Zulresso (brexanolone)
Antidepressant Neuroactive Steroid GABA-A Receptor Modulator Intravenous Vial (Ml)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Brexanolone, a gamma-aminobutyric acid type A (GABAA) receptor positive modulator, is an antidepressant.
Brexanolone is a solubilized preparation of the progesterone metabolite allopregnanolone, an endogenous neuroactive steroid. The precise mechanism of action of brexanolone in the treatment of postpartum depression is not fully understood, but is thought to be related to its positive allosteric modulation of the gamma-aminobutyric acid type A (GABAA) receptor. Brexanolone potentiates GABA-mediated signaling from recombinant human GABAA receptors expressing alpha1beta2gamma2, alpha4beta3delta, and alpha6delta3delta receptor subunits in vitro.
Although the exact etiology of postpartum depression is not known, fluctuations in plasma allopregnanolone concentrations and associated effects on GABA signaling have been implicated in the pathogenesis. During pregnancy, plasma concentrations of steroid hormones, including allopregnanolone, increase steadily, reaching a peak in the third trimester and decrease substantially and rapidly after parturition. This abrupt decline in plasma allopregnanolone concentrations and the ability of GABAA receptors to adapt in response is thought to play a role in the pathogenesis of postpartum depression.
The recommended dosage of brexanolone is intended to achieve plasma allopregnanolone concentrations equivalent to those achieved in the third trimester of pregnancy.
Brexanolone exhibits dose-proportional pharmacokinetics over an IV dosage range of 30-270 mcg/kg per hour. The drug is more than 99% bound to plasma proteins; protein binding is independent of drug concentration. Brexanolone is extensively metabolized via keto-reduction, glucuronidation, and sulfation to 3 major inactive metabolites.
Brexanolone is eliminated via feces and urine (47 and 42%, respectively), primarily as metabolites. Less than 1% of a dose is excreted in urine as unchanged drug. The terminal half-life of brexanolone is approximately 9 hours.
USES: This medication is used to treat a certain type of depression (postpartum depression). Brexanolone is thought to work by affecting the balance of certain natural substances in the brain.
Generic name: brexanolone
Pronunciation: (brex-AN-oh-lone)
Drug class: Antidepressant Neuroactive Steroid GABA-A Receptor Modulator
Therapeutic class: Central Nervous System Agents
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Zulresso
Indications
The following indications are listed for Zulresso:
- Postpartum Depression
Also known as: Postnatal Depression, Puerperal Depression.
Dosing
For the treatment of postpartum depression, brexanolone is administered as a continuous IV infusion over 60 hours as follows:
*0-4 hours: Initiate with a dosage of 30 mcg/kg per hour
*4-24 hours: Increase dosage to 60 mcg/kg per hour
*24-52 hours: Increase dosage to 90 mcg/kg per hour (may decrease to 60 mcg/kg per hour in patients who do not tolerate 90 mcg/kg per hour)
*52-56 hours: Decrease dosage to 60 mcg/kg per hour
*56-60 hours: Decrease dosage to 30 mcg/kg per hour
If excessive sedation occurs at any time during the infusion, the infusion should be interrupted immediately. Upon resolution of symptoms, the infusion may be resumed at the same or lower rate as clinically appropriate.
Brexanolone is administered by continuous IV infusion over 60 hours (2.5 days). The infusion should be initiated early enough during the day to allow for recognition of excessive sedation.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Brexanolone is not metabolized by cytochrome P-450 (CYP) isoenzymes. No formal drug interaction studies have been performed to date to evaluate the effects of other drugs on brexanolone.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*None.
There are no contraindication contraindications for this drug.
- Alcohol use disorder
- Pregnancy
- Suicidal ideation
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects occurring in >=5% of patients receiving brexanolone with an incidence at least twice that of placebo include sedation/somnolence, dry mouth, loss of consciousness, and flushing/hot flush.
Less Frequent
- Unconsciousness
Rare or Very Rare
- Hypoxia
More Frequent
- Dizziness
- Drowsy
- Sedation
- Syncope
- Vertigo
- Xerostomia
Less Frequent
- Diarrhea
- Drug-induced hot flash
- Dyspepsia
- Fatigue
- Flushing
- Injection site sequelae
- Pain in oropharynx
- Tachycardia
Rare or Very Rare
- Accidental fall
Precautions
No enhanced messaging available.
Safety and efficacy of brexanolone have not been established in pediatric patients younger than 15 years of age. Use of brexanolone in pediatric patients 15 to 17 years of age is supported by evidence from adequate and well-controlled studies in adults with postpartum depression, pharmacokinetic data in adults and patients 15 to 17 years of age, and safety data in patients 15 to 17 years of age.
There are no available data on use of brexanolone in pregnant women to inform a drug-associated risk of adverse maternal or fetal outcomes. However, based on published animal studies of other drugs that enhance gamma-aminobutyric acid (GABA) activity, brexanolone may cause fetal harm if administered to pregnant women. Widespread apoptotic neurodegeneration has been observed following administration of other drugs that enhance GABA to neonatal rats during the period of neurodevelopment that is thought to correlate with the third trimester of pregnancy in humans.
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. For more information, clinicians may contact the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visit https://womensmentalhealth.org/research/pregnancyregistry/antidepressants.
Brexanolone is distributed into milk in humans in relatively low concentrations. During infusion, the maximum relative infant dose is expected to be 1-2% of the maternal weight-adjusted dosage. In addition, because the oral bioavailability of brexanolone is less than 5% in adults, infant exposure is expected to be low.
Available data on the use of brexanolone during lactation do not suggest a clinically important risk of adverse reactions to breastfed infants from exposure to the drug. The benefits of breast-feeding should be considered along with the importance of brexanolone to the woman and any potential adverse effects on the breast-fed infant from the drug or the underlying maternal condition.
Effects of brexanolone on milk production have not been reported.
Postpartum depression is associated with pregnancy; therefore, brexanolone has not been studied in geriatric patients.
ICD codes
| Code | Type | Description |
|---|---|---|
| Postpartum depression | ||
| F53.0 | ICD10CM | Postpartum depression |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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