Transdermal therapeutic system (TTS) with a beige substrate, double adhesive layer and rectangular protective film overlapped, with recesses, round, with an overprint "AMCX" on the substrate of the plaster.
1 TTS release within 24 h
rivastigmine 9 mg 4.6 mg
Excipients: D, L -? - tocopherol - 0.03 mg, copolymer of methyl methacrylate and butyl methacrylate - 6 mg, copolymer of acrylic acid - 14.97 mg.
The composition of the adhesive layer: a silicone copolymer - 14.84 mg, dimethicone (silicone oil 12.500 cSt) - 0.15 mg, D, L -? Tocopherol - 0.015 mg.
Polymer films: polyethylene terephthalate substrate 23 Ојm - 5 cm 2 , protective fluoropolymer polyethylene terephthalate film 75 Ојm - 10.13 cm 2 .
1 PC. - bags made of laminated laminate (3) - cardboard packs.
1 PC. - bags made of laminated laminate (7) - cardboard packs.
1 PC. - sachets of multilayer laminate (30) - packs of cardboard.
Transdermal therapeutic system (TTS) with a beige substrate, double adhesive layer and rectangular protective film overlapped, with recesses, round, with an overprint "BHDI" on the substrate of the plaster.
1 TTS release within 24 h
rivastigmine 18 mg 9.5 mg
Excipients: D, L -? - tocopherol - 0.06 mg, copolymer of methyl methacrylate and butyl methacrylate - 12 mg, copolymer of acrylic acid - 29.94 mg.
Composition of the adhesive layer: a silicone copolymer - 29.67 mg, dimethicone (silicone oil 12.500 cSt) - 0.3 mg, D, L -? Tocopherol - 0.03 mg.
Polymer films: polyethylene terephthalate substrate 23 Ојm - 10 cm 2 , protective fluoropolymer polyethylene terephthalate film 75 Ојm - 20.25 cm 2 .
1 PC. - bags made of laminated laminate (3) - cardboard packs.
1 PC. - bags made of laminated laminate (7) - cardboard packs.
1 PC. - sachets of multilayer laminate (30) - packs of cardboard.
Transdermal therapeutic system (TTS) with a beige substrate, a double adhesive layer and a rectangular protective film overlapped, with recesses, round, with an overprint "CNFU" on the substrate of the patch.
1 TTS release within 24 h
rivastigmine 27 mg 13.3 mg
Excipients: D, L -? - tocopherol - 0.09 mg, copolymer of methyl methacrylate and butyl methacrylate - 18 mg, copolymer of acrylic acid - 44.91 mg.
Composition of the adhesive layer: silicone copolymer - 44.505 mg, dimethicone (silicone oil 12.500 cSt) - 0.45 mg, D, L -? Tocopherol - 0.045 mg.
Polymer films: polyethylene terephthalate substrate 23 Ојm - 15 cm 2 , protective fluoropolymer polyethylene terephthalate film 75 Ојm - 29.16 cm 2 .
1 PC. - bags made of laminated laminate (7) - cardboard packs.
1 PC. - sachets of multilayer laminate (30) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
PHARMACHOLOGIC EFFECT
Cholinesterase inhibitor. Rivastigmine, being a selective inhibitor of brain acetyl- and butyrylcholinesterase of the carbamate type, slows down the destruction of acetylcholine produced by functionally preserved neurons and improves synaptic transmission. The drug selectively increases the content of acetylcholine in the cerebral cortex and hippocampus and, thus, improves the cholinergic nerve transmission. Rivastigmine has a positive effect in reducing the cognitive function associated with acetylcholine deficiency, particularly in dementia associated with Alzheimer's disease and Parkinson's disease. In addition, there is evidence that the inhibition of cholinesterases can slow the formation of fragments of the beta-amyloid protein precursor, the accumulation of which leads to 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 a temporary inactivation of the enzyme.
In young healthy men, with rivastigmine at a dose of 3 mg, acetylcholinesterase activity in the cerebrospinal fluid (CSF) decreases by approximately 40% within the first 1.5 hours. After reaching the maximum inhibitory effect, the enzyme activity returns to the baseline level after about 9 hours. Inhibition of butyrylcholinesterase in the CSF also has a reversible character, the activity of the enzyme is restored to the initial level in 3.6 h.
