Deaths Attributed To The Alzheimer’s Disease Drug Galantamine (REMINYL)

The manufacturer of the Alzheimer’s disease drug galantamine (REMINYL) announced on January 22, 2005 that data from two clinical trials revealed that patients taking galantamine had a much higher risk of death than patients taking a placebo. In these trials, 2,000 patients in 16 countries over two years, 15 patients taking galantamine (1.5%) and five receiving a placebo (0.5%) died. The deaths were mainly the result of cardiovascular (heart attacks) and cerebrovascular (strokes) causes.

In the two clinical trials, galantamine was being used experimentally to treat patients with a condition known as mild cognitive impairment (MCI). This is a condition thought by some to be a harbinger of Alzheimer’s disease. A public health advisory issued to the media on January 21, 2005 by the Canadian producer of galantamine said “REMINYL was not shown to be effective in patients with MCI.”

Galantamine was approved by the FDA in February 2001 for the treatment of mild to moderate Alzheimer’s type dementia. Galantamine belongs to the family of drugs referred to as cholinesterase inhibitors that includes the other Alzheimer’s drugs donepezil (ARICEPT), rivastigmine (EXELON), and tacrine (COGNEX). All of these drugs work by inhibiting the enzyme acetylcholinesterase and increasing levels of the brain transmitter acetylcholine with the assumption that this might improve the symptoms of Alzheimer’s dementia.

Galantamine was first listed as a DO NOT USE drug in 2002 in The Companion to the 1999 edition of Worst Pills, Best Pills, primarily because of its minimal effectiveness and its gastrointestinal (GI) adverse effects.

The FDA medical officer who reviewed galantamine stated:

... it should again be noted that the beneficial effects of Reminyl are small, and similar to those of other cholinesterase inhibitors; only a small minority of patients actually improve in relation to baseline; and the efficacy of galantamine (Reminyl) beyond six months of treatment is uncertain, as randomized controlled studies longer than six months in duration have not been carried out. There is also no evidence that galantamine has a disease-modifying effect, and at least some evidence that it may not.

The editors of the highly respected Medical Letter on Drugs and Therapeutics, a resource we frequently cite because of its reputation for independence, reviewed galantamine in their June 25, 2001 issue and concluded:

Galantamine produces modest improvements in measures of cognition and functioning in patients with mild to moderate Alzheimer’s disease. Gastrointestinal symptoms have been the most common adverse effects. Whether galantamine offers any advantage over donepezil [ARICEPT] or rivastigmine [EXELON] remains to be established by comparative trials.

The exact way in which galantamine may have caused the deaths of the 15 patients in the two mild cognitive impairment studies is unclear. However, the drug does have adverse effects on the heart. Because it increases the levels of acetylcholine it can cause bradycardia (an abnormal slowing of the heart rhythm) and heart block (a disturbance of the normal electrical impulses in the heart).

The October 2004 Australian Adverse Drug Reactions Bulletin, a newsletter published by the Australian drug regulatory authority, reviewed reports of abnormal heart rhythm disturbances reported with the Alzheimer’s disease drugs donepezil, rivastigmine, and galantamine. The largest number of reports was seen with donepezil and was probably due to the greater usage of this drug. For example, it is a top seller in the U.S. with over 3.2 million prescriptions dispensed in 2003. According to the Australian authorities, the majority of patients recovered after the drug was stopped or in some cases after a reduction in dose. Many patients taking these drugs were hospitalized and in four cases a pacemaker was required to control their heart rhythm. Four elderly patients died from suspected heart attacks.

The table above summarizes the types of heart rhythm disturbances reported to the Australian authorities with the Alzheimer’s disease drugs and other effects, like syncope (loss of consciousness resulting from insufficient blood flow to the brain) that may be symptomatic of a heart rhythm disturbance.

What You Can Do

You should not use galantamine for Alzheimer’s disease. There is no evidence that it leads to substantial functional improvement or prevents the progression of the disease, and new evidence indicates that it may increase the risk of death.