Sunday, May 23, 2010

Drugs to Avoid in Women Taking Tamoxifen

Tamoxifen is metabolized mainly by CYP2C9, 2D6 and 3A4 enzymes. Tamoxifen is actually a "pro-drug" and the rate-limiting enzyme is CYP2D6, which converts it to its active metabolite endoxifen. Therefore, drugs that are strong inhibitors of CYP2D6 can interfere with its metabolism and result in decreased efficacy of tamoxifen.

Moderate to potent CYP2D6 inhibitors (AVOID):
  • antidepressants* that act as selective serotonin reuptake inhibitors (SSRIs) or selective noradrenergic reuptake inhibitors (SNRIs) — paroxetine, fluoxetine, bupropion, and duloxetine
  • antipsychotics — thioridazine, perphenazine, and pimozide
  • cardiac drugs — quinidine and ticlopidine
  • medications for infectious disease — terfenadine and quinidine
  • miscellaneous medication — cinacalcet.
*Note: serotonin reuptake inhibitor (SSRI) antidepressants are commonly prescribed to treat hot flashes in women who take tamoxifen

Alternative drugs expected to have little inhibition: :)
  • antidepressants (SSRIs/SNRIs) — venlafaxine, desvenlafaxine, reboxetine, escitalopram, and mirtazapine
  • antipsychotics — thiothixene, clozapine, risperidone, olanzapine, ziprasidone, and quetiapine
  • cardiac drugs — diltiazem
  • medications for infectious diseases — indinavir, saquinavir, nelfinavir, delavirdine, nevirapine, and efavirenz
  • miscellaneous medication — gabapentin.

In addition to the drug classes listed above, many drugs that fall into the antihistamine category are intermediate inhibitors of CYP2D6, the authors note. Alternative options that have little inhibition include chlorpheniramine, cetrizine, and loratadine.

Also, among the histamine H2-blockers, cimetidine is an intermediate inhibitor of CYP2D6, whereas ranitidine has little inhibition and is therefore preferable.

[Source: Medscape Medical News article 5 May 2010]
[Additional reading: CYP2D6 Genotype, Antidepressant Use, and Tamoxifen Metabolism During Adjuvant Breast Cancer Treatment]


Tamoxifen is an antineoplatic agent (estrogen receptor antagonist) used usually for the treatment of breast cancer. Dose: 20-40mg/day.

Other drug-interactions-->
  • Concommitant use of warfarin is contraindicated when used for cancer risk reduction.
  • CYP2C9 & CYP3A4 inhibitors increase levels of tamoxifen, vice versa for inducers
  • Tamoxifen nhibits CYP2C8, may increase levels of CYP2C8's substrates eg. paclitaxel, amiodarone, pioglitazone, repaglinide and rosiglitazone.
  • Herb: Avoid dong quai, black cohosh, St john's wort

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