Raloxifene and St. John's Wort: Can You Take Them Together?

Moderate — Timing Mattersconflict
Evidence-gradedLast reviewed June 1, 2026Source: Drugs.com: St. John's Wort Interactions
Learn about each ingredient:RaloxifeneSt. John's Wort

Quick answer

Although raloxifene is cleared primarily by glucuronidation rather than CYP3A4, St. John's Wort induces P-glycoprotein and other transporters that may reduce raloxifene exposure. Drug interaction databases list a documented reduction in raloxifene serum concentration with concurrent use, potentially undermining osteoporosis treatment.

Avoid combining St. John's Wort with raloxifene (Evista). If you take raloxifene for osteoporosis prevention or breast cancer risk reduction, choose alternative options for mood support that do not induce drug-metabolizing enzymes or transporters.

What happens when you take raloxifene with st. john's wort?

Raloxifene (brand name Evista) is a selective estrogen receptor modulator (SERM) used to prevent and treat osteoporosis in postmenopausal women and to reduce the risk of invasive breast cancer in high-risk women. Unlike many drugs, raloxifene is not cleared primarily by cytochrome P450 enzymes. It undergoes extensive first-pass glucuronidation in the intestine and liver, mediated by UGT1A1, UGT1A8, UGT1A9, and UGT1A10, and is then largely excreted in bile and feces.

St. John's Wort (Hypericum perforatum) is best known as an inducer of CYP3A4, but its activation of the pregnane X receptor also induces P-glycoprotein and may modulate certain UGT enzymes. Drug interaction databases including Drugs.com list a documented interaction in which St. John's Wort reduces serum concentrations of raloxifene. The exact magnitude in humans is not as well characterized as the CYP3A4 interactions with hormonal contraceptives or statins, but the direction is consistent: less drug exposure, potentially less benefit.

Why is this important?

The whole point of raloxifene therapy is to maintain bone mineral density and reduce vertebral fracture risk in postmenopausal women, or to reduce invasive breast cancer risk in selected high-risk women. Both endpoints are silent until they fail. If raloxifene serum concentrations are reduced, the consequences (a fracture, a missed reduction in breast cancer risk) may not become apparent for years.

St. John's Wort is also worth taking seriously because women on raloxifene are often perimenopausal or postmenopausal, an age group with a relatively high prevalence of low mood, sleep disturbance, and hot flashes, the very symptoms St. John's Wort is marketed to relieve. The temptation to combine these products is real.

What should you do?

Choose one or the other, and lean toward keeping raloxifene if you are taking it for a serious clinical indication.

  • Do not start St. John's Wort while taking raloxifene without first discussing it with your prescriber.
  • If you are already taking St. John's Wort and your doctor wants to start raloxifene, plan to stop the herb at least two to four weeks before initiating raloxifene to allow CYP3A4, P-glycoprotein, and UGT activity to return to baseline.
  • If you take raloxifene specifically for breast cancer risk reduction, the case for avoiding any herb that could lower drug exposure is strong, even if the magnitude is not fully quantified.
  • For mood symptoms in perimenopausal or postmenopausal women, ask your clinician about prescription antidepressants (SSRIs and SNRIs) that do not lower raloxifene exposure and may also help with hot flashes.
  • For hot flashes specifically, consider cognitive behavioral therapy, mindfulness-based programs, gabapentin, or low-dose paroxetine (Brisdelle), which is FDA-approved for vasomotor symptoms.

Which specific products are affected?

The interaction applies to raloxifene under the brand name Evista and to generic raloxifene 60 mg tablets. The same concern broadly extends to other SERMs (tamoxifen, bazedoxifene), although tamoxifen has its own distinct interactions because it relies on CYP2D6 and CYP3A4 activation to its active metabolite endoxifen, where St. John's Wort can have complex effects.

St. John's Wort itself appears as standardized extracts (commonly 300 mg dosed three times daily, standardized to 0.3 percent hypericin or 3 to 5 percent hyperforin) and is the main ingredient in mood support blends and some menopause formulas. Read every supplement label, including products marketed as "natural antidepressants" or "mood balance" formulas.

Note: not every "herbal" product reduces raloxifene exposure. Black cohosh, for example, does not appear to be a strong CYP3A4 or P-glycoprotein inducer based on current evidence, although it has its own safety considerations including rare reports of hepatotoxicity. Discuss any planned addition with your prescriber.

The bottom line

Drug interaction databases list a documented reduction in raloxifene serum concentration with St. John's Wort. Because raloxifene is taken to prevent fractures and reduce breast cancer risk (both silent endpoints), even a modest reduction in drug exposure is undesirable. Avoid the combination. If you need help with mood or hot flashes, work with your clinician on options that do not induce drug-metabolizing enzymes or transporters.

References

Primary evidence for this article. Always consult your healthcare provider for personal medical advice.

Drugs.com: St. John's Wort Interactions ↗

Reviewed June 1, 2026. How we grade evidence →

Related Topics

raloxifeneevistast johns wortsermosteoporosiscyp3a4p-glycoproteinherbal interaction

Related Interactions

Other interactions you should know about

Verapamil + St. John's Wort

high

St. John's wort is a potent inducer of intestinal CYP3A4 and P-glycoprotein. In a controlled study, two weeks of St. John's wort reduced the AUC of R- and S-verapamil by roughly 78-80%, dramatically lowering systemic drug exposure and likely therapeutic effect.

Digoxin + St. John's Wort

high

St. John's wort induces intestinal P-glycoprotein, increasing efflux of digoxin and reducing its absorption. Controlled studies show digoxin AUC falls roughly 25% and peak concentrations around 30-36% after two weeks of St. John's wort, potentially producing therapeutic failure in rate control or heart failure management.

Apixaban + St. John's Wort

high

St. John's wort strongly induces both CYP3A4 (apixaban's primary metabolizing enzyme) and P-glycoprotein (its efflux transporter). Co-use accelerates apixaban metabolism and clearance, lowering plasma concentrations and increasing the risk of stroke or thromboembolism.

Simvastatin + St. John's Wort

high

St. John's wort induces intestinal and hepatic CYP3A4 and P-glycoprotein, sharply increasing simvastatin's first-pass metabolism. In a crossover study of healthy adults, the AUC of active simvastatin hydroxy acid was cut roughly in half (to about 48% of placebo).

Dabigatran + St. John's Wort

high

St. John's wort is a potent inducer of P-glycoprotein (P-gp), the efflux transporter responsible for dabigatran disposition. Co-administration increases dabigatran efflux and reduces plasma concentrations, potentially leading to subtherapeutic anticoagulation and increased risk of stroke or thrombosis.

Digoxin + Hawthorn

moderate

Hawthorn (Crataegus) has digoxin-like positive inotropic activity, may modulate P-glycoprotein efflux, and can interfere with serum digoxin immunoassays. Concurrent use raises the risk of additive cardiac effects and erroneous digoxin level readings even though formal pharmacokinetic studies show little change in digoxin AUC.

Disclaimer: This article is for informational purposes only and is not a substitute for professional medical advice. Always consult your healthcare provider before making changes to your supplement or medication routine. Pilora does not diagnose, treat, cure, or prevent any disease.

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