PFPC Daily - January 4, 2004

The press release below reports on recent findings that Prozac and
Paxil may significanty alter levels of Tamoxifen in the body.
Tomoxifen is a drug commonly given against breast cancer. Effexor, a
non-fluorinated anti-depressant, showed the least inhibitatory
activity.

Interestingly, an article published in Fluoride (2003) by Czerny et
al. showed that tamoxifen and sodium fluoride had additive toxic
effects in rats. The researchers further showed that when tamoxifen
was administered together with fluoride, there was a decrease in
cytochrome P-450 content in the liver.(Tamoxifen is metabolized in
the liver though c. P-450.)

SEE:

Czerny B, Juzyszyn A, Mysliwiec Z, Put A - "Effect of tamoxifen and
NaF on serum and hepatic enzymes" Fluoride 36(3):170-176 (2003)
http://www.fluoride-journal.com/03-36-3/363-170.pdf

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"Antidepressants May Alter Levels of Tamoxifen in the Body"

Effect Greatest in Women with Certain Gene Variations

American Cancer Society - January 4, 2005

Some antidepressant medications may change the way the body processes
tamoxifen, researchers report in this week's issue of the Journal of
Clinical Oncology (Vol. 97, No. 1:30-39). The effect may be
especially great in women with a particular type of gene variation.

The researchers caution that it's too soon to know whether these
interactions make tamoxifen less effective against breast cancer. And
it's too soon to recommend genetic testing for the mutations
identified in the study.

But women taking both tamoxifen and an antidepressant may want to
talk with their doctor about switching to an antidepressant that has
less of an effect on tamoxifen, said lead researcher David Flockhart,
MD, PhD, of Indiana University School of Medicine.

"Women should not go off of tamoxifen or off antidepressants because
of these findings," he said. "But with what we know now, we think
[switching antidepressants] is a reasonable suggestion."
Effexor Had Least Effect

Flockhart and his colleagues studied 80 women who had just started
taking tamoxifen after a diagnosis of breast cancer. Twenty-three of
the women (29%) were also taking one of the following
antidepressants: paroxetine (Paxil), sertraline (Zoloft), citalopram
(Celexa), fluoxetine (Prozac), or venlafaxine (Effexor). These drugs,
known as selective serotonin reuptake inhibitors (SSRIs), are used to
treat depression and can also help relieve the hot flashes that are a
common side effect of tamoxifen therapy.

The researchers measured the level of tamoxifen and its byproducts in
the women's blood after 4 months on the breast cancer drug.

The women using antidepressants were found to have lower blood levels
of endoxifen, a tumor-fighting substance created when tamoxifen
breaks down in the body. Paxil and Prozac lowered endoxifen levels
the most, while Effexor lowered them least.

The researchers also compared endoxifen levels in women with
different types of genetic variations. Women with specific variations
in the CYP2D6 gene also had less endoxifen in their blood than other
women. And the women with variations who also took antidepressants
had even lower levels -- up to 58% lower.

Around 7% of whites and Hispanics, and around 3% of Asians and
African-Americans, carry these gene variations, Flockhart said.
A Step Toward Customized Treatment

The researchers don't know if lower levels of endoxifen mean the
tamoxifen isn't working as well as it might.

"We need more data related to outcomes -- [breast cancer] recurrence,
disease-free survival, and so forth," Flockhart said.

For that reason, he and his colleagues do not yet recommend genetic
testing for these variations.

For now, learning about the difference in genes is more of a step
along the road to customized treatment, Flockhart explained. Doctors
hope to use the information to develop tests that can help them
predict which drug -- tamoxifen, an aromatase inhibitor, or Faslodex,
for instance -- is likely to work best for a particular woman.

But switching to Effexor is a much easier precaution, Flockhart said,
as long as a woman consults her doctor first.

"There are some women who derive important, almost life-saving,
benefit from specific antidepressants," he said, "and we don't want
women who have been successfully treated for a long period of time to
compromise that treatment."

SOURCE:
http://tinyurl.com/4cmfs

SEE ALSO:
http://tinyurl.com/5yzl4