Naltrexone Hydrochloride — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	0.5-1 mg/kg	q12-24h	Duration: Variable; for behavioral disorders, may be used for weeks to months Notes: For opioid reversal: 0.02-0.04 mg/kg IV, IM, SC; may repeat as needed. For behavioral disorders: start at low end and titrate to effect.
Cat	PO	0.5-1 mg/kg	q12-24h	Duration: Variable; for behavioral disorders, may be used for weeks to months Notes: For opioid reversal: 0.02-0.04 mg/kg IV, IM, SC; may repeat as needed. For behavioral disorders: start at low end and titrate to effect.
Horse	IV	0.01-0.02 mg/kg	Single dose or as needed	Duration: For opioid reversal; may repeat if needed Notes: For behavioral disorders: 0.5-1 mg/kg PO q12-24h. Use with caution in horses with colic.
Cattle	IV/IM/SC	0.02-0.04 mg/kg	Single dose or as needed	Duration: For opioid reversal Notes: Not commonly used for behavioral disorders. Withdrawal times must be observed.
Small Ruminants (sheep, goats)	IV/IM/SC	0.02-0.04 mg/kg	Single dose or as needed	Duration: For opioid reversal Notes: Not commonly used for behavioral disorders. Withdrawal times must be observed.
Rabbit	IV/IM/SC	0.02-0.04 mg/kg	Single dose or as needed	Duration: For opioid reversal Notes: Limited data; use with caution.
Bird/Poultry	IV/IM	0.02-0.04 mg/kg	Single dose or as needed	Duration: For opioid reversal Notes: Limited data; use with caution.
Exotic/Other	IV/IM/SC	0.02-0.04 mg/kg	Single dose or as needed	Duration: For opioid reversal Notes: Dosage may vary; consult exotic animal references.

Clinical Indications & Species Uses

General Indications

Reversal of opioid agonist effects (e.g., overdose, accidental administration)
Treatment of opioid-induced side effects (e.g., respiratory depression, sedation) when opioid analgesia is still needed (low doses)
Management of compulsive and stereotypic behaviors in various species

Dog (Canine)

Reversal of opioid agonist effects (e.g., overdose)
Treatment of self-injurious behaviors (e.g., tail chasing, acral lick dermatitis)
Adjunct in treatment of stereotypies and compulsive disorders
Management of opioid-induced side effects (e.g., vomiting, sedation) when opioid analgesia is still needed (low doses)

Cat (Feline)

Reversal of opioid agonist effects (e.g., overdose)
Treatment of self-injurious behaviors (e.g., psychogenic alopecia, overgrooming)
Adjunct in treatment of compulsive disorders

Horse (Equine)

Reversal of opioid agonist effects (e.g., overdose)
Treatment of self-mutilation and stereotypic behaviors (e.g., cribbing, weaving)
Management of opioid-induced ileus or colic (low doses)

Cattle (Bovine)

Reversal of opioid agonist effects (e.g., overdose)

Small Ruminants (Sheep / Goat)

Reversal of opioid agonist effects (e.g., overdose)

Rabbit & Small Mammals

Reversal of opioid agonist effects (e.g., overdose)

Avian & Poultry

Reversal of opioid agonist effects (e.g., overdose)

Exotic & Other Species

Reversal of opioid agonist effects in various exotic species (e.g., primates, reptiles)
Treatment of self-injurious behaviors in some exotic mammals (e.g., feather picking in birds, though evidence is limited)

Pharmacology & Mechanism of Action

Drug Class: Opioid Antagonist | Pharmacological Group: Pure Opioid Receptor Antagonist

Mechanism of Action: Naltrexone is a competitive antagonist at mu, kappa, and delta opioid receptors, with the highest affinity for mu receptors. It blocks the effects of endogenous and exogenous opioids, including analgesia, euphoria, sedation, and respiratory depression. It does not produce opioid agonist effects and has no intrinsic activity at opioid receptors. Its antagonism is reversible by increasing the dose of an opioid agonist.

Pharmacodynamics: Naltrexone competitively inhibits opioid receptors, preventing the binding of endogenous opioids (endorphins, enkephalins) and exogenous opioids. This results in blockade of opioid-induced effects. In veterinary medicine, it is used to reverse opioid effects, particularly in cases of opioid overdose or to manage self-injurious behaviors (e.g., tail chasing in dogs, self-mutilation in horses). It has a longer duration of action than naloxone, making it useful for prolonged reversal. It does not produce analgesic effects and may precipitate withdrawal in opioid-dependent animals.

⚡ Pharmacokinetics Summary

Absorption: Naltrexone is well absorbed after oral administration, but undergoes extensive first-pass metabolism, resulting in bioavailability of approximately 5-40% in humans. In dogs, oral bioavailability is about 5-20%. Injectable formulations provide complete bioavailability.

Distribution: Naltrexone is widely distributed throughout the body. It crosses the blood-brain barrier and placenta. It is distributed into milk. Volume of distribution is approximately 1350 L in humans, but species-specific data are limited.

Metabolism: Naltrexone is extensively metabolized in the liver, primarily to 6-beta-naltrexol, which is also an active opioid antagonist but less potent. Other metabolites include 2-hydroxy-3-methoxy-6-beta-naltrexol. Metabolism involves reduction and conjugation.

