Uses
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Alzheimer's Disease
Rivastigmine is used orally and transdermally for the management of mild to moderate dementia of the Alzheimer's type (Alzheimer's disease). Efficacy of orally administered rivastigmine has been evaluated in 2 placebo-controlled clinical trials each of 26 weeks' duration utilizing a dual outcome assessment strategy; changes in cognitive performance were assessed by various instruments, including the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS cog), and changes in overall clinical effects were assessed using the Clinician's Interview-Based Impression of Change (CIBIC) that required the use of caregiver information (CIBIC plus). (For additional information on ADAS cog and CIBIC plus, see Uses: Alzheimer's Disease in Donepezil Hydrochloride 12:04.) Two dosage ranges (1-4 and 6-12 mg daily administered orally) were used in each study. Rivastigmine 6-12 mg daily was found to be more effective than placebo or rivastigmine 1-4 mg daily in both studies for improvements in cognitive function and overall clinical status as assessed by the ADAS cog and CIBIC plus scales. A third placebo-controlled clinical trial utilizing forced titration to fixed dosages (3, 6, or 9 mg daily administered orally) was performed employing the same outcome assessment tools. Rivastigmine was more effective than placebo at the 2 higher dosages for mean change from baseline on the ADAS cog scores. However, no substantial differences were observed between any of the rivastigmine dosage groups and placebo when CIBIC plus scores were compared.
Rivastigmine transdermal system has been evaluated for the management of dementia of the Alzheimer's type in a single, placebo-controlled, international clinical trial of 24 weeks' duration utilizing a dual outcome assessment strategy; changes in cognitive performance were assessed by various instruments, including the cognitive subscale of ADAS cog, and changes in overall clinical effects were assessed using the Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC), which is a more standardized form of CIBIC plus. Study participants were randomized to receive a target dose of one transdermal system delivering rivastigmine 9.5 mg/24 hours, one system delivering 17.4 mg/24 hours, rivastigmine 6 mg orally twice daily, or placebo. The first 16 weeks of the study was a dosage escalation phase, with initial dosages of one transdermal system delivering 4.6 mg/24 hours applied once daily or 3 mg daily (administered as 1.5 mg orally twice daily) gradually increased over 16 weeks to the target dosage; the 16-week dose escalation phase was followed by an 8-week maintenance phase. Results of this study indicate that efficacy of a system delivering 9.5 mg/24 hours was similar to that of orally administered rivastigmine. At week 24, rivastigmine transdermal system delivering 9.5 mg/24 hours, the transdermal system delivering 17.4 mg/24 hours, and orally administered rivastigmine (6 mg twice daily) were more effective than placebo for mean change from baseline on the ADAS cog scores. In addition, rivastigmine transdermal system delivering 9.5 mg/24 hours and orally administered rivastigmine were more effective than placebo for mean change from baseline on the ADCS-CGIC scale; no substantial differences were observed between the transdermal system delivering 17.4 mg/ 24 hours and placebo on change on the ADCS-CGIC scale.
For additional information on the management of Alzheimer's disease, .
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Dementia Associated with Parkinsonian Syndrome
Rivastigmine is used orally and transdermally for the management of mild to moderate dementia associated with Parkinson's disease. Dementia associated with Parkinson's disease generally is characterized by impairments in executive function, memory retrieval, and attention in patients with an established diagnosis of Parkinson's disease. However, the diagnosis of dementia associated with Parkinson's disease can be made without documenting these specific deficits in patients in whom a progressive dementia syndrome occurs at least 2 years after a diagnosis of Parkinson's disease has been made and in whom other causes of dementia have been ruled out.
Efficacy of orally administered rivastigmine has been evaluated for the management of dementia associated with idiopathic Parkinson's disease in a single, placebo-controlled, international clinical trial of 24 weeks' duration in patients with mild to moderate dementia with onset at least 2 years after the initial diagnosis of idiopathic Parkinson's disease. The first 16 weeks of the study was a dosage escalation phase, with initial dosages of 3 mg daily (administered orally as 1.5 mg twice daily) gradually increased by increments of 3 mg daily at intervals of at least 4 weeks up to a maximum dosage of 12 mg daily. The highest tolerated dosage was then maintained for the remainder of the study; dosages could be adjusted as needed because of adverse effects. The trial used a dual outcome assessment strategy; changes in cognitive performance were assessed by ADAS cog and changes in overall clinical effects were assessed using the Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC), which is a more standardized form of CIBIC plus. (For additional information on ADAS cog and CIBIC plus, see Uses: Alzheimer's Disease in Donepezil Hydrochloride 12:04.) Rivastigmine (mean final oral dosage 8.6 mg daily) was found to be more effective than placebo for improvements in cognitive performance and in overall clinical efficacy as assessed by the ADAS cog and ADCS-CGIC scales, respectively.