St. John's Wort - Ortho-Prefest (Estradiol, Norgestimate) Interaction
Herbal: St. John's Wort
Also Known As: Hypericum perforatum, Amber Touch-and-Heal, Barbe de Saint-Jean, Chasse-diable, Demon Chaser, Fuga Daemonum, Hardhay, Herbe Aux Mille Vertus, Hypereikon, Hyperici Herba, Hypericum, Millepertuis, Perforate St. John's Wort, Racecourse Weed, Rosin Rose, Saynt Johannes Wort
Drug: Estradiol, Norgestimate
Brand names:
Ortho-Prefest

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
May 04, 2025
Interaction Details
Estradiol, Norgestimate is classified as belonging to the following category: Cytochrome P450 1A2 (Cyp1A2) Substrates
St. John's wort may increase the metabolism and reduce the levels of CYP1A2 substrates.
Clinical and in vitro research shows that St. John's wort induces CYP1A2, but to a lesser extent than CYP3A4.
Interaction Rating
Likelihood of Occurrence
PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists
References
- Henderson L, Yue QY, Bergquist C, et al. St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002;54:349-56..
- Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42..
- Van Strater, A. C. and Bogers, J. P. Interaction of St John's wort (Hypericum perforatum) with clozapine. Int.Clin.Psychopharmacol. 2012;27(2):121-124.
- Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022.
Interaction Details
Estradiol, Norgestimate is classified as belonging to the following category: P-Glycoprotein Substrates
St. John's wort decreases the levels and clinical effects of P-glycoprotein substrates.
St. John's wort induces P-glycoprotein. P-glycoprotein is a carrier mechanism responsible for transporting drugs and other substances across cell membranes. When P-glycoprotein is induced in the gastrointestinal (GI) tract, it can prevent the absorption of some medications. In addition, induction of p-glycoprotein can decrease entry of drugs into the central nervous system (CNS) and decrease access to other sites of action.
Interaction Rating
Likelihood of Occurrence
ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
References
- Johne A, Brockmoller J, Bauer S, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Clin Pharmacol Ther 1999;66:338-45.
- Durr D, Stieger B, Kullak-Ublick GA, et al. St. John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 2000;68:598-604.
- Hennessy M, Kelleher D, Spiers JP, et al. St Johns wort increases expression of P-glycoprotein: implications for drug interactions. Br J Clin Pharmacol 2002;53:75-82.
- Kim RB. Drugs as P-glycoprotein substrates, inhibitors, and inducers. Drug Metab Rev 2002;34:47-54.
St. John's Wort Overview

St. John's Wort - More Interactions
St. John's Wort interacts with 1115 drugs
Interaction Rating Key
These severity listings are for informational use only. Never start, stop or otherwise change your therapy before speaking with your provider.
Major | The combined use of these agents is strongly discouraged as serious side effects or other negative outcomes could occur. |
Moderate | Use cautiously under the care of a healthcare professional or avoid this combination. A significant interaction or negative outcome could occur. |
Minor | Be aware that there is a chance of an interaction. Watch for warning signs of a potential interaction. |
Unknown | No interactions have been reported or no interaction data is currently available. |
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DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.
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