Aurobindo

Rivastigmine

Generic

Generic for Exelon

ID: 65862065160

NaN

Reviews

📜 Prescription Required

FORM

Capsule

STRENGTH

6 mg

QUANTITY

*Final prices are shown at checkout.

Don't have a prescription?

Do you already have an Rx?

How Medmind Works

Search for your medication

Find your prescription or over-the-counter medication using our comprehensive database.

Compare prices from multiple pharmacies

View prices from various pharmacies in your area to find the best deals.

Get your prescription filled

Choose your preferred pharmacy and get your medication at the best price.

TL;DR — Quick Summary

Key facts from the full medication guide below

1 INDICATIONS AND USAGE 1.1 Alzheimer s Disease 1.2 Parkinson s Disease Dementia 2 DOSAGE AND ADMINISTRATION 2.1 Dosing in Alzheimer's Disease

🩺What it's for

Rivastigmine tartrate capsules are an acetylcholinesterase inhibitor indicated for treatment of: Mild-to-moderate dementia of the Alzheimer s type (AD) (1.1) Mild-to-moderate dementia associated with Parkinson s disease (PD) (1.2)

💊How to take it

Alzheimer s Disease (2.1): Initial Dose: Initiate treatment with 1.5 mg twice a day. Dose Titration: After a minimum of 2 weeks, if tolerated, increase dose to 3 mg twice a day and further to 4.5 mg twice a day and 6 mg twice a day if tolerated with a minimum of 2 weeks at each dose Parkinson s Disease Dementia (PDD) (2.2): Initial Dose: Initiate treatment with 1.5 mg twice a day.

ℹ️Common side effects

Rivastigmine tartrate can cause gastrointestinal adverse reactions, including significant nausea, vomiting, diarrhea, anorexia/decreased appetite, and weight loss. Dehydration may result from prolonged vomiting or diarrhea and can be associated with serious outcomes. The incidence and severity of these reactions are dose-related [see Adverse Reactions (6.1)]. For this reason, patients should always be started at a dose of 1.5 mg twice a day and titrated to their maintenance dose.

⚠️Serious risks

Gastrointestinal adverse reactions may include significant nausea, vomiting, diarrhea, anorexia/decreased appetite, and weight loss, and may necessitate treatment interruption. Dehydration may result from prolonged vomiting or diarrhea and can be associated with serious outcomes. (5.1) Discontinue rivastigmine in case of disseminated allergic dermatitis, which may occur after oral or transdermal administration (4, 5.2).

📋Interactions & cautions

Concomitant use with metoclopramide, beta-blockers, or cholinomimetic and anticholinergic drugs is not recommended (7.1, 7.2, 7.3)

📦Storage & missed dose

Rivastigmine tartrate capsules, USP equivalent to 1.5 mg, 3 mg, 4.5 mg, or 6 mg of rivastigmine base are available as follows: Rivastigmine Tartrate Capsules USP, 1.5 mg are yellow cap and yellow body colored size 2 capsules imprinted in black ink with H on cap and 67 on body, containing white to off-white granular powder.

Check Interactions Ask a Pharmacist Transfer Prescription Ask MedMind AI

Ask MedMind

Questions answered from this medication guide. Sign in to personalize with your meds & labs.

