Tamoxifen and Letrozole Interaction

Drug interaction information between Tamoxifen and Letrozole.

Tamoxifen and Letrozole have a documented minor interaction in FDA labeling.

FDA drug labeling documents a minor-severity interaction between Tamoxifen and Letrozole. This page displays the available source-record category and label text. The category is not an individual risk estimate or medication-combination direction.

Drug A

Tamoxifen

Selective Estrogen Receptor Modulator (SERM)

Drug B

Letrozole

Aromatase Inhibitor (Off-Label Fertility)

How They Interact

Taking tamoxifen can lower the amount of letrozole in the blood by an average of 38 percent.

FDA Label Information

7 DRUG INTERACTIONS Tamoxifen Coadministration of Femara and tamoxifen 20 mg daily resulted in a reduction of letrozole plasma levels of 38% on average (Study P015). Clinical experience in the second-line breast cancer trials (AR/BC2 and AR/BC3) indicates that the therapeutic effect of Femara therapy is not impaired if Femara is administered immediately after tamoxifen.

Frequently Asked Questions

What SPL severity band is on file for Tamoxifen + Letrozole (Fertility)?

Compiled FDA labeling labels this pair minor. That is a source-record field, not an individual medication-combination decision.

Which drug in this pair has the larger labeled-interaction portfolio?

Tamoxifen has 10 labeled pairs on file vs Letrozole's 4. In the minor band specifically: Tamoxifen has 7 (also Bupropion, Desvenlafaxine, Levothyroxine, Liothyronine); Letrozole has 4 (also Warfarin, Cimetidine, Letrozole).

What mechanism field is on file for Tamoxifen and Letrozole (Fertility)?

Taking tamoxifen can lower the amount of letrozole in the blood by an average of 38 percent.

Tamoxifen carries more major-labeled pairs than Letrozole

SPL source-record counts only. This page's band is minor · classes on file: Tamoxifen (Selective Estrogen Receptor Modulator (SERM)); Letrozole (Aromatase Inhibitor (Off-Label Fertility)).

Tamoxifen has 2 major-labeled pairs vs Letrozole's 0. This page itself is in the minor band, not the major band.

Tamoxifen

2 major · 1 moderate · 7 minor · 10 total

Letrozole

0 major · 0 moderate · 4 minor · 4 total

Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. This registry does not provide individual medication-combination directions.