There are multiple interactions reported between these two agents.

Interaction Details

Bosentan is classified as belonging to the following category: Antihypertensive Drugs

Theoretically, taking pomegranate with antihypertensive drugs might increase the risk of hypotension.
Consuming pomegranate juice can modestly lower blood pressure.

Interaction Rating

Moderate

Likelihood of Occurrence

Possible

Interaction 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

  • Aviram M, Dornfeld L. Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure. Atherosclerosis 2001;158:195-8.
  • Aviram M, Rosenblat M, Gaitini D, et al. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin Nutr 2004;23:423-33.
  • Wright, H. and Pipkin F. B. Pomegranates (Punica granatum), kiwifruit (Actinidia deliciosa) and blood pressure: a pilot study. Proceedings of the Nutrition Society 2008;67(8):1.
  • Sohrab G, Sotoodeh G, Siasi F, et al. Effect of pomegranate juice consumption on blood pressure in type 2 diabetic patients. Iranian Journal of Endocrinology and Metabolism 2008;9:399-405, 470.

Interaction Details

Bosentan is classified as belonging to the following category: Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, pomegranate might increase levels of drugs metabolized by CYP2C9.
Some animal and in vitro research shows that pomegranate juice inhibits intestinal, but not hepatic, CYP2C9 isoenzyme activity. However, clinical research shows that neither pomegranate juice nor pomegranate extract have a significant effect on CYP2C9 activity in humans.

Interaction Rating

Minor

Likelihood of Occurrence

Unlikely

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans.

References

  • Nagata M, Hidaka M, Sekiya H, et al. Effects of pomegranate juice on human cytochrome P450 2C9 and tolbutamide pharmacokinetics in rats. Drug Metab Dispos 2007;35:302-5.
  • Hanley MJ, Masse G, Harmatz JS, et al. Pomegranate juice and pomegranate extract do not impair oral clearance of flurbiprofen in human volunteers: divergence from in vitro results. Clin Pharmacol Ther 2012;92(5):651-7.

Interaction Details

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

Theoretically, pomegranate might increase levels of drugs metabolized by CYP3A4, but most research suggests this interaction is unlikely to be clinically significant.
Pomegranate contains several polyphenols that have individually been shown to inhibit CYP3A4. However, there is contradictory evidence about the effect of whole pomegranate juice on CYP3A4 activity. In vitro, pomegranate juice significantly inhibits the CYP3A4 enzyme, with comparable inhibition to grapefruit juice. In an animal model, pomegranate juice inhibits CYP3A4 metabolism of carbamazepine and increases levels of carbamazepine by 1.5 times; however, in human volunteers, drinking a single glass of pomegranate juice 240 mL or taking 200 mL daily for 2 weeks does not significantly affect levels of the CYP3A4 substrate midazolam after oral or intravenous administration. Another study in healthy volunteers shows that consuming pomegranate juice 300 mL three times daily for three days also does not significantly affect levels of simvastatin, a CYP3A4 substrate This suggests that pomegranate is unlikely to significantly affect levels of CYP3A4 substrates in humans.

Interaction Rating

Minor

Likelihood of Occurrence

Unlikely

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans.

References

  • Hidaka M, Okumura M, Fujita K, et al. Effects of pomegranate juice on human cytochrome p450 3A (CYP3A) and carbamazepine pharmacokinetics in rats. Drug Metab Dispos 2005;33:644-8.
  • Farkas D, Oleson LE, Zhao Y, et al. Pomegranate juice does not impair clearance of oral or intravenous midazolam, a probe for cytochrome P450-3A activity: comparison with grapefruit juice. J Clin Pharmacol 2007;47:286-94.
  • Yeo C, Shon J, Liu K, et al. The effects of pomegranate juice on the pharmacokinetics of simvastatin in healthy Korean subjects (PI-63). Clin Pharmacol Ther 2006;79:23.
  • Farkas D, Greenblatt DJ. Influence of fruit juices on drug disposition: discrepancies between in vitro and clinical studies. Expert Opin Drug Metab Toxicol 2008;4:381-93.
  • Misaka S, Nakamura R, Uchida S, et al. Effect of 2 weeks' consumption of pomegranate juice on the pharmacokinetics of a single dose of midazolam: an open-label, randomized, single-center, 2-period crossover study in healthy Japanese volunteers. Clin Ther
  • Park SJ, Yeo CW, Shim EJ, et al. Pomegranate juice does not affect the disposition of simvastatin in healthy subjects. Eur J Drug Metab Pharmacokinet 2016;41(4):339-44.

Pomegranate Overview

Pomegranate Pomegranate is a fruit that is native to parts of the Middle East and South Asia and is currently cultivated around the world. It is known for its bright red, edible seeds and its tart, slightly sweet flavor. It is It is a rich source of antioxidants, vitamins, and minerals, and widely consumed as either the fresh fruit, or in different preparations (e.g., as a beverage). Pomegranate is believed to have a number of health benefits. In traditional medicine, it is most often used for its anti-inflammatory and antioxidant effects.
See More Information Regarding Pomegranate

Bosentan Overview

  • Bosentan is used to treat pulmonary arterial hypertension (PAH, high blood pressure in the vessels that carry blood to the lungs) in adults and children 3 years of age and older. Bosentan may improve the ability to exercise and slow the worsening of symptoms in patients with PAH. Bosentan is in a class of medications called endothelin receptor antagonists. It works by stopping the action of endothelin, a natural substance that causes blood vessels to narrow and prevents normal blood flow in people who have PAH.

See More Information Regarding Bosentan

Pomegranate - More Interactions

Pomegranate interacts with 876 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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Parts of this content are provided by the Therapeutic Research Center, LLC.

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.

© 2021 Therapeutic Research Center, LLC

Drug descriptions are provided by MedlinePlus.

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In addition to being a clinical pharmacist specializing in pharmacotherapy, Dr. Brian Staiger is a registered herbalist through the American Herbalist Guild. He has combined his passion for pharmacy practice with the study of medical ethnobotany to improve patient care. Feel free to reach out about any of your herbal or medication questions!

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