fflabeluse or misuse/abuse of ketamine. In clinical studies with SPRAVATO nasal spray, therewas a higher rate of lower urinary tract symptoms (pollakiuria, dysuria, micturition urgency,nocturia, and cystitis) in SPRAVATO-treated patients than in placebo-treated patients [seeAdverse Reactions (6)]. No cases of esketamine-related interstitial cystitis were observed in anyof the studies, which included treatment for up to a year.
Monitor for urinary tract and bladder symptoms during the course of treatment withSPRAVATO, and refer to an appropriate healthcare provider as clinically warranted.
5.10 Embryo-fetal Toxicity
Based on published findings from pregnant animals treated with ketamine, the racemic mixtureof arketamine and esketamine, SPRAVATO may cause fetal harm when administered topregnant women. Advise pregnant women of the potential risk to an infant exposed toSPRAVATO in utero. Advise women of reproductive potential to consider pregnancy planningand prevention [see Use in Specific Populations (8.1, 8.3)].
6 ADVERSE REACTIONS
The following adverse reactions are discussed in more detail in other sections of the labeling:
• Sedation [see Warnings and Precautions (5.1)]
• Dissociation [see Warnings and Precautions (5.2)]
• Increase in Blood Pressure [see Warnings and Precautions (5.6)]
• Cognitive Impairment [see Warnings and Precautions (5.7)]
• Impaired Ability to Drive and Operate Machinery [see Warnings and Precautions (5.8)]
• Ulcerative or Interstitial Cystitis [see Warnings and Precautions (5.9)]
• Embryo-fetal Toxicity [see Warnings and Precautions (5.10)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction ratesobserved in the clinical trials of a drug cannot be directly compared to rates in the clinical trialsof another drug and may not reflect the rates observed in clinical practice.
Patient Exposure
SPRAVATO was eva luated for safety in 1709 patients diagnosed with treatment resistantdepression (TRD) [see Clinical Studies (14.1, 14.2)] from five Phase 3 studies (3 short-term and2 long-term studies) and one Phase 2 dose-ranging study. Of all SPRAVATO-treated patients inthe completed Phase 3 studies, 479 (30%) received at least 6 months of treatment, and 178 (11%)received at least 12 months of treatment.
Adverse Reactions Leading to Discontinuation of TreatmentIn short-term studies in adults < 65 years old (Study 1 pooled with another 4-week study), theproportion of patients who discontinued treatment because of an adverse reaction was 4.6% inpatients who received SPRAVATO plus oral AD compared to 1.4% for patients who received
placebo nasal spray plus oral AD. For adults ≥ 65 years old, the proportions were 5.6% and3.1%, respectively. In Study 2, a long-term maintenance study, the discontinuation rates becauseof an adverse reaction were similar for patients receiving SPRAVATO plus oral AD and placebonasal spray plus oral AD in the maintenance phase, at 2.6% and 2.1%, respectively. Across allphase 3 studies, adverse reactions leading to SPRAVATO discontinuation in more than2 patients were (in order of frequency): anxiety (1.2%), depression (0.9%), blood pressureincreased (0.6%), dizziness (0.6%), suicidal ideation (0.5%), dissociation (0.4%), nausea (0.4%),
vomiting (0.4%), headache (0.3%), muscular weakness (0.3%), vertigo (0.2%), hypertension(0.2%), panic atta |
