Esketamine

SPRAVATO is indicated for the treatment of: Treatment-resistant depression (TRD) in adults as monotherapy or in conjunction with an oral antidepressant Depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior in conjunction with an oral antidepressant SPRAVATO is a non-competitive N -methyl D -aspartate (NMDA) receptor antagonist indicated for the treatment of: Treatment-resistant depression (TRD) in adults, as monotherapy or in conjunction with an oral antidepressant. Depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior in conjunction with an oral antidepressant. Limitations of Use: The effectiveness of SPRAVATO in preventing suicide or in reducing suicidal ideation or behavior has not been demonstrated.

Esketamine, the S-enantiomer of racemic ketamine, is a non-selective, non-competitive antagonist of the N -methyl- D -aspartate (NMDA) receptor, an ionotropic glutamate receptor. The mechanism by which esketamine exerts its antidepressant effect is unknown. The major circulating metabolite of esketamine (noresketamine) demonstrated activity at the same receptor with less affinity.

Administer SPRAVATO intranasally under the supervision of a healthcare provider. Assess blood pressure prior to and after administration. TRD: Evidence of therapeutic benefit should be evaluated at the end of the 4-week induction phase to determine need for continued treatment. Depressive symptoms in MDD with acute suicidal ideation or behavior: Evidence of therapeutic benefit should be evaluated after 4 weeks to determine need for continued treatment. Treatment beyond 4 weeks has not been systematically evaluated. See Full Prescribing Information for recommended dosage. See Full Prescribing Information for important administration instructions.

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

Boxed warning: Risk for sedation, dissociation, and respiratory depression after administration. Monitor patients for at least two hours after administration. Potential for abuse and misuse. Consider the risks and benefits of prescribing SPRAVATO prior to using in patients at higher risk of abuse. Monitor patients for signs and symptoms of abuse and misuse. SPRAVATO is only available through a restricted program called the SPRAVATO REMS. Increases in Blood Pressure: Patients with cardiovascular and cerebrovascular conditions and risk factors may be at an increased risk of associated adverse effects. Cognitive Impairment: SPRAVATO may impair attention, judgment, thinking, reaction speed and motor skills. Impaired Ability to Drive and Operate Machinery: Do not drive or operate machinery until the next day after a restful sleep. Embryo-fetal Toxicity: May cause fetal harm.

The following adverse reactions are discussed in more detail in other sections of the labeling: Sedation Dissociation Respiratory Depression Increase in Blood Pressure Cognitive Impairment Impaired Ability to Drive and Operate Machinery Ulcerative or Interstitial Cystitis Embryo-fetal Toxicity The most commonly observed adverse reactions (incidence ≥5% and at least twice that of placebo): TRD: dissociation, dizziness, nausea, sedation, vertigo, hypoesthesia, anxiety, lethargy, blood pressure increased, vomiting, feeling drunk, and headache. Treatment of depressive symptoms in adults with MDD with acute suicidal ideation or behavior: dissociation, dizziness, sedation, blood pressure increased, hypoesthesia, vomiting, euphoric mood, and vertigo.

Central Nervous System Depressants Concomitant use with CNS depressants (e.g., benzodiazepines, opioids, alcohol) may increase sedation. Closely monitor for sedation with concomitant use of SPRAVATO with CNS depressants.

Store at 20° to 25°C (68° to 77°F), excursions permitted from 15° to 30°C (59° to 86°F).