Subject: Opioid Reversal Agents Limit 1137-H P02-2025

Policy:

Indications

FDA-approved Indications

Kloxxado Nasal Spray

Kloxxado is indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression, for adult and pediatric patients.

Kloxxado is intended for immediate administration as emergency therapy in settings where opioids may be present.

Kloxxado is not a substitute for emergency medical care.

Naloxone Nasal Spray (OTC)

Uses

• to “revive” someone during an overdose from many prescription pain medications or street drugs such as heroin
• this medicine can save a life

Narcan Nasal Spray (naloxone nasal spray)

Narcan Nasal Spray is indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression.

Narcan Nasal Spray is intended for immediate administration as emergency therapy in settings where opioids may be present.

Narcan Nasal Spray is not a substitute for emergency medical care.

Narcan Nasal Spray (OTC)

Uses

• to “revive” someone during an overdose from many prescription pain medications or street drugs such as heroin
• this medicine can save a life

Opvee Nasal Spray

Opvee nasal spray is indicated for the emergency treatment of known or suspected overdose induced by natural or synthetic opioids in adults and pediatric patients aged 12 years and older, as manifested by respiratory and/or central nervous system depression.

Opvee nasal spray is intended for immediate administration as emergency therapy in settings where opioids may be present.

Opvee nasal spray is not a substitute for emergency medical care.

Rextovy Nasal Spray

Rextovy Nasal Spray is indicated for emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression, for adult and pediatric patients.

Rextovy Nasal Spray is intended for immediate administration as emergency therapy in settings where opioids may be present.

Rextovy Nasal Spray is not a substitute for emergency medical care.

Rezenopy Nasal Spray

Rezenopy nasal spray is indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression in adult and pediatric patients.

Rezenopy nasal spray is intended for immediate administration as emergency therapy in settings where opioids may be present.

Rezenopy nasal spray is not a substitute for emergency medical care.

RiVive Nasal Spray

Uses

• to “revive” someone during an overdose from many prescription pain medications or street drugs such as heroin
• this medicine can save a life

Zimhi

Zimhi is indicated in adults and pediatric patients for:

• the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression.

Zimhi is intended for immediate administration as emergency therapy in settings where opioids may be present.

Zimhi is not a substitute for emergency medical care.

Zurnai

Zurnai is indicated for the emergency treatment of known or suspected opioid overdose induced by natural or synthetic opioids in adults and pediatric patients aged 12 years and older, as manifested by respiratory and/or central nervous system depression.

Zurnai is intended for immediate administration as emergency therapy in settings where opioids may be present.

Zurnai is not a substitute for emergency medical care.

Initial Limit Quantity

Limits do not accumulate together; patient is allowed the maximum limit for each drug and strength.

The duration of 25 days is used for a 30-day fill period and 75 days is used for a 90-day fill period to allow time for refill processing.

Some products may only be available by prescription, some may only be available over-the-counter (OTC), and others may be available both by prescription and over-the-counter (OTC). The limits apply to all listed products, both prescription and over-the-counter (OTC), as available.

Drug (Prescription and OTC)	1 Month Limit	3 Month Limit
Kloxxado Nasal Spray (naloxone hydrochloride nasal spray)	2 cartons (4 nasal sprays) / 25 days	6 cartons (12 nasal sprays) / 75 days
naloxone hydrochloride nasal spray	2 cartons (4 nasal sprays) / 25 days	6 cartons (12 nasal sprays) / 75 days
Narcan Nasal Spray (naloxone hydrochloride nasal spray)	2 cartons (4 nasal sprays) / 25 days	6 cartons (12 nasal sprays) / 75 days
Opvee (nalmefene nasal spray)	2 cartons (4 nasal sprays) / 25 days	6 cartons (12 nasal sprays) / 75 days
Rextovy (naloxone hydrochloride nasal spray)	2 cartons (4 nasal sprays) / 25 days	6 cartons (12 nasal sprays) / 75 days
Rezenopy (naloxone hydrochloride nasal spray)	2 cartons (4 nasal sprays) / 25 days	6 cartons (12 nasal sprays) / 75 days
RiVive (naloxone hydrochloride nasal spray)	2 cartons (4 nasal sprays) / 25 days	6 cartons (12 nasal sprays) / 75 days
Zimhi (naloxone hydrochloride injection)	2 cartons (4 pre-filled syringes) / 25 days	6 cartons (12 pre-filled syringes / 75 days
Zurnai (nalmefene injection)	4 cartons (4 auto-injectors) / 25 days	12 cartons (12 auto-injectors) / 75 days

