Antidotes, opioid receptor antagonists
ATC code: V03AB15 (Naloxone)
Brand names
Narcan, Kloxxado
Competitive antagonist at all opioid receptor types (μ, κ, δ), with highest affinity for μ. Displaces opioids from receptors and rapidly restores breathing in opioid overdose. Onset 1–2 minutes IV, 2–3 minutes intranasal. Short half-life (30–90 minutes) — patients on long-acting opioids (methadone, buprenorphine, extended fentanyl) require repeat dosing and observation.
First line
First-line antidote in opioid overdose per 2014, SAMHSA, and Russian Ministry of Health. IV/IM 0.4–2 mg, repeatable every 2–3 minutes until breathing is restored. Intranasal 4 mg in one nostril (Narcan) — the popular option for lay bystanders. Since 2023, intranasal Narcan 4 mg is OTC in the US. After administration, hospital transport is mandatory — the opioid may resume action after naloxone wears off.
In an opioid overdose during pregnancy, naloxone is administered — fetal hypoxia risk exceeds the risk of precipitated withdrawal. Standard protocol applies.
Compatible with breastfeeding.
naloxone is evaluated for the following indications with varying evidence strength: Opioid overdose (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of naloxone (≥ 1 in 100): Acute opioid withdrawal syndrome: tachycardia, hypertension, nausea, vomiting, sweating, agitation, Return of pain in patients on opioid analgesia. See the Safety section for uncommon and serious reactions.
In an opioid overdose during pregnancy, naloxone is administered — fetal hypoxia risk exceeds the risk of precipitated withdrawal. Standard protocol applies.
Compatible with breastfeeding.
naloxone is contraindicated in: Hypersensitivity to components (extremely rare — does not justify withholding in opioid overdose). Full list in the Safety section.
widespread distribution of intranasal naloxone has reduced opioid overdose mortality in the US and Europe. There is no evidence base for 'moral hazard' in this area.
intranasal naloxone is specifically designed for bystander use; OTC in the US since 2023.