In patients with Alzheimer's disease, rivastigmine inhibition of acetylcholinesterase activity in CSF is dose-dependent in the studied dose range up to 6 mg 2 times / day (maximum dose). Inhibition of butyrylcholinesterase is also dose-dependent; Rivastigmine at a dose of 6 mg 2 times / day causes a decrease in enzyme activity by more than 60% compared to the initial one. This effect of the drug persisted for 12 months of therapy (the maximum period studied).
Statistically significant correlations were found between the inhibition of rivastigmine enzymes in both CSF enzymes and changes in cognitive function in patients with Alzheimer's disease; at the same time inhibition of butyrylcholinesterase in CSF significantly and stably correlates with improvement of memory test results, attention and reaction speed.
The use of Excellon in the form of TTS in patients with mild and moderate dementia in Alzheimer's disease (10-20 points on the Mini Mental State Examination, MMSE) leads to a significant improvement in cognitive functions (including attention, memory , speech), functional status and activity in everyday life compared with placebo.
PHARMACOKINETICS
Suction
Absorption of rivastigmine from TTC Exelon В® is slow. After applying the first dose of the drug, the time to reach the defined concentration of rivastigmine was 0.5-1 h. C max in plasma is reached after 10-16 h. After reaching C max , the plasma concentration slowly decreases during the remaining 24-hour period of application of the TTC Excelon В® .
C ss of rivastigmine after the replacement of the used TTC Excelon В® with a new one slowly decreases on average for about 40 min until the absorption of the active substance from the newly glued TTC Excelon В® begins to predominate over elimination. After this, the plasma concentration of rivastigmine begins to slowly rise and again reaches a maximum after about 8 hours. In the equilibrium state, the lowest concentration is approximately 50% of the maximum, as opposed to oral administration, in which the concentration in the plasma is virtually zero between the doses of the next dose. Similar temporal characteristics of the plasma concentration of rivastigmine were observed with the use of TTC Exelon В® in the dose range from 4.6 mg / 24 h to 13.3 mg / 24 h. Although the exposure (C max and AUC) of rivastigmine is obviously less than in oral use, its increase is directly proportional to the increase in the dose of TTC Excelon В® .
With an increase in the dose from the TTS from 4.6 mg / 24 hours to 9.5 mg / 24 hours, an increase in the AUC of rivastigmine was 2.6 times, with an increase to 4.9 times with 13.3 mg / 24 hours.
The relative difference between C max and C min of rivastigmine (vibration index, IR) when applying TTC Exelon В® ranged from 0.58 for a dosage of 4.6 mg / 24 h, 0.77 for a dosage of 9.5 mg / 24 h, 0.72 for a dosage of 13.3 mg / 24 h, which is significantly less than with oral administration (IR from 3.96 for a dosage of 6 mg / day and 4.15 for a dosage of 12 mg / day).
The amount of rivastigmine released within 24 hours from the TTC ExcelonВ® (dose in mg / 24 h) is not equivalent to the oral administration of the same dose of rivastigmine in capsules (the evaluation was performed on exposure to rivastigmine in blood plasma for 24 hours).
Exelon В® TTC 9.5 mg / 24 h is equivalent to the use of capsules for ingestion of the drug Exselon В® inside at a dose of 6 mg 2 times / day (12 mg / day).
In a direct comparison of the use of 1 dose of the TTC Excelon В® preparation and the capsules for ingestion, the interpopulation variable C max and AUC 0-24 hr ofrivastigmine was 43% and 49% for the TTC Excelon В® and 74% and 103% for the capsules, respectively. With multiple application and achievement of an equilibrium state, the interpopulation variability of Cmax and AUC of 0-24 hr of rivastigmine in patients with dementia in Alzheimer's disease was also significantly lower for ExcelВ® TTC compared to oral capsules: 45% and 43% for TTS and 71 % and 73% for the capsules, respectively.
In patients with dementia in Alzheimer's disease and body weight of 65 kg C ss, rivastigmine increased approximately 2-fold compared with patients with a body weight of 35 kg; while for patients with a body weight of 100 kg there was a decrease in C ss approximately 2-fold. The effect of body weight on the exposure of rivastigmine is particularly important for patients with very low body weight with increasing doses of the drug.
