1.5 mg, 3 mg, 4.5 mg and 6 mg capsules
Approved indication: Alzheimer's disease
Australian Medicines Handbook Section 16.5.1
Acetylcholinesterase inhibitors have been studied in Alzheimer's disease as they enhance the remaining cholinergic neurotransmission. Rivastigmine is the third inhibitor to be marketed. Tacrine and donepezil are already available.
Rivastigmine inhibits acetyl- and butyrylcholinesterase resulting in increased acetylcholine at cholinergic synapses. It is rapidly metabolized by cholinesterases and has a plasma half-life of one hour. Most of a dose is excreted by the kidneys with no unchanged drug appearing in the urine. The pharmacokinetics are non-linear; the bioavailability triples when the dose is doubled.
A multi centre trial studied 725 patients with mild to moderate Alzheimer's disease. These patients were randomised to receive rivastigmine1-4 mg/day or 6-12 mg/day or a placebo. The dose of rivastigmine was titrated in the first 12 weeks of the 26-week trial. There were 'meaningful' improvements of cognitive function in 24% of the 242 patients given the higher dose of rivastigmine and in 16% of the 238 patients given a placebo.1 The outcome for the lower dose was not significantly different from placebo.
Over 30% of the patients randomised to take the higher dose of rivastigmine discontinued, with approximately 23% withdrawing because of adverse events.1 Common adverse effects are nausea, vomiting, anorexia and dizziness. These adverse effects often occur while the dose is being titrated.
Although rivastigmine had advantages over placebo in the rating scales used in the trial1, their clinical relevance is uncertain. Significantly more patients taking higher doses of rivastigmine had an improvement of at least 10% on the progressive deterioration scale, however this difference is relatively small. In the placebo group 19% of the patients improved compared with 29% of those taking rivastigmine. As the clinical response cannot be predicted in the patients who can tolerate rivastigmine, treatment should stop if there is no benefit after 12 weeks. Alzheimer's disease is chronic and progressive so studies lasting longer than six months are needed.
- B303 Exelon Study Group. Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial. Br Med J 1999;318:633-8.