Zulresso (brexanolone)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Approval Status:

Approved March 2019

Specific Treatments:

postpartum depression

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General Information

Zulresso (brexanolone) is a neuroactive steroid gamma-aminobutyric acid (GABA) A receptor positive modulator.

Zulresso is specifically indicated for the treatment of postpartum depression (PPD) in adults.

Zulresso is supplied as a solution for intravenous administration. Administer Zulresso as a continuous intravenous (IV) infusion over a total of 60 hours (2.5 days) as follows:

• 0 to 4 hours: Initiate with a dosage of 30 mcg/kg/hour

• 4 to 24 hours: Increase dosage to 60 mcg/kg/hour

• 24 to 52 hours: Increase dosage to 90 mcg/kg/hour (a reduction in dosage to 60 mcg/kg/hour may be considered during this time period for patients who do not tolerate 90 mcg/kg/hour)

• 52 to 56 hours: Decrease dosage to 60 mcg/kg/hour

 • 56 to 60 hours: Decrease dosage to 30 mcg/kg/hour

If excessive sedation occurs at any time during the infusion, stop the infusion until the symptoms resolve. The infusion may be resumed at the same or lower dose as clinically appropriate.  

Clinical Results

FDA Approval

The efficacy of Zulresso in the treatment of postpartum depression (PPD) was demonstrated in two multicenter, randomized, double-blind, placebo-controlled studies (referred to as Studies 1 and 2) in women (18 to 45 years) with PPD who met the Diagnostic and Statistical Manual of Mental Disorders criteria for a major depressive episode (DSM-IV) with onset of symptoms in the third trimester or within 4 weeks of delivery. In these studies, patients received a 60-hour continuous intravenous infusion of Zulresso or placebo and were then followed for 4 weeks. Study 1 included patients with severe PPD (Hamilton Depression Rating Scale (HAM-D) score ≥ 26), and Study 2 included patients with moderate PPD (HAM-D score of 20 to 25). A titration to the recommended target dosage of 90 mcg/kg/hour was evaluated in both studies (patients received 30 mcg/kg/hour for 4 hours, 60 mcg/kg/hour for 20 hours, 90 mcg/kg/hour for 28 hours, followed by a taper to 60 mcg/kg/hour for 4 hours and then 30 mcg/kg/hour for 4 hours). A titration to a target dosage of 60 mcg/kg/hour (patients received 30 mcg/kg/hour for 4 hours, 60 mcg/kg/hour for 52 hours, then 30 mcg/kg/hour for 4 hours) was also evaluated in Study 1. The primary endpoint was the mean change from baseline in depressive symptoms as measured by the HAM-D total score at the end of the infusion (Hour 60).  In both placebo-controlled studies, titration to a target dose of Zulresso 90 mcg/kg/hour was superior to placebo in improvement of depressive symptoms. In a group of 38 patients in Study 1, a Zulresso titration to a target dose of 60 mcg/kg/hour was also superior to placebo in improvement of depressive symptoms.

Side Effects

Adverse effects associated with the use of Zulresso may include, but are not limited to, the following:

sedation/somnolence

dry mouth

loss of consciousness

flushing/hot flush

The Zulresso drug label comes with the following Black Box Warning: Patients are at risk of excessive sedation or sudden loss of consciousness during administration of Zulreso • 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). • Zulresso is available only through a restricted program called the Zulresso REMS.

 

 

Mechanism of Action

Zulresso (brexanolone) is an allosteric modulator of both synaptic and extrasynaptic GABAA receptors. Allosteric modulation of neurotransmitter receptor activity results in varying degrees of desired activity rather than complete activation or inhibition of the receptor. The mechanism of action of brexanolone in the treatment of PPD in adults is not fully understood, but is thought to be related to its positive allosteric modulation of GABAA receptors.

Additional Information

For additional information regarding Zulresso or post-partum depression please visit https://www.sagerx.com/