Can a patient taking atorvastatin, diltiazem extended‑release, sildenafil, apixaban (Eliquis), lisinopril, doxycycline, topical ciclopirox, topical clotrimazole, epinephrine auto‑injector, omeprazole (Prilosec), multivitamins, fish oil, and probiotics safely start St. John’s wort (Hypericum perforatum)?

No, This Patient Should Not Take St. John's Wort

This patient is taking multiple medications that have clinically significant, potentially dangerous interactions with St. John's wort, most critically apixaban (Eliquis), atorvastatin, diltiazem, and sildenafil—making St. John's wort absolutely contraindicated. 1, 2

Critical Drug Interactions in This Patient

Apixaban (Eliquis) – Life-Threatening Interaction

• St. John's wort is a potent inducer of CYP3A4 and P-glycoprotein, which will significantly decrease apixaban plasma levels, potentially leading to loss of anticoagulation and thromboembolic events including stroke. 1
• The European Heart Rhythm Association explicitly states that concomitant use of St. John's wort with NOACs (including apixaban) is not recommended due to the relevant decrease in NOAC levels. 1
• This interaction persists for several weeks after discontinuing St. John's wort due to the herb's long-lasting enzymatic effects. 2

Atorvastatin – Reduced Efficacy

• St. John's wort significantly reduces statin levels (atorvastatin, lovastatin, simvastatin) through CYP3A4 induction, potentially leading to inadequate lipid control and increased cardiovascular risk. 2, 3
• The American Heart Association notes that statins may have their levels significantly reduced due to CYP3A4 induction by St. John's wort. 2

Diltiazem – Cardiovascular Risk

• Diltiazem is a CYP3A4 substrate, and St. John's wort will reduce its plasma concentrations, potentially causing loss of blood pressure and heart rate control. 2
• This could lead to inadequate management of the patient's cardiovascular condition. 2

Sildenafil – Reduced Therapeutic Effect

• Sildenafil requires caution due to CYP3A4 metabolism, and St. John's wort will decrease drug levels, reducing therapeutic efficacy. 4

Additional Concerning Interactions

Omeprazole (Prilosec)

• St. John's wort has been shown to interact with proton pump inhibitors including omeprazole, potentially reducing its effectiveness. 3

Lisinopril – Indirect Consideration

• While lisinopril itself is not metabolized by CYP3A4, the overall cardiovascular medication regimen requires stable drug levels, which St. John's wort would disrupt. 2

Mechanism of Interaction

• St. John's wort induces CYP3A4 enzyme system and P-glycoprotein drug transporter in a clinically relevant manner, thereby reducing efficacy of co-medications. 5, 6
• The constituent hyperforin is responsible for CYP3A4 induction via activation of nuclear steroid/pregnane and xenobiotic receptor (SXR/PXR). 5
• These effects are irreversible and long-lasting, so timing separation of doses does not solve the problem. 4

Clinical Pitfalls to Avoid

• Do not assume that taking St. John's wort at a different time of day from other medications will prevent interactions—the enzymatic induction is continuous and persistent. 4
• Patients frequently consume St. John's wort unknowingly in dietary supplements marketed as "mood support," "stress relief," or menopause symptom relief products without prominent labeling. 7
• Between 31% to 68% of patients using supplements don't discuss this with physicians, highlighting the need for direct questioning about all herbal products. 7

Alternative Management

• For depression or mood symptoms, consider FDA-approved selective serotonin reuptake inhibitors (SSRIs) or cognitive-behavioral therapy instead of St. John's wort. 2
• If the patient is already taking St. John's wort, it must be discontinued immediately, and anticoagulation monitoring should be intensified for at least 2-4 weeks after discontinuation. 2
• The American Society of Anesthesiologists recommends discontinuing St. John's wort at least 2 weeks before any procedure due to multiple drug interactions. 2, 7

Monitoring Requirements if Inadvertently Combined

• If St. John's wort has been taken concurrently, immediately check apixaban levels (if available at specialized centers), monitor for signs of thromboembolism, and consider temporary bridging anticoagulation. 1
• Monitor lipid panel more frequently to assess atorvastatin efficacy. 2
• Monitor blood pressure and heart rate closely for diltiazem effectiveness. 2
• Drugs with a narrow therapeutic index should be monitored more closely when St. John's wort is added, discontinued, or the dosage is changed. 5