CLOSE

The site you are about to enter is intended for US healthcare providers only
.

Please confirm that you are a US healthcare provider.

Continue

Cancel

CLOSE

You are now leaving ZULRESSO.com, the official site for ZULRESSO® (brexanolone)
.

This link will take you to another Sage Therapeutics, Inc. website.

Continue

Cancel

CLOSE

You are now leaving ZulressoHCP.com, the official site for ZULRESSO® (brexanolone) and entering one that is not owned or controlled by Sage Therapeutics, Inc.
.

Sage Therapeutics, Inc. makes no representation as to the information contained on sites we do not own or control. Sage Therapeutics, Inc. does not recommend and does not endorse the content on any third-party websites. Your use of third-party websites is at your own risk and subject to the terms and conditions of use for such sites.

Continue

Cancel

CLOSE

You are now leaving ZULRESSO.com, the official site for ZULRESSO® (brexanolone). This link will take you to the Facebook page for ZULRESSO
.

Your use of a third-party website is at your own risk and subject to the terms and conditions of use of such sites.

Continue

Cancel

CLOSE

You are now leaving ZULRESSO.com, the official site for ZULRESSO® (brexanolone). This link will take you to the Instagram page for ZULRESSO
.

Your use of a third-party website is at your own risk and subject to the terms and conditions of use of such sites.

Continue

Cancel

Doctor talking to patient

Individual results may vary.

Not actual patients.

About ZULRESSO

ZULRESSO safety profile

Learn about the safety profile of ZULRESSO® (brexanolone) and consider if it may be right for your patients.


Excessive sedation and sudden loss of consciousness1

In clinical studies, ZULRESSO caused sedation and somnolence that required dose interruption or reduction in some patients during the infusion (5% of ZULRESSO-treated patients compared to 0% of placebo-treated patients). Some patients were also reported to have loss of consciousness (LOC) or altered state of consciousness during the ZULRESSO infusion (4% of the ZULRESSO-treated patients compared with 0% of the placebo-treated patients). Time to full recovery from loss or altered state of consciousness, after dose interruption, ranged from 15-60 minutes. All patients with loss of or altered state of consciousness recovered with dose interruption.

There was no clear association between loss or alteration of consciousness and pattern or timing of dose. Not all patients who experienced a loss or alteration of consciousness reported sedation or somnolence before the episode.

During the infusion

During the infusion, monitor patients for sedative effects every 2 hours during planned, non-sleep periods. Immediately stop the infusion if there are signs or symptoms of excessive sedation.

After symptoms resolve, the infusion may be resumed at the same or lower dose as clinically appropriate.

Immediately stop the infusion if pulse oximetry reveals hypoxia. After hypoxia, the infusion should not be resumed.

Caution patients

Patients should be cautioned against engaging in potentially hazardous activities requiring mental alertness, such as driving, after infusion until any sedative effects of ZULRESSO have dissipated. Patients must be accompanied during interactions with their child(ren) while receiving the infusion because of the potential for excessive sedation and sudden loss of consciousness.

Concomitant use

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.


ZULRESSO REMS1

ZULRESSO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy called the ZULRESSO REMS because excessive sedation or sudden loss of consciousness can result in serious harm.

See notable requirements of the ZULRESSO REMS


Suicidal thoughts and behaviors1

Risk in antidepressants

In pooled analyses of placebo-controlled trials of chronically administered antidepressant drugs (SSRls and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients.

Variation in risk

There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with major depressive disorder (MDD).

Considerations for ZULRESSO

ZULRESSO does not directly affect monoaminergic systems. Because of this and the comparatively low number of exposures to ZULRESSO, the risk of developing suicidal thoughts and behaviors with ZULRESSO is unknown. Consider changing the therapeutic regimen, including discontinuing ZULRESSO, in patients whose depression becomes worse or who experience emergent suicidal thoughts and behaviors.


ZULRESSO adverse reactions1

Adverse reactions reported in ≥2% of ZULRESSO-treated patients and greater than in placebo-treated patients during the 60-hour treatment period.

