day driving andthe effect of repeated administration of 84 mg of intranasal SPRAVATO on same-day drivingperformance (Study 3). For the single dose treatment phase, an ethanol-containing beverage wasused as a positive control. The SDLP after administration of single 84-mg dose of SPRAVATOnasal spray was similar to placebo 18 hours post-dose. For the multiple dose treatment phase, theSDLP after repeated administration of 84 mg intranasal SPRAVATO was similar to placebo6 hours post-dose on Day 11, Day 18, and Day 25.
A randomized, double-blind, cross-over, placebo-controlled study in 23 healthy subjectseva luated the effects of a single 84-mg dose of esketamine nasal spray on driving (Study 4).
Mirtazapine (30 mg) was used as a positive control. Driving performance was assessed at 8 hoursafter SPRAVATO or mirtazapine administration. The SDLP 8 hours after SPRAVATO nasalspray administration was similar to placebo. Two subjects discontinued the driving test afterreceiving SPRAVATO because of a perceived inability to drive after experiencing post-doseadverse reactions; one subject reported pressure behind the eyes and paresthesia of the hands andfeet, the other reported headache with light sensitivity and anxiety.
16 HOW SUPPLIED/STORAGE AND HANDLING
SPRAVATO nasal spray is available as an aqueous solution of esketamine hydrochloride in astoppered glass vial within a nasal spray device. Each nasal spray device delivers two sprayscontaining a total of 28 mg of esketamine (supplied as 32.3 mg of esketamine hydrochloride).
SPRAVATO is available in the following presentations:
• 56 mg Dose Kit: Unit-dose carton containing two 28 mg nasal spray devices (56 mg totaldose) (NDC 50458-028-02).
• 84 mg Dose Kit: Unit-dose carton containing three 28 mg nasal spray devices (84 mg totaldose) (NDC 50458-028-03).
Within each kit, each 28 mg device is individually packaged in a sealed blister(NDC 50458-028-00).
Storage
Store at 20° to 25°C (68° to 77°F); excursions permitted from 15° to 30°C (59° to 86°F) [see
USP Controlled Room Temperature].
Disposal
SPRAVATO nasal spray devices must be handled with adequate security, accountability, and
proper disposal, per facility procedure for a Schedule III drug product, and per applicable
federal, state, and local regulations.
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Sedation and Dissociation
Inform patients that SPRAVATO has potential to cause sedation, dissociative symptoms,
perception disturbances, dizziness, vertigo, and anxiety. Advise patients that they will need to be
observed by a healthcare provider until these effects resolve [see Boxed Warning, Warnings and
Precautions (5.1), Warnings and Precautions (5.2)].
Potential for Abuse, Misuse, and Dependence
Advise patients that SPRAVATO is a federally controlled substance because it can be abused orlead to dependence [see Warnings and Precautions (5.3), Drug Abuse and Dependence (9)].
SPRAVATO Risk eva luation and Mitigation Strategy (REMS)
SPRAVATO is available only through a restricted program called the SPRAVATO REMS [seeWarnings and Precautions (5.4)]. Inform the patient of the following notable requirements:
• Patients must be enrolled in the SPRAVATO REMS Program prior to administration.
• SPRAVATO must be administered under the direct observation of a healthcare provide |
