Naloxone

Naloxone is a short-acting opioid-receptor antagonist used for rapid reversal of unwanted opioid effects. Its principal veterinary application is reversal of opioid-associated respiratory or central nervous system depression, including overdose and anesthetic complications. It is also used when dysphoria, excitation or other opioid effects interfere with recovery or patient comfort.

Group

Opioid antagonist

Mechanism of Action

Naloxone competes with opioid agonists for receptor binding, particularly at mu receptors, with activity at other opioid receptor types. Displacement of the agonist reduces receptor-mediated suppression of respiration, arousal and other neural pathways. The extent of reversal depends on receptor occupancy and the agonist involved. Naloxone has little intrinsic agonist activity.

Dose Rates

Dogs

Use / stage	Dose	Route	Schedule	Instructions
Opioid reversal	0.01–0.04 mg/kg	IV, IM, SC	As needed	Full reversal commonly requires 0.04 mg/kg; titrate to the required degree of antagonism.
Opioid-associated dysphoria	0.01 mg/kg	IV	As needed	Low-dose partial reversal may retain analgesia.
Titrated partial reversal	Reference only	IV		Use 0.04 mg/mL solution in 1 mL increments every 30 seconds until dysphoria subsides; this is a titration protocol, not a universal fixed dose.
Opioid reversal	0.01–0.02 mg/kg	IM, IV, SC	As needed	Separate lower-dose alternative; monitor for resedation.
Opioid reversal	0.04 mg/kg	IV, IM, SC	As needed	Full-reversal alternative.
Pulseless electrical activity adjunct	0.02–0.04 mg/kg	IV		Reported adjunct in resuscitation; benefit is uncertain.

Cats

Use / stage	Dose	Route	Schedule	Instructions
Opioid reversal	0.01–0.04 mg/kg	IV, IM, SC	As needed	Full reversal commonly requires 0.04 mg/kg; titrate to the required degree of antagonism.
Opioid-associated dysphoria	0.01 mg/kg	IV	As needed	Low-dose partial reversal may retain analgesia.
Titrated partial reversal	Reference only	IV		Use 0.04 mg/mL solution in 1 mL increments every 30 seconds until dysphoria subsides; this is a titration protocol, not a universal fixed dose.
Opioid reversal	0.01–0.02 mg/kg	IM, IV, SC	As needed	Separate lower-dose alternative; monitor for resedation.
Pulseless electrical activity adjunct	0.02–0.04 mg/kg	IV		Reported adjunct in resuscitation; benefit is uncertain.
Postanesthetic opioid-associated hyperthermia	0.01 mg/kg	IM, SC		Reported when temperature exceeded 41.1 C; continue temperature and respiratory assessment.

Horses

Use / stage	Dose	Route	Schedule	Instructions
Opioid reversal	0.02–0.04 mg/kg	IV	As needed	Effect may last only about 20 minutes.
Opioid-associated locomotor excitation	0.01 mg/kg	IV

Rabbits

Use / stage	Dose	Route	Schedule	Instructions
Opioid reversal	0.005–0.1 mg/kg	IM, IV	As needed

Rodent

Use / stage	Dose	Route	Schedule	Instructions
Opioid reversal	0.01–0.1 mg/kg	SC, IP	As needed

Hamsters

Use / stage	Dose	Route	Schedule	Instructions
Opioid reversal	0.01–0.1 mg/kg	SC, IP	As needed

Gerbils

Use / stage	Dose	Route	Schedule	Instructions
Opioid reversal	0.01–0.1 mg/kg	SC, IP	As needed

Mice

Use / stage	Dose	Route	Schedule	Instructions
Opioid reversal	0.01–0.1 mg/kg	SC, IP	As needed

Rats

Use / stage	Dose	Route	Schedule	Instructions
Opioid reversal	0.01–0.1 mg/kg	SC, IP	As needed

Guinea pigs

Use / stage	Dose	Route	Schedule	Instructions
Opioid reversal	0.01–0.1 mg/kg	SC, IP	As needed

Chinchillas

Use / stage	Dose	Route	Schedule	Instructions
Opioid reversal	0.01–0.1 mg/kg	SC, IP	As needed

Indications

Reversal of opioid overdose or clinically important opioid-associated respiratory depression in veterinary patients.
Reduction of opioid-associated dysphoria, excessive sedation or excitation after analgesia or anesthesia.
Reversal of selected opioid-associated adverse effects, including some feline postanesthetic hyperthermia or equine locomotor excitation cases.
Reversal of opioid-based immobilization when naloxone is an appropriate antagonist for the drug used.

Contraindications

Abrupt reversal in a painful patient can cause severe distress.

Interactions

Antagonizes opioid analgesia; reversal of buprenorphine may be incomplete.

Adverse effects

Pain, agitation, hypertension, tachycardia and arrhythmias.

Toxicity

Very high exposure has occasionally provoked seizures. Abrupt opioid reversal can also precipitate pain, withdrawal and cardiovascular stimulation.

Preparations

Preparation	Form	Strength	Route
Naloxone injection 0.02 mg/mL	Injection	0.02 mg / mL	IV, IM, SC
Naloxone injection 0.4 mg/mL	Injection	0.4 mg / mL	IV, IM, SC
Naloxone injection 1 mg/mL	Injection	1 mg / mL	IV, IM, SC
Naloxone injection 50 mg/mL The 50 mg/mL presentation is a concentrated wildlife formulation.	Injection	50 mg / mL	IV, IM, SC

Monitoring and Administration

Titrate to respiratory and clinical response; monitor blood pressure, rhythm and comfort. Recurrent depression is possible because naloxone acts for less time than many opioids.

For infusion, 2 mg in 500 mL saline or 5% dextrose gives 4 mcg/mL; use within 24 hours. Avoid alkaline mixtures; protect from light.

Postoperative dysphoria protocol: prepare a total 4 mcg/kg in 10 mL and titrate 1 mL each minute to effect. Neonatal opioid depression after cesarean delivery has been treated with one drop of 0.4 mg/mL under the tongue; drop volume is unspecified.

Avoid mixtures containing sulfites, bisulfites, large anions or alkaline solutions. Opioid dependence can lead to withdrawal; preexisting cardiac disease increases reversal risk. Yohimbine may produce more CNS stimulation with naloxone. Buprenorphine respiratory depression may resist reversal.