About ZULRESSO
Dosing and administration with ZULRESSO
Recommended dosage is a titration to 90 mcg/kg/hour.
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Individual results may vary.
Not actual patients.
ZULRESSO® (brexanolone) is administered as a continuous intravenous infusion over 2.5* days1
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.
ZULRESSO is supplied in vials as a concentrated solution that requires dilution prior to administration1
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 5 infusion bags.
Prepare according to the following steps using aseptic technique:
Visual inspection
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.
Infusion bag preparation
The 60-hour infusion will generally require the preparation of 5 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, refrigerate 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 12 hours after infusion
Administration of ZULRESSO1
Prior to initiation and during therapy
When to initiate
Initiate ZULRESSO treatment early enough during the day to allow for recognition of excessive sedation.
Monitor the patient
A healthcare provider must be available onsite to continuously monitor the patient, and intervene as necessary, for the duration of the 60-hour (2.5 days) 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.
Administration instructions
ZULRESSO must be diluted before administration.
Use infusion pump
Use a programmable peristaltic infusion pump to ensure accurate delivery of ZULRESSO.
Administer with dedicated line
Administer ZULRESSO via a dedicated line. Do not inject other medications into the infusion bag or mix with ZULRESSO.
Prime infusion sets
Fully prime infusion administration sets with admixture before inserting into the pump and connecting to the venous catheter.
Use a PVC infusion set
Use a PVC, non-DEHP, nonlatex infusion set. Do not use in-line filter infusion sets.
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.
INDICATION
ZULRESSO is indicated for the treatment of postpartum depression (PPD) in patients 15 years and older.
IMPORTANT SAFETY INFORMATION
WARNING: EXCESSIVE SEDATION AND SUDDEN LOSS OF CONSCIOUSNESS
Patients treated with ZULRESSO are at risk of excessive sedation or sudden loss of consciousness during administration.
Because of the risk of serious harm, patients must be monitored for excessive sedation and sudden loss of consciousness and have continuous pulse oximetry monitoring. Patients must be accompanied during interactions with their child(ren).
Because of these risks, ZULRESSO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ZULRESSO REMS.
WARNINGS AND PRECAUTIONS
Excessive Sedation and Sudden Loss of Consciousness
In clinical studies in adults, ZULRESSO caused sedation and somnolence that required dose interruption or reduction in some patients during the infusion (5% of ZULRESSO-treated patients compared to 0% of placebo-treated patients). Some adult patients were also reported to have loss of consciousness or altered state of consciousness during the ZULRESSO infusion (4% of the ZULRESSO-treated patients compared with 0% of the placebo-treated patients). Time to full recovery from loss or altered state of consciousness, after dose interruption, ranged from 15 to 60 minutes in clinical studies in adults. A healthy 55-year-old man participating in a cardiac repolarization study experienced severe somnolence and <1 minute of apnea while receiving two times the maximum recommended dosage of ZULRESSO (180 mcg/kg/hour).
In an open-label clinical study in 20 patients ages 15 to 17 years, one patient experienced dizziness and loss of consciousness.
All patients with loss of or altered state of consciousness recovered with dose interruption. There was no clear association between loss or alteration of consciousness and pattern or timing of dose. Not all patients who experienced a loss or alteration of consciousness reported sedation or somnolence before the episode.
During the infusion, monitor patients for sedative effects every 2 hours during planned, non-sleep periods. Immediately stop the infusion if there are signs or symptoms of excessive sedation. After symptoms resolve, the infusion may be resumed at the same or lower dose as clinically appropriate. Immediately stop the infusion if pulse oximetry reveals hypoxia. After hypoxia, the infusion should not be resumed.
Concomitant use of opioids, antidepressants, or other CNS depressants such as benzodiazepines or alcohol may increase the likelihood or severity of adverse reactions related to sedation. Patients must be accompanied during interactions with their child(ren) while receiving the infusion because of the potential for excessive sedation and sudden loss of consciousness.
