Transdermal Rivastigmine Research Articles

Switching from Oral Cholinesterase Inhibitors to the Rivastigmine Transdermal Patch

Oral cholinesterase inhibitors (ChEIs) are associated with side effects such as nausea and vomiting. The use of transdermal patches for ChEI delivery may help to minimize these problems. The objective of this review was to consider available data from patients switching from oral ChEIs to transdermal rivastigmine treatment, and to suggest practical guidelines for patients wishing to do this. Literature database and reference list searches were performed to identify suitable publications. Data from two clinical trials and a series of open observational studies, in which patients were switched to the rivastigmine patch from oral rivastigmine, donepezil tablets, or galantamine, were evaluated. Adverse events were tabulated. In the studies reported here, nausea was reported in up to 3.2% and vomiting in up to 1.9% of patients switching to the rivastigmine patch from oral rivastigmine. Similar rates (up to 3.8% of patients for nausea and 0.8% of patients for vomiting) were reported when switching to the rivastigmine patch from donepezil tablets, and no nausea or vomiting was reported in a case study of patients switching to the rivastigmine patch from galantamine tablets. Switching regimes used in clinical trials appeared well tolerated. Data support recommendations for patients on high rivastigmine capsule doses to switch directly to the 9.5 mg/24 h rivastigmine patch, while those on lower oral rivastigmine doses should start on the 4.6 mg/24 h patch for 4 weeks before increasing to the 9.5 mg/24 h patch. This latter regimen is recommended for patients on other oral cholinesterase inhibitors if switching is medically indicated or requested by the patient or the caregiver.

Pharmacokinetics of a novel transdermal rivastigmine patch for the treatment of Alzheimer’s disease: a review

Background:Cholinesterase inhibitors have all been available in oral formulations, but a rivastigmine transdermal patch has now been developed and is approved in many countries worldwide for the treatment of mild-to-moderate Alzheimer’s disease (AD) (including the USA, Latin America, Europe and Asia).Objectives:To review the available pharmacokinetic data that supported the rationale behind the development of the rivastigmine transdermal patch and its clinical effects in dementia therapy. This article will also discuss how the patch may alter the treatment paradigm for patients with AD.Results:The 9.5 mg/24 h rivastigmine patch was shown to provide comparable exposure to the highest recommended doses of capsules (12 mg/day) with significantly lower maximum plasma concentration (Cmax 8.7 vs. 21.6 ng/ml) and slower absorption rate (tmax 8.1 vs. 1.4 h). In a clinical trial of 1195 AD patients, this translated into similar efficacy with three times fewer reports of nausea and vomiting (7.2% vs. 23.1%, and 6.2% vs. 17.0% respectively). Consequently, more patients in the 9.5 mg/24 h patch group achieved their target therapeutic dose at the end of the study, compared with those in the 12 mg/day capsule group (95.9% vs. 64.4%).Conclusion:The rivastigmine patch provides continuous drug delivery over 24 h and similar efficacy to the highest recommended dose of oral rivastigmine with improved tolerability. This may allow patients to achieve optimal therapeutic doses and to benefit from a longer duration of treatment.

Safety and Tolerability of the Rivastigmine Patch

The primary objective of the open-label extension was to evaluate the long-term safety and tolerability of a transdermal rivastigmine patch up to 1 year, as a novel approach to treatment in Alzheimer disease. This was a 28-week extension to a 24-week, double-blind, double-dummy, placebo-controlled, and active-controlled study evaluating rivastigmine patches [9.5 mg/24 h (10 cm2) and 17.4 mg/24 h (20 cm2)] and oral capsules (3 to 6 mg twice-daily). Patients entering the extension were switched directly to 9.5 mg/ 24 h rivastigmine patch and increased to 17.4 mg/24 h patch, irrespective of their double-blind study treatment. Primary measures included safety and tolerability assessments, including adverse events and serious adverse events. Of 1195 patients randomized to treatment, 870 (72.8%) completed the double-blind study and entered the open-label extension. During weeks 1 to 4 of the extension, 9.5 mg/24 h rivastigmine patch was well tolerated overall by patients formerly randomized to rivastigmine capsule or patch groups: < or =2.5% reported nausea and < or =1.9% reported vomiting. No unexpected safety issues arose, and skin tolerability was good; similar to the double-blind study. During the 28-week, open-label extension phase, the patch seemed to be well tolerated with a favorable safety profile.