Rivastigmine (Exelon) Prices

Current MedMind pricing — no insurance required

Neurologic Effects Extrapyramidal Symptoms: Cholinomimetics, including rivastigmine may exacerbate or induce extrapyramidal symptoms. Worsening of parkinsonian symptoms, particularly tremor has been observed in patients with dementia associated with Parkinson s disease who were treated with rivastigmine tartrate capsules. Seizures: Drugs that increase cholinergic activity are believed to have some potential for causing seizures. However, seizure activity also may be a manifestation of Alzheimer's disease. Peptic Ulcers/Gastrointestinal Bleeding Cholinesterase inhibitors, including rivastigmine, may be expected to increase gastric acid secretion due to increased cholinergic activity. Monitor patients using rivastigmine tartrate for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers, e.g., those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs). Clinical studies of rivastigmine have shown no significant increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding. Use with Anesthesia Rivastigmine, as a cholinesterase inhibitor, is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia. Cardiac Conduction Effects Because rivastigmine increases cholinergic activity, use of rivastigmine may have vagotonic effects on heart rate (e.g., bradycardia). The potential for this action may be particularly important in patients with sick sinus syndrome or other supraventricular cardiac conduction conditions. In clinical trials, rivastigmine was not associated with any increased incidence of cardiovascular adverse events, heart rate or blood pressure changes, or electrocardiogram (ECG) abnormalities. Syncopal episodes have been reported in 3% of patients receiving 6 mg to 12 mg per day of rivastigmine tartrate, compared to 2% of placebo patients. Genitourinary Effects Although not observed in clinical trials of rivastigmine, drugs that increase cholinergic activity may cause urinary obstruction. Pulmonary Effects Drugs that increase cholinergic activity, including rivastigmine, should be used with care in patients with a history of asthma or obstructive pulmonary disease.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Rivastigmine tartrate has been administered to over 5,297 individuals during clinical trials worldwide. Of these, 4,326 patients have been treated for at least 3 months, 3,407 patients have been treated for at least 6 months, 2,150 patients have been treated for 1 year, 1,250 patients have been treated for 2 years, and 168 patients have been treated for over 3 years. With regard to exposure to the highest dose, 2,809 patients were exposed to doses of 10 mg to 12 mg, 2,615 patients treated for 3 months, 2,328 patients treated for 6 months, 1,378 patients treated for 1 year, 917 patients treated for 2 years, and 129 patients treated for over 3 years. Mild-to-Moderate Alzheimer s Disease Most Common Adverse Reactions The most common adverse reactions, defined as those occurring at a frequency of at least 5% and twice the placebo rate, are largely predicted by rivastigmine tartrate's cholinergic effects. These include nausea, vomiting, anorexia, dyspepsia, and asthenia. Gastrointestinal Adverse Reactions Rivastigmine tartrate use is associated with significant nausea, vomiting, and weight loss [see Warnings and Precautions (5.1)]. Discontinuation Rates The rate of discontinuation due to adverse events in controlled clinical trials of rivastigmine tartrate was 15% for patients receiving 6 mg to 12 mg per day compared to 5% for patients on placebo during forced weekly dose titration. While on a maintenance dose, the rates were 6% for patients on rivastigmine tartrate compared to 4% for those on placebo. The most common adverse reactions leading to discontinuation, defined as those occurring in at least 2% of patients and at twice the incidence seen in placebo patients, are shown in Table 1. Table 1: Most Frequent Adverse Reactions Leading to Withdrawal from Clinical Trials During Titration and Maintenance in Patients Receiving 6 mg to 12 mg per day Rivastigmine Tartrate Using a Forced-Dose Titration Study Phase Titration Maintenance Overall Rivastigmine Tartrate 6 to 12 mg/day (n = 1,189) Placebo (n = 868) Rivastigmine Tartrate 6 to 12 mg/day (n = 987) Placebo (n = 788) Rivastigmine Tartrate 6 to 12 mg/day (n = 1,189) Placebo (n = 868) Event/% Discontinuing Nausea 8 < 1 1 < 1 8 1 Vomiting 4 < 1 1 < 1 5 < 1 Anorexia 2 0 1 < 1 3 < 1 Dizziness 2 < 1 1 < 1 2 < 1 Adverse Reactions Observed at an Incidence of at Least 2% Table 2 lists adverse reactions that occurred in at least 2% of patients in placebo-controlled trials, and for which the rate of occurrence was greater for patients treated with rivastigmine tartrate doses of 6 mg to 12 mg per day than for those treated with placebo. In general, adverse reactions were less frequent later in the course of treatment. No systematic effect of race or age could be determined from the incidence of adverse reactions in the controlled studies. Nausea, vomiting and weight loss were more frequent in women than men. Table 2: Proportion of Adverse Reactions Observed with a Frequency of Greater Than or Equal to 2% and at a Rate Greater than Placebo in Clinical Trials Body System/Adverse Reaction Rivastigmine Tartrate (6 to 12 mg/day) (n = 1,189) Placebo (n = 868) Percent