What is the maximum dose of Naloxone (Narcan)?

From the Guidelines

The maximum dose of Narcan (naloxone) is not strictly limited, as it can be administered repeatedly until the desired response is achieved, with doses up to 10-15 mg total potentially required in severe cases. For opioid overdose, the initial adult dose is typically 0.4-2 mg intravenously, intramuscularly, or intranasally, which can be repeated every 2-3 minutes as needed 1. The key principle is to administer enough naloxone to reverse respiratory depression while monitoring for withdrawal symptoms. Naloxone has a shorter duration of action (30-90 minutes) than many opioids, so patients should be monitored for at least 4-6 hours after administration as re-sedation may occur when naloxone wears off.

• The initial dose can be repeated every 2-3 minutes as needed, with some patients requiring higher doses to reverse intoxication with atypical opioids or following massive overdose 1.
• For the intranasal formulation, 4 mg per nostril can be given, repeating every 2-3 minutes in alternate nostrils.
• Healthcare providers should be prepared to provide additional doses or start a continuous infusion (0.4-0.8 mg/hour) in cases involving long-acting opioids.
• Naloxone works by competitively binding to opioid receptors, displacing the opioid and temporarily reversing its effects.
• Caution should be exercised in administering naloxone to patients with a history of chronic opioid or drug use because of the risk of inducing acute narcotic withdrawal 1.

From the FDA Drug Label

OVERDOSAGE There is limited clinical experience with naloxone hydrochloride injection overdosage in humans. Adult Patients In one small study, volunteers who received 24 mg/70 kg did not demonstrate toxicity. At doses of 2 mg/kg in normal subjects, cognitive impairment and behavioral symptoms, including irritability, anxiety, tension, suspiciousness, sadness, difficulty concentrating, and lack of appetite have been reported. Pediatric Patients Up to 11 doses of 0.2 mg of naloxone (2. 2 mg) have been administered to children following overdose of diphenoxylate hydrochloride with atropine sulfate.

The maximum dose of Naloxone is not explicitly stated in the provided drug label. However, it is mentioned that 24 mg/70 kg was administered to volunteers without demonstrating toxicity, and 2 mg/kg in normal subjects resulted in cognitive impairment and behavioral symptoms.

• The label does not provide a clear maximum dose.
• Dosing information is limited to specific studies and patient populations. The FDA label does not provide enough information to determine a maximum dose of Naloxone 2.

From the Research

Maximum Dose of Naloxone

• The maximum dose of Naloxone is not explicitly stated in the provided studies, but higher doses are being considered for emergency treatment of opioid-induced respiratory depression (OIRD) due to the increasing potency of synthetic opioids such as fentanyl 3.
• A study from 2006 found that increasing doses of naloxone (up to 7 mg) were effective in reversing buprenorphine-induced respiratory depression, but further increasing the dose (beyond 5 mg) caused a decline in reversal activity 4.
• Another study from 2019 reported the use of high-dose naloxone (up to 12 mg) in patients with suspected carfentanil overdose, with successful resuscitation in both cases 5.
• A phase I healthy volunteer study from 2018 found that concentrated naloxone nasal spray (up to 4 mg) was well-absorbed and provided early exposure comparable to intramuscular naloxone 6.

Considerations for Naloxone Dosing

• The potency of synthetic opioids such as fentanyl and carfentanil may require higher doses of naloxone for effective reversal of OIRD 3, 5.
• The risk of severe withdrawal symptoms or pulmonary edema from treatment with high-dose naloxone should be considered, but the balance of risks may point to administration of naloxone at the dose required to combat the overdose 3.
• Education about the benefits of naloxone and how to obtain it remains important, as well as the need for a call to emergency services after administering naloxone due to the short half-life of naloxone and the long-lasting potency of fentanyl and its analogs 3.