Place of Service:

Outpatient

The above policy is based on the following references:

1. Kloxxado Nasal Spray [package insert]. Columbus, OH: Hikma Specialty USA Inc.; April 2024.
2. Naloxone Nasal Spray RX [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc.; March 2023.
3. Naloxone Nasal Spray OTC [package insert]. Yeruham, Israel: Padagis Israel Pharmaceuticals Ltd; July 2024.
4. Narcan Nasal Spray RX [package insert]. Plymouth Meeting, PA: Emergent Devices Inc.; November 2020.
5. Narcan Nasal Spray OTC [package insert]. Plymouth Meeting, PA: Emergent Devices Inc.; August 2023.
6. Opvee Nasal Spray [package insert]. North Chesterfield, VA: Indivior Inc.; June 2023.
7. Rextovy Nasal Spray [package insert]. So. El Monte, CA: International Medication Systems, Limited; May 2024.
8. Rezenopy Nasal Spray [package insert]. Lexington, KY: Summit Biosciences Inc., April 2024.
9. RiVive Nasal Spray [package insert]. Bethesda, MD: Harm Reduction Therapeutics, Inc.; January 2024.
10. Zimhi [package insert]. San Diego, CA: Adamis Pharmaceuticals Corporation; October 2021.
11. Zurnai [package insert]. Stamford, CT: Purdue Pharm L.P.; August 2024.
12. Lexicomp Online, AHFS DI (Adult and Pediatric) Online. Waltham, MA: UpToDate, Inc.; 2024. https://online.lexi.com. Accessed November 26, 2023.
13. Lexicomp Online, Lexi-Drugs Online. Waltham, MA: UpToDate, Inc.; 2024. https://online.lexi.com. Accessed November 26, 2024.
14. Micromedex® (electronic version). Merative, Ann Arbor, Michigan, USA. Available at: https://www.micromedexsolutions.com/ (cited: 11.26.2024).
15. Substance Abuse and Mental Health Services Administration. SAMHSA Opioid Overdose Prevention Toolkit. HHS Publication No. (SMA) 18-4742. Rockville, MD: Substance Abuse and Mental Health Services Administration, First printed 2013. Revised 2014, 2016, 2018, 2024. https://store.samhsa.gov/sites/default/files/overdose-prevention-response-kit-prep23-03-00-001.pdf. Accessed November 26, 2024.
16. Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence. World Health Organization. Available at: https://www.who.int/publications/i/item/9789241547543. Accessed November 26, 2024.
17. U.S. Department of Health and Human Services. Substance Abuse and Mental Health Services Administration (SAMHSA). Treatment Improvement Protocol (TIP) Series 43. Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs. Available at: https://www.hrsa.gov/behavioral-health/tip-43-medication-assisted-treatment-opioid-addiction-opioid-treatment-programs-51.pdf. Accessed November 26, 2024.
18. U.S. Department of Health and Human Services. Substance Abuse and Mental Health Services Administration (SAMHSA). Treatment Improvement Protocol (TIP) Series 63: Medications for Opioid Use Disorder. Available at: https://store.samhsa.gov/product/TIP-63-Medications-for-Opioid-Use-Disorder-Full-Document/PEP21-02-01-002. Accessed November 26, 2024.
19. Substance Use Community Management of Opioid Overdose. World Health Organization. 2014. https://apps.who.int/iris/bitstream/handle/10665/137462/9789241548816_eng.pdf. Accessed November 26, 2024.

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

June 06, 2025