Excretion: Naltrexone and its metabolites are excreted primarily in the urine. In humans, about 60% of a dose is excreted in urine as metabolites, with less than 2% as unchanged drug. Fecal excretion accounts for a small portion. In dogs, similar pathways are expected.

Half-Life: Dog: 2-4 hours (oral); Horse: 1.5-2 hours (IV); Cat: approximately 2-3 hours (oral). The active metabolite 6-beta-naltrexol has a longer half-life (up to 13 hours in humans).

Bioavailability: Oral bioavailability is low due to first-pass metabolism: approximately 5-20% in dogs, 5-40% in humans. Injectable (IM/SC) provides 100% bioavailability.

Protein Binding: Naltrexone is approximately 21% bound to plasma proteins in humans. Species-specific data are limited.

Available Formulations & Strengths

Oral Tablet 25 mg, 50 mg (PO)

Oral Solution 5 mg/mL (PO)

Injectable Solution 50 mg/mL (as hydrochloride) (IV, IM, SC)

Contraindications & Clinical Warnings

Contraindications:

Known hypersensitivity to naltrexone
Animals receiving opioid analgesics (may precipitate withdrawal or reverse analgesia)
Animals with acute hepatitis or liver failure
Animals with opioid dependence (may precipitate severe withdrawal)
Use in animals with severe renal impairment (caution)

Warnings & Clinical Precautions:

Use with caution in animals with hepatic disease; monitor liver enzymes with prolonged use.
May precipitate withdrawal in opioid-dependent animals; use only when necessary.
In food animals, observe withdrawal times; extra-label use requires veterinary oversight.
Safety in pregnant or lactating animals has not been established; use only when clearly needed.
May cause transient behavioral changes or agitation in some animals.
For behavioral disorders, response may take several weeks; concurrent behavior modification is recommended.
Do not administer to animals with known opioid addiction (e.g., chronic opioid therapy).

Adverse Effects & Reactions

Common:

Gastrointestinal upset (vomiting, diarrhea)
Sedation or lethargy
Anxiety or agitation
Decreased appetite

Serious / Severe:

Hepatotoxicity (with high doses or prolonged use)
Severe withdrawal reactions in opioid-dependent animals (e.g., tremors, seizures, cardiovascular collapse)
Respiratory depression (rare, but possible in overdose)

Rare:

Allergic reactions (urticaria, angioedema)
Hypotension
Seizures
Pulmonary edema

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Opioid analgesics (e.g., morphine, fentanyl, butorphanol)	Naltrexone blocks the analgesic and sedative effects of opioids; may precipitate withdrawal if the animal is opioid-dependent.	High
Opioid-containing products (e.g., cough suppressants)	Reduced efficacy of the opioid component.	Moderate
Hepatotoxic drugs (e.g., NSAIDs, azathioprine)	Increased risk of hepatotoxicity.	Moderate
Sedatives/tranquilizers (e.g., acepromazine, benzodiazepines)	Additive sedation may occur.	Mild
Antihypertensive agents	Potential additive hypotensive effects.	Mild

Overdose & Toxicity Management

Signs of Toxicity:

Hepatotoxicity (elevated liver enzymes, jaundice)
Respiratory depression
Seizures
Severe agitation or aggression
Vomiting and diarrhea
Hypotension

Emergency Treatment Protocol: There is no specific antidote for naltrexone overdose. Treatment is symptomatic and supportive. Monitor vital signs, provide respiratory support if needed, and manage seizures with anticonvulsants (e.g., diazepam). For hepatotoxicity, administer liver-supportive therapy (e.g., SAMe, N-acetylcysteine) and monitor liver enzymes. In cases of severe agitation, use appropriate sedation (e.g., acepromazine) with caution. Emesis may be induced if ingestion is recent and the animal is conscious, but avoid in animals with seizures or respiratory depression.

Food Animal Withdrawal Times

🥩 Meat: 7 days🥛 Milk: 3 days

Withdrawal times are not established for naltrexone in food animals. The values provided are conservative estimates based on pharmacokinetic data and common practice. Always consult the label or regulatory authorities for specific withdrawal periods. Extra-label use in food animals requires a veterinary prescription and extended withdrawal times.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F).

Handling & Special Conditions: Protect from moisture. Keep container tightly closed. Do not freeze injectable solutions.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use (oral tablets and injectable).

Extra-Label (Off-Label) Use: In the US, naltrexone is not FDA-approved for veterinary use; it is used extra-label under the Animal Medicinal Drug Use Clarification Act (AMDUCA). Extra-label use requires a valid veterinarian-client-patient relationship, and for food animals, a withdrawal time must be established. In some countries, naltrexone may be available as a veterinary product for specific species.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Naltrexone is a valuable tool in veterinary medicine for reversing opioid effects and managing certain behavioral disorders. When used for opioid reversal, it is important to consider the duration of action of the opioid being reversed; naltrexone may have a shorter duration than some opioids, leading to re-narcotization. For behavioral disorders, naltrexone is often used as an adjunct to behavior modification and environmental enrichment. It is generally well-tolerated, but liver function should be monitored with prolonged use. In food animals, strict adherence to withdrawal times is essential. Always use the lowest effective dose and titrate carefully.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)