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Brexanolone

Medically reviewed by Drugs.com. Last updated on Aug 10, 2020.

Pronunciation

(brex AN oh lone)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Zulresso: 100 mg/20 mL (20 mL)

Brand Names: U.S.

  • Zulresso

Pharmacologic Category

  • Gamma-Aminobutyric Acid (GABA) A Receptor Positive Modulator

Pharmacology

Mechanism of action is not fully understood, but is thought to be related to positive allosteric modulation of GABA-A receptors.

Distribution

Vd: ~3 L/kg

Metabolism

Extensively metabolized by keto-reduction (AKRs), glucuronidation (UGTs), and sulfation (SULTs) to inactive metabolites

Excretion

Feces: 47%; Urine: 42% (<1% as unchanged drug)

Half-Life Elimination

~9 hours

Protein Binding

>99%

Use: Labeled Indications

Depression, postpartum: Treatment of postpartum depression (PPD) in adults

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosing: Adult

Depression, postpartum: IV: Note: Initiate 60-hour continuous infusion early enough in the day to allow for recognition of excessive sedation. Titrate the dose as detailed.

0 to 4 hours: 30 mcg/kg/hour

4 to 24 hours: 60 mcg/kg/hour

24 to 52 hours: 90 mcg/kg/hour; may reduce dose to 60 mcg/kg/hour based on tolerability

52 to 56 hours: 60 mcg/kg/hour

56 to 60 hours: 30 mcg/kg/hour

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Adjustment for Toxicity

Excessive sedation: Immediately stop infusion at any sign of excessive sedation. After symptoms resolve, infusion may be resumed at the same or reduced dose, as clinically appropriate.

Hypoxia: Immediately stop infusion if pulse oximetry indicates hypoxia. Do not resume therapy.

Reconstitution

Withdraw 20 mL of brexanolone from the vial and place in a polyolefin, non-DHEP, nonlatex bag. Dilute with 40 mL SWFI and further dilute with 40 mL NS to a total volume of 100 mL (target concentration 1 mg/mL). Each 60-hour infusion will generally require preparation of 5 infusion bags; additional bags may be required for patients weighing ≥90 kg.

Administration

IV: Administer as a continuous infusion over 60 hours in a dedicated line using a programmable peristaltic infusion pump. Prime infusion administration sets with admixture before inserting into the pump and connecting to the venous catheter. Use a PVC, non-DHEP, nonlatex infusion set; do not use in-line filter infusion sets.

Storage

Undiluted vials: Store vials at 2°C to 8°C (36°F to 46°F). Do not freeze. Protect from light.

Diluted infusion solution: Infusion bags may be used at room temperature for up to 12 hours or stored under refrigeration for up to 96 hours.

Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Consider therapy modification

BuPROPion: May enhance the CNS depressant effect of Brexanolone. Monitor therapy

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the CNS depressant effect of Brexanolone. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Consider therapy modification

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Isocarboxazid: May enhance the CNS depressant effect of Brexanolone. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Consider therapy modification

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Moclobemide: May enhance the CNS depressant effect of Brexanolone. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interupt oxybate salt treatment during short-term opioid use. Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Phenelzine: May enhance the CNS depressant effect of Brexanolone. Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the CNS depressant effect of Brexanolone. Monitor therapy

Selegiline: May enhance the CNS depressant effect of Brexanolone. Monitor therapy

Serotonin Reuptake Inhibitor/Antagonists: May enhance the CNS depressant effect of Brexanolone. Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the CNS depressant effect of Brexanolone. Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Tranylcypromine: May enhance the CNS depressant effect of Brexanolone. Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Adverse Reactions

>10%:

Cardiovascular: Presyncope (≤13%)

Central nervous system: Drowsiness (≤21%), sedated state (≤21%), dizziness (≤13%), vertigo (≤13%)

Gastrointestinal: Xerostomia (3% to 11%)

1% to 10%:

Cardiovascular: Flushing (≤5%), tachycardia (3%)

Central nervous system: Loss of consciousness (3% to 5%)

Endocrine & metabolic: Hot flash (≤5%)

Gastrointestinal: Diarrhea (2% to 3%), dyspepsia (2%)

Respiratory: Oropharyngeal pain (2% to 3%)

<1%, postmarketing, and/or case reports: Impaired consciousness

ALERT: U.S. Boxed Warning

Excessive sedation and sudden loss of consciousness:

Patients treated with brexanolone 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, brexanolone is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ZULRESSO REMS.

Warnings/Precautions

Concerns related to adverse effects:

• Excessive sedation and sudden loss of consciousness: [US Boxed Warning]: Patients treated with brexanolone 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). Consider dose interruption and/or reduction, or discontinuation with excessive sedation. Time to full recovery after dose interruption following altered or loss of consciousness ranged from 15 to 60 minutes. Caution patients about performing tasks that require mental alertness following the infusion (eg, operating machinery or driving).

• Suicidal thoughts and behaviors: The risk of suicidal thoughts and behaviors with brexanolone is unknown. Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor all patients for clinical worsening, suicidality, or unusual changes in behavior. Consider changing the therapeutic regimen, including discontinuing brexanolone, in patients who experience worsening depression or emergent suicidal thoughts and behaviors.

Disease-related concerns:

• Drug abuse and dependence: May lead to abuse and dependence. Taper according to dose recommendations unless toxicity requires immediate interruption/discontinuation.

Other warnings/precautions:

• Risk Evaluation and Mitigation Strategy (REMS): [US Boxed Warning]: Because of the risk of serious harm resulting from excessive sedation or sudden loss of consciousness, brexanolone is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ZULRESSO REMS. Healthcare facilities and pharmacies must be certified with the REMS program and patients must enroll in the program prior to administration. A list of certified healthcare facilities is available at www.zulressorems.com or 1-844-472-4379.

Monitoring Parameters

Continuous pulse oximetry; sedation every 2 hours during planned, non-sleep periods; suicidal ideation

Reproductive Considerations

In clinical studies for postpartum depression, treatment was started within 6 months after delivery. Study participants were required to have a negative pregnancy test and use contraception during therapy and for 30 days after completion of the brexanolone infusion (Meltzer-Brody 2018).

Pregnancy Considerations

Based on the mechanism of action and data from animal reproduction studies, in utero exposure to brexanolone may cause fetal harm.

Data collection to monitor pregnancy outcomes following exposure to brexanolone is ongoing. Health care providers are encouraged to enroll females exposed to brexanolone during pregnancy in the National Pregnancy Registry for Antidepressants (844-405-6185) or https://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants/.

Patient Education

What is this drug used for?

• It is used to treat postpartum depression (PPD).

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness

• Dry mouth

• Flushing

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Depression like thoughts of suicide, anxiety, emotional instability, or confusion.

• Agitation

• Irritability

• Panic attacks

• Behavioral changes

• Mood changes

• Severe fatigue

• Passing out

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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