Chart representing exposure to Zulresso in 140 patients across 3 studies

The data described in the table reflect exposure to ZULRESSO in 140 patients across 3 studies.1-3

Most common adverse reactions

The most common adverse reactions (incidence ≥5% and at least twice the rate of placebo) were sedation/somnolence, dry mouth, loss of consciousness, and flushing/hot flush.

Discontinuation

In the pooled placebo-controlled studies, the incidence of patients who discontinued due to any adverse reaction was 2% of ZULRESSO-treated patients compared to 1% of placebo-treated patients. The adverse reactions leading to treatment discontinuation in ZULRESSO-treated patients were sedation-related (loss of consciousness, vertigo, syncope, and presyncope) or infusion-site pain.

Interruption or reduction

In the pooled placebo-controlled studies, the incidence of patients who had an interruption or reduction of the dosage due to any adverse reaction was 7% of ZULRESSO-treated patients compared to 3% of placebo-treated patients. The adverse reactions leading to dose reduction or interruption in ZULRESSO-treated patients were sedation-related (loss of consciousness, syncope, somnolence, dizziness, fatigue), infusion-site events, changes in blood pressure, or medication error due to infusion pump malfunction. Three ZULRESSO-treated patients who had a dosage interruption because of loss of consciousness subsequently resumed and completed treatment after resolution of symptoms; two patients who had dosage interruption because of loss of consciousness did not resume the infusion.


Use in specific populations

Pregnancy: Based on findings from animal studies of other drugs that enhance GABAergic inhibition, ZULRESSO may cause fetal harm.

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants, including ZULRESSO, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/

Pediatric Use: The safety and effectiveness of ZULRESSO in pediatric patients have not been established.

Renal Impairment: Avoid use of ZULRESSO in patients with end-stage renal disease (ESRD) with eGFR of <15 mL/minute/1.73 m2 because of the potential accumulation of the solubilizing agent, betadex sulfobutyl ether sodium.


Breastfeeding considerations1

There are no data on the effects of ZULRESSO on a breastfed infant.

Lactation study information

  1. A study was conducted in 12 healthy adult lactating women treated with intravenous ZULRESSO according to the recommended 60-hour dosing regimen (maximum dosage was 90 mcg/kg/hour)
  2. The study indicated that brexanolone is transferred to breastmilk in nursing mothers
  3. Concentrations of ZULRESSO in breast milk were at low levels (<10 ng/mL) in >95% of women by 36 hours after the end of the infusion of ZULRESSO
  4. The calculated maximum relative infant dose for ZULRESSO during the infusion is 1% to 2% of the maternal weight-adjusted dosage

Risk considerations

  1. ZULRESSO has low oral bioavailability (<5%) in adults; therefore, infant exposure is expected to be low
  2. Available data on the use of ZULRESSO during lactation do not suggest a significant risk of adverse events to breastfed infants from exposure to ZULRESSO
  3. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZULRESSO and any potential adverse effects on the breastfed child from ZULRESSO or from the underlying maternal condition

Discuss the potential benefits and risks of breastfeeding during the infusion with your patients.


INDICATION

ZULRESSO® is indicated for the treatment of postpartum depression in adults.

IMPORTANT SAFETY INFORMATION

WARNING: EXCESSIVE SEDATION AND SUDDEN LOSS OF CONSCIOUSNESS

Patients treated with ZULRESSO are at risk of excessive sedation or sudden loss of consciousness during administration.

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).

Because of these risks, ZULRESSO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ZULRESSO REMS.

WARNINGS AND PRECAUTIONS

Excessive Sedation and Sudden Loss of Consciousness

In clinical studies, 5% of ZULRESSO-treated patients compared to 0% of placebo-treated patients experienced sedation and somnolence that required dose interruption or reduction. Loss of consciousness or altered state of consciousness was reported in 4% of ZULRESSO-treated patients compared with 0% of placebo-treated patients.

