Black Pepper - Prometrium (Progesterone (prescription drug)) Interaction
Herbal: Black Pepper
Also Known As: Piper nigrum, Black Peppercorn, Extrait de Poivre, Grain de Poivre, Hu Jiao, Kali Mirchi, Kosho, Marich, Maricha, Miris, Peber, Peper, Pepe, Peppar, Pepper, Pepper Extract, Peppercorn, Pfeffer, Pimenta, Pimienta, Pimienta Negra, Pipar, Piper, Piperine, Pippuri, Poivre
Drug: Progesterone (prescription drug)
Brand names:
Prometrium, Endometrin, Utrogestan

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
May 18, 2025
Interaction Details
Progesterone (prescription drug) is classified as belonging to the following category: Cytochrome P450 3A4 (Cyp3A4) Substrates
Theoretically, black pepper might increase levels of drugs metabolized by CYP3A4.
In vitro research shows that piperine, a constituent of black pepper, as well as the pepper fruit seem to inhibit CYP3A4. This has not been reported in humans.
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
- Bhardwaj RK, Glaeser H, Becquemont L, et al. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002;302:645-50.
- Usia, T., Iwata, H., Hiratsuka, A., Watabe, T., Kadota, S., and Tezuka, Y. CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants. Phytomedicine. 2006;13(1-2):67-73.
Black Pepper Overview

Progesterone (prescription drug) Overview
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Progesterone is used as a part of hormone replacement therapy in women who have passed menopause (the change of life) and have not had a hysterectomy (surgery to remove the uterus). Hormone replacement therapy usually includes estrogen, which is used to treat symptoms of menopause and reduce the risk of developing certain diseases. However, estrogen can also cause abnormal thickening of the lining of the uterus and increase the risk of developing uterine cancer. Progesterone helps to prevent this thickening and decreases the risk of developing uterine cancer. Progesterone is also used to bring on menstruation (period) in women of childbearing age who have had normal periods and then stopped menstruating. Progesterone is in a class of medications called progestins (female hormones). It works as part of hormone replacement therapy by decreasing the amount of estrogen in the uterus. It works to bring on menstruation by replacing the natural progesterone that some women are missing.
Black Pepper - More Interactions
Black Pepper interacts with 950 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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Drug descriptions are provided by MedlinePlus.