Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
4 mg, 8 mg and 12 mg tablets
Approved indication: Alzheimer's disease
Australian Medicines Handbook Section 16.5
There is now a choice of acetylcholinesterase inhibitors (donepezil, rivastigmine and tacrine) for the treatment of mild to moderate Alzheimer's disease. Galantamine is a new inhibitor of acetylcholinesterase which has been extracted from flower bulbs such as daffodils and snowdrops. In addition to increasing acetylcholine concentrations by inhibition galantamine is also thought to modulate nicotinic receptors. Activation of presynaptic nicotinic receptors can increase the release of acetylcholine.
Patients begin treatment with a twice daily dose of 4 mg. This can be increased to a total daily dose of 16 mg and then 24 mg at monthly intervals according to the patient's response and their ability to tolerate galantamine. The drug is rapidly absorbed. Although food slows the rate of absorption, it is recommended that galantamine is taken with meals. Approximately 20% of the drug is excreted unchanged in the urine. The metabolism of galantamine involves cytochrome P4502D6 and 3A4, so there is a potential for drugs which inhibit these enzymes, for example paroxetine and erythromycin, to increase the bioavailability of galantamine. Severe hepatic or renal impairment is a contraindication.
There have been several double-blind randomised placebo-controlled trials of galantamine. These trials used daily maintenance doses of 8 mg, 16 mg, 24mg or 32 mg and measured the effects on rating scales such as the cognitive subscale of the Alzheimer's disease assessment scale. In a study lasting five months there was a difference of 3.3-3.6 points on this 70 point scale.1 The difference between galantamine (24 mg daily) and placebo was 3.1 points in a study lasting six months,2 and 3.9 points halfway through a year-long study.3 Clinicians and carers both considered that galantamine was significantly more effective than placebo in all three trials.
Discontinuations because of adverse reactions were more frequent at higher doses. Common adverse effects include nausea, gastrointestinal upsets, weight loss and headache. Galantamine should be used cautiously in patients with acardiac conduction disorder and those who are taking drugs which reduce the heart rate. The cholinergic effects of the drug also preclude its use in patients with urinary outflow obstruction, severe asthma or obstructive pulmonary disease.
Approximately one patient in five will be unable to tolerate galantamine. Those that do may achieve a statistically significant benefit on rating scales, but the long-term clinical benefits are unclear. The clinical relevance of a three point change may vary considerably from one patient to another. In the study which continued for 12 months the patients' disability did not significantly change.3 Galantamine is not approved for more severe cases of dementia.
- The Galantamine USA-10 Study Group. A 5-month, randomized, placebo-controlled trial of galantamine in AD. Neurology 2000;54:2269-76.
- The Galantamine International-1 Study Group. Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: multi centre randomised controlled trial. Br Med J 2000;321:1-7.
- The Galantamine USA-1 Study Group. Galantamine in AD. A 6-month randomized, placebo-controlled trial with a 6-month extension. Neurology 2000;54:2261-8.