Grapefruit - Progesterone Interaction

Interaction Details

Progesterone is classified as belonging to the following category: Cytochrome P450 3A4 (Cyp3A4) Substrates

Grapefruit juice can increase levels of drugs metabolized by CYP3A4.
Clinical research shows that grapefruit juice can inhibit CYP3A4 metabolism of drugs, causing increased drug levels and potentially increasing the risk of adverse effects. When taken orally, effects of grapefruit juice on CYP3A4 levels appear to last at least 48 hours. Grapefruit's ability to inhibit CYP3A4 has even been harnessed to intentionally increase levels of venetoclax, which is metabolized by CYP3A4, in an elderly patient with acute myeloid leukemia who could not afford full dose venetoclax. The lower dose of venetoclax in combination with grapefruit juice resulted in serum levels of venetoclax in the therapeutic reference range of full dose venetoclax and positive treatment outcomes for the patient.
Professional consensus recommends the consideration of patient age, existing medical conditions, additional medications, and the potential for additive adverse effects when evaluating the risks of concomitant use of grapefruit juice with any medication metabolized by CYP3A4. While all patients are at risk for interactions with grapefruit juice consumption, patients older than 70 years of age and those taking multiple medications are at the greatest risk for a serious or fatal interaction with grapefruit juice.

Interaction Rating

Likelihood of Occurrence

Well-controlled human studies have demonstrated the likely existence of this interaction

References

• Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin. Clin Pharmacol Ther 1999;66:118-27.
• Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice-simvastatin interaction: effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors. Clin Pharmacol Ther 1998;64:477-83.
• Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, et al. Effects of grapefruit juice on the pharmacokinetics of sildenafil. Clin Pharmacol Ther 2002;71:21-9.
• Fuhr U, Muller-Peltzer H, Kern R, et al. Effects of grapefruit juice and smoking on verapamil concentrations in steady state. Eur J Clin Pharmacol 2002;58:45-53.
• Kanazawa S, Ohkubo T, Sugawara K. The effects of grapefruit juice on the pharmacokinetics of erythromycin. Eur J Clin Pharmacol 2001;56:799-803.
• Charbit, B., Becquemont, L., Lepere, B., Peytavin, G., and Funck-Brentano, C. Pharmacokinetic and pharmacodynamic interaction between grapefruit juice and halofantrine. Clin Pharmacol Ther 2002;72(5):514-523.
• Tanaka S, Uchida S, Miyakawa S, Inui N, Takeuchi K, Watanabe H, Namiki N. Comparison of inhibitory duration of grapefruit juice on organic anion-transporting polypeptide and cytochrome P450 3A4. Biol Pharm Bull. 2013;36(12):1936-41.
• Bailey DG. Predicting clinical relevance of grapefruit-drug interactions: a complicated process. J Clin Pharm Ther. 2017 Apr;42(2):125-27.
• Mouly S, Lloret-Linares C, Sellire PO, Sene D, Bergmann JF. Is the clinical relevance of drug-food and drug-herb interactions limited to grapefruit juice and Saint-John's Wort? Pharmacol Res. 2017 Apr;118:82-92.
• Loretz C, Ho MD, Alam N, Mitchell W, Li AP. Application of cryopreserved human intestinal mucosa and cryopreserved human enterocytes in the evaluation of herb-drug interactions: evaluation of CYP3A inhibitory potential of grapefruit juice and commercial f
• Long Z, Ruan M, Wu W, Zeng Q, Li Q, Huang Z. The successful combination of grapefruit juice and venetoclax in an unfit acute myeloid leukemia patient with adverse risk: A case report. Front Oncol 2022;12:912696.

Progesterone Overview

• 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.

Grapefruit - More Interactions

Grapefruit interacts with 962 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.