SPRAVATO

Esketamine exposure increases with dose from 28 mg to 84 mg. The increase in C max and AUC values was less than dose-proportional between 28 mg and 56 mg or 84 mg, but it was nearly dose proportional between 56 mg and 84 mg. No accumulation of esketamine in plasma was observed following twice a week administration.

AbsorptionThe mean absolute bioavailability is approximately 48% following nasal spray administration. The time to reach maximum esketamine plasma concentration is 20 to 40 minutes a...

14.1 Treatment-Resistant Depression Short-Term Study SPRAVATO was evaluated in a randomized, placebo-controlled, double-blind, multicenter, short-term (4-week), Phase 3 study (Study 1; NCT02418585) in adult patients 18 to <65 years old with treatment-resistant depression (TRD). Patients in Study 1 met DSM-5 criteria for major depressive disorder (MDD) and in the current depressive episode, had not responded adequately to at least two different antidepressants of adequate dose and duration. After discontinuing prior antidepressant treatments, patients in Study 1 were randomized to receive twice...

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) ] Respiratory Depression [see Warnings and Precautions (5.3) ] Increase in Blood Pressure [see Warnings and Precautions (5.7) ] Cognitive Impairment [see Warnings and Precautions (5.8) ] Impaired Ability to Drive and Operate Machinery [see Warnings and Precautions (5.9) ] Ulcerative or Interstitial Cystitis...

SPRAVATO is contraindicated in patients with: Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels) or arteriovenous malformation [see Warnings and Precautions (5.7) ] History of intracerebral hemorrhage [see Warnings and Precautions (5.7) ] Hypersensitivity to esketamine, ketamine, or any of the excipients. Aneurysmal vascular disease ...

Increases in Blood Pressure: Patients with cardiovascular and cerebrovascular conditions and risk factors may be at an increased risk of associated adverse effects. ( 5.7 ) Cognitive Impairment: SPRAVATO may impair attention, judgment, thinking, reaction speed and motor skills. ( 5.8 ) Impaired Ability to Drive and Operate Machinery: Do not drive or operate machinery until the next day after a restful sleep. ( 5.9 ) Embryo-fetal Toxicity: May cause fetal harm. Consider pregnancy planning and pre...

7 DRUG INTERACTIONS 7.1 Central Nervous System Depressants Concomitant use with CNS depressants (e.g., benzodiazepines, opioids, alcohol) may increase sedation [see Warnings and Precautions (5.1) ] . Closely monitor for sedation with concomitant use of SPRAVATO with CNS depressants. 7.2 Psychostimulants Concomitant use with psychostimulants (e.g., amphetamines, methylphenidate, modafinil, armodafi...