Esketamine Hydrochloride (Spravato) (SOLUTION) 28 mg/.2mL

Spravato is an NMDA receptor antagonist used in the treatment of major depressive disorders. It is specifically indicated for the following conditions:

• Treatment-resistant major depressive disorder: Used in combination with an oral antidepressant for adults who have not responded to at least two different treatments with antidepressants in the current moderate to severe depressive episode.
• Major depressive disorder with acute suicidal ideation or behavior: Used as acute short-term treatment for the rapid reduction of depressive symptoms which, according to clinical judgment, constitute a psychiatric emergency.
• Treatment-resistant depression: In clinical trials, Spravato has shown efficacy in reducing depressive symptoms in patients who have not responded to other treatments.

• Esketamine, the active ingredient in Spravato, works by antagonizing the NMDA receptor, an ionotropic glutamate receptor. This antagonism leads to a transient increase in glutamate release, which subsequently increases α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) stimulation. This process enhances neurotrophic signaling, contributing to the restoration of synaptic function in brain regions involved with the regulation of mood and emotional behavior. The restoration of dopaminergic neurotransmission and decreased stimulation of brain regions involved in anhedonia may contribute to the rapid antidepressant response.

Spravato may cause various side effects, which can be categorized as follows:

Common Side Effects

• Dizziness: A frequent side effect experienced by patients.
• Dissociation: A feeling of detachment from reality.
• Nausea: A common gastrointestinal side effect.
• Headache: Often reported by patients using Spravato.
• Somnolence: Feelings of drowsiness or sleepiness.
• Dysgeusia: Altered taste perception.
• Vertigo: A sensation of spinning or dizziness.
• Hypoaesthesia: Reduced sense of touch or sensation.
• Vomiting: Occasional gastrointestinal side effect.
• Increased blood pressure: Monitored closely during treatment.

Serious or Rare Side Effects

• Sedation: Patients may experience significant sedation.
• Respiratory depression: Rare but serious respiratory side effect.
• Psychotic symptoms: In rare cases, patients may experience psychotic symptoms.
• Dependency: Potential for dependency with long-term use.

Spravato should be used with caution and under medical supervision. Important precautions include:

• Monitoring: Patients must be monitored by a healthcare professional until they are considered clinically stable and ready to leave the healthcare setting due to the possibility of sedation, dissociation, and elevated blood pressure.
• Pregnancy: Esketamine is not recommended for pregnant or breastfeeding women unless the benefits outweigh the risks.
• Drug Interactions: Patients should inform their doctor about all medications they are taking to avoid potential drug interactions.
• Medical History: Patients with a history of psychotic disorders or substance abuse should be carefully evaluated before starting Spravato.
• Administration: Spravato should be administered under the supervision of a healthcare professional.
• Storage: Store at 2-8°C: keep refrigerated, protect from light, do not freeze or shake.

Spravato may interact with other medications, which can be categorized as follows:

Major Interactions (Avoid)

• CNS depressants: Avoid concomitant use with other CNS depressants due to the risk of increased sedation and respiratory depression.
• MAO inhibitors: Avoid use with MAO inhibitors due to potential for serious drug interactions.
• Alcohol: Avoid alcohol consumption during treatment with Spravato.

Moderate Interactions (Monitor Closely)

• Antidepressants: Monitor closely when used in combination with other antidepressants.
• Antipsychotics: Monitor for increased side effects when used with antipsychotic medications.
• Benzodiazepines: Monitor for increased sedation and respiratory depression.