brexanolone ZULRESSO
Class: Neuroactive SteroidFDA Indications: Postpartum Depression
Off-Label Use: Alzheimers Disease
Prescribing
FDA Schedule Pending FDA reviewForms: 100mg single-dose vial
Dose Range: 100 mg/day
Starting: Administered as a continuous intravenous infusion over 60 hours (2.5 days) as follows:
- 0–4°: Start at 30 mcg/kg/hr
- 4–24°: ↑ to 60 mcg/kg/hr
- 24–52°: ↑ to 90 mcg/kg/hr
- 52–56°: ↓ to 60 mcg/kg/hr
- 56–60°: ↓ to 30 mcg/kg/hr
Precautions
Contraindications: NoneSide Effects: sedation/somnolence, xerostomia, loss of consciousness, flushing
Pharmacodynamics
1° MOA: An analog of the endogenous hormone allopregnanolone, a neuroactive metabolite of progesterone, that is a GABAAR PAMTarget: GABAA
Pharmacokinetics
t½: 9° TMAX: ?°Substrate of: Non-CYP based pathways via three main routes: keto-reduction, glucuronidation, and sulfation
Inhibits: ∅ ; Induces: ∅
Active Metabolites: ∅
DDIs
- - Concomitant use of opioids, antidepressants, or other CNS depressants such as benzodiazepines or alcohol may increase the likelihood or severity of adverse reactions related to sedation
Misc
- - a healthcare provider must be available on site to continuously monitor patient and intervene as necessary, for the duration of the infusion
- - monitor patients for hypoxia using continuous SpO2 equipped with an alarm; assess for excessive sedation Q2° during planned, non-sleep periods
- - for hours 24-52 of the infusion, can continue 60 mcg/kg/hr rate if patient does't tolerate 90 mcg/kg/hr
- - available only through ZULRESSO REMS because excessive sedation or sudden loss of consciousness can result in serious harm
Special Populations
Category Not classified.—Based on findings from animal studies of other drugs that enhance GABAergic inhibition, may cause fetal harm. There are no available data on use in pregnant women to determine a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
With a low oral bioavailability (<5%) in adults, and an RID of only 1-2%, infant exposure is expected to be very low. There were no reports of effects on milk production. There are no data on the effects on a breastfed infant. Available data do not suggest a significant risk of adverse reactions to breastfed infants.
Avoid use in patients with ESRD with eGFR of <15 because of the potential accumulation of the solubilizing agent, betadex sulfobutyl ether sodium
No dose adjustment necessary.