FDA to Cite Interaction Risk of Antidepressants & Tamoxifen

[Daniel E.]

FDA to Cite Interaction Risk of Antidepressants, Tamoxifen
by Jennifer Corbett Dooren
Wall Street Journal (WSJ.com)
June 2, 2009

The Food and Drug Administration is planning to warn doctors about an interaction between the widely used breast-cancer drug tamoxifen and certain antidepressants after a study showed women on both drugs were more than twice as likely to see their cancer return.

The study involved about 1,300 women and was released this past weekend at the American Society of Clinical Oncology's annual meeting in Orlando, Fla. Researchers found that women who were taking antidepressants like Paxil, Prozac and Zoloft along with tamoxifen for at least one year had a breast-cancer recurrence rate of 16% -- compared with a recurrence rate of 7.5% for women not taking the drugs.

However, not all antidepressants strongly affect tamoxifen's usefulness, and the study showed that women on drugs like Celexa, Lexapro and Luvox didn't have a statistically higher rate of cancer recurrence.

Tamoxifen is an old but widely used treatment to prevent the return of breast cancers whose tumors were estrogen-dependent. This is one of the most common types of breast cancer.

The new study, which was led by researchers at Medco Health Solutions Inc., backs up prior laboratory studies that found drugs that interfere with an enzyme known as CYP2D6 also block the activation of tamoxifen. Antidepressants like Paxil and Prozac, which are also sold generically, are considered moderate-to-potent CYP2D6 inhibitors, while other commonly used antidepressants are considered weak CYP2D6 inhibitors.

Larry Lesko, director of the FDA's Office of Clinical Pharmacology, said now that the agency has evidence about clinical outcomes as a result of the drug interaction, the FDA is likely to add that information to tamoxifen's label. Placing information on FDA-approved drug labels is the main vehicle the agency uses to communicate with health-care professionals.

Julie Gralow, an associate professor in the oncology division of the University of Washington School, said she'd already been prescribing Wyeth's Effexor, which also doesn't appear to interfere with tamoxifen, primarily for the treatment of hot flashes that are a side effect of tamoxifen.

"This is what you'd predict," she said of the study, which also involved researchers at Indiana University School of Medicine.

"If we lower the effectiveness of tamoxifen, you'd get worse outcomes." Dr. Gralow said many doctors in the U.S. also prescribe aromatase inhibitors rather than tamoxifen to block estrogen in post-menopausal women to prevent breast cancer from returning, which also avoids the tamoxifen-antidepressant interaction.

Still, Robert Epstein, Medco's chief medical officer, said more than 500,000 women in the U.S. are taking tamoxifen and about 30% of those women are also prescribed antidepressants. He said Medco has been notifying doctors when it sees patients in its pharmacy-benefits database being given tamoxifen and an CYP2D6 inhibitor drug like tamoxifen, and found that some breast-cancer doctors weren't aware that another doctor had prescribed an antidepressant.

 

[Daniel E.]

Re: FDA to Cite Interaction Risk of Antidepressants, Tamoxifen

Tamoxifen and Antidepressants Don't Mix
USNews.com, On Women Health Blog
by Deborah Kotz
June 2, 2009

Breast cancer patients have it tough. Besides contending with the disease and its often harrowing treatments, they're also told to avoid certain medications—like hormone therapy for menopausal symptoms—because it could raise their likelihood of having a recurrence. In fact, many breast cancer patients are prescribed antidepressants to combat the hot flashes and mood swings of menopause. Or they're taking the drugs to cope with chronic depression. Unfortunately, these very same mood-lifters also appear to negate the effects of tamoxifen, a lifesaving breast cancer therapy given to women who have tumors that respond to estrogen.

Research presented Sunday at the American Society of Clinical Oncology finds that breast cancer patients taking antidepressants along with tamoxifen were more than twice as likely to have their tumors return after two years, compared with those who were taking tamoxifen alone. The Food and Drug Administration is poised to add a warning to tamoxifen's label alerting doctors to the drug's interaction with antidepressants, according to the Wall Street Journal.

But doctors who are up to date on the latest medical research should already know about this interaction. As early as six years ago, research indicated that tamoxifen was rendered ineffective by antidepressants in the family of selective serotonin reuptake inhibitors (Paxil, Prozac, Celexa, Lexapro, Zoloft). In 2005, oncology researcher Frankie Ann Holmes lamented in a paper published in the Journal of Oncology Practice that doctors still were prescribing Prozac with tamoxifen. "Conversations with colleagues," Holmes wrote, "indicated that this more sophisticated understanding of the peculiar pharmacokinetics of tamoxifen may not have been incorporated into clinical patient care, especially when patients receive medications from other non-oncology physicians."

I'm just wondering what's taken the FDA so long. Why wasn't the tamoxifen label changed years ago?

Breast cancer patients who are on tamoxifen have several options. Postmenopausal women can switch to an aromatase inhibitor, which has the same estrogen-blocking benefits as tamoxifen but doesn't interact with antidepressants. (Aromatase inhibitors aren't approved for use in premenopausal patients.) Women of any age can also switch to a non-SSRI antidepressant like Effexor. Those who aren't putting themselves at risk for a relapse of depression—check with your doctor before stopping an antidepressant—can also try to lift their mood using lifestyle measures like exercise, adequate sunlight, and fish oil. Here are some natural ways to treat depression and what to take for tamoxifen-triggered hot flashes.