ZULRESSO Solution for injection Ref.[9971] Active ingredients:

2.1 Important Considerations Prior to Initiating and During Therapy

A healthcare provider must be available on site to continuously monitor the patient, and intervene as necessary, for the duration of the ZULRESSO infusion.

Monitor patients for hypoxia using continuous pulse oximetry equipped with an alarm. Assess for excessive sedation every 2 hours during planned, non-sleep periods [see Warnings and Precautions (5.1)].

Initiate ZULRESSO treatment early enough during the day to allow for recognition of excessive sedation [see Warnings and Precautions (5.1)].

2.2 Recommended Dosage

Administer ZULRESSO as a continuous intravenous (IV) infusion over a total of 60 hours (2.5 days) as follows:

• 0 to 4 hours: Initiate with a dosage of 30 mcg/kg/hour
• 4 to 24 hours: Increase dosage to 60 mcg/kg/hour
• 24 to 52 hours: Increase dosage to 90 mcg/kg/hour (a reduction in dosage to 60 mcg/kg/hour may be considered during this time period for patients who do not tolerate 90 mcg/kg/hour)
• 52 to 56 hours: Decrease dosage to 60 mcg/kg/hour
• 56 to 60 hours: Decrease dosage to 30 mcg/kg/hour

If excessive sedation occurs at any time during the infusion, stop the infusion until the symptoms resolve. The infusion may be resumed at the same or lower dose as clinically appropriate.

2.3 Preparation and Storage Instructions

ZULRESSO is supplied in vials as a concentrated solution that requires dilution prior to administration. After dilution, the product can be stored in infusion bags under refrigerated conditions for up to 96 hours. However, given that the diluted product can be used for only 12 hours at room temperature, each 60-hour infusion will require the preparation of at least five infusion bags.

Prepare according to the following steps using aseptic technique:

• Visually inspect the vials of ZULRESSO for particulate matter and discoloration prior to administration. ZULRESSO is a clear, colorless solution. Do not use if the solution is discolored or particulate matter is present.
• The 60-hour infusion will generally require the preparation of five infusion bags. Additional bags will be needed for patients weighing ≥90 kg.
• For each infusion bag:
  • Prepare and store in a polyolefin, non-DEHP, nonlatex bag, only. Dilute in the infusion bag immediately after the initial puncture of the drug product vial.
  • Withdraw 20 mL of ZULRESSO from the vial and place in the infusion bag. Dilute with 40 mL of Sterile Water for Injection, and further dilute with 40 mL of 0.9% Sodium Chloride Injection (total volume of 100 mL) to achieve a target concentration of 1 mg/mL.
  • Immediately place the infusion bag under refrigerated conditions until use.

Diluted ZULRESSO storage instructions:

• If not used immediately after dilution, store under refrigerated conditions for up to 96 hours. Prolonged storage at room temperature may support adventitious microbial growth.
• Each prepared bag of diluted ZULRESSO may be used for up to 12 hours of infusion time at room temperature. Discard any unused ZULRESSO after 12 hours of infusion.

2.4 Administration Instructions

ZULRESSO must be diluted before administration [see Dosage and Administration (2.3)]. The following are important administration instructions:

• Use a programmable peristaltic infusion pump to ensure accurate delivery of ZULRESSO.
• Administer ZULRESSO via a dedicated line. Do not inject other medications into the infusion bag or mix with ZULRESSO.
• Fully prime infusion administration sets with admixture before inserting into the pump and connecting to the venous catheter.
• Use a PVC, non-DEHP, nonlatex infusion set. Do not use in-line filter infusion sets.

2.5 Recommendations in Patients with End Stage Renal Disease

Avoid use of ZULRESSO in patients with end stage renal disease (ESRD) with eGFR of <15 mL/minute/1.73 m² because of the potential accumulation of the solubilizing agent, betadex sulfobutyl ether sodium [see Clinical Pharmacology (12.3, 12.6)].

Human Experience

There is limited clinical trial experience regarding human overdosage with ZULRESSO. In premarketing clinical studies, two cases of accidental overdosage due to infusion pump malfunction resulted in transient loss of consciousness. Both patients regained consciousness approximately 15 minutes after discontinuation of the infusion without supportive measures. After full resolution of symptoms, both patients subsequently resumed and completed treatment. Overdosage may result in excessive sedation, including loss of consciousness [see Warnings and Precautions (5.1)] and the potential for accompanying respiratory changes.

Management of Overdose

In case of overdosage, stop the infusion immediately and initiate supportive measures as necessary. Brexanolone is rapidly cleared from plasma [see Clinical Pharmacology (12.3)]. Consult a Certified Poison Control Center at 1-800-222-1222 for latest recommendations.

Store the undiluted ZULRESSO product at 2°C to 8°C (36°F to 46°F). Do not freeze. Store protected from light.

The diluted product in the infusion bag can be used at room temperature for up to 12 hours. If the diluted product is not used immediately after dilution, store under refrigerated conditions for up to 96 hours [see Dosage and Administration (2.3)].