July 19 , 2006

Transdermal drug delivery systems (usually by drug “patches”) are designed to provide controlled, continuous delivery of drugs through the skin, thereby maintaining more consistent blood levels of the drug. Patches also minimize processing of the drug in the liver, stomach and intestines. Together, this may make it easier to achieve therapeutic levels of the drug in the bloodstream with lower dosages than pills, thereby possibly reducing side effects.

Since Alzheimer’s initially affects memory, reasoning and decision-making abilities, it can be a problem for people with the disease to take drugs on a regular schedule. As the disease advances, people may not know what drugs are for or even what they are. With further advance of the disease, sometimes the ability to swallow is affected. Transdermal drug delivery has the potential to eliminate issues about forgetting to take the drug or to take it at the right time, and also ease challenges associated with getting the person with Alzheimer’s to take or swallow a pill. It also provides visual reassurance for the caregiver that the medication has been taken. At the same time, possible skin irritation and the presence of a new or unknown object on their body may be confusing or annoying to the person with Alzheimer’s, so a skin patch may not work for everyone.

Bengt Winblad, M.D., Ph.D., of the Karolinska Institutet, Huddinge, Sweden, and colleagues at UCLA and Novartis sought to compare the efficacy, safety and tolerability of a novel, once-daily rivastigmine (Exelon, Novartis) patch with conventional, twice-daily rivastigmine capsules. Rivastigmine is an FDA and EMEA approved cholinesterase inhibitor for treatment of mild to moderate Alzheimer’s disease.

IDEAL (Investigation of TransDermal Exelon in ALzheimer’s disease) was a 24-week, multicenter, randomized, double-blind, placebo- and active-controlled evaluation of once-daily rivastigmine patches versus twice-daily capsules in 1,195 patients with moderate stage Alzheimer’s. Patients were 50 to 85 years of age. Tested patch sizes were 10 cm2 (9.5 mg/24-hr) or 20 cm2 (17.4 mg/24-hr), and capsules were 6 mg twice-daily. Primary outcome measures were the Alzheimer’s Disease Assessment Scale – Cognition (ADAS-cog) and Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC).

The researchers found that the rivastigmine patch showed statistically significant benefits versus placebo on both of these measures and the ability to perform activities of daily living. The recommended target dose 10 cm2 patch showed similar efficacy to the highest doses of rivastigmine capsules with three times fewer reports of nausea (7.2 percent vs. 23.1 percent) and vomiting (6.2 percent vs. 17.0 percent), which are well-known side effects of cholinesterase inhibitors. The 20 cm2 patch showed improved cognitive scores versus capsules and similar tolerability to capsules. Local skin tolerability was good. Abnormal redness of the skin was present at moderate or severe levels in only 7.6 percent and 6.2 percent of patients receiving 10 and 20 cm2 patches, respectively.

“The rivastigmine patch provides similar efficacy to the highest capsule doses, and both formulations were superior to placebo,” Winblad said. “The smaller patch had three times fewer gastrointestinal side effects than the capsule. A transdermal patch may prove to be the best way to deliver rivastigmine to treat Alzheimer’s.”

“We also gave a questionnaire to more than 1,000 caregivers whose loved ones with Alzheimer’s were in the IDEAL study. The caregivers significantly preferred the patch to capsules for ease of following the treatment schedule, overall ease of use, and less interference with daily life,” Winblad said.