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
Contraindicated (0)
Serious - Use Alternative (2)
- metoclopramide intranasal
brexanolone, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.
- selinexor
selinexor, brexanolone. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.
Monitor Closely (169)
- acetaminophen/phenyltoloxamine
brexanolone, acetaminophen/phenyltoloxamine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- acrivastine
brexanolone, acrivastine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- alfentanil
brexanolone, alfentanil. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- alprazolam
brexanolone, alprazolam. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- amobarbital
brexanolone, amobarbital. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- arbaclofen
brexanolone, arbaclofen. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- aripiprazole
brexanolone, aripiprazole. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- asenapine
brexanolone, asenapine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- baclofen
brexanolone, baclofen. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- benperidol
brexanolone, benperidol. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- benzhydrocodone/acetaminophen
brexanolone, benzhydrocodone/acetaminophen. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- brexpiprazole
brexanolone, brexpiprazole. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- brivaracetam
brexanolone, brivaracetam. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- brompheniramine
brexanolone, brompheniramine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- buprenorphine
brexanolone, buprenorphine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- buprenorphine buccal
brexanolone, buprenorphine buccal. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- buprenorphine subdermal implant
brexanolone, buprenorphine subdermal implant. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- buprenorphine transdermal
brexanolone, buprenorphine transdermal. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- buprenorphine, long-acting injection
brexanolone, buprenorphine, long-acting injection. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- buspirone
brexanolone, buspirone. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- butabarbital
brexanolone, butabarbital. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- butalbital
brexanolone, butalbital. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- butorphanol
brexanolone, butorphanol. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- calcium/magnesium/potassium/sodium oxybates
brexanolone, calcium/magnesium/potassium/sodium oxybates. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- carbamazepine
brexanolone, carbamazepine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- carbinoxamine
brexanolone, carbinoxamine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- cariprazine
brexanolone, cariprazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- carisoprodol
brexanolone, carisoprodol. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- cenobamate
cenobamate, brexanolone. Either increases effects of the other by sedation. Use Caution/Monitor.
- chloral hydrate
brexanolone, chloral hydrate. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- chlordiazepoxide
brexanolone, chlordiazepoxide. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- chlorpheniramine
brexanolone, chlorpheniramine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- chlorpromazine
brexanolone, chlorpromazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- chlorzoxazone
brexanolone, chlorzoxazone. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- clemastine
brexanolone, clemastine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- clobazam
brexanolone, clobazam. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- clonazepam
brexanolone, clonazepam. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- clonidine
brexanolone, clonidine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- clorazepate
brexanolone, clorazepate. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- clozapine
brexanolone, clozapine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- codeine
brexanolone, codeine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- cyclobenzaprine
brexanolone, cyclobenzaprine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- cyproheptadine
brexanolone, cyproheptadine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- dantrolene
brexanolone, dantrolene. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- desflurane
brexanolone, desflurane. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- deutetrabenazine
brexanolone, deutetrabenazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- dexbrompheniramine
brexanolone, dexbrompheniramine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- dexchlorpheniramine
brexanolone, dexchlorpheniramine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- diazepam
brexanolone, diazepam. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- diazepam intranasal
diazepam intranasal, brexanolone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.
- dimenhydrinate
brexanolone, dimenhydrinate. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- diphenhydramine
brexanolone, diphenhydramine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- diphenoxylate hcl
brexanolone, diphenoxylate hcl. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- dosulepin
brexanolone, dosulepin. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- doxylamine
brexanolone, doxylamine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- droperidol
brexanolone, droperidol. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- efavirenz
brexanolone, efavirenz. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- emedastine
brexanolone, emedastine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- esketamine intranasal
brexanolone, esketamine intranasal. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- estazolam
brexanolone, estazolam. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- eszopiclone
brexanolone, eszopiclone. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- ethanol
brexanolone, ethanol. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- ethosuximide
brexanolone, ethosuximide. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- ethotoin
brexanolone, ethotoin. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- ezogabine
brexanolone, ezogabine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- felbamate
brexanolone, felbamate. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- fenfluramine
fenfluramine, brexanolone. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration with drugs that increase serotoninergic effects may increase the risk of serotonin syndrome.
- fentanyl
brexanolone, fentanyl. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- fentanyl intranasal
brexanolone, fentanyl intranasal. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- fentanyl transdermal
brexanolone, fentanyl transdermal. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- fentanyl transmucosal
brexanolone, fentanyl transmucosal. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- flibanserin
brexanolone, flibanserin. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- fluphenazine
brexanolone, fluphenazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- flurazepam
brexanolone, flurazepam. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- fosphenytoin
brexanolone, fosphenytoin. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- gabapentin
brexanolone, gabapentin. Either increases toxicity of the other by sedation. Use Caution/Monitor.
gabapentin, brexanolone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation. - gabapentin enacarbil
brexanolone, gabapentin enacarbil. Either increases toxicity of the other by sedation. Use Caution/Monitor.
gabapentin enacarbil, brexanolone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation. - guanfacine
brexanolone, guanfacine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- haloperidol
brexanolone, haloperidol. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- hydrocodone
brexanolone, hydrocodone. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- hydromorphone
brexanolone, hydromorphone. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- hydroxyzine
brexanolone, hydroxyzine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- iloperidone
brexanolone, iloperidone. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- isoflurane
brexanolone, isoflurane. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- ketamine
brexanolone, ketamine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- lamotrigine
brexanolone, lamotrigine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- lasmiditan
lasmiditan, brexanolone. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
- lemborexant
lemborexant, brexanolone. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects. .