of Patients with any Adverse Event 92 79 Autonomic Nervous System Increased Sweating 4 1 Syncope 3 2 Body as a Whole Fatigue 9 5 Asthenia 6 2 Malaise 5 2 Decreased Weight** 3 < 1 Cardiovascular Disorders, General Hypertension 3 2 Central and Peripheral Nervous System Dizziness 21 11 Headache 17 12 Somnolence 5 3 Tremor 4 1 Gastrointestinal System Nausea* 47 12 Vomiting* 31 6 Diarrhea 19 11 Anorexia*** 17 3 Abdominal Pain 13 6 Dyspepsia 9 4 Psychiatric Disorders Insomnia 9 7 Confusion 8 7 Depression 6 4 Anxiety 5 3 Hallucination 4 3 Aggressive Reaction 3 2 Resistance Mechanism Disorders Urinary Tract Infection 7 6 *Nausea and Vomiting: In the controlled clinical trials, 47% of the patients treated with a rivastigmine tartrate dose in the therapeutic range of 6 mg to 12 mg per day (n = 1189) developed nausea (compared with 12% in placebo). A total of 31% of rivastigmine tartrate- treated patients developed at least 1 episode of vomiting (compared with 6% for placebo). The rate of vomiting was higher during the titration phase (24% versus 3% for placebo) than in the maintenance phase (14% versus 3% for placebo). The rates were higher in women than men. Five percent of patients discontinued for vomiting, compared to less than 1% for patients on placebo. Vomiting was severe in 2% of rivastigmine tartrate-treated patients and was rated as mild or moderate each in 14% of patients. The rate of nausea was higher during the titration phase (43% versus 9% for placebo) than in the maintenance phase (17% versus 4% for placebo). **Weight Decreased: In the controlled trials, approximately 26% of women on high doses of rivastigmine tartrate (greater than 9 mg per day) had weight loss equal to or greater than 7% of their baseline weight compared to 6% in the placebo-treated patients. About 18% of the males in the high-dose group experienced a similar degree of weight loss compared to 4% in placebo-treated patients. It is not clear how much of the weight loss was associated with anorexia, nausea, vomiting, and the diarrhea associated with the drug. ***Anorexia: In the controlled clinical trials, of the patients treated with a rivastigmine tartrate dose of 6 mg to 12 mg per day, 17% developed anorexia compared to 3% of the placebo patients. Neither the time course nor the severity of the anorexia is known. Mild-to-Moderate Parkinson s Disease Dementia Rivastigmine tartrate has been administered to 779 individuals during clinical trials worldwide. Of these, 663 patients have been treated for at least 3 months, 476 patients have been treated for at least 6 months, and 313 patients have been treated for 1 year. Most Common Adverse Reactions The most common adverse reactions, defined as those occurring at a frequency of at least 5% and twice the placebo rate, are largely predicted by rivastigmine tartrate's cholinergic effects. These include nausea, vomiting, tremor, anorexia, and dizziness. Discontinuation Rates The rate of discontinuation due to adverse events in the single placebo-controlled trial of rivastigmine tartrate was 18% for patients receiving 3 mg to 12 mg per day compared to 11% for patients on placebo during the 24-week study. The most frequent adverse reactions that led to discontinuation from this study, defined as those occurring in at least 1% of patients receiving rivastigmine tartrate and more frequent than those receiving placebo, were nausea (3.6% rivastigmine tartrate versus 0.6% placebo), vomiting (1.9% rivastigmine tartrate versus 0.6% placebo), and tremor (1.7% rivastigmine tartrate versus 0% placebo). Adverse Reactions Observed at an Incidence of at Least 2% Table 3 lists adverse reactions that occurred in at least 2% of patients in a single placebo-controlled trial and during the first 24 weeks of a 76-week open-label active-controlled trial for which the rate of occurrence was greater for patients treated with rivastigmine tartrate doses of 3 mg to 12 mg per day than for those treated with placebo in the placebo-controlled trial. In general, adverse reactions were less frequent later in the course of treatment. Table 3: Proportion of Adverse Reactions Observed at a Frequency Greater Than or Equal to 2% and Occurring at Rate Greater than Placebo in Clinical Trials Active-Controlled Study Placebo-Controlled Study Body System/Adverse Reaction Rivastigmine Tartrate (3 to 12 mg/day) (n = 294) Rivastigmine Tartrate (3 to 12 mg/day) (n = 362) Placebo (n = 179) Percent of Patients with any Adverse Event 88 84 71 Gastrointestinal Disorders Nausea 38 29 11 Vomiting 13 17 2 Diarrhea 8 7 4 Upper Abdominal Pain 4 4 1 Salivary hypersecretion 2 1 0 General Disorders and Administrative Site Conditions Fall 10 6 6 Fatigue 5 4 3 Asthenia 4 2 1 Metabolism and Nutritional Disorders Anorexia - 6 3 Decreased Appetite 5 8 5 Dehydration 1 2 1 Nervous System Disorders Tremor 23 10 4 Dizziness 8 6 1 Headache 4 4 3 Somnolence 6 4 3 Parkinson s Disease (worsening) -* 3 1 Bradykinesia 3 3 2 Dyskinesia 3 1 1 Cogwheel rigidity 3 1 0 Hypokinesia 2 1 0 Parkinsonism - 2 1 Psychiatric Disorders Anxiety 4 4 1 Insomnia 2 3 2 Restlessness 1 3 2 Skin and Subcutaneous Tissue Disorders Increased Sweating 2 2 1 *Parkinson s disease (worsening) in the active-controlled study was assessed by reported pre-identified adverse events (tremor, cogwheel rigidity, fall), each of them listed with corresponding frequencies.

