naloxone
Brand: Narcan, Kloxxado, Zimhi
Prototype Drug
Drug Class: opioid antagonist
Drug Family: opioid antagonist
Subclass: pure opioid antagonist
Organ Systems: cnstoxicology
Mechanism of Action
Competitive antagonist at all opioid receptor subtypes (mu, kappa, delta) with highest affinity for mu receptors; rapidly displaces opioids from receptors; no intrinsic agonist activity; reverses respiratory depression, sedation, and analgesia.
mu-opioid receptorskappa-opioid receptorsdelta-opioid receptors
Indications
- opioid overdose reversal
- opioid-induced respiratory depression
- opioid-induced pruritus (low-dose IV)
- opioid use disorder (with buprenorphine or extended-release naltrexone)
Contraindications
- none absolute in overdose setting
Adverse Effects
Common
- acute opioid withdrawal (pain, agitation, nausea, hypertension, tachycardia)
- sweating
- hypertension
Serious
- acute pulmonary edema (rare)
- ventricular fibrillation (rare, stress-related)
- seizures (in opioid-dependent patients with precipitated withdrawal)
Pharmacokinetics (ADME)
| Absorption | IV: 100%; IM/IN: ~50%; not effective orally (complete first-pass elimination) |
| Distribution | Protein binding ~46%; Vd ~2 L/kg; crosses BBB rapidly |
| Metabolism | Hepatic glucuronidation to inactive naloxone-3-glucuronide |
| Excretion | Renal |
| Half-life | 30–90 minutes (shorter than most opioids — resedation can occur) |
| Onset | IV: 2 minutes; IM/IN: 3–5 minutes |
| Peak | IV: 2–5 minutes |
| Duration | 45–90 minutes (shorter than duration of most opioids) |
| Protein Binding | 46% |
| Vd | ~2 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| buprenorphine | partial agonist — higher naloxone doses required to overcome buprenorphine's high receptor affinity | moderate |
| opioid analgesics | reverses analgesia — may precipitate severe pain in patients on therapeutic opioids | major |
Nursing Considerations
- Titrate to respiratory effect, not to full consciousness — goal is RR >10/min and adequate oxygenation, not full arousal (which precipitates severe withdrawal and agitation)
- Duration of naloxone (45–90 min) is shorter than most opioids — monitor for resedation; repeat doses or infusion may be required for long-acting opioids (methadone, extended-release formulations)
- Intranasal naloxone (Narcan 4 mg) is available without prescription for lay rescuers — educate patients on opioids and their family members on recognition and use
- After reversal, keep patient under observation for minimum 2–4 hours (longer for long-acting opioids); do not discharge after naloxone administration
Clinical Pearls
- Naloxone's short duration relative to opioids is the most clinically dangerous pharmacokinetic property — patients must be monitored for resedation after reversal, especially with fentanyl patches, extended-release opioids, or methadone
- In full opioid reversal, use small IV doses (0.04–0.1 mg) rather than full 0.4 mg to avoid precipitating severe withdrawal, agitation, and pulmonary edema
Safety Profile
Pregnancy generally-safe
Lactation safe
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.