Rivastigmine was well released from TTC Excelon В® during the 24-hour period of patch application to the skin (about 50% of the drug content). The highest AUC ?rivastigmine and the metabolite NAP266-90 was noted when the TTS was applied to the upper half of the back, thorax, or shoulder. If the above areas of the body are not available, gluing to the abdomen and thighs is possible, however, the physician should take into account that the AUC of rivastigmine is reduced by about 20-30%.
There was no significant cumulation of rivastigmine or metabolite NAP226-90 in blood plasma in patients with dementia in Alzheimer's disease. However, the plasma concentration of rivastigmine in the second application of TTC Excelon В® was higher than the first day.
Distribution
Rivastigmine weakly binds to plasma proteins (about 40%), easily penetrates the BBB. The apparent V d is 1.8 - 2.7 l / kg
Metabolism
Rivastigmine is rapidly and largely metabolized with T 1/2 of plasma from about 3.4 h after removal of the patch. Elimination was limited to the degree of absorption of rivastigmine (flip-flop kinetics), which explains the increase in T 1/2 after application of TTC Excelon В® (3.4 h) compared with oral or intravenously (1.4 and 1.7 h respectively) of the drug. Metabolism of rivastigmine occurs mainly by hydrolysis with cholinesterase to form a decarbamylated metabolite (NAP 226-90), which in vitro demonstrated a minimal ability to inhibit acetylcholinesterase (<10%). According to the data obtained in vitro and in experimental studies, the main isoenzymes of cytochrome P450 are minimally involved in the metabolism of rivastigmine. The total plasma clearance of rivastigmine is about 130 l / h after intravenous injection at a dose of 0.2 mg and is reduced to 70 l / h after IV administration of 2.7 mg, which is consistent with the non-linear, inverse proportionality of the pharmacokinetics of rivastigmine due to its elimination as it saturates .
Ratio of AUРЎ ? metabolite to the starting material was 0.7 for TTS vs. 3.5 for oral administration, indicating a lower rate of metabolism after dermal application. The formation of a smaller amount of the metabolite NAP226-90 is caused by the absence of pre-systemic metabolism (the effect of "first passage" through the liver).
Excretion
Rivastigmine is excreted mainly by kidneys in the form of metabolites; in an unchanged form in the urine is almost not detected. After 24 hours after taking more than 90% of the dose. With feces less than 1% of the dose is excreted.
Pharmacokinetics in elderly patients
In elderly patients with Alzheimer's disease, no changes in age-related bioavailability were detected with the use of the ExcelonВ® TTC.
Pharmacokinetics in patients with impaired hepatic function
The study of the use of TTC Exelon В® , in patients with impaired liver function was not performed. In patients with mild and moderate hepatic impairment following oral administration of rivastigmine, an increase in Cmax of about 60% and AUC more than 2-fold compared with healthy subjects were noted.
Pharmacokinetics in patients with impaired renal function
The study of the use of TTC Exelon В® , in patients with impaired renal function was not performed.
In patients with Alzheimer's disease and mild renal impairment following oral administration of rivastigmine, the increase in C max and AUC was more than 2-fold compared to healthy subjects; However, in patients with Alzheimer's disease and severe impairment of renal function, no changes in C max and AUC were observed.
INDICATIONS
- mild to moderate dementia of the Alzheimer's type.
DOSING MODE
Therapy with Exelon В® should be performed only under the supervision of a physician experienced in the treatment of patients with Alzheimer's dementia. Patients and caregivers should be instructed about the specific uses of the drug by competent medical personnel.
The amount of contained and released rivastigmine, depending on the dosage of TTC ExcelonВ®, is presented in the table.
TTC Excelon В® The amount of rivastigmine contained The amount of rivastigmine released in vivo for 24 h
TTC Exelon В® 4.6 mg / 24 h 9 mg 4.6 mg
TTC Exelon В® 9.5 mg / 24 h 18 mg 9.5 mg
TTC Excelon В® 13.3 mg / 24 h 27 mg 13.3 mg
The initial dose. Treatment with the drug should begin with the use of TTC Exelon В® 4.6 mg / 24 h 1 time / day.
