What is the recommended dose of naloxone (opioid antagonist) for treating opioid overdose?

Naloxone Dosing for Opioid Overdose

For suspected opioid overdose, administer 2 mg of naloxone intramuscularly or intranasally, repeated in 3-5 minutes if necessary, prioritizing airway management and breathing support first. 1, 2

Initial Dose Selection by Route

The American Heart Association provides clear guidance on route-specific dosing:

• Intramuscular (IM): 2 mg, repeated in 3-5 minutes if necessary 1, 2
• Intranasal (IN): 2 mg, repeated in 3-5 minutes if necessary 1, 2
• Intravenous (IV): 0.4-2 mg for adults in emergency overdose situations 3

The IV route provides the most rapid onset of action and is recommended in emergency situations when IV access is available. 3

Critical Management Priorities

Standard resuscitative measures (airway management, breathing support) must take priority over naloxone administration, especially in patients with cardiac arrest. 2 Naloxone should be administered to patients with suspected opioid overdose who have a pulse but no normal breathing or only gasping, while continuing standard BLS/ACLS care regardless of naloxone response. 2

Special Consideration: Opioid-Dependent Patients

For known opioid-dependent patients, consider lower initial doses (0.1-0.2 mg IV) to avoid precipitating severe withdrawal. 1, 4 The goal is to restore adequate ventilation, not full consciousness. 5 Withdrawal symptoms may include hypertension, tachycardia, vomiting, agitation, and drug cravings. 1, 2

Titration and Repeat Dosing

If no response occurs after 10 mg total naloxone, question the diagnosis of opioid-induced toxicity. 3 For postoperative opioid depression, use smaller incremental doses of 0.1-0.2 mg IV at 2-3 minute intervals to achieve adequate ventilation without reversing analgesia. 3

Duration of Action and Monitoring Requirements

Naloxone has a half-life of 30-45 minutes (60-120 minutes in some studies), which is shorter than most opioids' respiratory depressant effects. 1, 5 Patients must be observed in a healthcare setting until the risk of recurrent opioid toxicity is low and vital signs have normalized. 2 Repeated doses or continuous infusion may be necessary, especially with long-acting opioids like fentanyl. 1, 2

For continuous infusion when needed: use two-thirds of the effective bolus dose per hour (e.g., if 2 mg bolus worked, infuse at approximately 1.5 mg/hour). 6

Synthetic Opioid Considerations

Fentanyl and other synthetic opioids (up to 50 times more potent than heroin) likely require higher naloxone doses. 7 Higher-dose formulations (5 mg prefilled injection or 8 mg intranasal spray) are important additions for emergency treatment of synthetic opioid overdoses, especially by lay responders in the community. 7

Pediatric Dosing

• Initial dose: 0.01 mg/kg IV, IM, or subcutaneous 3
• If inadequate response: 0.1 mg/kg may be administered 3
• Postoperative depression: 0.005-0.01 mg IV at 2-3 minute intervals 3

Neonatal Dosing

For opioid-induced depression in neonates, the usual initial dose is 0.01 mg/kg administered IV, IM, or subcutaneously. 3

Common Pitfalls to Avoid

• Do not delay standard resuscitation while waiting for naloxone to take effect 2
• Avoid excessive doses that precipitate severe withdrawal in opioid-dependent patients 1, 8
• Recognize that naloxone will NOT reverse respiratory depression from benzodiazepines or xylazine 1, 2, 7
• Do not assume a single dose is sufficient—recurrent respiratory depression is common 1, 2, 5
• Avoid rapid IV administration in postoperative patients, which may cause nausea, vomiting, or circulatory stress 3

Safety Profile

Naloxone has an excellent safety profile with no known harms when administered to non-opioid intoxicated patients. 2 It is considered safe over a wide dose range up to 10 mg. 8 The primary risk is precipitating acute withdrawal syndrome in opioid-dependent patients. 1, 2, 8