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
Naloxone drip card and mL/h converterStart: Two-thirds of the bolus dose that restored breathing, per hour
| 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
- Naloxone (Narcan)EMS Field Drugs: Toxicology: opioid antagonist
- Reversal and antidotesPush and Emergency Meds: The bolus doses; full toxicology is on its cheat sheet
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
- Toxins, Stings and Anaphylaxis in the FieldRead this first: Ventilate before naloxone. Nothing by mouth if mental status may fall. Poison center early: 1-800-222-1222.
- EMT Drugs List: Medications EMTs Can GiveEMT drugs list at a glance: Under the National EMS Scope of Practice Model, EMTs can give oxygen, oral glucose, aspirin and naloxone, use an epinephrine auto-injector, give inhaled albuterol and ipratropium, and help a patient take their own nitroglycerin. Your state sets the final list and your medical director sets the protocol, so learn the national list for the exam and follow local protocol o
- 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
- ACLS Algorithms in BriefReversible causes: bedside clues and ultrasound: Toxins: History, pupils, wide QRS, long QT: Naloxone, lipid, bicarbonate or calcium as fits
- BLS, High-Quality CPR and ChokingSpecial situations: Suspected opioid overdose: CPR first if no pulse; naloxone if available, without interrupting compressions
- EMT By-Complaint Quick PagesEvery call at EMT scope: EMT drugs: oxygen to SpO2 94-98%, oral glucose, chewed aspirin 162-325 mg, the patient's own nitroglycerin, epinephrine auto-injector, naloxone, the patient's own inhaler; activated charcoal only per protocol. Doses: ems-pharmacology.
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In the algorithms
Other reversal agent drugs
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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 your local protocols and medical direction.