CurrentCentenePolicy CP.PHAR.638

Nalmefene (Opvee, Zurnai)

Covers medical necessity and prior authorization criteria for nalmefene products Opvee and Zurnai for treatment of known or suspected opioid overdose for Centene lines of business (Commercial, HIM, Medicaid), including dosing, quantities, and continuity rules.

Policy Summary

PayerCentene

PolicyNalmefene (Opvee, Zurnai)

Policy CodePolicy CP.PHAR.638

Change TypeMaterial updates (coding, product addition, state rules)

Effective Date09.01.23

Next Review Date

Key ActionSubmit prior authorization with documentation showing member meets opioid overdose criteria and requested quantity within product limits.

SourceLink

POLICY UPDATE CHANGES

Added disclaimer that medical management techniques, including quantity management, beyond step therapy is not allowed for members in NV per SB 43.

RT4: added newly approved Zurnai to the policy.

HCPCS code G0532 added to coding implications.

3Q 2025 annual review: added step therapy bypass for IL HIM per IL HB 5395.

Age ≥ 12Minimum age

2 boxesOpvee limit

4 autoinjectorsZurnai limit

3Lines of Business

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria

Initial Therapy - Opioid Overdose

Covered when ALL of the following are met for Opioid Overdose:

Opioid Overdose Initial: 1) Member may have access to opioids; 2) Age ≥ 12 years; 3) Medical justification supports inability to use generic naloxone nasal spray or naloxone solution for injection (e.g., contraindications or clinically adverse effects to naloxone, or member is prescribed a long-acting opioid); 4) Requested quantity does not exceed either: a) Opvee: two boxes (4 nasal spray devices) per prescription, OR b) Zurnai: 4 autoinjectors per prescription.

For members in Nevada, medical management techniques, including quantity management, beyond step therapy is not allowed. For Illinois HIM requests, the step therapy requirements do not apply to formulary agents as of 1/1/2026 per IL HB 5395.

Continuation Therapy - Opioid Overdose

Covered when ALL of the following are met for Continued Therapy:

Opioid Overdose Continued: 1) Member meets one of the following: a) Currently receiving medication via Centene benefit or previously met initial approval criteria, OR b) Member is currently receiving medication and is enrolled in a state/product with continuity of care regulations (see state addendums CC.PHARM.03A and CC.PHARM.03B); 2) If request is for a dose increase, requested quantity does not exceed either: a) Opvee: two boxes (4 nasal spray devices) per prescription, OR b) Zurnai: 4 autoinjectors per prescription.

For members in Nevada, medical management techniques, including quantity management, beyond step therapy is not allowed.

Other Indications - Referral to formulary/off-label policies

Requests for uses not detailed in policy:

Other Indications: 1) If the drug has undergone a label change within the last 6 months not yet reflected in this policy, refer to: a) no coverage criteria policy for formulary agents for the relevant line of business (CP.CPA.190 commercial, HIM.PA.33 health insurance marketplace, CP.PMN.255 Medicaid), OR b) non-formulary policy for drugs not on formulary/PDL (CP.CPA.190 commercial, HIM.PA.103 health insurance marketplace, CP.PMN.16 Medicaid). 2) If the requested use is not listed under section III and criterion 1 does not apply, refer to the off-label use policy for the relevant line of business (CP.CPA.09 commercial, HIM.PA.154 health insurance marketplace, CP.PMN.53 Medicaid).

Follow referenced formulary/non-formulary or off-label policies per line of business.

Non‑FDA approved indications that are not specifically addressed in this nalmefene policy are not authorized unless there is sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies or an evidence of coverage document. Refer to the off‑label policies CP.CPA.09 (commercial), HIM.PA.154 (health insurance marketplace), or CP.PMN.53 (Medicaid) for requirements when seeking coverage for a non‑FDA indication.

Use of nalmefene for non‑FDA approved indications without adequate documentation demonstrating efficacy and safety per the referenced off‑label use policies is considered not authorized. Providers should submit the documentation required by the applicable off‑label policy to support medical necessity for such uses.

Initial Therapy

Initial coverage for opioid overdose when all criteria met:

Initial Therapy: See Initial Approval criteria: member may have access to opioids; age ≥ 12 years; medical justification for inability to use naloxone nasal spray or naloxone injection; requested quantity within product limits (Opvee two boxes/4 nasal spray devices per prescription; Zurnai 4 autoinjectors per prescription).

