Interaction Details

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

Bitter orange might increase levels of drugs metabolized by CYP3A4.
Small clinical studies suggest that single or multiple doses of freshly squeezed bitter orange juice 200-240 mL can inhibit CYP3A4 metabolism of drugs, causing increased drug levels and potentially increasing the risk of adverse effects. However, the extent of the effect of bitter orange on CYP3A4-mediated drug interactions is unknown. Some evidence suggests that bitter orange selectively inhibits intestinal CYP3A4, but not hepatic CYP3A4. Its effect on P-glycoprotein, which strongly overlaps with CYP3A4 interactions, is unclear. One small clinical study shows that drinking 8 ounces of freshly squeezed bitter orange juice has no effect on cyclosporine, which seems to be more dependent on hepatic CYP3A4 and P-glycoprotein than intestinal CYP3A4.

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

  • Malhotra S, Bailey DG, Paine MF, Watkins PB. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. Clin Pharmacol Ther 2001;69:14-23.
  • Penzak SR, Acosta EP, Turner M, et al. Effect of Seville orange juice and grapefruit juice on indinavir pharmacokinetics. J Clin Pharmacol 2002;42:1165-70.
  • Edwards DJ, Fitzsimmons ME, Schuetz EG, et al. 6',7'-Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein. Clin Pharmacol Ther 1999;65:237-44.
  • Di Marco MP, Edwards DJ, Wainer IW, Ducharme MP. The effect of grapefruit juice and seville orange juice on the pharmacokinetics of dextromethorphan: the role of gut CYP3A and P-glycoprotein. Life Sci 2002;71:1149-60.
  • Abdelkawy KS, Donia AM, Turner RB, Elbarbry F. Effects of Lemon and Seville Orange Juices on the Pharmacokinetic Properties of Sildenafil in Healthy Subjects. Drugs R D. 2016 Sep;16(3):271-278.

Bitter Orange Overview

Bitter Orange Bitter orange, also known as Seville orange or sour orange, is a type of citrus fruit that is native to Southeast Asia. It is closely related to the sweet orange, but has a much more bitter and sour flavor. Bitter orange is a rich source of vitamin C and other nutrients, including calcium, potassium, and folate. It is also a good source of antioxidants. Bitter orange has been used in traditional medicine for a number of purported health benefits, including improved digestion, improved immune function, and reduced inflammation. Bitter orange also contains synephrine, a compound similar in structure to ephedrine. Synephrine is thought to have stimulant effects and is often used to increase energy, improve athletic performance, and as a weight loss supplement. When used as a dietary supplement, the dosage is typically standardized by its synephrine content.
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Upadacitinib Hemihydrate Overview

  • Upadacitinib is used alone or with other medications to treat rheumatoid arthritis (condition in which the body attacks its own joints causing pain, swelling, and loss of function) in people who are unable to take or have not responded well to one or more tumor necrosis factor (TNF) inhibitor medication(s). It is also used to treat psoriatic arthritis (a condition that causes joint pain and swelling and scales on the skin) in adults who are unable to take or did not respond to or tolerate one or more TNF inhibitor medication(s). Upadacitinib is also used to treat symptoms of eczema (atopic dermatitis; a skin disease that causes the skin to be dry and itchy and to sometimes develop red, scaly rashes) in adults and children 12 years and older who cannot use other medications for their condition or whose eczema has not responded to other medications. It is also used to treat ulcerative colitis (a condition that causes swelling and sores in the lining of the colon [large intestine] and rectum) in adults who are unable to take or who did not respond to one or more TNF inhibitor medication(s). Upadacitinib is used to treat ankylosing spondylitis (a condition in which the body attacks the joints of the spine and other areas, causing pain, swelling, and joint damage) in adults who are unable to take or who did not respond to one or more TNF inhibitor medication(s). Upadacitinib is in a class of medications called Janus kinase (JAK) inhibitors. It works by decreasing the activity of the immune system.

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Bitter Orange - More Interactions

Bitter Orange interacts with 911 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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