Rivastigmine shows linear pharmacokinetics up to 3 mg twice a day but is nonlinear at higher doses. Doubling the dose from 3 mg to 6 mg twice a day results in a 3-fold increase in area under the curve (AUC). The elimination half-life is about 1.5 hours, with most elimination as metabolites via the urine. Absorption Rivastigmine is rapidly and completely absorbed. Peak plasma concentrations are reached in approximately 1 hour. Absolute bioavailability after a 3 mg dose is about 36%. Administration of rivastigmine tartrate with food delays absorption (Tmax) by 90 minutes lowers Cmax by approximately 30% and increases AUC by approximately 30%. Distribution Rivastigmine is weakly bound to plasma proteins (approximately 40%) over the therapeutic range. It readily crosses the blood-brain barrier, reaching CSF peak concentrations in 1.4 to 2.6 hours. It has an apparent volume of distribution (VD) in the range of 1.8 to 2.7 L/kg. Metabolism Rivastigmine is rapidly and extensively metabolized, primarily via cholinesterase-mediated hydrolysis to the decarbamylated metabolite. Based on evidence from in vitro and animal studies, the major cytochrome P450 isozymes are minimally involved in rivastigmine metabolism. Consistent with these observations is the finding that no drug interactions related to cytochrome P450 have been observed in humans. Elimination The major pathway of elimination is via the kidneys. Following administration of 14C-rivastigmine to 6 healthy volunteers, total recovery of radioactivity over 120 hours was 97% in urine and 0.4% in feces. No parent drug was detected in urine. The sulfate conjugate of the decarbamylated metabolite is the major component excreted in urine and represents 40% of the dose. Mean oral clearance of rivastigmine is 1.8 0.6 L/min after 6 mg twice a day. Age Following a single 2.5 mg oral dose to elderly volunteers (60 years and older, n = 24) and younger volunteers (n = 24), mean oral clearance of rivastigmine was 30% lower in elderly (7 L/min) than in younger subjects (10 L/min). Gender and Race Population pharmacokinetic analysis of oral rivastigmine indicated that neither gender (n = 277 males and 348 females) nor race (n = 575 Caucasian, 34 Black, 4 Asian, and 12 Other) affected clearance of the drug. Body Weight A relationship between drug exposure at steady-state (rivastigmine and metabolite NAP226-90) and body weight was observed in Alzheimer s dementia patients. Rivastigmine exposure is higher in subjects with low body weight. Compared to a patient with a body weight of 65 kg, the rivastigmine steady-state concentrations in a patient with a body weight of 35 kg would be approximately doubled, while for a patient with a body weight of 100 kg the concentrations would be approximately halved. Renal Impairment Following a single 3 mg dose, mean oral clearance of rivastigmine is 64% lower in moderately impaired renal patients (n = 8, GFR = 10 to 50 mL/min) than in healthy subjects (n = 10, GFR greater than or equal to 60 mL/min); CL/F=1.7 L/min and 4.8 L/min, respectively. In patients with severe renal impairment (n = 8, GFR less than 10 mL/min), mean oral clearance of rivastigmine is 43% higher than in healthy subjects (n = 10, GFR greater than or equal to 60 mL/min); CL/F = 6.9 L/min and 4.8 L/min, respectively. For unexplained reasons, the severely impaired renal patients had a higher clearance of rivastigmine than moderately impaired patients. Hepatic Impairment Following a single 3 mg dose, mean oral clearance of rivastigmine was 60% lower in hepatically impaired patients (n = 10, biopsy proven) than in healthy subjects (n = 10). After multiple 6 mg twice a day oral dosing, the mean clearance of rivastigmine was 65% lower in mild (n = 7, Child-Pugh score 5 to 6), and moderate (n = 3, Child-Pugh score 7 to 9) hepatically impaired patients (biopsy proven, liver cirrhosis) than in healthy subjects (n = 10). Smoking Following oral rivastigmine administration (up to 12 mg per day) with nicotine use, population pharmacokinetic analysis showed increased oral clearance of rivastigmine by 23% (n = 75 smokers and 549 nonsmokers). Drug Interaction Studies Effect of Rivastigmine on the Metabolism of Other Drugs Rivastigmine is primarily metabolized through hydrolysis by esterases. Minimal metabolism occurs via the major cytochrome P450 isoenzymes. Based on in vitro studies, no pharmacokinetic drug interactions with drugs metabolized by the following isoenzyme systems are expected: CYP1A2, CYP2D6, CYP3A4/5, CYP2E1, CYP2C9, CYP2C8, CYP2C19, or CYP2B6. No pharmacokinetic interaction was observed between rivastigmine taken orally and digoxin, warfarin, diazepam or fluoxetine in studies in healthy volunteers. The increase in prothrombin time induced by warfarin is not affected by administration of rivastigmine. Effect of Other Drugs on the Metabolism of Rivastigmine Drugs that induce or inhibit CYP450 metabolism are not expected to alter the metabolism of rivastigmine. Population pharmacokinetic analysis with a database of 625 patients showed that the pharmacokinetics of rivastigmine taken orally were not influenced by commonly prescribed medications such as antacids (n = 77), antihypertensives (n = 72), beta-blockers (n = 42), calcium channel blockers (n = 75), antidiabetics (n = 21), NSAIDs (n = 79), estrogens (n = 70), salicylate analgesics (n = 177), antianginals (n = 35) and antihistamines (n = 15).

