Sweet Orange - Tolvaptan Interaction
Herbal: Sweet Orange
Also Known As: Citrus sinensis, Blood Orange, Citri Sinensis, Citrus Peel Extract, Extrait de Zeste d'Agrume, Jaffa Orange, Naranja Dulce, Navel Orange, Orange, Orange de Jaffa, Orange Douce, Red Orange, Shamouti Orange, Shamouti Sweet Orange, Valencia Orange, Wild Orange, Wild Sweet O
Drug: Tolvaptan
Brand names:
Samsca, Jynarque

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Jun 15, 2025
Interaction Details
Tolvaptan is classified as belonging to the following category: P-Glycoprotein Substrates
Sweet orange juice seems to modulate P-glycoprotein (P-gp), which might affect the blood levels of P-gp substrates.
Animal and in vitro research suggest that orange juice extract inhibits drug efflux by P-gp, increasing absorption and levels of P-gp substrates. In contrast, pharmacokinetic research in humans shows that drinking large amounts of sweet orange juice decreases absorption and levels of the P-gp substrate celiprolol. This suggests that orange juice actually induces drug efflux by P-gp or affects drug levels by another mechanism such as inhibiting the gut drug transporter called organic anion transporting polypeptide (OATP). Until more is known, sweet orange juice should be used cautiously in people taking P-gp substrates.
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
- Bailey DG, Dresser GK, Munoz C, et al. Reduction of fexofenadine bioavailability by fruit juices. Clin Pharmacol Ther 2001;69:P21.
- Lilja JJ, Juntti-Patinen L, Neuvonen PJ. Orange juice substantially reduces the bioavailability of the beta-adrenergic-blocking agent celiprolol. Clin Pharmacol Ther 2004;75:184-90.
- Tian R, Koyabu N, Takanaga H, et al. Effects of grapefruit juice and orange juice on the intestinal efflux of P-glycoprotein substrates. Pharm Res 2002;19:802-9.
- Takanaga H, Ohnishi A, Yamada S, et al. Polymethoxylated flavones in orange juice are inhibitors of P-glycoprotein but not cytochrome P450 3A4. J Pharmacol Exp Ther 2000;293:230-6.
Sweet Orange Overview

Tolvaptan Overview
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Tolvaptan (Jynarque) is used to slow the worsening of kidney function in certain patients with autosomal dominant polycystic kidney disease (ADPKD; a certain type of inherited kidney disease). Tolvaptan (Jynarque) is in a class of medications called vasopressin V2 receptor antagonists. It works by increasing the amount of water released from the body as urine and decreases the growth of cysts in the kidneys. Removing fluid from the body and slowing the growth of cysts helps to slow the worsening of kidney function.
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Tolvaptan is also available as a tablet (Samsca) to treat low blood levels of sodium in people who have heart failure or certain other conditions. This monograph only gives information about tolvaptan tablets (Jynarque) to slow the worsening of kidney function in patients with ADPKD. If you are using this medication to treat low levels of sodium in the blood, read the monograph entitled tolvaptan (low blood sodium).
Sweet Orange - More Interactions
Sweet Orange interacts with 239 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.