Opioid Toxicity Medication

Updated: Aug 08, 2023
  • Author: Everett Stephens, MD; Chief Editor: Jeter (Jay) Pritchard Taylor, III, MD  more...
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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.


Opioid Reversal Agents

Class Summary

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

Naloxone (Zimhi)

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)

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.