Spravato Adverse Reactions

Summary of the safety profile: The most commonly observed adverse reactions in patients treated with Spravato were dizziness (31%), dissociation (27%), nausea (27%), headache (23%), somnolence (18%), dysgeusia (18%), vertigo (16%), hypoaesthesia (11%), vomiting (11%), and blood pressure increased (10%).
Tabulated list of adverse reactions: Adverse reactions reported with esketamine are listed in Table 11. Within the designated system organ classes, adverse reactions are listed under headings of frequency, using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data). (See Table 11.)

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Description of selected adverse reactions: Dissociation: Dissociation (27%) was one of the most common psychological effects of esketamine. Other related terms included derealisation (2.2%), depersonalisation (2.2%), illusions (1.3%), and distortion of time (1.2%). These adverse reactions were reported as transient and self-limited and occurred on the day of dosing. Dissociation was reported as severe in intensity at the incidence of less than 4% across studies. Dissociation symptoms typically resolved by 1.5 hours post-dose and the severity tended to reduce over time with repeated treatments.
Sedation/somnolence/respiratory depression: In clinical trials, adverse reactions of sedation (9.3%) and somnolence (18.2%) were primarily mild or moderate in severity, occurred on the day of dosing and resolved spontaneously the same day. Sedative effects typically resolved by 1.5 hours post-dose. Rates of somnolence were relatively stable over time during long-term treatment. In the cases of sedation, no symptoms of respiratory distress were observed, and haemodynamic parameters (including vital signs and oxygen saturation) remained within normal ranges. During post-marketing use, rare cases of respiratory depression have been observed (see Precautions).
Changes in blood pressure: In clinical trials for treatment-resistant Major Depressive Disorder, increases in systolic and diastolic blood pressure (SBP and DBP) over time were about 7 to 9 mmHg in SBP and 4 to 6 mmHg in DBP at 40 minutes post-dose and 2 to 5 mmHg in SBP and 1 to 3 mmHg in DBP at 1.5 hours post-dose in patients receiving Spravato plus oral antidepressants (see Precautions). The frequency of markedly abnormal blood pressure elevations of SBP (≥40 mmHg increase) ranged from 8% (<65 years) to 17% (≥65 years) and DBP (≥25 mmHg increase) ranged from 13% (<65 years) to 14% (≥65 years) in patients receiving esketamine plus oral antidepressant. The incidence of increased SBP (≥180 mmHg) was 3% and DBP (≥110 mmHg) was 4%.
Cognitive and memory impairment: Cognitive and memory impairment have been reported with long-term ketamine use or drug abuse. These effects did not increase over time and were reversible after discontinuing ketamine. In long-term clinical trials, the effect of esketamine nasal spray on cognitive functioning was evaluated over time and performance remained stable.
Urinary tract symptoms: Cases of interstitial cystitis have been reported with daily and long-term ketamine use at high doses. In clinical studies with esketamine, there were no cases of interstitial cystitis, however a higher rate of lower urinary tract symptoms was observed (pollakiuria, dysuria, micturition urgency, nocturia, and cystitis) in esketamine-treated patients compared with placebo-treated patients.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.