Rivastigmine Skin Patch for Alzheimer Disease Approved
ARTICLE IN BRIEF
- ✓ A new rivastigmine transdermal patch may be easier to use for patients with mild to moderate Alzheimer disease and Parkinson disease dementia, but experts noted that the effects of the agent on cognition were modest at best.
On July 6, the FDA approved the rivastigmine transdermal system (Exelon patch), the first skin patch for mild to moderate forms of Alzheimer disease (AD) and Parkinson disease (PD) dementia. In late June, the agency had also approved rivastigmine — in capsule form — for mild to moderate forms of Parkinson disease (PD) dementia.
In interviews with Neurology Today, experts expressed optimism about the ease of use of the patch but noted that the effects of rivastigmine on cognition were modest at best.
Rivastigmine is one of three approved inhibitors of cholinesterase, which prevent the breakdown of acetylcholine into acetate and choline, making more transmitters available for synaptic transmission. Since patients with Alzheimer disease and other forms of dementia are thought to lack sufficient acetylcholine in the brain, any drug that increases the amount of the neurotransmitter should help. But the effects of rivastigmine and other approved cholinesterase inhibitors — donepezil (Aricept) and galantamine (Reminyl, Razadine) — have been modest, and not disease modifying, experts said.
The new patch delivers rivastigmine transdermally continuously for 24 hours a day. FDA approval was based on results from the international IDEAL (Investigation of Transdermal Exelon in Alzheimer's disease) clinical trial, a six-month, randomized, double-blind, placebo-controlled trial, which involved 1,195 patients aged 50 to 85 years old with mild to moderate AD (Int J Geriatr Psychiatry 2007;22(5):456–467).
The trial compared the efficacy, safety, and tolerability of the once-daily patch with conventional twice-daily capsules in patients with moderate AD. The primary outcome measures were the Alzheimer's Disease Assessment Scale-cognitive subscale and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change.
The target dose (9.5 mg/24 hours) of the patch provided efficacy similar to the highest doses of capsules (12mg/day) — with equal improvement in overall functioning versus placebo (p<.05) — with a “superior tolerability profile.” There were three times fewer reports of gastrointestinal side effects (nausea and vomiting) than the capsules.
According to Novartis, the patch was created with patient compliance in mind. A 24-week, randomized, controlled trial comparing caregiver preference of the patch versus the capsule and placebo found that more than 70 percent of caregivers preferred the patch, significantly because of ease of use and less interference in daily life (Int Geriatr Psychiatry 2007;22(5):485–491).
Carol F. Lippa, MD, professor of neurology and the director of the Memory Disorders Program at Drexel University College of Medicine in Philadelphia, said that gastrointestinal upset — nausea and vomiting — is a common side effect of cholinesterase inhibitors. The patch promotes bioavailability, however, while bypassing the gastrointestinal tract.
Both she and Sid Gilman, MD, the William J. Herdman Distinguished University Professor of Neurology and director of the Michigan Alzheimer's Disease Research Center at the University of Michigan, agreed that the side effect profile of the patch is better than that of the capsules because there are fewer adverse gastrointestinal effects. Beginning with the lower-dose patch and then moving to a higher dose is designed to minimize side effects.
They also agreed that the patch is convenient to use. “This [new formulation] is a good idea, as the patch needs to be applied only once per day whereas the pill has to be taken twice a day. Also, the patch can be applied to the back so that a patient will not be able to take it off, which AD patients can do at times when they become confused or forget why they have the patch attached to their skin,” Dr. Gilman said.
But Dr. Gilman noted that that the drug's effects on cognition are modest. “I would expect a more smooth effect on cognition from the slow absorption through the skin than from taking the pill orally, but have seen no data on this point,” he said.
The patch could be beneficial for patients who dislike taking pills or cannot swallow. However, experts cautioned that the main problem with the patch is skin reactions. “Also, one wonders if some dementia patients would forget why they were wearing the patch and remove it, or become confused by it,” Dr. Lippa remarked.
Both experts said they will prescribe the low-dose patch for those who experience gastrointestinal discomfort with the pill form of cholinesterase inhibitors or those who have difficulty taking pills, since the low-dose patch provides similar efficacy as the maximal recommended pill form of rivastigmine.
Dr. Lippa pointed out that patients with dementia and Lewy body pathology have greater cholinesterase losses than those with AD. “Therefore, these agents theoretically have a greater chance of helping those with PD dementia than AD patients,” she said.
Dr. Gilman concluded: “To keep all this in perspective, patients with AD and PD dementia derive some clinical benefit from cholinesterase inhibitors, and in moderate to severe dementia in AD, additional benefit from memantine (Namenda). The effects, however, are modest and are most certainly not disease modifying, but only symptomatic. We await more effective, disease-modifying therapies for these two disorders.”