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Exelon is a selective acetyl- and butyrylcholinesterase inhibitor of the brain used to treat Alzheimer's disease and dementia in Parkinson's disease.
Rivastigmine slows down the destruction of the acetylcholine mediator produced by functionally intact neurons. While rivastigmine selectively increases the content of acetylcholine in the cerebral cortex and the hippocampus, and, thus, helps to improve cholinergic nervous transmission.
Ekselon may have a positive effect on reducing cognitive functions associated with acetylcholine deficiency, particularly in dementia associated with Alzheimer's disease and Parkinson's disease.
In addition, there is evidence that inhibition of cholinesterase can slow down the formation of fragments of the protein precursor of beta-amyloid, which is involved in amyloidogenesis, and thus slow down the formation of amyloid plaques, which is 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. It was shown that in young healthy men after taking Ekselon at a dose of 3 mg, acetylcholinesterase activity 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 the activity of butyrylcholinesterase in CSF in young healthy volunteers is inhibited reversibly and is restored to the original after 3-6 hours. In patients with Alzheimer's disease, rivastigmine inhibition of acetylcholinesterase activity in CSF is dose-dependent in the studied dose range (up to the highest dose of 6 mg twice a day). AND
The inhibition of butyrylcholinesterase is also dose-dependent: a dose of 6 mg 2 times a day causes a decrease in enzyme activity by more than 60% compared to the original. This effect of Ekselon remained for 12 months of therapy (the maximum studied period). Statistically significant correlations between the degree of rivastigmine inhibition of both enzymes in CSF and changes in cognitive functions in patients with Alzheimer's disease were shown; at the same time, it is precisely inhibition of butyrylcholinesterase in CSF that reliably and stably correlates with an improvement in the results of tests of memory, attention and speed of reaction.
The efficacy of treatment with Exelon in Alzheimer's disease has been shown in patients with mild to moderate dementia (10–24 points on the short scale for assessing mental status, 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 a decrease in the severity of the disease and severity of mental and behavioral manifestations (such as agitation, tearfulness, illusions, hallucinations, etc.).
Studies have shown that the effect of treatment with Ekselon is observed at about the 12th week and lasts for 6 months of therapy, while during the control period in the group of patients who received placebo, the deterioration of the corresponding indicators was observed.
In dementia associated with Parkinson's disease, the efficacy of Exelon has been demonstrated in a 24-week placebo-controlled study in patients with mild and moderate dementia (10 - 24 points for MMSE). In patients treated with Exelon, there was a statistically significant improvement in cognitive functions (attention, memory, speech, etc.), while in patients treated with placebo, similar indicators worsened.
Mild or moderately severe Alzheimer's-type dementia:
- Probable Alzheimer's disease.
- Alzheimer's disease.
1 TTS contains:
Active substances: rivastigmine 13.3 mg.
Excipients: D, L-α-tocopherol, poly (butyl methacrylate, methyl methacrylate), acrylic copolymer.
The composition of the adhesive layer: silicone copolymer, dimethicone (silicone oil 12.500 cSt), D, L-α-tocopherol.
Rivastigmine is marketed under different brands and generic names, and comes in different dosage forms:
|Brand name||Manufacturer||Country||Dosage form|
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Dosage and Administration
The patient should be informed that in order to achieve the maximum contraceptive effect, it is necessary to strictly follow the instructions on the use of Evr TTC. Only one TTS can be used at a time.
Each used TTC is removed and immediately replaced with a new one on the same day of the week (“replacement day”) on the 8th and 15th days of the menstrual cycle (2nd and 3rd week). TTC can be changed at any time of the day of replacement. During the 4th week, from the 22nd to the 28th day of the cycle, TTC is not used. A new contraceptive cycle begins the day after the end of the 4th week; the following TTS should be stuck, even if the menstruation was not or it has not ended.
Under no circumstances should the break in the TTS Evra application be longer than 7 days, otherwise the risk of pregnancy is increased. In such situations, for 7 days it is necessary to simultaneously use a barrier method of contraception, since The risk of ovulation increases with each day that the recommended duration of the period, free from the use of TTC, is exceeded. In the case of sexual intercourse during such an extended period, the probability of conception is very high.
