- NRx Pharmaceuticals has filed a Citizen Petition with the FDA to remove benzethonium chloride from ketamine products.
- The preservative has known toxicity and is no longer allowed in hand sanitizers or topical antiseptics.
- Ketamine is increasingly used off-label for treating suicidal depression and PTSD.
- The company argues repeated exposure to benzethonium chloride through IV use poses unnecessary health risks.
- NRx has submitted data showing its preservative-free ketamine maintains sterility and stability for three years.
- The company is pursuing FDA approval for both its preservative-free ketamine (“NRX-100”) and oral NMDA-targeting drug (“NRX-101”).
NRx Pharmaceuticals (NASDAQ: NRXP), a clinical-stage biopharmaceutical company, has submitted a formal Citizen Petition to the U.S. Food and Drug Administration (“FDA”), urging the agency to prohibit the use of benzethonium chloride in all ketamine products sold in the United States. According to the company, this chemical preservative presents known toxicity risks and is not Generally Recognized as Safe and Effective (“GRASE”) for pharmaceutical use in parenteral or topical formulations (https://ibn.fm/kYR0g).
Benzethonium chloride (“BZT”) is part of a broader class of quaternary ammonium preservatives linked to cellular and neurological toxicity. While previously used in a variety of over-the-counter products, the FDA has already removed BZT from hand cleansers and topical antiseptics, citing safety concerns. The European Medicines Agency has also advised against its use in injectable medications.
According to Dr. Jonathan Javitt, CEO of NRx Pharmaceuticals, when it was first introduced in the 1970s, ketamine was developed as an anesthetic and was never intended to be administered repeatedly to patients. However, it is now widely used on a repeated basis as the only currently marketed drug that has shown benefit in treating suicidal depression and PTSD, although this is currently not a labeled indication, he added. The concern, according to NRx, is that long-term exposure to BZT may lead to cumulative health risks in these patients.
“Hence, patients who receive intravenous ketamine on a repeated basis are exposed to a known toxic preservative that cannot be used today in hand cleaner, antiseptics, and other topical products. The European Medicines Agency has warned against its use,” Javitt explained. “We believe that our Citizen Petition aligns with priorities articulated by current leadership of the U.S. Department of Health and Human Services to remove potentially toxic additives and preservatives from the U.S. Food and Drug supply and to re-shore the U.S. Drug Supply.”
The company is advancing an alternative: NRX-100, a preservative-free intravenous formulation of ketamine. In June 2025, NRx filed an Abbreviated New Drug Application (“ANDA”) for NRX-100, including data demonstrating its sterility and three-year shelf life at room temperature without the use of preservatives.
NRx also submitted a patent covering its preservative-free manufacturing process, which challenges prior assumptions that BZT or similar agents were required to maintain long-term sterility in ketamine products. As the company announced, it has already set up high-volume U.S.-based manufacturing capacity in anticipation of eventual FDA approval.
In parallel, NRx is seeking approval under the FDA Commissioner’s National Priority Voucher Program, which is designed to accelerate the review of drugs for urgent public health needs. The company aims to secure a labeled indication for the use of ketamine in suicidal depression.
The initiative follows NRx’s broader development pipeline, which includes NRX-101, an oral therapeutic targeting the NMDA (N-methyl-D-aspartate) receptor system for the treatment of bipolar depression with suicidality or akathisia. The FDA has already granted NRX-101 Breakthrough Therapy Designation, and the company plans to submit a New Drug Application (“NDA”) for accelerated approval.
If the FDA agrees to ban benzethonium chloride from ketamine products, it would open the door to new manufacturing standards across the industry and potentially favor companies like NRx that have already committed to preservative-free solutions.
For more information, visit the company’s website at www.NRxPharma.com.
NOTE TO INVESTORS: The latest news and updates relating to NRXP are available in the company’s newsroom at https://ibn.fm/NRXP