Nevada: medical management beyond step therapy not allowed. Illinois HIM: step therapy waived for formulary agents as of 1/1/2026 per IL HB 5395.

Continuation Therapy

Continuation criteria for members already receiving therapy:

Continuation: Member is currently receiving medication via Centene benefit or previously met initial approval criteria, OR member is receiving medication and is enrolled in a state/product with continuity of care regulations; dose increases limited to product quantity limits (Opvee two boxes/4 nasal spray devices per prescription; Zurnai 4 autoinjectors per prescription).

Refer to state addendums CC.PHARM.03A and CC.PHARM.03B for continuity of care details. Nevada: medical management beyond step therapy not allowed.

Coding

Relevant HCPCSHCPCS

G0532

Take-home supply of nasal nalmefene hydrochloride; one carton of two, 2.7 mg per 0.1 ml nasal sprays (provision by a Medicare-enrolled opioid treatment program)

Minimum age

Minimum ageAge ≥ 12 years

FDA indication age languageOpvee and Zurnai indicated for adults and pediatric patients aged 12 years and older

Policy threshold sourceInitial therapy criterion requires age ≥ 12 years for coverage

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required for Nalmefene Products

Prior authorization is required for nalmefene products (Opvee, Zurnai). Requests must demonstrate that the member meets the policy criteria for the opioid overdose indication and that requested quantities do not exceed established limits.

Affected products: Opvee (nalmefene nasal spray), Zurnai (nalmefene autoinjector)
Quantity limits: Opvee — two boxes (4 nasal spray devices) per prescription; Zurnai — 4 autoinjectors per prescription
HCPCS: G0532 (Take-home supply of nasal nalmefene hydrochloride) — informational only

Step Therapy

Step Therapy and Bypass Rules

Step therapy requires providers to document medical justification for inability to use generic naloxone nasal spray or naloxone injection (examples include contraindications, clinically significant adverse effects, or clinical situations such as being prescribed a long-acting opioid). Certain state-specific exceptions (e.g., Illinois HIM per IL HB 5395) may bypass step therapy for formulary agents.

Step Therapy

Requirement	Details
Step therapy requirement
Require trial of or documented inability to use generic naloxone (intranasal naloxone nasal spray or naloxone solution for injection) prior to coverage of nalmefene unless a medical justification is provided (examples: contraindication, clinically significant adverse reaction to naloxone, member prescribed a long‑acting opioid).
State-specific bypass / limits
Nevada: medical management techniques beyond step therapy, including additional quantity management, are not allowed per SB 43. Illinois HIM: step therapy requirements do not apply to formulary agents as of 1/1/2026 per IL HB 5395 (step therapy bypass).

Quantity Limits

Opvee (nalmefene nasal spray)

Packaging / Quantity limitTwo boxes (4 nasal spray devices) per prescription

Product formulation and dose per sprayOpvee is an intranasal nalmefene delivering 2.7 mg per spray

Dosing instructionsInitial dose: one spray intranasally; repeat every 2–5 minutes using a new device if needed

Zurnai (nalmefene autoinjector)

Packaging / Quantity limit4 autoinjectors per prescription

Product formulation and dose per autoinjectorZurnai is a pre-filled single-dose autoinjector delivering 1.5 mg nalmefene per dose

Site of Care

Note

Intended for emergency use in home, first‑responder, and emergency settings

These products are intended for immediate emergency administration in settings where opioids may be present (home, first‑responder, emergency). Zurnai autoinjector may be administered intramuscularly or subcutaneously into the anterolateral thigh, through clothing if necessary.

Opvee and Zurnai are not a substitute for emergency medical care; intended for emergency use where opioids may be present.
Zurnai dosing: administer IM or SC into the anterolateral thigh; may be given through clothing.

Definitions

Product descriptions

Opvee — formulation & doseIntranasal nalmefene; each Opvee spray delivers 2.7 mg nalmefene per dose

Zurnai — formulation & dosePre-filled single-dose autoinjector for IM/SC use; each Zurnai delivers 1.5 mg nalmefene

Intended useBoth products indicated for emergency treatment of known or suspected opioid overdose in patients aged ≥12 years

Administration settingIntended for immediate administration in settings where opioids may be present; not a substitute for emergency medical care

Background

Nalmefene is an opioid antagonist indicated for the emergency treatment of known or suspected opioid overdose in patients aged 12 years and older. It is intended for immediate administration in settings where opioids may be present and is not a substitute for emergency medical care; requests for other uses should follow the off‑label and formulary referral processes described in policy.