Start applying TTC Evra
If during the previous menstrual cycle a woman did not use a hormonal contraceptive
Contraception using TTC Evra begin on the first day of menstruation. One TTC Evra is glued to the skin and is used all week (7 days). The day of sticking the first TTS Evra (1st day / start day) determines the next days of replacement. Replacement day will be on the same day of each week (8th and 15th days of the cycle). On the 22nd day of the cycle, the TTC is removed, and from the 22nd to the 28th day of the cycle, the woman does not use the ETC TTC. The next day is considered the first day of the new contraceptive cycle. If a woman starts using TTC Evra not from the first day of the cycle, then barrier methods of contraception should be used simultaneously for the first 7 days of the first contraceptive cycle.
If a woman switches from using a combined oral contraceptive to using TTC Evra
TTC Evra should be applied to the skin on the 1st day of menstruation, which began after discontinuation of the combined oral contraceptive use. If menstruation does not begin within 5 days after taking the contraceptive pill, then it is necessary to exclude pregnancy before starting using TTC Evra.
If the use of Evra begins after the 1st day of menstruation, then within 7 days it is necessary to simultaneously use barrier methods of contraception.
If more than 7 days have passed after taking the last contraceptive pill, then a woman may experience ovulation, and therefore she should consult a doctor before starting to use TTC Evra. Sexual intercourse during this prolonged period, free from taking contraceptive pills, can lead to pregnancy.
If a woman moves from using drugs containing progestogen only to using TTC Evra
A woman can go on any day with a drug containing only progestogen (on the day the implant is removed, on the day when another injection should be given), but during the first 7 days of using ETC TTS, a barrier method should be used to enhance the contraceptive effect.
After abortion or miscarriage
After an abortion or miscarriage before the 20th week of pregnancy, you can immediately start applying TTC Evra. If a woman begins to use TTC Evra immediately after an abortion or miscarriage, then additional methods of contraception are not required. A woman should know that ovulation can occur within 10 days after an abortion or miscarriage. After an abortion or miscarriage in the 20th week of pregnancy or later, the use of Evra TTC can be started on the 21st day after the abortion or miscarriage, or on the 1st day of the first menstruation.
Women who do not breastfeed should begin using the Evra TTC no earlier than 4 weeks after delivery. If a woman begins to use TTC Evra later, then during the first 7 days she should additionally use a barrier method of contraception. If there was sexual intercourse, it is necessary to exclude pregnancy before starting the use of TTC Evra, or a woman must wait for the first menstruation.
With full or partial peeling off TTC Evra
If TTC Evra is completely or partially peeled off, then an insufficient amount of its active ingredients enters the blood.
Even with a partial peeling of the TTC Evra in less than a day (up to 24 hours): you should re-glue the TTC Evra in the same place or immediately replace it with a new TTC Evra. Additional contraceptives are not required. The next TTC Evra needs to be glued on a regular “replacement day”.
With a partial peeling off for more than a day (24 hours or longer), and also if a woman does not know exactly when TTC Evra is partially or completely peeled off - the onset of pregnancy is possible. A woman should immediately start a new cycle, sticking a new TTC Evra and consider this day as the first day of the contraceptive cycle. Barrier contraceptive methods should be used at the same time only in the first 7 days of the new cycle.
You should not try to re-glue TTC Evra if she lost her adhesive properties; instead, you must immediately glue the new TTC Evra. Do not use additional adhesive tapes or bandages to hold TTC Evra in place.
If the next days of replacing TTC Evra are missed
At the beginning of any contraceptive cycle (1st week / 1st day): with an increased risk of pregnancy, a woman should stick the first TTS of Evra of a new cycle as soon as she remembers. This day is considered a new "1st day" and a new "replacement day" is being counted. Non-hormonal contraception should be simultaneously applied during the first 7 days of the new cycle. In the case of sexual intercourse during such an extended period, conception may occur without the use of Evra's TTC.
In the middle of the cycle (2nd week / 8th day or 3rd week / 15th day):
—If 1 day or 2 days have passed from the day of replacement (up to 48 hours): the woman should immediately paste the new TTC. The following TTC needs to be glued on a regular “replacement day”. If during the 7 days preceding the first missed day of TTS attachment, the use of TTS was correct, then additional contraception is not required;
—If more than 2 days have passed since the replacement date (48 hours or more): there is an increased risk of pregnancy. A woman should stop the current contraceptive cycle and immediately start a new 4-week cycle by pasting a new Evra TTC. This day is considered a new "1st day" and a new "replacement day" is being counted. Barrier contraception should be applied simultaneously during the first 7 days of the new cycle;
—At the end of the cycle (4th week / 22nd day): if the TTC is not deleted at the beginning of the 4th week (22nd day), then it should be removed as soon as possible. The next contraceptive cycle should begin on the regular “replacement day”, which is the day after the 28th day. Additional contraception is not required.