After 4 weeks of treatment, with good tolerability, the dose of the drug can be increased by applying TTC Exelon В® 9.5 mg / 24 h.
Supported dose.
For prolonged treatment in the presence of therapeutic efficacy, the use of TTC Excelon В® 9.5 mg / 24 h is recommended in the patient.
Dose build-up
For prolonged treatment with therapeutic effectiveness, the patient is recommended the use of TTC Exelon В® 9.5 mg / 24 h. With good drug tolerability and at least after 6 months of treatment with ExcelВ® 9.5. mg / 24 h, the attending physician may increase the dose to 13.3 mg / 24 h in patients who need to achieve an additional therapeutic effect despite the use of the TTC Excelon В® 9 . 5 mg / 24 h, there is a significant impairment of cognitive functions (eg, worsening of the results of CSRVS) and / or impairment of functional status (based on the subjective evaluation of the physician).
It is necessary to regularly evaluate the clinical effect of therapy with the drug Excelon В® TTC. If there is no clinical effect of therapy with the use of optimal doses of TTS Excelon В® , discontinue therapy with the drug.
It is necessary to temporarily stop therapy with the drug in case of undesirable phenomena on the part of the digestive system and / or worsen existing extrapyramidal symptoms (including tremor) prior to their resolution. If the break in the use of the drug was no more than three days, you can resume the use of the drug in the same dose. In the case of a longer period of cancellation, treatment should be resumed from the initial dose (ExcelonВ® TTS 4.6 mg / 24 h).
Patients treated with rivastigmine in the form of capsules or oral solution can switch to treatment with TTC Excelon В® , as follows:
- In patients who received oral rivastigmine therapy at a dose of less than or equal to 6 mg / day, treatment should begin with the use of TTC Excelon В® 4.6 mg / 24 h.
- in patients receiving oral rivastigmine therapy in a stable and well-tolerated dose of 9 mg / day, treatment can begin immediately with the use of TTC Exelon В® 9.5 mg / 24 hours. But if oral therapy was not stable and good
tolerable, the transition to the transdermal form is recommended to begin with a dose of 4.6 mg / 24 hours.
- in patients receiving oral therapy with rivastigmine at a dose of 12 mg / day, treatment can be started immediately with the use of TTC Exelon В® 9.5 mg / 24 h.
After 4 weeks of treatment, at a minimum, with good tolerability, the dose of TTC Excelon В® 4/6 mg / 24 h can be increased by applying TTC Exelon В® 9.5 mg / 24 h.
Treatment of TTC Excelon В® is recommended starting the day after the last oral dose of rivastigmine.
Patients weighing less than 50 kg
Patients with a body weight of less than 50 kg experienced a more frequent development of adverse events and withdrawal of therapy, so with increasing doses in this group of patients, special care should be taken, the dose should be carefully titrated and observed for adverse events (eg, excessive nausea or vomiting) and also consider the possibility of reducing the dose of TTC Excelon В® to 4.6 mg / 24 h if such undesirable events develop.
Use in children
The use of rivastigmine in children has not been studied, so it is not recommended to prescribe the drug to children.
Patients with impaired hepatic and renal function
Correction of the dosing regimen of TTC Excelon В® is not required. However, due to an increased exposure of rivastigmine in patients with impaired renal function, as well as in patients with impaired liver function, it is recommended that the dose of rivastigmia is carefully titrated in accordance with individual tolerability in this category of patients.
Patients with clinically significant impairment of liver and kidney function may experience a more frequent development of adverse events, which is why the use of the Excelon В® TTC 4.6 mg / 24 hour as an initial and maximum dose is recommended for this category of patients.
The study of the use of TTC Excelon В® in patients with severe impairment of liver function was not performed (see sections "Special instructions", "Pharmacological action").
Instructions for the use of TTC Exelon В®
1.TTS Exelon В® paste on a clean, dry, intact skin with minimal scalp.
2. Do not use creams, lotions, oils, powders, and other means for skin care in the area of attachment of the drug to prevent it from peeling.
3. TTS Exelon В® can not stick to the reddened coated rash, irritated or damaged skin.
4. Only one TTC Exelon should stick В® per day to only one of the body portions:
- left or right shoulder; - the upper part of the chest on the left or right side (do not stick to the breast region); - the top part of the back to the left or right; - lower back left or right.
