brexanolone

Absorption: IV administration results in complete absorption.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Extensively metabolized via keto-reduction, glucuronidation, and sulfation to inactive metabolites. Primarily excreted in feces (47%) and urine (42%) as metabolites.

Half-Life: 9 hr.

Time/Action Profile ⬆ ⬇

(reduction in depressive symptoms)

ROUTE	ONSET	PEAK	DURATION
IV	1–2 hr	60–72 hr	At least 30 days

Contraind./Precautions ⬆ ⬇

Contraindicated in:

End-stage renal disease (CCr <15 mL/min) (↑ accumulation of solubilizing agent).

Use Cautiously in:

OB: Safety not established;
Lactation: Enters breast milk; use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: May risk of suicidal thoughts/behaviors;
Pedi: Children 15 yr (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

CV: tachycardia

Derm: flushing

GI: dry mouth, diarrhea, dyspepsia, oropharyngeal pain

Neuro: dizziness, presyncope, sedation, vertigo, altered consciousness, loss of consciousness, SUICIDAL THOUGHTS/BEHAVIORS

Interactions ⬆ ⬇

Drug-drug:

Use with benzodiazepines or other CNS depressants, including opioids, non-benzodiazepine sedative/hypnotics, anxiolytics, muscle relaxants, and alcohol may cause profound sedation, loss of consciousness, and/or respiratory depression; avoid concurrent use, if possible.

Route/Dosage ⬆ ⬇

IV (Adults and Children ≥15 yr): 30 mcg/kg/hr for 4 hr, then ↑ to 60 mcg/kg/hr for 20 hr, then ↑ to 90 mcg/kg/hr for 28 hr, then ↓ to 60 mcg/kg/hr for 4 hr, then ↓ to 30 mcg/kg/hr for 4 hr, then discontinue. Total duration of infusion = 60 hr.

Availability ⬆ ⬇

Solution for injection: 5 mg/mL

Assessment ⬆ ⬇

Monitor for hypoxia using continuous pulse oximetry equipped with alarm. Assess for excessive sedation every 2 hr during planned, non-sleep periods. Stop infusion immediately if signs or symptoms of excessive sedation occur. Time to full recovery from loss or altered state of consciousness ranges from 15–60 min after infusion is stopped. Infusion may be resumed at same or lower dose after symptoms resolve. If hypoxia occurs, immediately stop infusion and do not resume.
Assess for suicidal tendencies, especially during early therapy. Risk may be increased in adults ≤24 yr. Consider changing therapeutic regimen, including discontinuing brexanolone, in patients whose depression becomes worse or who experience emergent suicidal thoughts and behaviors.

Implementation ⬆ ⬇

Start brexanolone therapy early enough during the day to allow for recognition of excessive sedation.
- Brexanolone is only available through a restricted Risk Evaluation and Mitigation Strategy (REMS) called the Zulresso REMS due to potential harm from excessive sedation or sudden loss of consciousness. Healthcare facilities must enroll to ensure medication is only given to patients enrolled in program. Pharmacies must be certified with the program. Patients must be enrolled before receiving brexanolone.
Prepare 5 infusion bags for 60 hr period, more if patient weighs ≥90 kg. For each bag, prepare and store in polyolefin, non-DEHP, nonlatex bag, only. Dilute in infusion bag immediately after initial puncture of vial. Withdraw 20 mL of brexanolone from vial and place in infusion bag.Diluent: Dilute with 40 mL of sterile water for injection, and further dilute with 40 mL of 0.9% NaCl 100 mL volume.Concentration: 1 mg/mL. Immediately place infusion bag in refrigerator until use. Solution is clear and colorless; do not administer solutions that are discolored or contain particulate matter. Solution is stable for up to 96 hr if refrigerated. Diluted solution is stable for 12 hr at room temperature. Each 60 hr infusion requires at least 5 bags. Discard bag after 12 hr of infusion.
Rate: Use a programmable peristaltic infusion pump to ensure accurate delivery. See Route and Dosage for rate. Use a dedicated line; do not mix with other medications in bag or line. Prime infusion line with admixture before inserting into pump and connecting to venous catheter. Use a PVC, non-DEHP, nonlatex infusion set. Do not use in-line filter infusion sets.

Patient/Family Teaching ⬆ ⬇

Explain purpose of medication to patient and family and requirements of Zulresso REMS program. Advise patient to read Medication Guide before starting brexanolone.
Advise patient to notify health care professional if excessive sedation occurs during infusion. Patients must not be the primary caregiver of dependents and must be accompanied during interactions with their child(ren).
Caution patient to avoid driving and activities requiring alertness until response from medication is known.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications. Advise patient to avoid taking other CNS depressants or alcohol.
Rep: Advise females of reproductive potential to notify health care professional if they could possibly be pregnant prior to therapy. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Encourage patient to enroll in the registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. To register patients, healthcare professionals should call the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or online at https://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants/.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