Mild-to-Moderate Alzheimer s Disease The effectiveness of rivastigmine tartrate as a treatment for Alzheimer's disease is demonstrated by the results of 2 randomized, double-blind, placebo-controlled clinical investigations (Study 1 and Study 2) in patients with Alzheimer's disease [diagnosed by NINCDS-ADRDA and DSM-IV criteria, Mini-Mental State Examination (MMSE) greater than or equal to 10 and less than or equal to 26, and the Global Deterioration Scale (GDS)]. The mean age of patients participating in rivastigmine tartrate trials was 73 years with a range of 41 to 95. Approximately 59% of patients were women and 41% were men. The racial distribution was Caucasian 87%, Black 4%, and other races 9%. In each study, the effectiveness of rivastigmine tartrate was evaluated using a dual outcome assessment strategy. The ability of rivastigmine tartrate to improve cognitive performance was assessed with the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), a multi-item instrument that has been extensively validated in longitudinal cohorts of Alzheimer's disease patients. The ADAS-cog examines selected aspects of cognitive performance including elements of memory, orientation, attention, reasoning, language, and praxis. The ADAS-cog scoring range is from 0 to 70, with higher scores indicating greater cognitive impairment. Elderly normal adults may score as low as 0 or 1, but it is not unusual for non-demented adults to score slightly higher. The patients recruited as participants in each study had mean scores on ADAS-cog of approximately 23 units, with a range from 1 to 61. Experience gained in longitudinal studies of ambulatory patients with mild-to-moderate Alzheimer's disease suggests that they gain 6 to 12 units a year on the ADAS-cog. Lesser degrees of change, however, are seen in patients with very mild or very advanced disease because the ADAS-cog is not uniformly sensitive to change over the course of the disease. The annualized rate of decline in the placebo patients participating in rivastigmine tartrate trials was approximately 3 to 8 units per year. The ability of rivastigmine tartrate to produce an overall clinical effect was assessed using a Clinician's Interview-Based Impression of Change (CIBIC) that required the use of caregiver information, the CIBIC-Plus. The CIBIC-Plus is not a single instrument and is not a standardized instrument like the ADAS-cog. Clinical trials for investigational drugs have used a variety of CIBIC formats, each different in terms of depth and structure. As such, results from a CIBIC-Plus reflect clinical experience from the trial or trials in which it was used and cannot be compared directly with the results of CIBIC-Plus evaluations from other clinical trials. The CIBIC-Plus used in the rivastigmine tartrate trials was a structured instrument based on a comprehensive evaluation at baseline and subsequent time-points of 3 domains: patient cognition, behavior and functioning, including assessment of activities of daily living. It represents the assessment of a skilled clinician using validated scales based on his/her observation at interviews conducted separately with the patient and the caregiver familiar with the behavior of the patient over the interval rated. The CIBIC-Plus is scored as a 7-point categorical rating, ranging from a score of 1, indicating "markedly improved," to a score of 4, indicating "no change" to a score of 7, indicating "marked worsening." The CIBIC-Plus has not been systematically compared directly to assessments not using information from caregivers or other global methods. U.S. 26-Week Study of Rivastigmine Tartrate in Mild-to-Moderate Alzheimer s Disease (Study 1) In a study of 26 weeks duration, 699 patients were randomized to either a dose range of 1 mg to 4 mg or 6 mg to 12 mg of rivastigmine tartrate per day or to placebo, each given in divided doses. The 26-week study was divided into a 12-week forced-dose titration phase and a 14-week maintenance phase. The patients in the active treatment arms of the study were maintained at their highest tolerated dose within the respective range. Figure 1 illustrates the time course for the change from baseline in ADAS-cog scores