5. Every 24 hours to be removed previous TTC Exelon В® before one new transdermal paste Exelon В® .
To avoid skin irritation each subsequent TTC Exelon В® should stick to the other area of the skin (it is possible within the same anatomical region). For example, if you attached the TTC Exelon В® in the lumbar region to the right, then the next place to the left. To minimize the risk of skin irritation TTS can be stuck on the same skin area with only two weeks apart.
Attaching the TTS Exelon В®
TTS Exelon В®It is a thin, opaque, plastic patch for application to the skin. Do not remove the TTC Exelon В® from the sealed package and remove the previous TTC Exelon В® , if you do not plan to glue the new one.
The preparation should be used immediately after removal from the sealed package.
1. Carefully remove the previous TTC Exelon В® .
2. When you first start treatment with the drug or resume treatment after a break, please follow the instructions for the attachment of the TTS Exelon В® , starting with the next item.
3. The drug is removed from the sealed package just before use.
4. To retrieve a TTS Exelon В®cut package indicated by the dotted line or a groove.
5. The adhesive side TTC Exelon В® covered with a protective film. It should be carefully remove the protective film which protects the adhesive side TTC Exelon В® , without touching the adhesive surface of the fingers.
7. Immediately after removal of the protective film paste TTC Exelon В® on the skin of the upper or lower half of the back, shoulder or chest.
8. Remove the other protective layer after attaching the transdermal therapeutic system to the skin.
9. It should be tightly pressed palm TTC Exelon В® at the site of attachment for at least 30 seconds. You must ensure that the system adheres to the skin, especially around the edges.
If necessary, after application, you can write to a transdermal therapeutic system fine ballpoint pen attaching a date (for example, day of the week).
TTC Exelon В® must be worn constantly and replaced with a new 24 h.
Attaching a transdermal therapeutic system in the different areas of the skin allows you to select the most suitable areas of the body where the system will not come into contact with a tight-fitting clothing.
How to remove Exelon transdermal В®
1. gently tilting one of the corners, slowly and carefully remove the transdermal therapeutic system.
2. If you have on your skin glue remains, slightly moisten the area with warm water and mild soap and water or use baby oil to remove adhesive residue. Do not use alcohol or other liquid solvents (nail polish remover or other solvents).
3. It is necessary to wash your hands thoroughly with soap and water after the attachment or removal of the TTS Exelon В® . In case of contact with eyes or redness of the eye after the attachment or removal of the TTS Exelon В® , immediately flush eyes with plenty of water and, if symptoms persist, seek medical attention.
Disposing a used transdermal Exelon В®
1. Bend the used transdermapnuyu therapeutic system half and connect the adhesive portion between them.
2. Place the used TTS Exelon В® in the package. The package used with a transdermal therapeutic system should be thrown out of the reach of children. After the disposal of the drug should wash their hands with soap and water.
Condition wearing TTSEkselon В® (water treatment, long stay away from heat sources)
1.TTS Exelon В® does not come unstuck when procedures water (shower, bath, basin).
2. During the water treatment is necessary to ensure that the system adheres to the skin, especially around the edges.
3. Patients using TTS Exelon В®Should not be permanently located near any external heat sources (excessive solar radiation, saunas, solaria).
What should I do if the TTC Exelon В® unstuck
If the transdermal Exelon В® come off it must be replaced with a new transdermal therapeutic system before the end of the day. The next day, as usual should attach a new TTC Exelon В® .
When and how long to apply Exelon transdermal В®
To maximize the effectiveness of drug treatment should apply new TTC each day, preferably at the same time.
When applying more than one transdermal Exelon В® simultaneously
All TTS should be removed immediately from your skin, and inform your doctor about the incident. You may need medical treatment, in some cases, the overdose occurred nausea, vomiting, diarrhea, increased blood pressure, hallucinations. It is also possible occurrence of bradycardia and / or syncope.
If you forget to paste another TTS in the usual time, it is necessary to stick it immediately. The use of the following TTS possible the next day at the usual time. It should not stick two TTC to compensate for the missed dose.
