New higher-dose naloxone nasal spray approved for opioid analgesic overdose

May 12, 2021 · Clinical Team

The U.S. Food and Drug Administration (FDA) approved a higher-dose naloxone hydrochloride nasal spray – Kloxxado™ (8 mg) – on April 30, 2021. Naloxone is indicated for the emergency treatment of known or suspected opioid analgesic overdose, as manifested by respiratory and/or central nervous system (CNS) depression, for adults and pediatric patients.

Kloxxado Nasal Spray (8 mg) will likely compete with Narcan^® Nasal Spray (4 mg), which is commonly prescribed to treat opioid-related overdose. Kloxxado Nasal Spray was approved under the FDA’s 505(b)(2) approval pathway, allowing the manufacturer – Hikma Pharmaceuticals – to use the safety and efficacy of previously approved naloxone hydrochloride injection to support its approval, in addition to their own data.

Hikma also cited a survey of community organizations and a separate study published in 2019 indicating that multiple doses of naloxone are often administered to patients during emergency treatment of an opioid-related overdose.

Availability of Kloxxado Nasal Spray is not expected until the second half of 2021, according to Hikma, and the cost has not yet been published.

Naloxone nasal spray similarities

Both naloxone nasal spray formulations (Narcan Nasal Spray and Kloxxado Nasal Spray):

May be administered to a patient by a family member or caregiver
Work within minutes, when administered quickly, to reverse opioid overdose effects
Are not a substitute for emergency medical care, i.e., received by calling 911 after giving the first dose
Are single-use nasal sprays designed to be used one time only
Are available in a needle-free, intranasal (in the nose) formulation
Contain two individual blister packages per container

Naloxone place in therapy

Treatment guidelines generally recommend prescribing naloxone when factors that increase the risk for opioid analgesic overdose are present. Additionally, state-specific rules and regulations regarding prescribing opioid analgesics and co-prescribing naloxone may vary and should be followed. For more information about naloxone, click here.

Naloxone may be appropriate for claimants in the following situations (list is not all-inclusive):

Active abusers of opioid analgesics or other scheduled medications
History of opioid analgesic-related overdose (e.g., fentanyl, hydrocodone, morphine, oxycodone)
History of substance abuse disorder
Higher opioid analgesic doses, i.e., greater than 50 morphine equivalent doses (MED) per day
Also taking a benzodiazepine (e.g., alprazolam, clonazepam, diazepam) or other CNS depressant (e.g., sedative-hypnotic, skeletal muscle relaxant, antidepressant, anticonvulsant)
History of certain comorbid conditions (e.g., chronic obstructive pulmonary disease, mental illness)
Lives alone or in a remote location and takes high doses of opioid analgesics

Impact on workers’ compensation and auto no-fault industry

When reviewing claims where naloxone is prescribed, claims professionals and/or clinicians should review the claimant’s current medication and medical records, understand its place in therapy (as mentioned above in accordance with treatment guidelines and regulations) and consider the following:

If a claimant is taking one or more opioid analgesic, naloxone nasal spray may be appropriate
Once prescribed, only one package should be dispensed (or authorized) at a time
Requests for renewals should be based on the expiration date or damage to the package
If naloxone has been used to treat an opioid analgesic-related overdose, further evaluation of the claimant by the treating prescriber is recommended
If there is no evidence of an opioid analgesic being prescribed, or if ongoing use of an opioid analgesic is no longer required, the use of any formulation of naloxone would be unnecessary

Narcan Nasal Spray is considered a first-line option when naloxone is necessary. For this reason, it is allowed on our formularies where the use of opioid analgesics may be appropriate, such as the global workers’ compensation, auto and standard injury-based formularies, with maximum fill limits. Therefore, Kloxxado Nasal Spray will be evaluated by our Pharmacy and Therapeutics (P&T) Committee in the near future to assess its formulary status on our standard plans.

If you have any questions, please contact your account manager, clinical liaison or our Clinical Services team at 1-877-275-7674 ext. 8612.

Sources:

Hikma announces US FDA approval of Kloxxado^™ (naloxone hydrochloride) nasal spray 8mg [press release]. London, UK: Hikma Pharmaceuticals USA Inc.; April 30, 2021. Available at https://www.hikma.com/newsroom/article.
FDA approves higher dosage of naloxone nasal spray to treat opioid overdose [press release]. Silver Spring, MD: US Food and Drug Administration; April 30, 2021. Available at https://www.fda.gov/news-events/press-announcements.
FDA Advisory Committee on the Most Appropriate Dose or Doses of Naloxone to Reverse the Effects of Life-threatening Opioid Overdose in the Community Settings, p. 149, 2016. Available at https://www.fda.gov/media/100409/download.
Geiger et. al., Who receives naloxone from emergency medical services? Characteristics of calls and recent trends, Substance Abuse, 41:3, 400-407, July 30, 2019. Available at https://www.tandfonline.com/doi/abs/10.1080/08897077.2019.1640832.
Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain-United States, 2016. MMWR Recomm Rep 2016;65:1-49
ODG by MCG Treatment Guidelines [database online]. An MCG Health Company. Accessed on May 4, 2021.
Kloxxado (naloxone hydrochloride nasal spray) [package insert]. Columbus, OH: Hikma Pharmaceuticals USA, Inc.; April 2021.
Narcan (naloxone hydrochloride nasal spray) [package insert]. Plymouth Meeting, PA: Adapt Pharma, Inc.; August 2020.