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Breast cancer is the most common cancer in women, and tamoxifen (NOLVADEX) is used commonly in the treatment and sometimes in the prevention of this disease. In 2007, 1.7 million prescriptions were filled for tamoxifen. However, recent evidence suggests that certain other drugs can reduce the anti-cancer effects of tamoxifen, potentially increasing cancer recurrence and reducing survival. Certain antidepressants, such as fluoxetine (PROZAC), paroxetine (PAXIL) and bupropion (WELLBUTRIN),...
Breast cancer is the most common cancer in women, and tamoxifen (NOLVADEX) is used commonly in the treatment and sometimes in the prevention of this disease. In 2007, 1.7 million prescriptions were filled for tamoxifen. However, recent evidence suggests that certain other drugs can reduce the anti-cancer effects of tamoxifen, potentially increasing cancer recurrence and reducing survival. Certain antidepressants, such as fluoxetine (PROZAC), paroxetine (PAXIL) and bupropion (WELLBUTRIN), could reduce the effect of tamoxifen because they are among the most potent CYP2D6 inhibitors.
Why are drug interactions a problem for tamoxifen?
Tamoxifen is a "prodrug," which means that the drug molecules in the medication itself are inactive; they must be transformed by the body to the active molecules that actually produce the beneficial effects. The enzyme that activates tamoxifen is CYP2D6.
Some people may have a genetic CYP2D6 deficiency that may interfere with the effectiveness of tamoxifen (see Box).
What drugs may reduce the effect of tamoxifen?
Among the most important CYP2D6 inhibitors are antidepressants, because patients with breast cancer may be taking these medications. Fluoxetine, paroxetine and bupropion are at the top of the list of drugs to watch out for. Other antidepressants are weaker inhibitors of CYP2D6, such as sertraline (ZOLOFT), escitalopram (LEXAPRO) and citalopram (CELEXA), while still others have little or no effect on CYP2D6, such as venlafaxine (EFFEXOR).
Although the problem of using antidepressants with tamoxifen has received the most attention in the medical literature, keep in mind that many other medications also inhibit CYP2D6: heart drugs, antifungal agents, analgesics and even antihistamines such as diphenhydramine (BENADRYL, DYTAN SUSPENSION, DYTAN-D SUSPENSION, SOMINEX FORMULA; see Table for more).
Note that the accompanying Table includes only those drugs with substantial inhibition of CYP2D6. Many other drugs are moderate to weak in-hibitors of CYP2D6, and, depending on the dose of the drug, they could potentially inhibit the conversion of tamoxifen to its active forms.
What You Can Do
If you are a candidate for tamoxifen therapy to treat breast cancer, talk with your physician about the CYP2D6 issue. If CYP2D6 testing is needed but is not covered by your insurance you may consider trying to pay for it out of pocket.
If you are a candidate for tamoxifen (or are already taking tamoxifen), avoid taking any of the CYP2D6 inhibitors listed in the Table. Also, check all of the other medications you take to make sure that they are not CYP2D6 inhibitors. Most pharmacists have sources of information that provide information on which drugs affect which drug metabolizing enzymes.
If you are already taking tamoxifen and the response is inadequate, discuss with your physician whether you may be genetically deficient in CYP2D6 or may be taking drugs that are CYP2D6 inhibitors.
Genetic deficiency of CYP2D6 and tamoxifenPeople with no CYP2D6 activity are called "poor metabolizers," meaning that they have inherited a nonfunctional gene from each parent. Complete CYP2D6 deficiency occurs in about 6 to 10 percent of Caucasians, 3 to 6 percent of Mexican Americans, 2 to 5 percent of African Americans, and about 1 percent of Asians. Several studies have looked at whether poor metabolizers for CYP2D6 who receive tamoxifen have lower survival rates than people with normal CYP2D6 function who receive the drug. Some studies ("positive studies") showed exactly what one would expect — tamoxifen does not work as well in people who do not have normal amounts of CYP2D6. Other "negative" studies did not find this correlation, but none of these studies considered whether or not the patients received drugs that inhibit CYP2D6. In other words, these studies could have been "negative" for a genetic effect simply because so many of the women were using drugs that inhibited the CYP2D6 enzyme that it swamped out the ability to detect the role of the genetic effect. This is a serious flaw, and at this point it would be prudent, if possible, to take into account both genetic CYP2D6 differences and drugs that may inhibit CYP2D6 in every patient who is considered for tamoxifen treatment. |
Table. Drugs That Inhibit CYP2D6
|
Drug Name |
Brand Name |
|---|---|
|
Amiodarone |
CORDARONE, PACERONE *** |
|
Bupropion |
WELLBUTRIN** |
|
Chloroquine |
ARALEN |
|
Chlorpheniramine |
ALERMINE, CHLOR-TRIMETON |
|
Chlorpromazine |
THORAZINE** |
|
Cinacalcet |
SENSIPAR |
|
Diphenhydramine |
BENADRYL, DYTAN SUSPENSION, DYTAN-D SUSPENSION, SOMINEX FORMULA |
|
Duloxetine |
CYMBALTA |
|
Fluoxetine |
PROZAC, SERAFEM** |
|
Haloperidol |
HALDOL** |
|
Halofantrine |
HALFAN |
|
Imatinib |
GLEEVEC |
|
Paroxetine |
PAXIL, PEXEVA** |
|
Perphenazine |
TRILAFON |
|
Propafenone |
RYTHMOL |
|
Propoxyphene |
DARVON, DARVON-N* |
|
Quinidine |
DURAQUIN, QUINAGLUTE DURA-TABS, QUINIDEX** |
|
Terbinafine |
LAMISIL* |
|
Thioridazine |
MELLARIL* |
* Do Not Use in Worst Pills, Best Pills
** Limited Use in Worst Pills, Best Pills
*** Last Choice Drug in Worst Pills, Best Pills