- levetiracetam
brexanolone, levetiracetam. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- levorphanol
brexanolone, levorphanol. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- lorazepam
brexanolone, lorazepam. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- loxapine
brexanolone, loxapine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- loxapine inhaled
brexanolone, loxapine inhaled. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- loxicodegol
brexanolone, loxicodegol. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- lurasidone
brexanolone, lurasidone. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- maprotiline
brexanolone, maprotiline. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- meclizine
brexanolone, meclizine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- meperidine
brexanolone, meperidine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- meprobamate
brexanolone, meprobamate. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- metaxalone
brexanolone, metaxalone. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- methadone
brexanolone, methadone. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- methocarbamol
brexanolone, methocarbamol. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- methohexital
brexanolone, methohexital. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- methsuximide
brexanolone, methsuximide. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- midazolam
brexanolone, midazolam. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- midazolam intranasal
midazolam intranasal, brexanolone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.
- mirtazapine
brexanolone, mirtazapine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- molindone
brexanolone, molindone. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- morphine
brexanolone, morphine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- nalbuphine
brexanolone, nalbuphine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- nitric oxide gas
brexanolone, nitric oxide gas. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- olanzapine
brexanolone, olanzapine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- oliceridine
brexanolone, oliceridine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- opium tincture
brexanolone, opium tincture. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- orphenadrine
brexanolone, orphenadrine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- oxazepam
brexanolone, oxazepam. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- oxycodone
brexanolone, oxycodone. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- oxymorphone
brexanolone, oxymorphone. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- paliperidone
brexanolone, paliperidone. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- pentazocine
brexanolone, pentazocine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- pentobarbital
brexanolone, pentobarbital. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- perampanel
brexanolone, perampanel. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- perphenazine
brexanolone, perphenazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- pheniramine
brexanolone, pheniramine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- phenobarbital
brexanolone, phenobarbital. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- phenytoin
brexanolone, phenytoin. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- pimavanserin
brexanolone, pimavanserin. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- pimozide
brexanolone, pimozide. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- pomalidomide
brexanolone, pomalidomide. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- pregabalin
brexanolone, pregabalin. Either increases toxicity of the other by sedation. Use Caution/Monitor.
pregabalin, brexanolone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation. - primidone
brexanolone, primidone. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- prochlorperazine
brexanolone, prochlorperazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- promazine
brexanolone, promazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- promethazine
brexanolone, promethazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- quazepam
brexanolone, quazepam. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- quetiapine
brexanolone, quetiapine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- ramelteon
brexanolone, ramelteon. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- remifentanil
brexanolone, remifentanil. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- remimazolam
remimazolam, brexanolone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.
- risperidone
brexanolone, risperidone. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- scopolamine
brexanolone, scopolamine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- secobarbital
brexanolone, secobarbital. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- sevoflurane
brexanolone, sevoflurane. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- sodium oxybate
brexanolone, sodium oxybate. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- stiripentol
brexanolone, stiripentol. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- sufentanil
brexanolone, sufentanil. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- sufentanil SL
brexanolone, sufentanil SL. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- sulpiride
brexanolone, sulpiride. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- suvorexant
brexanolone, suvorexant. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- tapentadol
brexanolone, tapentadol. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- tasimelteon
brexanolone, tasimelteon. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- temazepam
brexanolone, temazepam. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- tetrabenazine
brexanolone, tetrabenazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- thalidomide
brexanolone, thalidomide. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- thioridazine
brexanolone, thioridazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- thiothixene
brexanolone, thiothixene. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- tiagabine
brexanolone, tiagabine. Either increases levels of the other by sedation. Use Caution/Monitor.
- tizanidine
brexanolone, tizanidine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- topiramate
brexanolone, topiramate. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- tramadol
brexanolone, tramadol. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- triazolam
brexanolone, triazolam. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- trifluoperazine
brexanolone, trifluoperazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- triprolidine
brexanolone, triprolidine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- valerian
brexanolone, valerian. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- vigabatrin
brexanolone, vigabatrin. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- zaleplon
brexanolone, zaleplon. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- ziconotide
brexanolone, ziconotide. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- ziprasidone
brexanolone, ziprasidone. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- zolpidem
brexanolone, zolpidem. Either increases toxicity of the other by sedation. Use Caution/Monitor.
Minor (0)
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
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