Patients should be cautioned against engaging in potentially hazardous activities requiring mental alertness, such as driving, after infusion until any sedative effects of ZULRESSO have dissipated.
ZULRESSO Risk Evaluation and Mitigation Strategy (REMS)
ZULRESSO is available only through a restricted program under a REMS called the ZULRESSO REMS because excessive sedation or sudden loss of consciousness can result in serious harm.
Notable requirements of the ZULRESSO REMS include:
- Healthcare facilities must enroll in the program and ensure that ZULRESSO is only administered to patients who are enrolled in the
ZULRESSO REMS - Pharmacies must be certified with the program and must only dispense ZULRESSO to healthcare facilities who are certified in the
ZULRESSO REMS - Patients must be enrolled in the ZULRESSO REMS prior to administration of ZULRESSO
- Wholesalers and distributors must be registered with the program and must only distribute to certified healthcare facilities and pharmacies
Further information, including a list of certified healthcare facilities, is available at www.zulressorems.com or call 1-844-472-4379.
Suicidal Thoughts and Behaviors
In pooled analyses of placebo-controlled trials of chronically administered antidepressant drugs (SSRIs and other antidepressant classes) that include approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with major depressive disorder (MDD).
ZULRESSO does not directly affect monoaminergic systems. Because of this and the comparatively low number of exposures to ZULRESSO, the risk of developing suicidal thoughts and behaviors with ZULRESSO is unknown. If depression becomes worse or patients experience emergent suicidal thoughts and behaviors, consider changing the therapeutic regimen, including discontinuing ZULRESSO.
Adverse Reactions
The most common adverse reactions (incidence ≥5% and at least twice the rate of placebo) were sedation/somnolence, dry mouth, loss of consciousness, and flushing/hot flush.
Adverse reactions reported in an open-label study in patients 15 to 17 years were generally similar to those observed in clinical studies of ZULRESSO in adults with PPD.
Use in Specific Populations
- Pregnancy: Based on findings from animal studies of other drugs that enhance GABAergic inhibition, ZULRESSO may cause fetal harm
- There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants, including ZULRESSO, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/
- Lactation: Brexanolone is transferred to breastmilk in nursing mothers. There are no data on the effects of ZULRESSO on a breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZULRESSO and any potential adverse effects on the breastfed child from ZULRESSO or from the underlying maternal condition
- Pediatric Use: The safety and effectiveness of ZULRESSO for the treatment of PPD have been established in patients 15 to 17 years. The safety and effectiveness of ZULRESSO in patients less than 15 years of age have not been established
- Renal Impairment: No dosage adjustment is recommended in patients with mild, moderate, or severe renal impairment. Avoid use of ZULRESSO in patients with end stage renal disease (ESRD)
Controlled Substance
ZULRESSO contains brexanolone, a Schedule IV controlled substance under the Controlled Substances Act.
Please also see Full Prescribing Information including Boxed Warning and Medication Guide for ZULRESSO.
To report SUSPECTED ADVERSE REACTIONS, contact Sage Therapeutics, Inc. at 1-844-4-SAGERX (1-844-472-4379) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
INDICATION
ZULRESSO® is indicated for the treatment of postpartum depression in patients 15 years and older.
IMPORTANT SAFETY INFORMATION
WARNING: EXCESSIVE SEDATION AND SUDDEN LOSS OF CONSCIOUSNESS
Patients treated with ZULRESSO are at risk of excessive sedation or sudden loss of consciousness during administration.
Because of the risk of serious harm, patients must be monitored for excessive sedation and sudden loss of consciousness and have continuous pulse oximetry monitoring. Patients must be accompanied during interactions with their child(ren).
Because of these risks, ZULRESSO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ZULRESSO REMS.
Reference
- ZULRESSO Prescribing Information. Cambridge, MA: Sage Therapeutics, Inc; 6/2022.