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Pilot Study Finds Low-Hyperforin St. John’s Wort Extract Does Not Interact with Oral Contraceptive

Reviewed: Will-Shahab L, Bauer S, Kunter U, Roots I, Brattström A. St. John’s wort extract (Ze 117) does not alter the pharmacokinetics of a low-dose oral contraceptive. Eur J Clin Pharmacol. 2009;65(3):287-294.

St. John’s wort (SJW, Hypericum perforatum, Clusiaceae) is widely used in the treatment of mild to moderate depression. Previous studies have demonstrated that SJW interferes with the metabolism of certain drugs when they are taken at the same time. SJW formulations can vary considerably in composition and dosage, and this variability may produce different effects on drug-metabolizing enzymes. SJW may interact with hormones found in oral contraceptives, and this interaction could diminish the effectiveness of the contraceptives. The purpose of this study was to investigate the effects of SJW extract Ze 117 (Zeller AG; Romanshorn, Switzerland)—standardized to contain a low content of hyperforin—on the pharmacokinetics of 2 hormones after the administration of oral contraceptives.

The open-label, uncontrolled pilot trial was conducted at the University Medical Centre Benjamin Franklin, Free University of Berlin, Germany. Sixteen healthy women who had taken the low-dose oral contraceptive Lovelle® (Organon; Oberschleissheim, Germany) for at least 3 months were enrolled in the trial. Lovelle contains 0.02 mg ethinylestradiol and 0.15 mg desogestrel per tablet. The women were instructed to take 1 tablet of SJW twice daily for 14 days (day 7 through day 21 of the Lovelle cycle). Each tablet contained 250 mg of Ze 117 extract, which is prepared using a 50% ethanol extraction and is standardized to 0.2% hypericin and less than 0.2% hyperforin. The daily dose of hypericin was about 1 mg and the daily dose of hyperforin was less than 1 mg.

Blood concentrations of hypericin were measured after taking Ze 117 for 7 days and 14 days to assess compliance with the tablets. Urine samples were collected before and after taking Ze 117 to assess the effects of Ze 117 on the cytochrome P450 drug-metabolizing enzymes (CYP2D6, CYP2C19, and CYP3A4). The subjects were hospitalized for a 24-hour period before starting Ze 117 and after taking Ze 117 for 14 days. Blood samples were collected from an intravenous catheter 17 times over the 24-hour period to assess the pharmacokinetics of ethinylestradiol and 3-ketodesogestrel.

The average age of the subjects was 31.8 years, and all 16 subjects completed the study. No adverse events were reported, and none of the women experienced spotting or break-through bleeding during the trial. Blood concentrations of hypericin revealed that all subjects were compliant with the Ze 117 tablets. The ethinylestradiol and 3-ketodesogestrel pharmacokinetic parameters of area under the concentration time curve, maximum peak concentration, and peak time did not change significantly after 14 days of Ze 117 treatment, nor did Ze 117 influence the activity of the 3 cytochrome P450 enzymes. This is consistent with other studies of Ze 117 suggesting a lack of interaction with the immunosuppressant drug cyclosporin, the anti-anxiety drug alprazolam (Xanax®, Pfizer), or the cardiac medication digoxin.

The authors conclude that SJW extracts with reduced hyperforin content, such as Ze 117, are less likely to interact with the hormones in oral contraceptives. The authors explain that previous studies suggesting an interaction between SJW and oral contraceptives used higher doses and methanolic extracts, leading to much higher intakes of hypericin and hyperforin. The authors suggest that results of this and other studies demonstrate that the known drug interactions of SJW are primarily due to the level of hyperforin content, and that use of reduced-hyperforin preparations may lower the risk of serious herb-drug interactions. Clinical trials have shown that Ze 117 appears to be as efficacious as other preparations of SJW at the same dose of 500mg/day, and some literature suggests that hyperforin is not necessary for the antidepressant effect of this herb. It is unclear if doses of Ze 117 larger than 500 mg per day might induce interactions with oral contraceptives and other drugs.

—Heather S. Oliff, PhD