Naloxone
Naloxone hydrochloride, N-allylnoroxymorphone
Also known as: Narcan · N-allylnoroxymorphone · naloxona · EN-15304 · naloxoni · Naloxonum · Naloxone hydrochloride
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Audited v13 dosing evidence
Reviewed non-calculator evidenceReviewed non-calculator evidence (2)
Evidence only — not for automatic calculation
Green tree monitors/reversal of butorphanol
TABLE 127.5. Agent: Naloxone. Dosage: 4 mg/kg IM95. Species/Comments: Green tree monitors/reversal of butorphanol.
Evidence only — not for automatic calculation
Corn snakes, bearded dragons, red-eared sliders/µ-opioid agonist reversal
TABLE 127.5. Agent: Naloxone. Dosage: 0.04–2 mg/kg SC304,305,307,309. Species/Comments: Corn snakes, bearded dragons, red-eared sliders/µ-opioid agonist reversal.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Naloxone is a pure opioid antagonist used primarily in veterinary medicine to reverse the effects of opioid agonists, specifically respiratory depression, sedation, and dysphoria. It is considered a life-saving antidote in cases of opioid overdose.
Beyond its primary use as a reversal agent, naloxone is being investigated for the treatment of various forms of shock (septic, hypovolemic, or cardiogenic) and may be employed as a diagnostic or therapeutic tool to curb self-mutilating behaviors (like tail-chasing) by blocking endogenous endorphins.
Clinical Pearl: Naloxone has no analgesic activity of its own. When used to reverse opioid-induced respiratory depression, it will simultaneously reverse the analgesic effects of the opioid, potentially leading to a sudden return of pain and subsequent catecholamine release.
Mechanism of action
Naloxone acts as a competitive antagonist at opioid receptors. It binds primarily to the mu (μ) receptor, but also has affinity for kappa (κ) and sigma (σ) receptors.
By occupying these receptors without activating them, it displaces opioid agonists → rapid reversal of opioid-induced respiratory and CNS depression.
At very high doses, naloxone may exhibit additional pharmacologic activity, including GABA antagonism and the ability to increase dopamine levels.
Safety & warnings
Contraindications
- Hypersensitivity to naloxone
- Indiscriminate use in animals that have undergone major surgery or trauma (due to severe pain from analgesia reversal)
Adverse effects
- Reversal of analgesia (return of pain)
- Acute withdrawal syndrome in opioid-dependent patients
- CNS excitement (especially if used in meperidine overdose)
- Seizures (at very high doses, likely secondary to GABA antagonism)
- Acute severe discomfort or pain (due to sudden loss of analgesia)
- Antanalgesic effects in opioid-naïve subjects
- Transient elevation of unconsciousness (at low doses)
Precautions
Important Warning: The duration of action of naloxone (45-90 minutes) is often shorter than the opioid it is reversing. Patients may slip back into respiratory depression and require re-dosing or continuous ventilatory support.
- Use with caution in animals with preexisting cardiac abnormalities.
- Use cautiously in opioid-dependent animals or those that have received exceedingly large doses of narcotics, as it may precipitate an acute withdrawal syndrome.
- Meperidine Toxicity: Naloxone is reportedly not effective for reversing meperidine-induced seizures and may elicit CNS excitement if normeperidine excitotoxicity is present. Avoid unless severe respiratory depression is present without ventilatory support.
- Buprenorphine: Naloxone is not a good reversal agent for buprenorphine due to buprenorphine's high receptor affinity; massive doses (100X usual) may be required.
Drug interactions
Naloxone may antagonize the effects of these agents (respiratory depression, analgesia). It should not be relied upon to treat respiratory depression caused by buprenorphine.
Naloxone may reduce the hypotensive and bradycardic effects of clonidine; potentially useful for clonidine overdoses.
Naloxone may increase the CNS effects of yohimbine (anxiety, tremors, nausea, palpitations) and increase plasma cortisol levels.
Naloxone reverses the analgesic, sedative, and respiratory depressant effects of opioid agonists.
Buprenorphine binds tightly to opioid receptors; naloxone may not fully reverse its effects or may require much higher doses.
Monitoring
- Respiratory rate and depth
- CNS function (level of sedation/arousal)
- Pain associated with opiate reversal
- Respiratory rate and effort
- Level of consciousness / sedation score
- Pain score (monitor for acute pain upon reversal)
- Heart rate and blood pressure
Pharmacokinetics
Half-life
Absorption
Minimally absorbed orally (rapidly destroyed in the GI tract). Very rapid onset of action when given IV (1-2 minutes). IM onset is generally within 5 minutes. Duration of action usually persists from 45-90 minutes, but may act for up to 3 hours.
Distribution
Distributed rapidly throughout the body with high levels found in the brain, kidneys, spleen, skeletal muscle, lung, and heart. Readily crosses the placenta.
Metabolism
Metabolized in the liver, principally via glucuronidative conjugation.
Elimination
Metabolites are excreted into the urine.
Overdose
Naloxone is considered a very safe agent with a very wide margin of safety. However, massive overdoses have initiated seizures in a few patients, which is theorized to be secondary to GABA antagonism.
Available products
Formulations
- Injection: 0.4 mg/mL
- Neonatal Injection: 0.02 mg/mL
- Injectable: 0.02 mg/ml solution
- Injectable: 0.4 mg/ml solution
Veterinary
- Naloxone 0.02 mg/ml injectable solution
- Naloxone 0.4 mg/ml injectable solution
Human-labeled
- Naloxone HCl Injection: 0.4 mg/mL (400 micrograms/mL) in 1 mL amps, syringes and 1 mL, 2 mL, & 10 mL vials (Narcan)
- Naloxone HCl Neonatal Injection: 0.02 mg/mL in 2 mL vials
- Narcan 0.4 mg/ml injectable solution
- Narcan nasal spray
Regulatory status
POM (Prescription Only Medicine)
POM-V
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store at room temperature (15-30°C) and protect from light. Sterile water for injection is the recommended diluent. When given as an IV infusion, either D5W or normal saline should be used. Do not mix with solutions containing sulfites, bisulfites, long-chain or high molecular weight anions, or any solutions at alkaline pH.
Client information
- Purpose: Naloxone is an emergency medication used to reverse the effects of opioid pain medications or treat opioid overdoses.
- What to Expect: Your pet may wake up quickly from sedation. Because naloxone reverses the pain medication, your pet might experience a sudden return of pain.
- Monitoring: The effects of naloxone can wear off before the opioid does. Watch your pet closely for a return of extreme sleepiness, slow breathing, or unresponsiveness.
- Administration: Usually given by a veterinary professional, but in some cases (like for newborn puppies or kittens), you may be instructed to place a drop under the tongue.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.