SIDE EFFECT
The overall incidence of adverse events during therapy TTC Exelon В® 9.5 / 24 h (50.5%) was lower as compared with oral therapy with capsules at a daily dose of 12.3 mg (63.3%) (compared to the placebo group this indicator was 46%).
Incidence and severity of adverse events tend to increase with increasing dose, especially immediately after a dose change. If break in the application of the drug was more than 3 days, should resume treatment with the initial dose (Exelon В® TTS 4.6 mg / 24 hours).
The most common adverse events were skin reactions at the site of sticking (erythema usually mild to moderate severity). Further frequency are undesirable phenomena of the digestive system: nausea (7.2%) and vomiting (6.2%) had significantly less when applying the TTS Exelon В® 9.5 mg / 24 hours compared with capsules for oral administration, 23.1% and 17.0%, respectively (in the placebo group the same figures were 5.0% and 3.3%).
The frequency of adverse reactions in patients (854 men) with dementia of the Alzheimer type, treated with TTS Exelon В®(all dosages) are estimated as follows: "very often" -> 1/10, "often" -> 1/100, <1/10, "rarely" -> 1/1000, <1/100, rare> 1 / 10000, <1/1000, very rare <1/10000, it presents an undesirable reaction with an unspecified speed.
Patients with Alzheimer type dementia who received drug therapy Exelon В® TTS, these undesirable phenomena were noted:
Infectious and parasitic diseases: often - urinary tract infection.
From a metabolism: often - anorexia, decreased appetite; infrequently - dehydration.
From the nervous system:often - headache, fainting, dizziness; rarely - psychomotor hyperactivity; very rarely - extrapyramidal disorders; the frequency is not known - seizures, worsening of Parkinson's disease symptoms.
Of the heart: infrequently - bradycardia; frequency is not known - tachycardia, AV-block, atrial fibrillation, sick sinus syndrome.
From the side of blood vessels: the frequency is not known - increased blood pressure.
From the digestive system: often - nausea, vomiting, diarrhea, dyspepsia, abdominal pain; infrequently - a stomach ulcer; the frequency is not known - pancreatitis.
Of the liver and biliary tract: the frequency is not known - Hepatitis, elevated liver function.
From the skin and subcutaneous tissues: often - a rash; frequency is not known - pruritus, erythema, urticaria, blistering, allergic dermatitis, skin allergic reactions common.
On the part of the kidney and urinary tract: often - urinary incontinence.
General disorders and in the place of attachment of the TTS: often - dermal site reactions sticking (erythema, pruritus, edema, dermatitis, irritant et al.), Tiredness, fatigue, fever, weight loss; rarely - accidental falls.
In a clinical study in the application of the drug at doses above 3.13 mg / 24 hours The following adverse events were more frequent than in groups TTC ExelonВ®13.3 mg / 24 h, and placebo: insomnia, heart failure (possibly associated with an increase in dose). The frequency of these adverse events during therapy TTC EkselonВ® 13.3 mg / 24 hours was similar to that in the placebo group.
The following adverse reactions were observed only in the treatment of dementia capsules or a solution of Exelon В® for ingestion and have not been reported in clinical studies in the application of TTS Exelon В® :
Frequently - sleepiness, malaise, tremor, confusion, increased sweating.
Rarely - duodenal ulcer, angina.
Very rarely - gastrointestinal bleeding, hallucinations.
The frequency is not known - severe vomiting, leading to rupture of the esophagus.
Skin irritation
In applying the TTS Exelon В® most frequently noted redness (erythema) at the sticking usually disappear in most patients within 24 hours. In a clinical study in the application of TTS Exelon В® 9.5 mg / 24 hours was noted very slight (21.8%), lung (12.5%), moderate (6.5%) Skin redness, itching very mild (11.9%), mild (7.3%) and moderate (5.0%) degree. The therapy TTC Exelon В® 9.5 mg / 24 hr itch and severe erythema were observed in 1.7% and 1.1%, respectively. Most skin reactions were developed only in the field of sticking the TTS. In applying the TTS Exelon В® 9.5 mg / 24 hours of treatment discontinuation due to development of dermatological reactions observed only in 2.4% of cases.