Change day replacement
In order to postpone menstruation for one cycle, a woman must glue a new TTC Evra at the beginning of the 4th week (22nd day), thereby skipping the period free from using TTC Evra. Intermenstrual bleeding or spotting may occur. After 6 consecutive weeks of TTS use, there should be a 7-day interval free from TTS use. After the end of this interval, regular use of the drug is resumed.
If a woman wants to change the replacement day on the day appointed for this purpose during the week free of use, she must complete the current cycle by removing the third TTC of Evra; A woman can choose a new replacement day by sticking the first TTS of Evra of the next cycle on the selected day. In no case should the period free from using TTC Evra be more than 7 days. The shorter this period, the higher the likelihood that a woman will not have another menstruation, and during the next contraceptive cycle, intermenstrual bleeding or spotting may occur.
Mode of application
TTC Evra should be glued to clean, dry, intact and healthy skin of the buttocks, abdomen, outer surface of the upper part of the shoulder or upper body with minimal hair growth, in areas where it will not come into contact with tight clothing.
In order to avoid possible irritation, each following TTS of Evra should be glued to another area of skin, this can be done within the same anatomical region.
TTC Evra must be pressed tightly so that its edges are in good contact with the skin. To prevent the adhesive properties of TTS from falling, Evra should not apply make-up, creams, lotions, powders and other local products on those areas of the skin where it is glued or will be glued.
A woman should inspect the TTS Evra on a daily basis in order to be confident in its firm attachment.
Used TTC must be carefully disposed of in accordance with the instructions.
From the side of the central nervous system and peripheral nervous system: dizziness, migraine, paresthesia, hypesthesia, convulsions, tremor, emotional lability, depression, anxiety, insomnia, drowsiness.
Since the cardiovascular system: increased blood pressure, palpitations, edematous syndrome, varicose veins.
From the digestive system: gingivitis, anorexia or increased appetite, gastritis, gastroenteritis, dyspepsia, abdominal pain, vomiting, diarrhea, flatulence, constipation, hemorrhoids.
On the part of the respiratory system: infections of the upper respiratory tract, shortness of breath, bronchial asthma.
From the reproductive system: pain during sexual intercourse (dyspareunia), vaginitis, dysmenorrhea, decreased libido, breast enlargement, menstrual disorders (including intermenstrual bleeding, hypermenorrhea), changes in vaginal secretion, changes in cervical mucus, lactation arising not in connection with childbirth , ovarian dysfunction, mastitis, breast fibroadenomas, ovarian cysts.
From the urinary system: urinary tract infection.
From the musculoskeletal system: muscle cramps, myalgia, arthralgia, ostalgia (including back pain, pain in the lower extremities), tendinosis (tendon changes), muscle weakness.
Dermatological reactions: pruritus, urticaria, skin rash, contact dermatitis, bullous rash, acne, discoloration of the skin, eczema, increased sweating, alopecia, photosensitization, dry skin.
On the part of the organ of vision: conjunctivitis, visual disturbances.
Metabolism: weight gain, hypertriglyceridemia, hypercholesterolemia.
Other: flu-like syndrome, fatigue, allergic reactions, chest pain, asthenic syndrome, syncope, anemia, abscesses, lymphadenopathy.
Seldom (with frequency from> 0.01% to less than 0.1%): hypertonus or hypotonia of muscles, incoordination, dysphonia, hemiplegia, neuralgia, stupor, increased libido, depersonalization, apathy, paranoia, benign breast tumors, cervical cancer in situ, perineal pain, ulceration of the genitals, atrophy of the mammary glands, reduction of blood pressure , enanthema, dry mouth or increased salivation, colitis, pain during urination, hyperprolactinemia, melanosis, skin pigmentation disorders, chloasma, xerophthalmia, weight loss or obesity, inflammation of the subcutaneous tissue, non-swollen imost alcohol, cholecystitis, cholelithiasis, abnormal liver function, purpura, "tides" of blood to the face, venous thrombosis (including deep vein thrombosis, thrombosis, pulmonary embolism), thrombophlebitis of superficial veins, pain in veins, pulmonary embolism.
