Codeine Phosphate — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	0.5-2 mg/kg	q6-8h	Duration: As needed for pain or cough Notes: Analgesic efficacy is variable; may be less effective than other opioids. For cough: 0.1-0.3 mg/kg q6-8h.
Cat	PO	0.5-1 mg/kg	q6-8h	Duration: As needed for pain or cough Notes: Use with caution; may cause excitation. Efficacy is questionable due to poor metabolism to morphine.
Horse	PO	0.5-1 mg/kg	q6-12h	Duration: As needed Notes: Not commonly used; may cause CNS excitation.
Cattle	Not recommended	Not established	Not established	Duration: Not established Notes: Not approved for food animals; withdrawal times not established.

Clinical Indications & Species Uses

General Indications

Mild to moderate pain management
Antitussive for non-productive cough

Dog (Canine)

Mild to moderate pain
Cough suppression (antitussive)

Cat (Feline)

Mild to moderate pain (though efficacy is questionable)
Cough suppression (rarely used)

Horse (Equine)

Mild to moderate pain

Pharmacology & Mechanism of Action

Drug Class: Opioid Analgesic | Pharmacological Group: Phenanthrene Opioid Agonist

Mechanism of Action: Codeine is a weak opioid agonist that primarily exerts its analgesic effects through binding to mu-opioid receptors in the central nervous system, leading to inhibition of ascending pain pathways and alteration of pain perception and emotional response. A significant portion of its analgesic effect is attributed to its metabolism to morphine via CYP2D6, which has higher affinity for mu receptors. Additionally, codeine has antitussive effects by depressing the cough center in the medulla.

Pharmacodynamics: Codeine produces analgesia, sedation, and antitussive effects. It also causes respiratory depression, cough suppression, and can induce euphoria or dysphoria. In veterinary species, the analgesic efficacy is variable due to differences in metabolism and receptor affinity. It may cause histamine release leading to vasodilation and hypotension.

⚡ Pharmacokinetics Summary

Absorption: Codeine is well absorbed after oral administration, with peak plasma concentrations occurring within 1-2 hours in most species. Bioavailability is variable due to first-pass metabolism.

Distribution: Codeine is widely distributed throughout the body, crosses the blood-brain barrier, and can cross the placenta. It has a volume of distribution of approximately 3-6 L/kg in dogs.

Metabolism: Codeine is metabolized in the liver primarily by glucuronidation to codeine-6-glucuronide and by O-demethylation via CYP2D6 to morphine, which is the active metabolite. In dogs, the extent of conversion to morphine is lower than in humans, which may explain its reduced efficacy in this species.

Excretion: Codeine and its metabolites are excreted primarily in the urine, with about 5-15% excreted as free codeine. Biliary excretion also occurs.

Half-Life: Dog: 1-2 hours; Cat: 1-2 hours; Horse: 1-2 hours; Cattle: 1-2 hours (estimated)

Bioavailability: Oral bioavailability in dogs is approximately 60-70% but with high interindividual variability.

Protein Binding: Approximately 7-25% bound to plasma proteins.

Available Formulations & Strengths

Oral Tablet 15 mg, 30 mg, 60 mg (PO)

Oral Solution Various concentrations (e.g., 15 mg/5 mL) (PO)

Injectable Solution 30 mg/mL, 60 mg/mL (IM, SC, IV (slow))

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to codeine or other opioids
Severe respiratory depression
Acute or severe asthma
Concurrent use with MAO inhibitors
Premature or low-birth-weight neonates
Use in animals with head trauma or increased intracranial pressure
Use in animals with impaired consciousness

Warnings & Clinical Precautions:

Use with caution in animals with hepatic or renal impairment
Use with caution in animals with hypothyroidism, Addison's disease, or prostatic hypertrophy
May cause histamine release; administer slowly IV to avoid hypotension
May cause constipation; monitor bowel function
In cats, may cause CNS excitation or mania
In horses, may cause excitation and colic
Tolerance and dependence may develop with prolonged use
Use with caution in debilitated or geriatric animals
Avoid in animals with cough that is productive or due to respiratory disease

Adverse Effects & Reactions

Common:

Sedation
Constipation
Nausea
Vomiting
Urinary retention
Miosis

Serious / Severe:

Respiratory depression
Hypotension
Bradycardia
CNS excitation (especially in cats and horses)
Ileus
Seizures (rare)

Rare:

Allergic reactions
Anaphylaxis
Hepatotoxicity (with chronic use)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Other CNS depressants (e.g., barbiturates, benzodiazepines, anesthetics)	Additive CNS depression and respiratory depression	High
MAO inhibitors	Severe hypotension, respiratory depression, and coma	High
Tricyclic antidepressants	Increased risk of serotonin syndrome and respiratory depression	Moderate
Anticholinergics	Increased risk of urinary retention and constipation	Moderate
CYP2D6 inhibitors (e.g., fluoxetine, amiodarone)	Reduced conversion to morphine, decreasing analgesic efficacy	Moderate
CYP3A4 inducers (e.g., rifampin)	Increased metabolism of codeine, reducing efficacy	Mild

Overdose & Toxicity Management

Signs of Toxicity:

Respiratory depression
CNS depression
Miosis
Hypotension
Bradycardia
Hypothermia
Muscle flaccidity
Pulmonary edema (rare)

Emergency Treatment Protocol: Provide supportive care, maintain airway and ventilation, administer naloxone (0.01-0.04 mg/kg IV, IM, SC; may repeat as needed) as a specific opioid antagonist. Monitor for seizures and treat symptomatically. Consider activated charcoal if recent oral ingestion.

Food Animal Withdrawal Times

Not approved for use in food animals in the US; no withdrawal times established. If used extra-label, consult FARAD for guidance.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F)

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from light and moisture. Store in a tightly closed container. Keep out of reach of children and animals.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Codeine is not FDA-approved for veterinary use in animals, but it is available as a generic drug and can be used extra-label.

Extra-Label (Off-Label) Use: Extra-label use in food animals is prohibited in the US due to lack of established withdrawal times and potential for residues. In non-food animals, extra-label use is permitted under AMDUCA with appropriate veterinary oversight.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Codeine is a weak opioid that is sometimes used for mild to moderate pain or as an antitussive in veterinary medicine. However, its analgesic efficacy is variable across species due to differences in metabolism; in dogs, it is less effective than other opioids like morphine or butorphanol. In cats, it may cause excitation and is generally not recommended. For cough suppression, it can be effective but should be used with caution in animals with productive coughs. Due to its controlled substance status and potential for abuse, it should be used with caution and proper record-keeping. Alternative analgesics such as NSAIDs or other opioids may be preferred for pain management. Always monitor for adverse effects, especially respiratory depression and sedation.

References & Literature

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