for all 3 dose groups over the 26 weeks of the study. At 26 weeks of treatment, the mean differences in the ADAS-cog change scores for the rivastigmine tartrate-treated patients compared to the patients on placebo were 1.9 and 4.9 units for the 1 mg to 4 mg and 6 mg to 12 mg treatments, respectively. Both treatments were statistically significantly superior to placebo and the 6 mg to 12 mg per day range was significantly superior to the 1 mg to 4 mg per day range. Figure 2 illustrates the cumulative percentages of patients from each of the 3 treatment groups who had attained at least the measure of improvement in ADAS-cog score shown on the x-axis. Three change scores, (7-point and 4-point reductions from baseline or no change in score) have been identified for illustrative purposes, and the percent of patients in each group achieving that result is shown in the inset table. The curves demonstrate that both patients assigned to rivastigmine tartrate and placebo have a wide range of responses, but that the rivastigmine tartrate groups are more likely to show the greater improvements. A curve for an effective treatment would be shifted to the left of the curve for placebo, while an ineffective or deleterious treatment would be superimposed upon, or shifted to the right of the curve for placebo, respectively. Figure 3 is a histogram of the frequency distribution of CIBIC-Plus scores attained by patients assigned to each of the 3 treatment groups who completed 26 weeks of treatment. The mean rivastigmine tartrate-placebo differences for these groups of patients in the mean rating of change from baseline were 0.32 units and 0.35 units for 1 mg to 4 mg and 6 mg to 12 mg of rivastigmine tartrate, respectively. The mean ratings for the 6 mg to 12 mg per day and 1 mg to 4 mg per day groups were statistically significantly superior to placebo. The differences between the 6 mg to 12 mg per day and the 1 mg to 4 mg per day groups were statistically significant. Global 26-Week Study in Mild-to-Moderate Alzheimer's Disease (Study 2) In a second study of 26 weeks duration, 725 patients were randomized to either a dose range of 1 mg to 4 mg or 6 mg to 12 mg of rivastigmine tartrate per day or to placebo, each given in divided doses. The 26-week study was divided into a 12-week forced-dose titration phase and a 14-week maintenance phase. The patients in the active treatment arms of the study were maintained at their highest tolerated dose within the respective range. Figure 4 illustrates the time course for the change from baseline in ADAS-cog scores for all 3 dose groups over the 26 weeks of the study. At 26 weeks of treatment, the mean differences in the ADAS-cog change scores for the rivastigmine tartrate-treated patients compared to the patients on placebo were 0.2 and 2.6 units for the 1 mg to 4 mg and 6 mg to 12 mg treatments, respectively. The 6 mg to 12 mg per day group was statistically significantly superior to placebo, as well as to the 1 mg to 4 mg per day group. The difference between the 1 mg to 4 mg per day group and placebo was not statistically significant. Figure 5 illustrates the cumulative percentages of patients from each of the 3 treatment groups who had attained at least the measure of improvement in ADAS-cog score shown on the x-axis. Similar to the U.S. 26-week study, the curves demonstrate that both patients assigned to rivastigmine tartrate and placebo have a wide range of responses, but that the 6 mg to 12 mg per day rivastigmine tartrate group is more likely to show the greater improvements. Figure 6 is a histogram of the frequency distribution of CIBIC-Plus scores attained by patients assigned to each of the 3 treatment groups who completed 26 weeks of treatment. The mean rivastigmine tartrate-placebo differences for these groups of patients for the mean rating of change from baseline were 0.14 units and 0.41 units for 1 mg to 4 mg and 6 mg to 12 mg of rivastigmine tartrate, respectively. The mean ratings for the 6 mg to 12 mg per day group were statistically significantly superior to placebo. The comparison of the mean ratings for the 1 mg to 4 mg per day group and placebo group was not statistically significant. U.S. Fixed-Dose