Summary

St. John's wort can significantly reduce letrozole effectiveness by increasing its metabolism through CYP3A4 enzyme induction. This interaction may compromise breast cancer treatment outcomes and should be avoided in patients taking letrozole.

Introduction

Letrozole is an aromatase inhibitor primarily used to treat hormone receptor-positive breast cancer in postmenopausal women by blocking estrogen production. St. John's wort (Hypericum perforatum) is a popular herbal supplement commonly used for mild to moderate depression and mood disorders. While both may be used by cancer patients, their concurrent use poses significant therapeutic concerns due to a clinically important drug interaction.

Mechanism of Interaction

St. John's wort contains hyperforin and other compounds that act as potent inducers of the cytochrome P450 enzyme CYP3A4. Letrozole is primarily metabolized by CYP3A4 and CYP2A6 enzymes. When St. John's wort induces CYP3A4, it significantly increases the metabolism and clearance of letrozole from the body. This enhanced metabolism can reduce letrozole plasma concentrations by up to 40%, potentially compromising its therapeutic efficacy in treating hormone-sensitive breast cancer.

Risks and Symptoms

The primary risk of this interaction is reduced letrozole effectiveness, which could lead to inadequate estrogen suppression and potentially compromise breast cancer treatment outcomes. Decreased letrozole levels may result in higher estrogen levels, potentially promoting cancer cell growth in hormone receptor-positive breast cancer. This interaction is considered clinically significant and may increase the risk of cancer recurrence or progression. The onset of this interaction typically occurs within 1-2 weeks of starting St. John's wort and may persist for several weeks after discontinuation.

Management and Precautions

Patients taking letrozole should avoid St. John's wort supplementation entirely. Healthcare providers should counsel patients about this interaction and screen for herbal supplement use at each visit. If a patient is currently using both medications, St. John's wort should be discontinued immediately, and letrozole levels may need monitoring. Alternative treatments for depression or mood disorders should be considered, such as conventional antidepressants that don't interact with letrozole. Patients should be advised to consult their oncologist before starting any herbal supplements or over-the-counter medications during letrozole therapy.