Reversal agent · Antidote
Naloxone (Narcan)
Also called Narcan
Indications
- Opioid overdose with respiratory or CNS depression
- Postoperative or procedural opioid respiratory depression, in small titrated doses
- Suspected opioid-associated cardiac arrest, if it does not delay CPR (AHA 2025)
- Diagnostic trial in coma with small pupils and slow breathing
- Itching from neuraxial opioids, as a low-dose infusion (off-label)
Dosing
Infusion start: Two-thirds of the bolus dose that restored breathing, per hour. Titration: To breathing, not to full alertness.
| Where | Dose |
|---|---|
| Cardiac arrest | Naloxone: 0.4–2 mg IV/IM/IN for suspected opioid overdose with a pulse |
| Reversal and antidotes | Naloxone: 0.04–0.4 mg IV titrated to breathing (2 mg if apneic); repeat or infuse (two-thirds of the effective dose per hour) |
On the quick cards
Mechanism of action
Naloxone is a competitive antagonist at opioid receptors, with highest affinity for μ, lower for κ and δ, and no agonist activity. It displaces agonists, so Gi/o signaling stops: cAMP recovers, GIRK potassium channels close and calcium channels reopen, restoring firing in respiratory and arousal neurons within minutes. Because binding is competitive and naloxone is cleared faster than many opioids, the agonist can reoccupy the receptors and sedation can return.
Pharmacology
- CNS: reverses opioid sedation, miosis and analgesia; in dependent patients precipitates withdrawal within minutes (agitation, vomiting, diarrhea, yawning, piloerection)
- Respiratory: restores ventilatory drive; abrupt reversal can cause pulmonary edema
- Cardiovascular: a catecholamine surge on abrupt reversal can cause hypertension, VT or VF and cardiac arrest (label)
- Other: no effect without an opioid present; does not reverse benzodiazepines, alcohol or xylazine; buprenorphine needs large doses (label)
Pharmacokinetics
| Onset | IV within 2 min; slightly slower but longer-lasting IM or SC (label); intranasal over several minutes |
|---|---|
| Duration | 30–90 min, by dose and route; often shorter than the opioid |
| Half-life | 30–81 min in adults (mean 64 min); about 3 h in neonates (label) |
| Distribution | Rapid; Vd about 200 L; enters the brain quickly and crosses the placenta |
| Protein binding | Weak, mostly albumin (label) |
| Metabolism | Liver glucuronidation, mainly to naloxone-3-glucuronide (label) |
| Elimination | Urine as metabolites: 25–40% in 6 h, about 50% in 24 h, 60–70% in 72 h (label) |
| Bioavailability | Oral negligible (first pass); intranasal about 40–50% |
Chemistry
- Semisynthetic N-allyl analog of oxymorphone (17-allyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one): swapping the N-methyl for an allyl turns an agonist into an antagonist
- Natural (−) isomer; amine pKa 7.9 and phenol pKa 9.4, so about a fifth is un-ionized at pH 7.4; log P about 1.5–2, enough for fast brain entry
- Injection 0.4 or 1 mg/mL in saline, pH 3–6.5; nasal spray 4 or 8 mg; infusions in saline or D5W last 24 h; protect from light (label)
Adverse effects and cautions
In the one-pagers
- Toxidromes and AntidotesReversal antidotes: Opioids: Naloxone 0.2–2 mg IV/IM/IO or 2–4 mg nasal, every 2–3 min: Goal is breathing; may wear off first
- BLS, High-Quality CPR and ChokingSpecial situations: Suspected opioid overdose: CPR first if no pulse; naloxone if available, without interrupting compressions
- High-Alert Meds and InsulinOpioids and naloxone: Respiratory depression: stop the opioid, stimulate, support breathing, give naloxone.
- End of Life, Hospice, Pain and SleepOpioids: around the clock and breakthrough: Respiratory depression: Rare with careful titration; stimulate, support breathing, naloxone titrated slowly
- Perioperative CarePACU priorities: After naloxone or flumazenil, watch longer: sedation and respiratory depression can return
- Pharmacology by Class and SuffixAntidotes and reversal: Opioids: Naloxone; may wear off first
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Sources
- FDA label: Naloxone HCl Injection, Dr. Reddy's (2026)
- FDA label: Naloxone HCl Injection, Hospira (2023)
- PubChem: naloxone
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.