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# FDA Advisors Nix IV Tramadol
- URL: https://www.fdaweb.com/fda-advisors-nix-iv-tramadol/
- Published: 2022-02-16T12:00:00.000Z
- Updated: 2026-09-14T17:32:57.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5151172

Members of the FDA Anesthetic and Analgesic Drug Products Advisory Committee and Drug Safety and Risk Management Advisory Committee voted 14-8 on 2/15 that Avenue Therapeutics did not submit adequate information to support its position that the benefits of IV tramadol outweighed its risks in managing acute pain severe enough to require an opioid in an inpatient setting. FDA had rejected Avenue NDAs for IV tramadol in [2020](https://www.fdaweb.com/avenue-gets-complete-response-on-pain-drug/) and [2021](https://www.fdaweb.com/avenues-2nd-complete-response-on-pain-nda/) due to safety concerns.

*MedPageToday* [reports](https://www.medpagetoday.com/painmanagement/opioids/97218?ref=fdaweb.com) that after the 2021 rejection, Avenue submitted a formal dispute resolution request and FDA [asked](https://www.fdaweb.com/advisory-committee-to-hear-avenue-dispute-resolution/) for additional input from an outside panel before making a decision, leading to the joint advisory committee meeting.

The report quotes CDER Office of New Drugs medical officer **Lisa Wiltrout** as telling the committees that “Tramadol IV’s delayed onset of analgesia, combined with its inability to be titrated to effect, leads to a serious safety concern of additive opioid-related adverse events from use of opioids in succession, also referred to as opioid stacking.”

Advisory committee member **Maryam Jowza**, of the University of North Carolina at Chapel Hill, said efficacy data were demonstrated and the risk related largely to opioid stacking, which she said could be mitigated with proper use and education.

But other panelists had a different opinion. The news service quotes Stanford University School of Medicine’s **Brian Bateman** that “the delayed onset and the unpredictable pharmacokinetics of this drug, coupled with the inability to titrate the drug, make this quite a problematic formulation. I think we need trials to better reflect the type of setting where this drug would be administered, where opioids would be able to be used for continued pain or breakthrough pain. There’s no compelling evidence presented that there’s less abuse liability with this formulation compared to Schedule 2 opioids. We really have no data to suggest that the use of inpatient IV opioids and the differences between them could impact long-term misuse, abuse, or the development of opioid-use disorder.”