NRx Pharmaceuticals Petitions FDA to Ban Toxic Ketamine Preservative

NRx Pharmaceuticals Inc. has submitted a formal Citizen Petition to the U.S. Food and Drug Administration urging the agency to prohibit the use of benzethonium chloride in all ketamine products sold in the United States. The clinical-stage biopharmaceutical company argues that this chemical preservative presents known toxicity risks and is not Generally Recognized as Safe and Effective for pharmaceutical use in parenteral or topical formulations.

Benzethonium chloride is part of a broader class of quaternary ammonium preservatives linked to cellular and neurological toxicity. The FDA has already removed this preservative from hand sanitizers and topical antiseptics, citing safety concerns, yet it remains in some ketamine formulations. This regulatory discrepancy raises important questions about pharmaceutical safety standards and consistency in FDA oversight.

The petition comes at a critical time as ketamine is increasingly used off-label for treating severe mental health conditions, including suicidal depression and post-traumatic stress disorder. The growing off-label use of ketamine for these conditions means that more patients are potentially being exposed to this preservative through intravenous administration. NRx Pharmaceuticals contends that repeated exposure to benzethonium chloride through IV use poses unnecessary health risks to patients already suffering from serious mental health challenges.

NRx has submitted supporting data showing that its preservative-free ketamine formulation, designated NRX-100, maintains sterility and stability for three years without the need for toxic preservatives. The company is simultaneously pursuing FDA approval for both its preservative-free ketamine and an oral NMDA-targeting drug called NRX-101. This dual approach addresses both immediate safety concerns and longer-term treatment options for mental health conditions.

The petition's outcome could have significant implications for mental health treatment protocols and pharmaceutical manufacturing standards. If successful, it would force manufacturers to reformulate ketamine products, potentially improving patient safety but also possibly affecting drug availability and costs. The move also highlights ongoing concerns about preservative safety in injectable medications and may prompt broader FDA review of preservative use across pharmaceutical products.