In a clinical study TTC Exelon В® 9.5 mg / 24 hours transdermal and Exelon В® 13.3 mg / 24 h undesirable reactions (erythema, itching) in place of sticking of the drug were observed mainly in the first 6 months. application. Discontinuation of treatment due to the development of pruritus was observed in 1.1% of patients. In most cases, the reaction at the site of sticking the TTS were slightly or moderately expressed, severe adverse reactions were observed in less than 2% of patients.
CONTRAINDICATIONS
- increased sensitivity to rivastigmine and other ingredients;
- increased sensitivity to other carbamate derivatives or other components within the drug;
- allergic contact dermatitis history arising during treatment with the drug Exelon В® TTS;
- age to 18 years.
With caution should be used rivastigmine in patients with sick sinus syndrome or conduction disorders (sinoatrial block, AV-block).
Cholinergic stimulation may cause:
- an increase of acid secretion in the stomach, so caution should be exercised when assigning rivastigmine in patients with gastric ulcer and duodenal ulcer in the acute stage, or patients predisposed to these conditions;
- to develop or aggravate urinary tract obstruction and seizures, so caution should be exercised in the appointment of rivastigmine to patients predisposed to these conditions.
Precautions should be used on patients with asthma or obstructive airways diseases in history.
PREGNANCY AND LACTATION
Experimental data showed that rivastigmine has no teratogenic properties and no effect on fertility but can cause an increase in the period of gestation. However, the safety of rivastigmine in human pregnancy has not yet been established, so the drug should not be used for pregnant women except in cases where the application of the expected benefit to the mother outweighs the potential risk to the fetus.
It is not known if rivastigmine is excreted in breast milk in humans. Therefore, during the use of the drug should abandon breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
In patients with impaired renal function correct dosing regimen TTC Exelon В® is not required. Patients with symptomatic hepatic impairment can be observed more frequent development of undesirable phenomena, due to which this category of patients recommended application - preparation Exelon В® TTS 4.6 mg / 24 hours as the initial and maximum dose.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Precautions should be selection of a dose of the drug in patients with severe hepatic impairment (because perhaps more frequent development of undesirable reactions). Patients with symptomatic hepatic impairment can be observed more frequent development of undesirable phenomena, due to which this category of patients recommended application - preparation Exelon В® TTS 4.6 mg / 24 hours as the initial and maximum dose.
APPLICATION FOR CHILDREN
The use of rivastigmine in children has not been studied, so it is not recommended to prescribe a drug for children and adolescents under 18 years .
SPECIAL INSTRUCTIONS
Patients should avoid hand contact with the eyes immediately after the attachment or removal of the TTS. You must wash your hands thoroughly with soap and water after the attachment or removal of the TTS. In case of contact with eyes or redness of the eye after the attachment or removal of the TTS, immediately flush eyes with plenty of water and, if symptoms persist, seek medical attention.
When receiving rivastigmine may increase the severity or occurrence of extrapyramidal disorders.
Disorders from the digestive tract
The frequency and severity of side effects normally increases with increasing dose rivastigmine, especially during dose changes.
Intensity of dose-dependent adverse effects on the gastrointestinal tract, such as nausea, vomiting and diarrhea, observed at the beginning of the treatment or at an elevated dose may not decrease at lower doses rivastigmiia, in the absence of the effect of therapy should be discontinued TTC Exelon В® . These adverse events were more common in women. Patients who have developed signs of dehydration due to prolonged diarrhea or vomiting, it is recommended intravenous fluids and dose reduction or cancellation of rivastigmine therapy, because of the possible risk of serious complications.
Weight loss
Because patients with Alzheimer's disease on therapy with cholinesterase inhibitors, including rivastigmine, there may be a reduction in body weight during treatment TTC Exelon В® is necessary to control the weight of the patients.
It should be remembered that patients weighing less than 50 kg - more likely to develop adverse drug reactions Exelon В® .
Reaction at the site of attachment TTC Exelon В® and skin reactions
skin reactions occurring on the background of the drug Exelon В® TTS usually mild or moderate severity. These reactions are not an indication of sensitization of the patient to rivastigmine. However, during treatment with the drug Exelon В®TTS may allergic contact dermatitis. Allergic contact dermatitis should be suspected if in the place of attachment of the TTS
The information is provided for your information, do not self-medicate, it is dangerous for your health.
