Tramadol/Selected Moderate to Strong CYP2D6 Inhibitors Interactions

This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.

Medical warning:

Moderate. These medicines may cause some risk when taken together. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.

How the interaction occurs:

Abiraterone, asunaprevir, berotralstat, bupropion, cinacalcet, dacomitinib, dronedarone, duloxetine, eliglustat, escitalopram, fluoxetine, hydroquinidine, levomethadone, lorcaserin, mirabegron, paroxetine, quinidine, rolapitant, oral terbinafine, and tipranavir may decrease the pain relieving effects of tramadol by interfering with how the body activates tramadol. These medications may also increase your risk for seizures or serotonin side effects due to tramadol.

What might happen:

Tramadol may not work as well for pain after starting abiraterone, asunaprevir, berotralstat, bupropion, cinacalcet, dacomitinib, dronedarone, duloxetine, eliglustat, escitalopram, fluoxetine, hydroquinidine, levomethadone, lorcaserin, mirabegron, paroxetine, quinidine, rolapitant, oral terbinafine, and tipranavir.High serotonin levels may cause changes in body temperature, blood pressure and behavior, leading to a medical condition called Serotonin Syndrome. Serotonin Syndrome may be life threatening.

What you should do about this interaction:

Let your healthcare professionals (e.g. doctor or pharmacist) know that you are taking these medicines together.Do not take more than the prescribed dose of tramadol.Your healthcare professionals may already be aware of this interaction and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.If you experience muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, severe diarrhea, or think you may have had a seizure, contact your doctor right away.

View Reference
  • 1.Ultram (tramadol) US prescribing information. Janssen Pharmaceutical, Inc. October, 2019.
  • 2.US Food and Drug Administration (FDA). Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. Available at: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and- drug-interactions-table-substrates-inhibitors-and-inducers. Updated 11/14/2017.
  • 3.Lamisil (terbinafine hydrochloride) tablet US prescribing information. Novartis Pharmaceuticals Corporation June, 2013.
  • 4.Wellbutrin (bupropion hydrochloride) US prescribing information. GlaxoSmithKline November, 2019.
  • 5.Sensipar (cinacalcet hydrochloride) US prescribing information. Amgen Inc. March, 2019.
  • 6.Nuedexta (dextromethorphan hydrobromide and quinidine sulfate) US prescribing information. Avanir Pharmaceuticals June, 2019.
  • 7.Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005 Mar 17; 352(11):1112-20.
  • 8.Subrahmanyam V, Renwick AB, Walters DG, Young PJ, Price RJ, Tonelli AP, Lake BG. Identification of cytochrome P-450 isoforms responsible for cis-tramadol metabolism in human liver microsomes. Drug Metab Dispos 2001 Aug;29(8):1146-55.
  • 9.Stamer UM, Lehnen K, Hothker F, Bayerer B, Wolf S, Hoeft A, Stuber F. Impact of CYP2D6 genotype on postoperative tramadol analgesia. Pain 2003 Sep;105(1-2):231-8.
  • 10.Stamer UM, Musshoff F, Kobilay M, Madea B, Hoeft A, Stuber F. Concentrations of tramadol and O-desmethyltramadol enantiomers in different CYP2D6 genotypes. Clin Pharmacol Ther 2007 Jul;82(1):41-7.
  • 11.Myrbetriq (mirabegron) US prescribing information. Astellas Pharma Technologies, Inc. March 25, 2021.
  • 12.Varubi (rolapitant) US prescribing information. Tesaro Inc. August, 2020.
  • 13.Saarikoski T, Saari TI, Hagelberg NM, Backman JT, Neuvonen PJ, Scheinin M, Olkkola KT, Laine K. Effects of terbinafine and itraconazole on the pharmacokinetics of orally administered tramadol. Eur J Clin Pharmacol 2015 Mar;71(3):321-7.
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CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.