Do not use on the area of the mammary glands, as well as on hyperemic, irritated or damaged skin.
WITH caution should be used with family history indications of venous or arterial thromboembolism in siblings or parents at a relatively young age; with prolonged immobilization; obesity (body mass index more than 30 kg / m2calculated as the ratio of body weight in kilograms to the square of height in meters); thrombophlebitis of superficial veins and varicose veins; dyslipoproteinemia; hypertension; lesions of the valvular apparatus of the heart; atrial fibrillation; diabetes; systemic lupus erythematosus; hemolytic-uremic syndrome; Crohn's disease; ulcerative colitis; abnormal liver function; hypertriglyceridemia (including in family history); acute liver dysfunction during a previous pregnancy or previous use of sex hormones; in violation of the menstrual cycle; impaired renal function.
Hydantoins, barbiturates, primidone, carbamazepine and rifampicin, as well as oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin, modafinil, and phenylbutazone, can cause an acceleration of the metabolism of sex hormones, which can lead to interfusional bleeding or ineffectiveness, and can be ineffective or cause ineffective. of pregnancy. The mechanism of interaction of these drugs and the active ingredients of TTC Evra is based on the ability of the above listed drugs to induce liver enzymes, with the participation of which the sex hormones are metabolized. The maximum induction of enzymes is usually achieved no earlier than 2-3 weeks, and can last for at least 4 weeks after discontinuation of the corresponding drug.
Acceptance of herbal preparations containing St. John's wort (Hypericum perforatum) concurrently with the use of Evra TTC may lead to a loss of contraceptive effect. Women who have taken these herbal remedies may experience intermenstrual bleeding and unwanted pregnancy. This is due to the fact that St. John's wort induces enzymes that metabolize sex hormones. Inducing effect may persist for 2 weeks. after the abolition of the herbal preparation containing St. John's wort.
The loss of the contraceptive effect may be caused by antibiotics (including ampicillin and tetracyclines). A study of pharmacokinetic interactions showed that oral administration of tetracycline hydrochloride 3 days before and for 7 days while using TTC Evra does not have a significant effect on the pharmacokinetics of norelgestromin or ethinyl estradiol.
Pregnancy and Lactation
The drug Evra is contraindicated during pregnancy and lactation.
There is no clinical evidence that, in any aspect, the transdermal contraceptive system is safer than oral contraceptives.
Before starting or resuming the use of Evra TTS, a detailed medical history (including family history) should be collected and pregnancy should be excluded. It is necessary to measure blood pressure and conduct a physical examination, taking into account contraindications and warnings.
If hereditary susceptibility to venous thromboembolism is suspected (if venous thromboembolism occurred in a brother, sister or parents at a relatively young age), a woman should be referred for consultation to a specialist before deciding on the use of hormonal contraception.
The risk of vascular complications is increased in women with superficial vein thrombophlebitis and varicose veins, as well as in obesity (body mass index of more than 30 kg / m2).
With prolonged immobilization, after extensive surgery on the lower limbs or severe injury, it is recommended to stop the use of hormonal contraceptives (during a planned operation, this should be done 4 weeks before it) and resume hormonal contraception no earlier than 2 weeks. after complete remobilization.
Some epidemiological studies have revealed an increased risk of cervical cancer in women who have been using combined oral contraceptives for a long time.
Women taking combined oral contraceptives may develop liver tumors, which can cause life-threatening intra-abdominal bleeding. If women who use TTC Evra have severe upper abdominal pain, an enlarged liver or symptoms of intra-abdominal bleeding, a differential diagnosis should be made to rule out a possible liver tumor.
In women with hypertriglyceridemia or this disease in the family history, the risk of pancreatitis in the case of the use of combined hormonal contraceptives may be increased.
If a pharmacologically uncontrolled arterial hypertension occurs in women during the use of combined hormonal contraceptives, the drug should be canceled. The use of TTC Evra can be resumed after the normalization of blood pressure.
