Dosing & Uses
Dosage Forms & Strengths
intravenous solution: Schedule IV
- 5mg/mL (100mg/20mL single-dose vial)
Postpartum Depression
Indicated for treatment of postpartum depression (PPD)
Administer as a continuous IV infusion over a total of 60 hr (2.5 days) in a monitored health setting that is able to intervene as necessary with continuous pulse oximetry
Dosing
- 0-4 hours: Initiate at 30 mcg/kg/hr
- 4-24 hours: Increase to 60 mcg/kg/hr
- 24-52 hours: Increase to 90 mcg/kg/hr (if not tolerated, consider reducing to 60 mcg/kg/hr)
- 52 to 56 hours: Decrease to 60 mcg/kg/hr
- 56 to 60 hours: Decrease to 30 mcg/kg/hr
Dosage Modifications
Excessive sedation
- If excessive sedation occurs at any time, stop infusion until symptoms resolve
- May resume infusion at the same or lower dose as clinically appropriate
Hypoxia
- Immediately stop the infusion if pulse oximetry reveals hypoxia
- After hypoxia, do not resume the infusion
Renal impairment
- Mild-to-severe (eGFR ≥15 mL/min/1.73m²): No dose adjustment necessary
- End-stage renal disease (eGFR <15 mL/min/1.73m²): Avoid use; potential accumulation of the solubilizing agent used for brexanolone (ie, betadex sulfobutyl ether sodium)
Hepatic impairment
- No dose adjustment necessary
Dosing Considerations
Healthcare provider must be available on site to continuously monitor the patient, and intervene as necessary, for the duration of the infusion
Monitor for hypoxia using continuous pulse oximetry equipped with an alarm
Assess for excessive sedation q2hr during planned, nonsleep periods
Initiate treatment early enough during the day to allow for recognition of excessive sedation
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Sedation, somnolence (13-21%)
Dizziness, presyncope, vertigo (12-13%)
Dry mouth (3-11%)
1-10%
Loss of consciousness (3-5%)
Flushing, hot flush (2-5%)
Tachycardia (3%)
Diarrhea (2-3%)
Oropharyngeal pain (2-3%)
Dyspepsia (2%)
Warnings
Black Box Warnings
Patients treated with brexanolone are at risk of excessive sedation or sudden loss of consciousness during administration
Because of the risk of serious harm, monitor patients 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, brexanolone is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Zulresso REMS
Patient must enroll in REMS before receiving drug; healthcare facilities and pharmacies must be registered and certified in the REMS program
Contraindications
None
Cautions
Sedation and sudden loss of consciousness
- Sedation and somnolence occurred during clinical trials that required dose interruption or reduction in some patients during infusion
- There was no clear association between loss or altered consciousness and pattern or timing of dose
- Not all patients who experienced a loss of or altered consciousness reported sedation or somnolence before the episode
- Caution against engaging in potentially hazardous activities requiring mental alertness (eg, driving) after infusion until sedative effects dissipate
- Monitor oxygenation with continuous pulse oximetry
Suicidal thoughts and behaviors
- In pooled analyses of placebo-controlled trials of long-term administration of antidepressant drugs (SSRIs and other antidepressants) that included ~77,000 adults and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients aged ≤24 yr was greater than in placebo-treated patients
- Brexanolone does not directly affect monoaminergic systems; because of this and the comparatively low number of exposures to brexanolone, risk of developing suicidal thoughts and behaviors is unknown
Drug interaction overview
- Coadministration with CNS depressants (eg, opioids, benzodiazepines) may increase the likelihood or severity of adverse reactions related to sedation
- In the placebo-controlled studies, a higher percentage of brexanolone-treated patients who used concomitant antidepressants reported sedation-related events
Pregnancy
Pregnancy
Data are not available regarding use in pregnant women
Based on findings in animals of other drugs that enhance GABAergic inhibition, brexanolone may cause fetal harm
Antidepressant pregnancy registry
- Pregnancy exposure registry monitors pregnancy outcomes in women exposed to antidepressants during pregnancy
- Clinicians are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185, OR
- Online at: https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants
Animal studies
- Malformations were not seen in rats or rabbits at plasma levels up to 5 and 6 times the maximum recommended human dose (MRHD), respectively
- Developmental toxicities were seen in the fetuses of rats and rabbits at 5 and ≥3 times the plasma levels at the MRHD, respectively
- Brexanolone administered to pregnant rats during pregnancy and lactation resulted in lower pup survival at doses associated with ≥2 times the plasma levels at the MRHD and a neurobehavioral deficit in female offspring at 5 times the plasma levels at the MRHD
Lactation
Data from a lactation study in 12 women indicate that brexanolone is transferred to breastmilk in nursing mothers; however, the relative infant dose (RID) is low, 1-2% of the maternal weight-adjusted dosage
Available data do not suggest a significant risk of adverse reactions to breastfed infants from exposure
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Mechanism of action for the treatment of PPD is not fully understood
It is believed to be related to positive allosteric modulation of both synaptic and extrasynaptic GABA-A receptors
Absorption
Plasma concentration (mean steady-state)
- 52 ng/mL (at 60 mcg/kg/hr)
- 79 ng/mL (at 90 mcg/kg/hr)
Distribution
Vd: 3 L/kg
Protein bound: >99%
Metabolism
Extensively metabolized by non-CYP based pathways via keto-reduction (AKRs), glucuronidation (UGTs), and sulfation (SULTs)
3 major circulating metabolites are pharmacologically inactive
Elimination
Half-life: ~9 hr
Total plasma clearance: ~1 L/hr/kg
Excretion: 47% feces (primarily as metabolites); 42% urine (<1% unchanged)
Administration
IV Preparation
Supplied in vials as a concentrated solution that requires dilution prior to administration
After dilution, product can be stored in infusion bags under refrigerated conditions for up to 96 hr; however, the diluted product can be used for only 12 hr at room temperature
Each 60-hr infusion requires preparing at least 5 infusion bags (additional bags needed if weight ≥90 kg
Visually inspect vials for particulate matter and discoloration; solution should appear clear and colorless; do not use if discolored or particulate matter observed
For each infusion bag
- Prepare and store only in polyolefin, non-DEHP, and nonlatex bag
- Dilute drug in the infusion bag immediately after the initial puncture of the vial
- Withdraw 20 mL (100 mg) from the vial and place in the infusion bag, and then dilute with sterile water for injection 40 mL, and then further dilute with 0.9% NaCl 40 mL (total volume of 100 mL) to achieve a target concentration of 1 mg/mL
- Immediately refrigerate infusion bag until use
IV Administration
Brexanolone is available only through a restricted program that requires the drug be administered by a health-care provider in a certified healthcare facility to provide constant monitoring and provide necessary intervention if needed
Patient must have continuous pulse oximetry with an alarm and be monitored q2hr during planned nonsleep periods
Infuse by continuous IV infusion using a programmable peristaltic infusion pump to ensure accurate infusion rate
Administer via a dedicated IV line; do not inject other medications into the infusion bag or mix with brexanolone
Fully prime infusion administration sets with admixture before inserting into the pump and connecting the venous catheter
Use a PVC, non-DEHP, nonlatex infusion set; do not use in-line filter infusion sets
Storage
Unopened vial: Store at 2-8°C (36-46°F); do not freeze and protect from light
Diluted solution in infusion bag: Store room temperature for up to 12 hr or refrigerate for up to 96 hr
Images
Patient Handout
Formulary
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