Rhubarb - Acetaminophen, Butalbital, Caffeine, Codeine Interaction
Herbal: Rhubarb
Also Known As: Rheum officinale, Chinese Rhubarb, Da Huang, Garden Rhubarb, Himalayan Rhubarb, Indian Rhubarb, Medicinal Rhubarb, Radix et Rhizoma Rhei, Rhapontic Rhubarb, Rhei, Rewandchini, Rheum, Rhei Radix, Rhubarbe, Rhubarbe de Chine, Rhubarbe Indienne
Drug: Acetaminophen, Butalbital, Caffeine, Codeine
Brand names:
Esgic with Codeine, Fioricet w/ Codeine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
May 04, 2025
Interaction Details
Acetaminophen, Butalbital, Caffeine, Codeine is classified as belonging to the following category: Nephrotoxic Drugs
Theoretically, long-term use of anthraquinones from rhubarb might increase the risk of nephrotoxicity when used with nephrotoxic drugs.
The anthraquinone constituents of rhubarb have been shown to induce nephrotoxicity in animal research. Additionally, in a case report, a 23-year old female presented with kidney failure after taking 6 tablets of a proprietary slimming agent (found to contain the anthraquinones emodin and aloe-emodin from rhubarb) daily for 6 weeks and then adding diclofenac 25 mg 4 times daily for 2 days. The authors postulate that the anthraquinone constituents of rhubarb contributed to the renal dysfunction, and the addition of diclofenac, a nephrotoxic drug, led to renal failure. Until more is known, advise patients to avoid taking rhubarb if they are taking other potentially nephrotoxic drugs.
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
- Kwan TH, Tong MK, Leung KT, et al. Acute renal failure associated with prolonged intake of slimming pills containing anthraquinones. Hong Kong Med J 2006;12:394-7.
- Yan, M., Zhang, L. Y., Sun, L. X., Jiang, Z. Z., and Xiao, X. H. Nephrotoxicity study of total rhubarb anthraquinones on Sprague Dawley rats using DNA microarrays. J Ethnopharmacol. 4-15-2006;
Interaction Details
Acetaminophen, Butalbital, Caffeine, Codeine is classified as belonging to the following category: Hepatotoxic Drugs
Theoretically, concomitant use of rhubarb with potentially hepatotoxic drugs might increase the risk of developing liver damage.
Some animal research suggests that anthraquinones in rhubarb might have hepatotoxic effects. Also, rhubarb use has been linked to at least 24 cases of liver injury, although details on the dose of rhubarb and duration of use in these cases is unclear.
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
- Byeon JH, Kil JH, Ahn YC, Son CG. Systematic review of published data on herb induced liver injury. J Ethnopharmacol 2019;233:190-6.
- Zhao D, Feng SX, Zhang HJ, et al. Pharmacokinetics, tissue distribution and excretion of five rhubarb anthraquinones in rats after oral administration of effective fraction of anthraquinones from rheum officinale. Xenobiotica. 2021;51(8):916-925.
Rhubarb Overview

Rhubarb - More Interactions
Rhubarb interacts with 631 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. |
Return to the main supplement interaction checker page
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.