Patients treated with brexanolone 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, brexanolone is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ZULRESSO REMS.
Depression, postpartum: Note: A health care provider must be onsite to monitor and intervene as necessary for entire duration of the infusion.
Adolescents ≥15 years: Continuous IV infusion over 60 hours; initiate continuous infusion early enough in the day to allow for recognition of excessive sedation; titrate the dose as follows:
0 to 4 hours: IV: 30 mcg/kg/hour.
4 to 24 hours: IV: 60 mcg/kg/hour.
24 to 52 hours: IV: 90 mcg/kg/hour; may reduce to 60 mcg/kg/hour if higher dose not tolerated.
52 to 56 hours: IV: 60 mcg/kg/hour.
56 to 60 hours: IV: 30 mcg/kg/hour.
Dosage adjustment for toxicity: Adolescents ≥15 years:
Excessive sedation: Immediately stop infusion at any sign of excessive sedation; after resolution, may resume infusion at the same or reduced dose, as clinically appropriate.
Hypoxia: Immediately stop infusion if pulse oximetry indicates hypoxia; do not resume therapy.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Adolescents ≥15 years:
eGFR ≥15 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <15 mL/minute/1.73 m2: Avoid use due to potential accumulation of solubilizing agent, betadex sulfobutyl ether sodium.
Adolescents ≥15 years: No dosage adjustment necessary.
(For additional information see "Brexanolone: Drug information")
Depression, postpartum: IV: Note: Initiate 60-hour continuous infusion early enough in the day to allow for recognition of excessive sedation. Titrate the dose as detailed.
0 to 4 hours: 30 mcg/kg/hour
4 to 24 hours: 60 mcg/kg/hour
24 to 52 hours: 90 mcg/kg/hour; may reduce dose to 60 mcg/kg/hour based on tolerability
52 to 56 hours: 60 mcg/kg/hour
56 to 60 hours: 30 mcg/kg/hour
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
eGFR ≥15 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <15 mL/minute/1.73 m2: Use not recommended.
No dosage adjustment necessary.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Presyncope (≤13%)
Central nervous system: Drowsiness (≤21%), sedated state (≤21%), dizziness (≤13%), vertigo (≤13%)
Gastrointestinal: Xerostomia (3% to 11%)
1% to 10%:
Cardiovascular: Flushing (≤5%), tachycardia (3%)
Central nervous system: Loss of consciousness (3% to 5%)
Endocrine & metabolic: Hot flash (≤5%)
Gastrointestinal: Diarrhea (2% to 3%), dyspepsia (2%)
Respiratory: Oropharyngeal pain (2% to 3%)
<1%, postmarketing, and/or case reports: Impaired consciousness
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Excessive sedation and sudden loss of consciousness: Time to full recovery after dose interruption following altered or loss of consciousness ranged from 15 to 60 minutes. Caution patients about performing tasks that require mental alertness following the infusion (eg, operating machinery or driving).
• Suicidal thoughts and behaviors: The risk of suicidal thoughts and behaviors with brexanolone is unknown. Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor all patients for clinical worsening, suicidality, or unusual changes in behavior. Consider changing the therapeutic regimen, including discontinuing brexanolone, in patients who experience worsening depression or emergent suicidal thoughts and behaviors.
Disease-related concerns:
• Drug abuse and dependence: May lead to abuse and dependence. Taper according to dose recommendations unless toxicity requires immediate interruption/discontinuation.
