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Medication

Medication Summary

Naloxone is a pure competitive antagonist of opioid receptors and lacks any agonist activity. Adverse effects are rare at therapeutic doses. Effects of withrawal may follow administration, and may be confused as adverse effects by the the layperson. Naloxone can be given by the intravenous (IV), intramuscular (IM), endotracheal (ET), subcutaneous (SC), or intranasal (IN) route. IN naloxone has the advantage of posing no risk of needlestick injury.

By the IV or ET route, the onset of action of naloxone is 1-2 minutes. A second dose can be repeated every 2-3 minutes. With IM, SC, or IN administration, onset is 2-5 minutes. Discontinue treatment as soon as the desired degree of opioid reversal is achieved. Higher doses may be necessary to reverse the effects of methadone, diphenoxylate, propoxyphene, butorphanol, pentazocine, nalbuphine, designer drugs, or veterinary tranquilizers.

Nalmefene (Revex) and naltrexone are newer opioid antagonists that have longer half-lives than naloxone (4-8 h and 8-12 h vs 1 h). The routine use of a long-acting antagonist in the patient who is unconscious for unknown reasons is not recommended. In addition, the fear of precipitating prolonged opioid withdrawal likely prevents the widespread use of these antagonists for emergency reversal of opiate intoxication.

Class Summary

These agents reduce or eliminate the effects of opioid agents on their receptors.

Naloxone (Zimhi)

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Historically, naloxone is the most commonly used opioid receptor antagonist in the United States. It is used to reverse opioid intoxication or overdose. Prevents or reverses opioid effects (hypotension, respiratory depression, sedation), possibly by displacing opiates from their receptors. Half-life is 1 h. The injectable solution is available in vials and syringes (0.4 mg/mL, 1 mg/mL) for IV/IM/SC administration. A high-dose (5 mg/0.5 mL) IM/SC injectable solution in a prefilled syringe (Zimhi) is also available. In pharmacokinetic studies, a single IM dose of 5-mg provided significantly higher peak plasma concentration and area under the curve (AUC) compared with a single 2-mg IM injection.

If patients do not respond to multiple doses of naloxone, consider alternative causes of unconsciousness.

Naloxone intranasal (Kloxxado, Narcan Nasal Spray, RiVive)

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Competitive opioid antagonist that antagonizes opioid effects by competing for the same receptor sites. The intranasal form is indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. The brand name product (ie, Narcan Nasal Spray) was the first opioid antagonist granted over-the-counter (OTC) designation, in March 2023, and delivers a 4-mg dose. A second OTC product (RiVive) was approved in July 2023; it delivers a 3-mg dose. A higher concentration intranasal product (Kloxxado) that is available by prescription delivers 8 mg/actuation. Generics that deliver 4 mg/actuation are also prescription products.

Questions

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Author

Everett Stephens, MD Assistant Clinical Professor, Department of Emergency Medicine, University of Louisville School of Medicine

Everett Stephens, MD is a member of the following medical societies: American Academy of Emergency Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Michael J Burns, MD Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center

Michael J Burns, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Jeter (Jay) Pritchard Taylor, III, MD Assistant Professor, Department of Surgery, University of South Carolina School of Medicine; Attending Physician / Clinical Instructor, Compliance Officer, Department of Emergency Medicine, Prisma Health Richland Hospital

Jeter (Jay) Pritchard Taylor, III, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Columbia Medical Society, Society for Academic Emergency Medicine, South Carolina College of Emergency Physicians, South Carolina Medical Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Employed contractor - Chief Editor for Medscape.

Additional Contributors

Mark Louden, MD Assistant Professor of Clinical Medicine, Division of Emergency Medicine, Department of Medicine, University of Miami, Leonard M Miller School of Medicine

Mark Louden, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Opioid Toxicity Medication

Medication Summary

Opioid Reversal Agents

Class Summary

Naloxone (Zimhi)

Naloxone (Zimhi)

Naloxone intranasal (Kloxxado, Narcan Nasal Spray, RiVive)

Naloxone intranasal (Kloxxado, Narcan Nasal Spray, RiVive)

Opioid Toxicity Medication

Medication Summary

Opioid Reversal Agents

Class Summary

Naloxone (Zimhi)

Naloxone (Zimhi)

Naloxone intranasal (Kloxxado, Narcan Nasal Spray, RiVive)

Naloxone intranasal (Kloxxado, Narcan Nasal Spray, RiVive)

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