Usual Adult Dose for Depression

INDUCTION PHASE:
Weeks 1 to 4:

• Day 1: 56 mg intranasally ONCE
• Subsequent doses: 56 to 84 mg intranasally 2 times a week

MAINTENANCE PHASE:
Weeks 5 to 8: 56 to 84 mg intranasally once a week
Week 9 and after: 56 to 84 mg intranasally every 2 weeks OR once a week

Comments:

• IMPORTANT CONSIDERATION: Treatment sessions should be directly supervised by a healthcare provider; treatment sessions should include nasal administration of the dose and post-administration observation.
• Patients who require nasal corticosteroids/decongestants should use the agent(s) at least 1 hour before using this drug.
• Patients should be advised to avoid eating foods for at least 2 hours before, and to avoid drinking liquids for at least 30 minutes before administration.
• After the induction phase, evidence of therapeutic benefit should be evaluated to determine the need for continued treatment.
• After Week 8, the dosing frequency should be individualized to the least frequent dosing to maintain remission.

Use: In combination with an oral antidepressant for the treatment of treatment-resistant depression (TRD)

Usual Adult Dose for Depressive Disorder, Other

84 mg intranasally 2 times a week for 4 weeks

• After 4 weeks, evidence of therapeutic benefit should be evaluated to determine the need for continued treatment.

Comments:

• The dosage may be decreased to 56 mg intranasally 2 times a week if intolerable symptoms occur.
• LIMITATION OF USE: Efficacy in suicide prevention or in reducing suicidal behavior or ideation has not been demonstrated beyond 4 weeks; this drug does not preclude hospitalization if clinically warranted, even if patients improve after an initial dose of treatment.
• IMPORTANT CONSIDERATION: Treatment sessions should be directly supervised by a healthcare provider; treatment sessions should include nasal administration of the dose and post-administration observation.
• Patients who require nasal corticosteroids/decongestants should use the agent(s) at least 1 hour before using this drug.
• Patients should be advised to avoid eating foods for at least 2 hours before, and to avoid drinking liquids for at least 30 minutes before administration.

Use: In combination with an oral antidepressant for the treatment of depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior

Usual Adult Dose for Major Depressive Disorder

84 mg intranasally 2 times a week for 4 weeks

• After 4 weeks, evidence of therapeutic benefit should be evaluated to determine the need for continued treatment.

Comments:

• The dosage may be decreased to 56 mg intranasally 2 times a week if intolerable symptoms occur.
• LIMITATION OF USE: Efficacy in suicide prevention or in reducing suicidal behavior or ideation has not been demonstrated beyond 4 weeks; this drug does not preclude hospitalization if clinically warranted, even if patients improve after an initial dose of treatment.
• IMPORTANT CONSIDERATION: Treatment sessions should be directly supervised by a healthcare provider; treatment sessions should include nasal administration of the dose and post-administration observation.
• Patients who require nasal corticosteroids/decongestants should use the agent(s) at least 1 hour before using this drug.
• Patients should be advised to avoid eating foods for at least 2 hours before, and to avoid drinking liquids for at least 30 minutes before administration.

Use: In combination with an oral antidepressant for the treatment of depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Mild liver dysfunction (Child-Pugh class A): Data not available
Moderate liver dysfunction (Child-Pugh class B): Monitoring for a longer duration post-administration should be considered.
Severe liver dysfunction (Child-Pugh class C): Not recommended.

Dose Adjustments

Missed treatment session(s):

• Per clinical judgement, healthcare providers may consider returning to the previous dosing schedule in patients with worsening depression symptoms who missed treatment session(s).

Precautions

CONTRAINDICATIONS:

• Hypersensitivity to the active component, ketamine, or to any of the ingredients
• Patients with a history of intracerebral hemorrhage
• Patients with aneurysmal vascular disease (including abdominal and thoracic aorta, intracranial, and peripheral vessels) and/or arteriovenous malformation

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for Spravato. It includes elements to assure safe use and an implementation system. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS:
ABUSE AND MISUSE:

• This drug has the potential to be abused and misused.

Recommendations:

• The risks and benefits of prescribing this drug should be considered prior to use in patients at higher risk of abuse.
• Patients should be monitored for signs/symptoms of abuse/misuse.
• Because of the risks of serious adverse outcomes resulting from abuse and misuse, this drug is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Spravato REMS.

DISSOCIATION:

• Patients are at risk of dissociative/perceptual changes after administration.

Recommendations:

• Because of the dissociation risk, patients must be monitored for at least 2 hours at each treatment session, followed by an assessment to determine when the patient is considered clinically stable and ready to leave the healthcare setting.
• Because of the risks of serious adverse outcomes resulting from dissociation, this drug is only available through a restricted program under a REMS called the Spravato REMS.

SEDATION:

• Patients are at risk for sedation after administration of this drug.

Recommendations:

• Because of the sedation risk, patients must be monitored for at least 2 hours at each treatment session, followed by an assessment to determine when the patient is considered clinically stable and ready to leave the healthcare setting.
• Because of the risks of serious adverse outcomes resulting from sedation, this drug is only available through a restricted program under a REMS called the Spravato REMS.

SUICIDAL THOUGHTS AND BEHAVIORS:

• Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adults in short-term studies.

Recommendations:

• All antidepressant-treated patients should be closely monitored for clinical worsening and for the emergence of suicidal thoughts and behaviors.
• This drug is not approved for use in pediatric patients.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule III

Dialysis

Data not available

Other Comments

Administration advice:

• Nasal formulations of this drug should be taken with an oral antidepressant.
• Patients should be advised to avoid eating foods for at least 2 hours before, and to avoid drinking liquids for at least 30 minutes before administration.
• Blood pressure should be monitored prior to and during treatment; risks should be considered prior to administration in patients with elevated baseline blood pressures.
• The manufacturer product information should be consulted regarding specific nasal device administration.
• Parenteral doses should be determined by patient-specific factors, and doses should be titrated based on requirements.

Storage requirements:

• Parenteral solution: The manufacturer product information should be consulted.

Reconstitution/preparation techniques:

• Infusion solutions may be given undiluted or may be diluted prior to administration.
• COMPATIBLE: 0.9% sodium chloride or 5% glucose
• INCOMPATIBLE: 4-hydroxybutyric acid, barbiturates, diazepam, furosemide, sodium, sodium bicarbonate, theophylline

General:

• LIMITATION OF USE: Some manufacturers state that parenteral formulations should be restricted to hospital use, and should be given by a healthcare provider specializing in anesthesiology or emergency medicine.
• Respiratory depression may result from high doses or too rapid IV administration.

Monitoring:

• CARDIOVASCULAR: Blood pressure prior to starting treatment, approximately 40 minutes after administration, and subsequently as clinically appropriate
• GENERAL: Clinical stability following dosing (including blood pressure)
• RENAL: Signs/symptoms of cystitis

Patient advice:

• Read the US FDA-approved patient labeling (Patient Information and Instructions for Use).
• Patients should be advised that they will be required to be observed for at least 2 hours after administration and will need to arrange for transportation home following home after treatment.
• Inform patients that they should avoid driving or operating machinery until the next day after a restful sleep.
• Advise patients to speak to their healthcare provider if they become pregnant, intend to become pregnant, or are breastfeeding.
• Patients should be counseled to report new/unusual changes in thinking or behavior or worsening of depression.

Frequently asked questions

• Is Spravato (esketamine) a controlled substance?