oncentrated solution that requires dilution prior toadministration. After dilution, the product can be stored in infusion bags under refrigeratedconditions for up to 96 hours. However, given that the diluted product can be used for only12 hours at room temperature, each 60-hour infusion will require the preparation of at least fiveinfusion bags.
Prepare according to the following steps using aseptic technique:
• Visually inspect the vials of ZULRESSO for particulate matter and discoloration prior toadministration. ZULRESSO is a clear, colorless solution. Do not use if the solution isdiscolored 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:
o Prepare and store in a polyolefin, non-DEHP, nonlatex bag, only. Dilute in theinfusion bag immediately after the initial puncture of the drug product vial.
o Withdraw 20 mL of ZULRESSO from the vial and place in the infusion bag. Dilutewith 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 concentrationof 1 mg/mL.
o 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 to96 hours. Prolonged storage at room temperature may support adventitious microbialgrowth.
• Each prepared bag of diluted ZULRESSO may be used for up to 12 hours of infusiontime 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)]. Thefollowing are important administration instructions:
• Use a programmable peristaltic infusion pump to ensure accurate delivery ofZULRESSO.
• Administer ZULRESSO via a dedicated line. Do not inject other medications into theinfusion bag or mix with ZULRESSO.
• Fully prime infusion administration sets with admixture before inserting into the pumpand 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 DiseaseAvoid use of ZULRESSO in patients with end stage renal disease (ESRD) with eGFR of< 15 mL/minute/1.73 m2because of the potential accumulation of the solubilizing agent, betadexsulfobutyl ether sodium [see Clinical Pharmacology (12.3, 12.6)].
3 DOSAGE FORMS AND STRENGTHS
Injection: 100 mg/20 mL (5 mg/mL) clear, colorless solution in a single-dose vial.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Excessive Sedation and Sudden Loss of ConsciousnessIn clinical studies, ZULRESSO caused sedation and somnolence that required dose interruptionor reduction in some patients during the infusion (5% of ZULRESSO-treated patients comparedto 0% of placebo-treated patients). Some patients were also reported to have loss of
consciousness or altered state of consciousness during the ZULRESSO infusion (4% of theZULRESSO-treated patients compared with 0% of the placebo-treated patients). Time to fullrecovery from loss or altered state of consciousness, after dose interruption, ranged from 15 to60 minutes. A healthy 55-yea
