Which herb can modify the activity of various cytochrome P450 (CYP) enzymes, resulting in significant interactions with many prescription medications?

St. John's Wort is the Herb That Modifies Cytochrome P450 Enzymes

St. John's wort is a potent inducer of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp), which significantly decreases plasma concentrations and effectiveness of many prescription medications, potentially leading to treatment failure and serious adverse clinical outcomes. 1

Mechanism of Action

St. John's wort acts as an enzyme inducer rather than an inhibitor, which distinguishes it from many other herbal products:

• It induces CYP3A4 and P-gp, accelerating the metabolism and elimination of substrate drugs, thereby reducing their therapeutic effectiveness 2, 1
• This contrasts with other herbs like ginkgo, ginger, ginseng, and garlic, which primarily inhibit the cytochrome P450 system, resulting in prolonged drug effects and increased blood concentrations 2

Critical Drug Interactions

Cardiovascular Medications

• Warfarin: Patients must avoid St. John's wort due to risk of reduced anticoagulant effect, potentially leading to thrombotic events 1
• Ivabradine: Specifically contraindicated with St. John's wort due to reduced effectiveness 1
• Statins: As CYP3A4 substrates (atorvastatin, lovastatin, simvastatin), their levels may be significantly reduced 2

Contraceptives and Psychiatric Medications

• Oral contraceptives: St. John's wort reduces effectiveness, potentially causing unintended pregnancy 1
• SSRIs and MAOIs: Concomitant use is contraindicated due to serotonin syndrome risk 1

Other High-Risk Interactions

• HIV medications: Significantly decreases plasma concentrations of protease inhibitors and non-nucleoside reverse transcriptase inhibitors 1
• Anticonvulsants: May decrease levels of carbamazepine, phenytoin, and phenobarbital 1
• Chemotherapy agents: Imatinib plasma concentrations may be decreased, requiring dose adjustments 1
• Immunosuppressants: Affects midazolam, cyclosporine, and tacrolimus concentrations 2

Clinical Management

Perioperative Considerations

• Discontinue St. John's wort at least 2 weeks before surgery due to multiple potential drug interactions and effects on serotonin levels 1
• This timeframe allows for washout of the enzyme induction effects 1

Monitoring Requirements

• If a patient is taking St. John's wort with interacting medications, implement more frequent monitoring of drug levels or therapeutic effects 1
• Always obtain a complete herbal supplement history, as patients often fail to disclose use unless specifically asked 2

Important Caveats

Regulatory Issues

• St. John's wort is not FDA-regulated, with no standardization of content or potency 1
• Product variability means the degree of enzyme induction may differ between formulations 1

Documentation Requirements

• Patients must disclose St. John's wort use to all healthcare providers, particularly before starting new medications or undergoing surgical procedures 1
• Include specific queries about herbal medicines in the medication history, as this is vital for safe patient care 2

Comparison to Other Herbs

While St. John's wort is the most clinically significant CYP450 modifier, other herbs also affect this system but through different mechanisms. Grapefruit juice, for example, inhibits intestinal CYP3A4, increasing drug bioavailability rather than decreasing it 2. This distinction is critical for predicting the direction of drug interactions.