, Alzheimer's disease is being diagnosed more and more often. Of course, the best treatment option is in a specialized hospital, where full patient care is provided, but some prefer to stay at home as long as possible. In any of the options, you will have to use suitable pharmaceutical products. As can be seen from the instructions, “Exelon” is one of these. This patch contains a substance that selectively inhibits the activity of acetylcholinesterase present in the human brain. The drug is usually prescribed as an element of complex treatment.
In addition to the patch, on the pharmacy market you can find capsules and bottles with liquid for internal use containing rivastigmine. The transdermal system is considered one of the most preferred options, but the choice in favor of a specific type remains with the doctor. The doctor analyzes the characteristics of the patient’s body to determine which form will be effective.
Interaction
There have been no specialized studies of the interaction of the drug Exelon in the form of a patch with other medications.
Due to the fact that the metabolic transformations of rivastigmine predominantly occur with the participation of esterases through hydrolysis and with minimal influence of the cytochrome P450 , its pharmacokinetic interaction with other drugs whose metabolism depends on the cytochrome P450 is unlikely.
In studies of rivastigmine in healthy volunteers, no pharmacokinetic interactions were found with Diazepam , Digoxin , Fluoxetine and Warfarin . The increase in prothrombin time caused by taking Warfarin with parallel use of rivastigmine remained unchanged. The combined use of rivastigmine with Digoxin did not lead to an adverse effect of this combination on intracardiac conduction .
Co-administration of rivastigmine with oral hypoglycemic drugs, antacids , antianginal drugs, antihistamines , antiemetics , estrogens centrally acting antihypertensive drugs, analgesics (including NSAIDs), beta-blockers, benzodiazepines , calcium channel blockers and drugs with positive inotropic effects was not accompanied by significant changes in the pharmacokinetic parameters of rivastigmine or an increased risk of serious adverse effects.
Due to the effect of rivastigmine on cholinergic structures, its simultaneous use with cholinomimetic drugs .
In the case of parallel prescription of anticholinergic drugs, it is necessary to take into account the multidirectional effects of these drugs with the action of Exelon.
anesthesia during therapy using Exelon , it should be remembered that the effects of rivastigmine are aimed at inhibiting cholinesterase , which can lead to an increase in the effect of depolarizing muscle relaxants .
Mutual influence
The active ingredient of the Exelon patch is capable of adjusting the effectiveness of a number of pharmacologically active substances. This forces us to take a responsible approach to drawing up a combined therapeutic course. Rivastigmine corrects the performance of cholinergic structures. Combination with cholinomimetics should be avoided. If there is a need for combination with anticholinergic drugs, the doctor must analyze the different directions of the drugs. The effect of muscle relaxants may increase while receiving rivastigmine.
special instructions
When increasing dosages of rivastigmine, the possible increase in the incidence of side effects and their severity should be taken into account.
The severity of the negative effects of rivastigmine on the gastrointestinal tract , including symptoms of nausea / vomiting , most often observed at the beginning of therapy and at the time of increasing dosages, may decrease with a decrease in the dose of Exelon.
In the event of a forced break in treatment with Exelon for several days, a return to the use of the patch should begin with the administration of its minimum daily dose of 4.6 mg.
While treating patients with Alzheimer's disease , there is a possibility of reducing their weight , and therefore it is necessary to constantly monitor this physical parameter.
Alzheimer's disease , as well as the therapy for this disease itself, are most often incompatible with performing precise and dangerous work, as well as driving a car.
Analogs
Level 4 ATX code matches:
Nivalin
Alzepil
Reminyl
Axamon
Galantamine
Arisept
- Galnora SR;
- Alzepil;
- Galantamine;
- Arisept;
- Nivalin;
- Reminyl;
- Palixid;
- Yasnal.
During pregnancy (and lactation)
According to experimental data, the teratogenic properties of rivastigmine have not been established. The drug does not affect observed fertility , but may lead to an increase in gestational . comprehensive data on the safety of using the Exelon patch for the treatment of pregnant women , and therefore its use during pregnancy is contraindicated. The use of Exelon by pregnant women is allowed in exceptional cases, when the benefits of such treatment for the expectant mother are many times greater than the possible risk of negative effects for the fetus.
rivastigmine passing into the milk of a nursing mother has not been studied, which is the reason for abstaining from treatment or refusing to breastfeed .
How to use?
The patch containing rivastigmine must be used as directed by your doctor. The object is attached to a clean area of skin that is not damaged. You need to choose an area that has no or almost no hair. The optimal areas are the sternum, back from below or above, and shoulder. It is advisable to choose areas that do not come into close contact with clothing. It is prohibited to use lotions and other cosmetic products for the skin near the patch. Otherwise, the product may come loose. Do not stick it to areas covered with rashes or areas of redness or irritation. The patch is not applied to damaged areas.
Do not use the patch in direct sunlight. It is prohibited to use it in the sauna. In general, water treatments do not affect the ability of the patch to remain in a stable position on the body. You can wear the patch under your swimming clothes, but you must specifically check that the item is in place each time. A day after fastening, the product is removed and replaced with a new one. It is very important to maintain consistent replacement times. There can only be one patch on a person's body at a time.
Reviews about Exelon
Reviews about the Exelon patch are quite rare, as a result of which it is very difficult to conduct any comparative analysis of the effectiveness of this drug. From the reviews about Exelon that exist on the Internet, one can glean a positive experience of using TTC, including its inhibitory effect on the development of Alzheimer’s disease and improving the general condition of the patient, but unfortunately, there is no talk of a complete recovery from this, of course, serious disease. If, in the opinion of the doctor, the use of the Exelon patch is necessary, you should listen to his recommendations and strictly follow the instructions for use of the drug.
How to apply?
Each package of the drug contains instructions for using Exelon, which regulate the subtleties of its use. Here we describe step by step how to treat with a patch. First, the package is opened (there is a special line for this) and the item is removed. As soon as you take it out of the tightly closed bag, you need to use the product immediately. You can neither bend nor break the integrity. There is a film on the sticky side. It is removed only from one half of the object, without touching the sticky areas, and the object is attached to the back, sternum, shoulder. Then remove the remaining film and press the patch against the skin with your hand for a few seconds. It is necessary to check how tightly the edges of the patch fit. If there is a need for this, after fixing the product on it with a regular pen, write down the date and time of application.
If the patch suddenly comes off during daytime use, you must replace it with a new one. The next day, at a stable time, the item is again changed to a new one. The instructions for using Exelon specify that removing the product is quite simple - you just need to pull the edge. The item can be removed quickly and without problems. Having removed it, bend the sticky parts towards each other, squeeze, put it in a package and throw it away where children or animals will not find the patch. It must be taken into account that sometimes a small amount of the active component, which is potentially dangerous, remains on the surface. The patch is intended for lifelong use and is used to slow the progression of dementia. Proper use helps to preserve a person’s ability to contact the world and communicate with people longer.
Exelon price, where to buy
The price of Exelon (a patch with any mass content of the active ingredient), depending on the pharmacy chain, fluctuates around 3500-4000 rubles.
- Online pharmacies in RussiaRussia
ZdravCity
- Exelon TTS 13.3 mg/24h n30LTS Lohmann Therapy-System AG/Novartis Pharma GmbH RUB
3,597 order - Exelon transderm. therapist. syst. 4.6 mg/24h 30 pcs. LTS Lohmann Therapy-System AG/Novartis Pharma GmbH
RUB 1851 order
- Exelon transderm. therapist. syst. 9.5 mg/24h 30 pcs. LTS Lohmann Therapy-System AG/Novartis Pharma GmbH
RUB 2,726 order
