What medications interact with St. John's Wort (Hypericum perforatum)?

Medications That Interact with St. John's Wort

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

Major Drug Interactions with St. John's Wort

Anticoagulants

• St. John's wort can decrease the effectiveness of warfarin by inducing CYP3A4, potentially leading to subtherapeutic anticoagulation and increased risk of thrombotic events 2
• Patients taking warfarin should avoid St. John's wort due to the risk of reduced anticoagulant effect 1

Immunosuppressants

• Cyclosporine levels can be significantly decreased when taken with St. John's wort, potentially leading to organ rejection in transplant patients 3
• The FDA label for cyclosporine specifically lists St. John's wort as a drug that decreases cyclosporine concentrations 3

Oral Contraceptives

• St. John's wort can reduce the effectiveness of oral contraceptives, potentially leading to unintended pregnancy 1, 4
• Women taking hormonal contraceptives containing ethinyl estradiol/norethindrone or ethinyl estradiol/drospirenone should avoid St. John's wort 1

Antidepressants

• Concomitant use with selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors (MAOIs) is contraindicated due to risk of serotonin syndrome 1
• St. John's wort should be discontinued at least 2 weeks before surgery due to potential serotonergic effects 1

Cardiovascular Medications

• Reduces plasma concentrations of drugs like amiodarone, verapamil, and digoxin 1
• Ivabradine is specifically contraindicated with St. John's wort due to reduced effectiveness 1

Antiretrovirals

• St. John's wort can significantly decrease the plasma concentration of HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors 1, 4
• Patients on antiretroviral therapy should avoid St. John's wort to prevent treatment failure 1

Anticancer Drugs

• Imatinib plasma concentrations may be decreased when taken with St. John's wort, potentially requiring dose adjustments 1
• The National Comprehensive Cancer Network specifically warns about this interaction 1

Anticonvulsants

• May decrease levels of anticonvulsants like carbamazepine, phenytoin, and phenobarbital 1, 2

Direct-Acting Oral Anticoagulants (DOACs)

• St. John's wort may significantly decrease the effectiveness of dabigatran by inducing P-glycoprotein 1
• Product information for dabigatran advises caution with P-gp inducers like St. John's wort 1

Clinical Implications and Management

Preoperative Considerations

• St. John's wort should be discontinued at least 2 weeks before surgery due to multiple potential drug interactions and effects on serotonin levels 1
• This is particularly important for patients who will receive medications during the perioperative period 1

Monitoring Recommendations

• If a patient is taking St. John's wort with medications known to interact, more frequent monitoring of drug levels or therapeutic effects is recommended 1, 2
• For warfarin, more frequent INR monitoring is advisable 2

Alternative Options

• For patients with depression requiring medications that interact with St. John's wort, conventional antidepressants or cognitive behavioral therapy may be more appropriate options 1
• Despite St. John's wort showing comparable efficacy to SSRIs for mild to moderate depression, the risk of drug interactions often outweighs the benefits 5, 6

Important Considerations

• St. John's wort is not regulated by the FDA, and there is no standardization of content or potency 1
• The herb contains multiple active constituents (hyperforin, hypericin) that contribute to its pharmacological effects and drug interactions 4, 7
• The induction of CYP3A4 and P-gp by St. John's wort can take 1-2 weeks to develop fully and may persist for 1-2 weeks after discontinuation 1
• Patients should always disclose use of St. John's wort to healthcare providers, particularly before starting new medications or undergoing surgical procedures 1, 2

Remember that St. John's wort's drug interactions can significantly impact morbidity and mortality, especially in patients with serious conditions requiring medications with narrow therapeutic windows 1, 3.