The FDA is warning healthcare professionals of potential risks associated with compounded ketamine nasal spray (here). The Agency states that there is no approved ketamine nasal spray. Hey, wait a minute! (you might say); I could have sworn that I read about a ketamine nasal spray approval? Well, close! The product you may be thinking of is Spravato (esketamine), which is the S‑enantiomer of ketamine and is “a nasal spray for treatment‑resistant depression in adults and depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior, in conjunction with an oral antidepressant.”
The FDA-approved product has a strict REMS program that requires (among other things) administration in a healthcare setting with patient monitoring. The compounded form of ketamine is the racemic mixture, and the FDA considers it an unapproved product. The Agency has received numerous reports of severe adverse events with its use. The FDA reports it has found significant strength variations (ranging from 125‑200 mg/mL) of the compounded product. In addition, the FDA has not been able to determine the difference in quantity delivered by the off-the-shelf nasal spray bottles that are being used in pharmacy compounding settings. This could further lead to significantly higher doses and translate into severe adverse events.
However, “Ketamine hydrochloride[a] (tradename: Ketalar) is a Schedule III controlled substance that is FDA-approved as an intravenous or intramuscular injection solution for induction and maintenance of general anesthesia” and is not approved for use in treatment‑resistant depression. Use of these compounded products, which are used outside of the controls of a strict RMES program in combination with unknown dose delivery, can exacerbate the ADE profile of the compounded product with lack of sufficient protection for the patient’s safety.
