SUMMARY

• Esketamine nasal spray contains esketamine hydrochloride, the (S)-enantiomer of ketamine and a Schedule III controlled substance under the Controlled Substances Act.¹
• SPRAVATO is intended for administration by the patient under the direct supervision of a healthcare professional, using 2 devices (for a 56 mg dose) or 3 devices (for an 84 mg dose), with a 5-minute rest between use of each device.¹
• Because of the risks of sedation and dissociation, patients must be monitored for at least 2 hours at each treatment session, followed by an assessment to determine when the patient is considered clinically stable and ready to leave the healthcare setting.¹
• Since SPRAVATO is administered in the presence of healthcare professionals, the potential for overdose is low.²
• Across clinical trials, there have been no reported cases of overdose with SPRAVATO. The clinical trial program included safety data for 2,283 subjects who received at least 1 dose across completed phase 1, phase 2, and phase 3 studies. Two completed phase 1 studies in healthy volunteers included subjects that received doses higher than the maximum prescribed dose of 84 mg. The maximum dose tested in those 2 studies was 112 mg.²
  • In one phase 1 study (14 subjects), the incidence of treatment-emergent adverse events (TEAEs) having at least 3 reported events in the esketamine (ESK) 112 mg group was >2 times higher than in the ESK 84 mg group for dizziness postural, head discomfort, feeling hot, and hyperhidrosis.²
  • In another phase 1 study (37 subjects), the incidence of the following TEAEs was reported in at least 3 subjects were >2 times higher in the ESK 112 mg group compared to the ESK 84 mg group: dizziness and nasal congestion.² This study also showed that the 112 mg group experienced much higher scores for “hallucinating”, “floating”, “detached”, and “spaced out” measures than in the 84 mg group at 1 hour postdose.¹
• A multidimensional analysis evaluating the abuse potential of SPRAVATO reported 8 cases of overdose (including 3 cases of intentional overdose) from the United States (US) Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database.³
  • Due to the limitations of the FAERS database, a causal relationship cannot be established, and reports do not always contain enough detail to properly evaluate an event. There may also be duplicate reports; therefore, the incidence of an AE cannot be determined.⁴
• There is no specific antidote for SPRAVATO overdose. In the case of overdose, the possibility of multiple drug involvement should be considered. Contact a Certified Poison Control Center for the most up-to-date information on the management of overdosage (1-800-222-1222 or www.poison.org).

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 25 February 2024.