Novel Regimens and Delivery Systems in the Pharmacological Treatment of Alzheimerʼs Disease

The mainstay of current management of patients with Alzheimer's disease involves drugs that provide symptomatic therapy. Research approaches for future therapy of Alzheimer's disease are focusing on disease modifying and/or preventive approaches. Two classes of medications have been approved by the US FDA for the treatment of Alzheimer's disease: the cholinesterase inhibitors (tacrine, donepezil, rivastigmine, galantamine), mostly for mild to moderate Alzheimer's disease, and the noncompetitive NMDA receptor antagonist memantine for the moderate to severe stages of Alzheimer's disease. Management of comorbid medical problems can be more complex in patients with dementia than in those without dementia. Unfortunately, medication adherence in Alzheimer's disease is low and good adherence is essential for attempting to slow disease progression and improve or stabilize quality of life. Simplifying treatment regimens and providing more caregiver- and patient-friendly modes of administration that fit in better with daily routines can ease caregiver stress which, in turn, may have a favourable impact on the patient's condition. To overcome problems of medication adherence in the elderly, simple, user-friendly dosage regimens should be prescribed for all medications; thus the need for novel regimens and delivery systems in the pharmacological treatment of Alzheimer's disease, such as once-daily donepezil, memantine and galantamine, and transdermal rivastigmine.

Table of Contents

AbstractStudy Finds New Transdermal Rivastigmine Patch may be Optimal way to Deliver TreatmentPramipexole as Adjunctive Treatment in African, Asian and Hispanic Parkinson's Disease PatientsEarly Onset Tardive Dyskinesia Possibly Induced by OlanzapineProlonged Release 24‐Hour Ropinirole Reduces “off” Time in Parkinson'sCaregivers Prefer Rivastigmine Patch Over CapsulePharmacokinetic SubstudyExperimental Drug Pristiq Effective in Low Doses Against Hot Flashes and DepressionLong‐Term Escitalopram Treatment of Major Depression in the ElderlyValproic Acid‐Induced Cognitive Impairment in an Elderly ManPergolide Withdrawn from the Market

Transdermal rivastigmine more IDEAL than oral in Alzheimer's disease?

Transdermal rivastigmine more IDEAL than oral in Alzheimer's disease?

Transdermal Rivastigmine Treatment Does Not Worsen Impaired Performance of Complex Motions in Patients with Alzheimer’s Disease

There is a debate about the deterioration of fine motor behavior during treatment with cholinesterase inhibitors. We used an instrumental motor test, which demands a complex motion series. Thereby we assessed motor function in patients with Alzheimer's disease (AD), in patients with mild cognitive impairment (MCI), and in controls. We also performed this task and a complex reaction time paradigm (CRT) during a six-week open-label safety study using transdermal delivery of the cholinesterase inhibitor rivastigmine. To investigate (1) the performance of complex movements during deterioration of cognitive function and (2) the impact of rivastigmine on fine motor behavior and CRT outcomes in AD patients. There were significant differences in the motor test outcomes, particularly when performed with the left non-dominant hand, between controls and patients with AD and MCI. Rivastigmine did not deteriorate assessed fine motor skills and CRT results. Our study shows an impaired carrying out of complex motion series during neurodegeneration associated with cognitive dysfunction. Rivastigmine selectively inhibits the predominant cortical and hippocampal G1 cholinesterase isoform; therefore, hypothetically no deterioration of fine motor behavior appeared during transdermal rivastigmine treatment. We assume that a putative drug-induced increase in speed and attention did not offset a deterioration of motion performance because we found no significant changes in the CRT results.