The precise mechanism of action of the reversible cholinesterase inhibitor rivastigmine is unknown, but it has been suggested that the agent exerts its therapeutic effect by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by cholin-esterase, thus enhancing cholinergic function. Rivastigmine was previously available in capsule and oral solution formulations. This transdermal formulation was approved on July 6, 2007, for the treatment of mild-to-moderate dementia of the Alzheimer's disease (AD) type and for the treatment of mild-to-moderate dementia associated with Parkinson disease (PD).

Efficacy. The efficacy of transdermal rivastigmine was evaluated in a single randomized, double-blind, controlled trial in patients with AD; other efficacy results were based on previous studies of oral rivastigmine in patients with AD or dementia associated with PD. In the study that specifically evaluated transdermal rivastigmine, 1,195 patients were randomized to 1 of 4 treatment regimens: transdermal rivastigmine 9.5 mg/24 h, transdermal rivastigmine 17.4 mg/24 h, rivastigmine capsules at a dose of 6 mg BID, or placebo. The 24-week trial included a 16-week titration phase and an 8-week maintenance phase. The efficacy of transdermal rivastigmine was assessed using the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog) and the Alzheimer's Disease Cooperative Study–Clinical Global Impression of Change (ADCS-CGIC). At 24 weeks, all rivastigmine treatment groups had experienced significant improvements from baseline in mean ADAS-Cog scores versus placebo (transdermal rivastigmine 9.5 mg/24 h, 1.8 units; transdermal rivastigmine 17.4 mg/24 h, 2.9 units; rivastigmine capsules 6 mg BID, 1.8 units). ADCS-CGIC scores also improved significantly among rivastigmine-treated patients; at 24 weeks, the mean difference in ADCS-CGIC scores in each of the rivastigmine treatment groups was 0.2 units versus placebo.

Safety. Treatment with rivastigmine has been associated with significant gastro-intestinal adverse reactions including nausea, vomiting, diarrhea, anorexia/decreased appetite, and weight loss. Cholinesterase inhibitors have also been associated with an increase in gastric acid secretion due to their mechanism of action; therefore, patients should be monitored closely for symptoms of active or occult gastrointestinal bleeding. Drugs that increase cholinergic activity can have vagotonic effects on heart rate, may cause urinary obstruction, and have the potential to cause seizures. Rivastigmine may exacerbate or induce extrapyramidal symptoms. This agent should be used with caution in patients with a history of asthma or chronic obstructive pulmonary disease (COPD). The most common adverse events reported in association with rivastigmine treatment include nausea, vomiting, diarrhea, anorexia/ decreased appetite, and weight loss.