Naloxone

Antidotes, opioid receptor antagonists

ATC code: V03AB15

Brand names: Narcan, Kloxxado

Updated 24 Sep 2026 · Methodology

Indications

Opioid overdose

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.

Sources

ICD-10: T40.2 · ICD-11: NE60

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Chronic fatigue

Not recommended

Naloxone is an opioid receptor antagonist. It is prescribed for opioid overdose reversal (heroin, fentanyl, oxycodone) and in combination with buprenorphine for opioid use disorder (, ASAM 2020). Naloxone at very low doses (LDN, low-dose naltrexone, 1.5–4.5 mg) is promoted in alt circles for chronic fatigue, fibromyalgia, and autoimmune diseases. Clinical studies of low-dose naltrexone (a related drug) in fibromyalgia are small and heterogeneous; for chronic fatigue, an evidence base is essentially absent. International clinical guidelines do not include naloxone/naltrexone for chronic fatigue. If naloxone or LDN was recommended for fatigue, consider seeking a second opinion.

Sources

ICD-10: R53 · ICD-11: MG22

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

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.

Safety

Contraindications

Hypersensitivity to components (extremely rare — does not justify withholding in opioid overdose)

Serious adverse effects

Severe cardiovascular events (pulmonary edema, arrhythmia) in patients with serious cardiac disease — rare
Seizures with severe withdrawal

Common adverse effects

Acute opioid withdrawal syndrome: tachycardia, hypertension, nausea, vomiting, sweating, agitation
Return of pain in patients on opioid analgesia

Pregnancy: can you take Naloxone?

AEMPS summary of product characteristics (section 4.6): there are not enough clinical data on naloxone exposure in pregnancy. Animal studies have shown reproductive toxicity, and the potential risk in humans is unknown. Naloxone is not used in pregnancy unless clearly necessary. It can cause withdrawal symptoms in newborns.

Breastfeeding: can you take Naloxone?

Compatible with breastfeeding.

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

If opioid overdose is suspected (respiratory depression, miosis, loss of consciousness) — call EMS and administer naloxone immediately. Intranasal form (4 mg): spray in one nostril with the patient supine. If no effect in 2–3 minutes — second dose in the other nostril. After administration: recovery position, monitor breathing until EMS arrives.

Special situations

In opioid-tolerant patients, naloxone may precipitate acute withdrawal — tachycardia, hypertension, vomiting, agitation, seizures. When feasible, titrate (0.04 mg every minute to restore breathing) to minimize withdrawal. In neonates of opioid-dependent mothers, do not give naloxone — it can cause severe withdrawal; supportive care is preferred.

Common myths

Myth: 'naloxone encourages users to overdose again'. Fact: 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.

Myth: 'naloxone must be given only by medical personnel'. Fact: intranasal naloxone is specifically designed for bystander use; OTC in the US since 2023.

Label mentions10 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

Moderatebetabloqueantesclass named in the label
«Se ha notificado que el hidrocloruro de naloxona induce hipotensión, hipertensión, taquicardia ventricular, fibrilación y edema pulmonar. Estas reacciones adversas se han observado en el periodo…»
AEMPS, section 4.4 · Open on CIMA
ModerateDigoxin
«Se ha notificado que el hidrocloruro de naloxona induce hipotensión, hipertensión, taquicardia ventricular, fibrilación y edema pulmonar. Estas reacciones adversas se han observado en el periodo…»
AEMPS, section 4.4 · Open on CIMA
Moderateopioidesclass named in the label
«Después del uso de opioides durante la cirugía, debe evitarse dosis excesiva de hidrocloruro de naloxona, ya que puede causar excitación, aumento de la presión sanguínea y reversión clínicamente…»
AEMPS, section 4.4 · Open on CIMA
Minorbarbitúricosclass named in the label
«Con una dosis habitual de hidrocloruro de naloxona no hay ninguna interacción con barbitúricos ni con tranquilizantes.»
AEMPS, section 4.5 · Open on CIMA
Clonidine
«Con la administración del hidrocloruro de naloxona en casos de coma causado por sobredosis de clonidina se ha notificado hipertensión grave.»
AEMPS, section 4.5 · Open on CIMA

From other drugs’ labels

Darunavir
«Established and Other Potentially Significant Drug Interactions: Narcotic analgesics/treatment of opioid dependence : buprenorphine, buprenorphine/naloxone methadone « buprenorphine, naloxone …»
FDA, section 7 · Open on DailyMed
Fluvoxamine
«Los efectos serotoninérgicos de la fluvoxamina se pueden mejorar cuando se usan en combinación con otros agentes serotoninérgicos (incluyendo tramadol, buprenorfina, buprenorfina/naloxona, triptanos…»
AEMPS, section 4.5 · Open on CIMA
Methadone
«Antagonistas opiáceos: Naloxona antagoniza la depresión respiratoria y del sistema nervioso central y el efecto analgésico de metadona. La administración de naltrexona a un paciente adicto a…»
AEMPS, section 4.5 · Open on CIMA
Morphine
«Dependencia y tolerancia: También pueden presentarse síntomas de abstinencia después de la administración de un antagonista opiáceo (Naloxona o Naltrexona) o de un agonista/antagonista (pentazocina)…»
AEMPS, section 4.4 · Open on CIMA
Voriconazole
«Opioides: Opi á ceos de acci ó n corta [sustratos del CYP 3A4] Alfentanilo (dosis ú nica de 20 μ g/kg, con naloxona de forma concomitante) Fentanilo (dosis ú nica de 5 μ g/kg)»
AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Naloxone used for?

Naloxone is evaluated for the following indications with varying evidence strength: Opioid overdose (evidence tier A), Chronic fatigue (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Naloxone?

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.

Is Naloxone safe during pregnancy?

Is Naloxone compatible with breastfeeding?

Compatible with breastfeeding.

Who should not take Naloxone?

Naloxone is contraindicated in: Hypersensitivity to components (extremely rare — does not justify withholding in opioid overdose). Full list in the Safety section.

naloxone encourages users to overdose again

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.

naloxone must be given only by medical personnel

intranasal naloxone is specifically designed for bystander use; OTC in the US since 2023.

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMA
EMALabel dated 11/09/2017
FDA / DailyMedLabel dated 06/18/2026

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