Spravato 28 mg nasal spray, solution

PSUSA/00010825/202403: Annual PBRER for esketamine (05Mar23-04Mar24): Add ADRs for bradycardia and seizure

PSUSA/00010825/202403: Annual PBRER for esketamine (05Mar23-04Mar24): Add ADRs for bradycardia and seizure

EMEA/H/C/004535/R/0023: Spravato 5-year renewal procedure

-Includes removal of black inverted triangle

-Moving information on 'Food and drink' from Section 3 to Section 2 'Spravato with food, drink and alcohol' and adding information on alcohol that was previously contained in 'Other medicines and Spravato' to this section

EMEA/H/C/004535/R/0023: Spravato 5-year renewal procedure

-Includes removal of black inverted triangle

-Removal of information on Special Population: Japanese and Chinese patients with treatment resistant Major Depressive Disorder

-Minor administrative updates

EMEA/H/C/004535/II/024: Safety variation to implement CCDS v 11 (addition of uncommon ADR of “hypotension” to SmPC and Package Leaflet). There were two changes:

Section 4.2:

Paediatric population

The safety and efficacy of Spravato in paediatric patients aged 17 years and younger have not been established. No data are available. There is no relevant use of Spravato in children less than 7 years of age.

Section 4.8:

Addition of hypotension as uncommon ADR

EMEA/H/C/004535/II/024: Safety variation to implement CCDS v 11 (addition of uncommon ADR of “hypotension” to SmPC and Package Leaflet)

Removal of the phrase in strikethrough from the section ‘Disturbances in Consciousness’: ‘In clinical trials, all cases of sedation resolved spontaneously; no respiratory depression was observed, and haemodynamic parameters remained within the normal range’. There were also some small administrative changes made.

EMEA/H/C/004535/II/020: Inclusion of the high-level safety findings from the safety extension study TRD3008

Updated contact telephone number, and addition of email address, to local representative details in Section 6.

Additional clinical data

Shelf life has been updated from 3 to 4 years.

The adverse events section has been updated to add respiratory depression as a rare adverse event. The ‘Disturbances in consciousness (sedation)’ section has been updated as follows: ‘In clinical trials, all cases of sedation resolved spontaneously; no respiratory depression was observed, and haemodynamic parameters remained within the normal range. During post-marketing use, rare cases of respiratory depression have been observed.’

Disturbances in consciousness (sedation) section of the Patient Guide has been updated as follows:

In clinical trials, all All the people who experienced sedation were able to breathe normally, had normal vital signs, and most recovered on the same day.^1,3  During post-marketing use, rare cases of difficulty in breathing have been observed.

Section 4 - updated respiratory side effect

EUPI update: warnings & precautions section 4.4, isolated cases of respiratory depression observed with post marketing use implementing identical wording in CCDS v8 (adverse reactions section).

During the EMA PSUR procedure, EMA PRAC requested some rewording to the SmPC section 4.4 warning; addition of respiratory depression as an ADR at section 4.8 and addition of respiratory depression to the description of adverse events (SmPC section 4.8).

SmPC: Section 4.4 and 4.8

Patient Leaflet: Section 4

Changes to the PIL for updating:

- how to report a side effect

- marketing authorisation holder

- date of revision of the text

Administrative changes only 

Addition of 'Table 3' in section 4.8

Definition of MINI in section 5.1