Other warnings/precautions:
• Risk Evaluation and Mitigation Strategy (REMS): Because of the risk of serious harm resulting from excessive sedation or sudden loss of consciousness, brexanolone is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ZULRESSO REMS. Health care facilities and pharmacies must be certified with the REMS program and patients must enroll in the program prior to administration. A list of certified healthcare facilities is available at www.zulressorems.com or 1-844-472-4379.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous [preservative free]:
Zulresso: 100 mg/20 mL (20 mL [DSC])
No
Solution (Zulresso Intravenous)
100 mg/20 mL (per mL): $447.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
C-IV
IV: Administer as a continuous IV infusion over 60 hours; infusion rate is weight-based and titrated throughout infusion (see "Dosing: Pediatric"); use a dedicated line using a programmable peristaltic infusion pump. Prime infusion administration sets with admixture before inserting into the pump and connecting to the venous catheter. Use a PVC, non-DHEP, nonlatex infusion set; do not use in-line filter infusion sets. Monitor sedation levels and pulse oximetry for duration of the infusion.
IV: Administer as a continuous infusion over 60 hours in a dedicated line using a programmable peristaltic infusion pump. Prime infusion administration sets with admixture before inserting into the pump and connecting to the venous catheter. Use a PVC, non-DHEP, nonlatex infusion set; do not use in-line filter infusion sets.
Undiluted vials: Store vials at 2°C to 8°C (36°F to 46°F). Do not freeze. Protect from light.
Diluted infusion solution: Infusion bags may be used at room temperature for up to 12 hours or stored under refrigeration for up to 96 hours.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Zulresso: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/211371s007lbl.pdf#page=20
Treatment of postpartum depression (FDA approved in ages ≥15 years and adults).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification
BuPROPion: May increase CNS depressant effects of Brexanolone. Risk C: Monitor
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification
Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
CNS Depressants: May increase CNS depressant effects of Brexanolone. Risk C: Monitor
Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification
Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor
DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification
HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification
Isocarboxazid: May increase CNS depressant effects of Brexanolone. Risk C: Monitor
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification
Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Moclobemide: May increase CNS depressant effects of Brexanolone. Risk C: Monitor
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: CNS Depressants may increase CNS depressant effects of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider Therapy Modification
OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Phenelzine: May increase CNS depressant effects of Brexanolone. Risk C: Monitor
Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor
Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification
ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor
Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor
Selective Serotonin Reuptake Inhibitor: May increase CNS depressant effects of Brexanolone. Risk C: Monitor
Selegiline: May increase CNS depressant effects of Brexanolone. Risk C: Monitor
Serotonin Reuptake Inhibitor/Antagonists: May increase CNS depressant effects of Brexanolone. Risk C: Monitor
Serotonin/Norepinephrine Reuptake Inhibitor: May increase CNS depressant effects of Brexanolone. Risk C: Monitor
Suvorexant: CNS Depressants may increase CNS depressant effects of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid
Tranylcypromine: May increase CNS depressant effects of Brexanolone. Risk C: Monitor
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Zolpidem: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to brexanolone may cause fetal harm.
Untreated and undertreated mental health conditions are associated with adverse pregnancy outcomes (ACOG 2023). Untreated postpartum depression (PPD) is associated with impaired infant attachment and feeding, which is then associated with long-term impact on development (Saharoy 2023). Although PPD may have an onset during the third trimester, brexanolone is initiated after delivery. Management should be made as part of a shared decision-making process. Agents other than brexanolone should be used when treatment for depression requires initiation during pregnancy (ACOG 2023).
Data collection to monitor pregnancy and infant outcomes following exposure to antidepressant medications is ongoing. Pregnant patients 45 years and younger with a history of psychiatric illness are encouraged to enroll in the National Pregnancy Registry for Antidepressants (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/antidepressants).
Continuous pulse oximetry; sedation level every 2 hours during planned, nonsleep periods; suicidal ideation.
Mechanism of action is not fully understood, but is thought to be related to positive allosteric modulation of GABA-A receptors.
Distribution: Vd: ~3 L/kg
Protein binding: >99%
Metabolism: Extensively metabolized by keto-reduction (AKRs), glucuronidation (UGTs), and sulfation (SULTs) to inactive metabolites
Half-life elimination: ~9 hours
Excretion: Feces: 47%; Urine: 42% (<1% as unchanged drug)