It was reported that oral administration of combined hormonal contraceptives may cause or worsen the diseases listed below, but there is no convincing evidence of their connection with the use of combined oral contraceptives. These include: jaundice and / or pruritus associated with cholestasis; cholelithiasis; porphyria; systemic erythematosus; hemolytic uremic syndrome; Chorea Sydenham; gestational herpes associated with otosclerosis hearing loss. Hormonal contraceptives can affect some endocrine parameters, liver function markers and blood components:
- increases the concentration of prothrombin and coagulation factors VII, VIII, IX and X; decreases the level of antithrombin III; decreases the level of protein S; increased norepinephrine platelet aggregation;
- increases the concentration of thyroxin-binding globulin, which causes an increase in the concentration of total thyroid hormone, which is measured by the content of iodine associated with protein, the content of T4 (determined using chromatography or radioimmunoassay); reduced binding of free T3 ion exchange resin, as evidenced by the increase in the concentration of thyroxin-binding globulin, the concentration of free T4 does not change. Serum concentration of other binding proteins may be increased;
- increases the concentration of globulins that bind sex hormones, which leads to an increase in concentrations of total circulating endogenous sex hormones. However, concentrations of free or biologically active sex steroids are reduced or remain unchanged.
Women using TTC Evra may slightly increase concentrations of LDL-C, total cholesterol, LDL-C and TG, while the ratio of LD-C / LDL / C-HDL may remain unchanged.
Hormonal contraceptives may cause a decrease in serum folate concentrations. This can have potentially clinically significant consequences if a woman has a pregnancy shortly after withdrawing a hormonal contraceptive. Currently, all women are advised to take folic acid during and after hormonal contraception.
Combined hormonal contraceptives can affect peripheral insulin resistance and glucose tolerance, but there is no evidence of the need to change the treatment of diabetes mellitus during the use of combined hormonal contraceptives. At the same time, the condition of diabetic patients should be carefully monitored, especially at the early stage of the use of the Evra TTC.
Exacerbation of endogenous depression, epilepsy, Crohn's disease and ulcerative colitis has been reported in women taking combined oral contraceptives.
Women who have had hyperpigmentation of their skin during pregnancy should avoid exposure to sunlight or artificial ultraviolet light while wearing TTC Evra.Often, such hyperpigmentation is not completely reversible.
Women should be informed that hormonal contraceptives do not protect against HIV infection (AIDS) and other sexually transmitted diseases.
Women who take drugs that induce microsomal enzymes (hydantoins, barbiturates, primidone, carbamazepine, rifampicin, oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin, modafinil, and phenylbutazone), and antibiotics (except tetracycline) should temporarily use a barrier method of contraception in addition to the use of TTC Evra or choose another method of contraception. The barrier method should be applied during the course of treatment with the above preparations, as well as within 28 days after discontinuation of the inducers of microsomal enzymes and within 7 days after discontinuation of antibiotics. If the period for taking concomitant drugs exceeds the 3-week cycle of using ETC's TTC, then a new contraceptive cycle should be started immediately after the previous one, that is, without the usual period free from the use of TTC. Women receiving long-term therapy with drugs that induce liver enzymes should choose another method of contraception.
When prescribing Evra drugs that are metabolized by CYP3A4, CYP2C19 isoenzymes, especially those with a narrow therapeutic index (for example, cyclosporine), against the background of TTC use, exclude the possibility of a clinically significant interaction.
When using any combined hormonal contraceptives, the menstrual cycle may be disturbed (spotting or intermenstrual bleeding), especially in the first months of using these remedies. The duration of the adaptation period is about three cycles.
If during the use of TTS Evra in accordance with the recommendations, the persistence of intermenstrual bleeding is observed or such bleeding occurs after previous regular cycles, then other reasons besides the use of TTC should be taken into account. It should be borne in mind the possibility of non-hormonal causes of menstrual disorders and, if necessary, conduct an adequate diagnostic examination to exclude organic disease or pregnancy.
Some women in the period, free from the use of TTC Evra menstruation may not occur. If a woman violated the instructions for use in the period preceding the first failed menstruation, or if she did not have two menstruations after interruptions in the use of TTC, it is necessary to exclude pregnancy before continuing to use TTC Evra.
In some women, the abolition of hormonal contraceptives can provoke the occurrence of amenorrhea or oligomenorrhea, especially if they are present before the onset of hormonal contraception.
If the application of TTS Evra causes skin irritation, you can glue the new TTS to another area of skin and wear it until the next day of replacement.
