CurrentAvMedPolicy N/A

Zulresso Injection (Medical)

Defines prior authorization clinical criteria, dosing limits, monitoring, age and diagnostic requirements, REMS and pharmacy/administration site requirements for coverage of a single 60-hour Zulresso infusion for postpartum depression. Specifies documentation and authorization process for AvMed members.

Policy Summary

PayerAvMed

PolicyZulresso Injection (Medical)

Policy CodePolicy N/A

Change TypeNo material change

Effective DateN/A

Next Review DateN/A

Key ActionPrescriber must complete the AvMed Medical Prior Authorization/Step-Edit request form with required documentation (including validated rating scale, DSM-5 diagnosis support, prior therapy failure evidence, weight, date of delivery, and site NPI/DEA or specialty pharmacy) and fax to 1-877-535-1391.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes were reported in this update.

1One-time infusion limit per pregnancy

60 hrsAuthorized infusion duration

15+Minimum age (yrs)

≤90 mcg/kg/hrMax hourly dose

Coverage Summary

Covers a single 60‑hour continuous IV infusion of Zulresso (brexanolone) for treatment of moderate to severe postpartum depression, with coverage contingent on REMS registration and required facility monitoring during the infusion; key thresholds include age ≥15 years, postpartum timing limits (onset no earlier than third trimester and no later than 4 months postpartum; member ≤6 months postpartum), prior antidepressant trial duration of ≥6 weeks, and a maximum infusion dose of ≤90 mcg/kg/hr.

Thresholds / Dosing Limits

One-time infusion limit per pregnancy1

Authorized infusion duration60 hours

Minimum age>= 15 years

Maximum hourly dose<= 90 mcg/kg per hour over 60 hours

Dose schedule (0-4 hrs)30 mcg/kg per hour

Dose schedule (4-24 hrs)60 mcg/kg per hour

Dose schedule (24-52 hrs)90 mcg/kg per hour (60 mcg/kg/hr alternative if not tolerated)

Dose schedule (52-56 hrs)60 mcg/kg per hour

Dose schedule (56-60 hrs)30 mcg/kg per hour

Medically Necessary / Approval Criteria

All criteria must be met for approval. To support each line checked, all documentation, including lab results, diagnostics, and/or chart notes, must be provided or request may be denied.

Member is 15 years of age or older

Medication is prescribed by, or in consultation with a psychiatrist

Diagnosis: moderate to severe postpartum depression supported by ALL of the following

Member meets DSM-5 criteria for major depressive disorder (single or recurrent episode)
Clinical diagnosis, made by a psychiatrist or other specialist in the field of psychiatry (e.g., PNP), of moderate to severe postpartum depression
Diagnosis and severity of depression is supported by a validated rating scale (scale and date completed must be attached)
Onset of symptoms occurred no earlier than the third trimester of pregnancy, no later than 4 months postpartum
Member is 6 months or less postpartum

Prior pharmacotherapy failure

Member must have experienced clinical failure with at least ONE oral antidepressant therapy
Failure must include adequate dose (maximally tolerated)
Failure must include adequate duration (at least 6 weeks)
Adherent fills required (verified by pharmacy claims)
Failures must occur during current depressive episode

Member does NOT have active psychosis or a history of bipolar disorder

Healthcare facility, pharmacy, and patient are registered with the REMS program

Monitoring and administration requirements

Member will be appropriately monitored for the duration of the infusion
Healthcare provider will be available on site
Hypoxia monitoring using continuous pulse oximetry equipped with an alarm
Excessive sedation monitoring every two hours during planned, non-sleep periods
Dosing schedule (must follow one of following dosing steps exactly)
- Step 1: 0 to 4 hours: Initiate with a dosage of 30 mcg/kg per hour

Administration location / supplier

Location/site of drug administration with NPI or DEA # of administering location
Specialty Pharmacy - PropriumRx (medication being provided by PropriumRx)

Approval limit: one-time, 60-hour infusion per pregnancy. Member's ≤ 90kg: 5 vials.

Provider Actions & Documentation Requirements

Prior Authorization

Prior authorization required

Prescriber must complete the AvMed Medical Prior Authorization/Step-Edit request form with prescriber signature and all required fields, then fax to 1-877-535-1391.

Required fields: diagnosis, validated rating scale (with date), prior therapy failures, weight, date of delivery
Site NPI or DEA number of administering location or specialty pharmacy information
Prescriber signature required

Documentation Required

Attach supporting documentation

Attach supporting documentation with the prior authorization request. Missing or incomplete documentation may result in denial.

Validated rating scale with date completed
Documentation supporting DSM-5 diagnosis of major depressive disorder and clinical diagnosis of moderate to severe postpartum depression
Chart notes or pharmacy claims verifying prior antidepressant failure (adequate dose/duration and adherent fills)
Verification of REMS registration (facility, pharmacy, and patient)
Monitoring plan for infusion (site monitoring, pulse oximetry, sedation checks)

Documentation Required

Facility/provider monitoring requirements

Facility must meet monitoring requirements for the duration of the 60-hour infusion.

Healthcare provider available on site
Continuous pulse oximetry with an alarm for hypoxia monitoring
Excessive sedation monitoring every two hours during planned, non-sleep periods for the duration of the infusion

Billing Rule

Approval limit per pregnancy

Approval is limited to a one-time, 60-hour infusion per pregnancy. For members who weigh ≤ 90 kg, authorize 5 vials.

J1632

Denial Risk

Denial if criteria not met

Claims may be denied if all listed clinical and monitoring criteria are not met or if required documentation is incomplete.

Background

Zulresso (brexanolone) is FDA‑approved for treatment of moderate to severe postpartum depression and is administered as a continuous IV infusion over 60 hours. Because of risks including excessive sedation and hypoxia, administration requires enrollment in a REMS program. AvMed requires that the facility, pharmacy, and patient be registered in the REMS program, that the infusion be delivered in a monitored facility with on‑site provider availability, continuous pulse oximetry with alarm, and sedation checks, and that prior authorization/step‑edit documentation (including diagnosis, validated rating scale, prior therapy failure evidence, weight, delivery date, and administration site NPI/DEA or specialty pharmacy) be submitted to ensure safety and appropriate use.

REMS: Risk Evaluation and Mitigation Strategy (REMS) registration is required for the facility, pharmacy, and patient before administration of Zulresso due to risks such as excessive sedation and hypoxia; documentation of REMS enrollment must be provided as part of the prior authorization.

Name	Type	Number	Effective Date
Medicare Coverage for outpatient (Part B) drugs	NCD

Policy Summary

PayerAvMed

PolicyZulresso Injection (Medical)

Policy CodePolicy N/A

Change TypeNo material change

Effective DateN/A

Next Review DateN/A

SourceLink

On This Page

OpenPayer

Zulresso Injection (Medical)

Coverage Summary

Medically Necessary / Approval Criteria

Not Medically Necessary / Investigational

Coding

Provider Actions & Documentation Requirements

Background

Medicare Determinations

Revision History