During the infusion, monitor patients for sedative effects every 2 hours during planned, non-sleep periods. Immediately stop the infusion if there are signs or symptoms of excessive sedation. After symptoms resolve, the infusion may be resumed at the same or lower dose as clinically appropriate. Immediately stop the infusion if pulse oximetry reveals hypoxia. After hypoxia, the infusion should not be resumed.

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. Patients must be accompanied during interactions with their child(ren) while receiving the infusion because of the potential for excessive sedation and sudden loss of consciousness.

Patients should be cautioned against engaging in potentially hazardous activities requiring mental alertness, such as driving, after infusion until any sedative effects of ZULRESSO have dissipated.

ZULRESSO Risk Evaluation and Mitigation Strategy (REMS)

ZULRESSO is available only through a restricted program under a REMS called the ZULRESSO REMS because excessive sedation or sudden loss of consciousness can result in serious harm.

Notable requirements of the ZULRESSO REMS include:

  • Healthcare facilities must enroll in the program and ensure that ZULRESSO is only administered to patients who are enrolled in the
    ZULRESSO REMS
  • Pharmacies must be certified with the program and must only dispense ZULRESSO to healthcare facilities who are certified in the
    ZULRESSO REMS
  • Patients must be enrolled in the ZULRESSO REMS prior to administration of ZULRESSO
  • Wholesalers and distributors must be registered with the program and must only distribute to certified healthcare facilities and pharmacies

Further information, including a list of certified healthcare facilities, is available at www.zulressorems.com or call 1-844-472-4379.

Suicidal Thoughts and Behaviors

In pooled analyses of placebo-controlled trials of chronically administered antidepressant drugs (SSRIs and other antidepressant classes) that include approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with major depressive disorder (MDD).

ZULRESSO does not directly affect monoaminergic systems. Because of this and the comparatively low number of exposures to ZULRESSO, the risk of developing suicidal thoughts and behaviors with ZULRESSO is unknown. If depression becomes worse or patients experience emergent suicidal thoughts and behaviors, consider changing the therapeutic regimen, including discontinuing ZULRESSO.

Adverse Reactions

The most common adverse reactions (incidence ≥5% and at least twice the rate of placebo) were sedation/somnolence, dry mouth, loss of consciousness, and flushing/hot flush.

Use in Specific Populations

  • Pregnancy: Based on findings from animal studies of other drugs that enhance GABAergic inhibition, ZULRESSO may cause fetal harm
  • Lactation: Brexanolone is transferred to breastmilk in nursing mothers. There are no data on the effects of ZULRESSO on a breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZULRESSO and any potential adverse effects on the breastfed child from ZULRESSO or from the underlying maternal condition
  • Pediatric Use: The safety and effectiveness of ZULRESSO in pediatric patients have not been established
  • Renal Impairment: No dosage adjustment is recommended in patients with mild, moderate, or severe renal impairment. Avoid use of ZULRESSO in patients with end stage renal disease (ESRD)

Controlled Substance

ZULRESSO contains brexanolone, a Schedule IV controlled substance under the Controlled Substances Act.

Please also see Full Prescribing Information including Boxed Warning and Medication Guide for ZULRESSO.

To report SUSPECTED ADVERSE REACTIONS, contact Sage Therapeutics, Inc. at 1-844-4-SAGERX (1-844-472-4379) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

INDICATION
ZULRESSO® is indicated for the treatment of postpartum depression in adults.

IMPORTANT SAFETY INFORMATION
WARNING: EXCESSIVE SEDATION AND SUDDEN LOSS OF CONSCIOUSNESS
Patients treated with ZULRESSO are at risk of excessive sedation or sudden loss of consciousness during administration.
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).
Because of these risks, ZULRESSO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ZULRESSO REMS.

References

  1. ZULRESSO Prescribing Information. Cambridge, MA: Sage Therapeutics, Inc; 6/2019.
  2. Meltzer-Brody S, Colquhoun H, Riesenberg R, et al. Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet. 2018;392(10152):1058-1070.
  3. Kanes S, Colquhoun H, Gunduz-Bruce H, et al. Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial. Lancet. 2017;390(10093):480-489.