In women weighing 90 kg or more, the effectiveness of contraception can be reduced.
If symptoms of liver dysfunction occur, the use of combined hormonal contraceptives should be stopped until the normalization of liver function markers.
In case of a relapse of pruritus associated with cholestasis, which occurred during a previous pregnancy or prior use of sex hormones, the combined hormonal contraceptives should be canceled.
The safety and effectiveness of TTC Evra are established only for women from 18 to 45 years.
Immediately after removing the TTS from the bag, it should be firmly glued to the skin. After removing TTC, it still contains significant amounts of active ingredients.Residual hormones can harm the environment if they enter the water, and therefore used TTC should be carefully disposed of. To do this, separate the special adhesive film from the outside of the bag. Place the used TTS in the bag in such a way that its sticky side faces the painted area on the bag, and lightly press it to seal. The sealed bag is thrown away. Used TTC should not be thrown into the toilet or into the sewer.
Symptoms: nausea, vomiting, vaginal bleeding.
Treatment: there is no specific antidote. TTC should be removed and symptomatic therapy should be performed.
- Brand name: Evra
- Active ingredient: Norelgestromin, Ethinyl Estradiol
- Dosage form: transdermal therapeutic system (TTS)
- Manufacturer: Janssen Pharmaceuticals N.V.
- Country of Origin: Belgium
- Drug treatment of Alzheimer's disease and responders to rivastigmine beyond 12 weeks
- Rivastigmine in the treatment of dementia with Lewy bodies: preliminary findings from an open trial
- Variability of AChE, BChE, and ChAT genes in the late-onset form of Alzheimer's disease and relationships with response to treatment with Donepezil and Rivastigmine
- Development and validation of a HPLC method for quantification of rivastigmine in rat urine and identification of a novel metabolite in urine by LC-MS/MS
- A simple, rapid and sensitive method for simultaneous determination of rivastigmine and its major metabolite NAP 226-90 in rat brain and plasma by reversed-phase liquid chromatography coupled to electrospray ionization mass spectrometry
- ChemInform Abstract: Synthesis and Cholinesterase Activity of Phenylcarbamates Related to Rivastigmine, a Therapeutic Agent for Alzheimer′s Disease.
- ChemInform Abstract: Novel Convenient Synthesis of Rivastigmine.
- ChemInform Abstract: An Improved Process for the Production of Rivastigmine Tartrate, a Cholinesterase Inhibitor.
- ChemInform Abstract: Chemoenzymatic Asymmetric Total Synthesis of (S)-Rivastigmine Using ω-Transaminases.
- Sensitive Method for Enantioseparation of Rivastigmine with Highly Sulfated Cyclodextrin as Chiral Selector by Capillary Electrophoresis
- Memantine does not influence AChE inhibition in rat brain by donepezil or rivastigmine but does with DFP and metrifonate in in vivo studies
- Donepezil- or rivastigmine-induced acetylcholinesterase inactivation is not modulated by neramexane in rat brain
- Simultaneous determination of galantamine, rivastigmine and NAP 226-90 in plasma by MEKC and its application in Alzheimer's disease
- Efficacy of rivastigmine in subjects with moderately severe Alzheimer's disease
- Review of donepezil, rivastigmine, galantamine and memantine for the treatment of dementia in Alzheimer's disease in adults with Down syndrome: implications for the intellectual disability population
- Delirium in elderly hospitalised patients: protective effects of chronic rivastigmine usage
- Rivastigmine in the treatment of dementia in Alzheimer's disease in adults with Down syndrome
- A systematic review of the clinical effectiveness of donepezil, rivastigmine and galantamine on cognition, quality of life and adverse events in Alzheimer's disease
- Discontinuation of rivastigmine in routine clinical practice
- Risperidone and rivastigmine and agitated behaviour in severe Alzheimer's disease: a randomised double blind placebo controlled study
- A six-month double-blind, randomized, placebo-controlled study of a transdermal patch in Alzheimer's disease–– rivastigmine patch versus capsule
- Caregiver preference for rivastigmine patch relative to capsules for treatment of probable Alzheimer's disease
- Safety and tolerability of rivastigmine capsule with memantine in patients with probable Alzheimer's disease: a 26-week, open-label, prospective trial (Study ENA713B US32)
- Efficacy of rivastigmine transdermal patch on activities of daily living: item responder analyses