Last January, Johnson & Johnson announced that the FDA was reviewing safety data on galantamine hydrobromide (Reminyl®), a cholinesterase inhibitor that has been approved for mild to moderate Alzheimer disease (see ARF related news story). Now, that reappraisal has resulted in a voluntary relabeling of the prescription drug (see WedMD article).

The initial review and the new labeling arose from an unexpected number of deaths reported in clinical trial data. In January 2005, Johnson & Johnson reported preliminary results from two pivotal studies of approximately 2,000 patients (The GAL-INT-11 and GAL-INT-18 trials), in which 15 people taking Reminyl died, compared to only five deaths in the placebo group (see Johnson &Johnson statement).

In a March 31 letter to healthcare professionals, Ortho-McNeil Neurologics Inc., a Johnson & Johnson subsidiary, report that the drug label will now carry a precautionary note. This reflects a more thorough evaluation of the trial data. In fact, only 13 patients on Reminyl died during these trials, but there was only one death in the placebo groups. Though this discrepancy seems cause for concern, it should be noted that the number of deaths in the placebo groups was lower than expected. In addition, the numbers are probably not large enough to draw any firm conclusions about safety (see comment from AD clinician John Morris in ARF related news story) on this issue.

Reminyl has also been renamed to avoid confusion with the similarly sounding Amaryl,® which is used to treat diabetes. Galantamine will now be marketed as Razadyne™ (see statement on FDA website).—Tom Fagan.

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  1. While the data on mortality in these investigative studies with galantamine in mild cognitive impairment (MCI) obviously give rise to the usual extra caution for treating this older group of patients, it is necessary to put the data in the right context.

    The 2-year study on about 1,000 patients/treatment arm found one death in the placebo group and 13 deaths in the galantamine group, corresponding to a mortality rate of 0.05 percent per year/1,000 patients in the placebo group versus 0.65 percent per year/1,000 patients in the galantamine group.

    Recently, a similar study of the effects of donepezil and vitamin E versus placebo in MCI patients has been published (Petersen, 2005). This allows us to compare the death rate in placebo and treated arms of the galantamine study with the same parameters in the donepezil/vitamin E study. In the latter 3-year study, 7/253 patients died in the donepezil group, 5/257 in the vitamin E group and 5/259 in the placebo group. This corresponds to a mortality rate of 0.92% percent per year/1,000 patients in the donepezil arm, 0.64 percent per year/1,000 patients in the vitamin E group and 0.62% percent per year/1,000 patients in the placebo group.

    In summary, the mortality rate with galantamine observed in the 2-year study is very comparable to similar mortality rates in other clinical trials in the same patient population, whereas the placebo mortality rate in the galantamine trial was about tenfold lower than in similar experimental clinical conditions.

    However, as always with all AChE inhibitors, cautious clinical judgment is appropriate when treating this older patient population.

    References:

    . Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005 Jun 9;352(23) Epub 2005 Apr 13 PubMed.

References

News Citations

  1. Safety Concerns over Galantamine; Fallout from Rofecoxib Debacle Grows

External Citations

  1. WedMD article
  2. Johnson &Johnson statement
  3. March 31 letter
  4. statement

Further Reading

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