Medical Policy: 05.01.115 

Original Effective Date: August 2016 

Reviewed: June 2018 



Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.


This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.



Naloxone is indicated for the complete or partial reversal of opioid depression (including respiratory depression) induced by natural and synthetic opioids (eg, propoxyphene, methadone, nalbuphine, butorphanol, pentazocine). Naloxone is also indicated for the diagnosis of suspected or known acute opioid over-dosage. It is available as a nasal spray, auto-injector, vials for intramuscular injection, and prefilled syringes for intranasal use.


Evzio is supplied as an auto-injector and indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. Evzio is intended for immediate administration as emergency therapy in settings where opioids may be present and is not a substitute for emergency medical care.


Prior Approval:

Not applicable



Evzio (naloxone auto-injector) is considered not medically necessary for all applications because there are equivalent and less expensive forms of the drug available for nasal or injectable administration.


Clinical Rationale

Evzio is similar to an EpiPen in that it is a handheld, single-use auto-injector that is prefilled to quickly deliver a single dose of medication. Each carton of Evzio contains a pair of 0.4-mg auto-injectors and a single needle-free Evzio Trainer to practice using the device. Every device is equipped with visual and voice instructions for guidance to inject the medication. Evzio received approval from the Federal Drug Administration (FDA) in 2014. The price of the auto-injector has since risen over 17-fold in the past two years and continues to rise.


Other lower cost options are available in a different dosage form. Narcan nasal spray is available as a needle-free, ready-to-use nasal spray to deliver a single 4-mg dose of naloxone. One carton contains 2 blister packages, each with a single nasal spray that can’t be reused. It costs around $75 per nasal spray, a fraction of the cost of Evzio.


Naloxone can also be supplied in vials for intramuscular injection, or in prefilled syringes for intranasal use. For intramuscular use, it is recommended that naloxone be provided as 0.4 mg/mL in two 2 mL single-dose vials or one 10 mL multi-dose vial. For each injection, a 23 gauge, 3 cc syringe with a 1-inch needle will be needed. For intranasal administration using the injectable solution, two naloxone 2 mg/2 mL luer-lock prefilled syringes are needed along with two mucosal atomization devices that fit into the luer-lock of the syringe.


Procedure Codes and Billing Guidelines:

To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.

  • J3490 Unclassified drugs [when specified as naloxone hcl]
  • Auto-injector (Evzio): NDC 60842-030-01


Selected References:

  • Evzio [package insert]. Richmond, VA: kaleo, Inc.; April 2014.
  • Drug Facts and Comparisons on-line. (, Wolters Kluwer Health, St. Louis, MO. Updated periodically.
  • Narcan [package insert]. Radnor, PA: Adapt Pharma, Inc.; November 2015.


Policy History:

  • June 2018 - Annual Review, Policy Renewed
  • June 2017 - Annual Review, Policy Renewed
  • August 2016 - New Policy

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark 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 Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.


*CPT® is a registered trademark of the American Medical Association.