What is the duration St. John's wort (Hypericum perforatum) remains in the system after discontinuation?

How Long Does St. John's Wort Stay in Your System After Discontinuing

St. John's wort (Hypericum perforatum) should be discontinued at least 2 weeks before surgery or when stopping use due to its long-acting constituents like hypericin and its effects on drug metabolism through cytochrome P450 induction. 1

Pharmacokinetics and Elimination

St. John's wort contains multiple active constituents with different half-lives and elimination rates:

• Hypericin: One of the primary active constituents with a longer half-life
• Hyperforin: Another major active constituent responsible for many of the antidepressant effects
• Flavonoids and other compounds: Additional bioactive components

The elimination of St. John's wort from the body is not determined by a single compound but rather by multiple constituents with varying pharmacokinetic profiles. The most significant concern is its effect on drug metabolism rather than the direct presence of the herb itself in the body.

Clinical Implications of St. John's Wort Discontinuation

Drug Interaction Effects

St. John's wort is a strong P-glycoprotein (P-gp) inducer that can significantly affect drug metabolism 1. This effect:

• Persists for a period after discontinuation due to the need for enzyme systems to return to baseline
• Can significantly decrease the bioavailability of P-gp substrates like dabigatran etexilate
• May reduce the effectiveness of many medications

Perioperative Considerations

According to the Society for Perioperative Assessment and Quality Improvement (SPAQI) consensus statement:

• St. John's wort should be held for 2 weeks before surgery due to its multiple constituents with long half-lives (such as hypericin)
• This washout period is necessary because of its known effect of inducing cytochrome P450 3A4 (CYP3A4), which may reduce plasma concentrations of drugs metabolized by this enzyme 1

Return to Baseline Metabolism

After discontinuation, the body requires time to:

• Restore normal enzyme activity levels
• Eliminate the active constituents from the system
• Return to baseline drug metabolism patterns

Factors Affecting Elimination Time

Several factors can influence how long St. John's wort remains active in your system:

• Duration of use: Longer-term use may require more time for enzyme systems to normalize
• Dosage: Higher doses may take longer to clear
• Individual metabolism: Variations in individual metabolic rates affect clearance
• Concurrent medications: May influence the elimination process
• Liver function: Impaired liver function may prolong the elimination

Clinical Recommendations

1. For surgical patients: Discontinue St. John's wort at least 2 weeks before any surgical procedure 1

2. For medication changes: When switching to medications with potential interactions (especially antidepressants, anticoagulants, or immunosuppressants), allow a 2-week washout period

3. For monitoring: Be aware that the effects on drug metabolism may persist for up to 2 weeks after discontinuation

4. For restarting supplements: Similar considerations to any other medication should apply when restarting St. John's wort after surgery, with particular attention to potential drug interactions 1

The 2-week discontinuation period is the standard recommendation to ensure that the herb's effects on drug metabolism have sufficiently diminished, allowing for safer medication management and reduced risk of adverse interactions.