Study in Mild-to-Moderate Alzheimer's Disease (Study 3) In a study of 26 weeks duration, 702 patients were randomized to doses of 3 mg, 6 mg, or 9 mg per day of rivastigmine tartrate or to placebo, each given in divided doses. The fixed-dose study design, which included a 12-week forced-dose titration phase and a 14-week maintenance phase, led to a high dropout rate in the 9 mg per day group because of poor tolerability. At 26 weeks of treatment, significant differences were observed for the ADAS-cog mean change from baseline for the 9 mg per day and 6 mg per day groups, compared to placebo. No significant differences were observed between any of the rivastigmine tartrate-dose groups and placebo for the analysis of the CIBIC-Plus mean rating of change. Although no significant differences were observed between rivastigmine tartrate treatment groups, there was a trend toward numerical superiority with higher doses. Mild-to-Moderate Parkinson s Disease Dementia International 24-Week Study (Study 4) The effectiveness of rivastigmine tartrate as a treatment for dementia associated with Parkinson s disease is demonstrated by the results of 1 randomized, double-blind, placebo-controlled clinical investigation in patients with mild-to-moderate dementia, with onset at least 2 years after the initial diagnosis of idiopathic Parkinson s disease. The diagnosis of idiopathic Parkinson s disease was based on the United Kingdom Parkinson s Disease Society Brain Bank clinical criteria. The diagnosis of dementia was based on the criteria stipulated under the DSM-IV category Dementia Due To Other General Medical Condition (code 294.1x), but patients were not required to have a distinctive pattern of cognitive deficits as part of the dementia. Alternate causes of dementia were excluded by clinical history, physical and neurological examination, brain imaging, and relevant blood tests. Patients enrolled in the study had a MMSE score greater than or equal to 10 and less than or equal to 24 at entry. The mean age of patients participating in this trial was 72.7 years with a range of 50 to 91 years. Approximately, 35.1% of patients were women and 64.9% of patients were men. The racial distribution was 99.6% Caucasian and other races 0.4%. This study used a dual outcome assessment strategy to evaluate the effectiveness of rivastigmine tartrate. The ability of rivastigmine tartrate to improve cognitive performance was assessed with the ADAS-cog. The ability of rivastigmine tartrate to produce an overall clinical effect was assessed using the Alzheimer s Disease Cooperative Study Clinician s Global Impression of Change (ADCS-CGIC). The ADCS-CGIC is a more standardized form of CIBIC-Plus and is also scored as a 7-point categorical rating, ranging from a score of 1, indicating "markedly improved," to a score of 4, indicating "no change" to a score of 7, indicating "marked worsening". In this study, 541 patients were randomized to a dose range of 3 mg to 12 mg of rivastigmine tartrate per day or to placebo in a ratio of 2:1, given in divided doses. The 24-week study was divided into a 16-week titration phase and an 8-week maintenance phase. The patients in the active treatment arm of the study were maintained at their highest tolerated dose within the specified dose range. Figure 7 illustrates the time course for the change from baseline in ADAS-cog scores for both treatment groups over the 24-week study. At 24 weeks of treatment, the mean difference in the ADAS-cog change scores for the rivastigmine tartrate-treated patients compared to the patients on placebo was 3.8 points. This treatment difference was statistically significant in favor of rivastigmine tartrate when compared to placebo. Figure 8 is a histogram of the distribution of patients scores on the ADCS-CGIC (Alzheimer s Disease Cooperative Study - Clinician s Global Impression of Change) at 24 weeks. The mean difference in change scores between the rivastigmine tartrate and placebo groups from baseline was 0.5 points. This difference was statistically significant in favor of rivastigmine tartrate treatment. Patients age, gender, or race did not predict clinical outcome of rivastigmine tartrate treatment.