Codeine
**Codeine** is a phenanthrene-derivative opiate agonist used in veterinary medicine primarily as an **antitussive** (cough suppressant) and mild **analgesic**. It is also occasionally used as an antidiarrheal agent. * **Analgesia**: Used for mild to moderate pain, often when NSAIDs are ineffective or contraindicated. * **Antitussive**: Highly effective for suppressing non-productive coughs (e.g., tracheal collapse, chronic bronchitis). * **Antidiarrheal**: Decreases gastrointestinal motility. > **Clinical Pearl**: While widely used in human medicine, codeine's use in dogs is controversial. Dogs absorb oral codeine very poorly and lack the robust enzymatic pathways to convert it to its active metabolite (morphine). Therefore, its analgesic efficacy in dogs is highly variable and generally considered inferior to other opioids like buprenorphine or methadone.
Mechanism: Codeine acts as a weak agonist at **mu (ฮผ) opioid receptors**. * **Analgesia**: Binds to **ฮผ-receptors** in the central nervous system โ inhibits the release of excitatory neurotransmitters (such as Substance P) in ascending pain pathways โ alters the perception of and response to pain. * **Antitussive**: Causes direct depression of the **medullary cough center** in the brainstem. * **Antidiarrheal**: Binds to **enteric ฮผ-receptors** โ decreases gastrointestinal motility and increases sphincter tone. * **Metabolism Note**: In humans, codeine is a prodrug metabolized by the enzyme **CYP2D6** โ **morphine**. Dogs lack significant CYP2D6-equivalent activity, relying mostly on codeine-6-glucuronide for any analgesic effect, which explains its limited efficacy in this species.
Dosing by species
- Analgesic (mild to moderate acute pain) ยท 0.5-2 mg/kg PO titrated to effect q6-12h ยท PO ยท q6-12h ยท May use for chronic pain at lowest effective dose. Do NOT use combination products containing acetaminophen.
- Analgesic ยท 0.5-2 mg/kg PO q6-8h ยท PO ยท q6-8h ยท Do NOT use combination products containing acetaminophen.
- Analgesic ยท 0.5 mg/kg PO q6h ยท PO ยท q6h ยท Do NOT use combination products containing acetaminophen.
- Antitussive / Analgesia ยท 0.5 - 2 mg/kg ยท PO ยท q6h-q8h ยท As directed ยท Rarely used. MUST ensure the product does NOT contain paracetamol.
- Analgesic ยท 1 mL in 10-20 mL of drinking water ยท PO ยท Continuous ยท Using acetaminophen and codeine elixir. Add dextrose to enhance palatability.
- Antitussive ยท 1-2 mg/kg PO q6-12h ยท PO ยท q6-12h
- Antitussive ยท 0.1-0.3 mg/kg PO q8-12h up to 1-2 mg/kg PO q6-12h ยท PO ยท q6-12h ยท Whatever the starting point, the dose may need to be increased to achieve a satisfactory effect.
- Analgesic (mild to moderate acute pain) ยท 0.5-2 mg/kg PO titrated to effect q6-12h ยท PO ยท q6-12h ยท May use for chronic pain at lowest effective dose.
- Analgesic (in combination with acetaminophen) ยท 1-2 mg/kg (of the codeine) PO q6-8h ยท PO ยท q6-8h ยท Using a 60 mg codeine and 300 mg acetaminophen fixed-dose tablet. Do not use in cats.
Routes of administration
Contraindications
- Hypersensitivity to narcotic analgesics
- Patients receiving monoamine oxidase inhibitors (MAOIs) like amitraz or selegiline
- Diarrhea caused by toxic ingestion (until toxin is eliminated)
- Repeated use in severe inflammatory bowel disease
- Scorpion stings (Centruroides sculpturatus and C. gertschi) as it may potentiate venom
- Combination products containing acetaminophen are STRICTLY CONTRAINDICATED in cats
- Hypersensitivity to opioids
- Severe respiratory depression or asthma
- Cats (especially if using combination products containing paracetamol)
Adverse effects
- Sedation (most common)
- Constipation
- Anorexia
- Vomiting
- Ileus
- Biliary and pancreatic duct spasms
- Respiratory depression (at high doses)
- Cats: CNS stimulation, hyperexcitability, tremors, seizures
- Sedation
- Nausea
Drug interactions
- Anticholinergic drugs ยท May increase the chances of constipation developing
- Antidepressants (TCAs/MAOIs) ยท May potentiate CNS depressant effects
- CNS Depressants (anesthetics, antihistamines, phenothiazines, barbiturates, tranquilizers) ยท May cause increased CNS or respiratory depression
- Quinidine ยท May inhibit the transformation of codeine to morphine in the liver, decreasing its efficacy
- CNS Depressants (e.g., phenobarbital, diazepam) ยท Additive CNS and respiratory depression ยท moderate
- SSRIs / MAOIs ยท Increased risk of serotonin syndrome ยท major
- CNS Depressants (e.g., sedatives, anesthetics, antihistamines) ยท Additive CNS and respiratory depression ยท major
- Monoamine Oxidase Inhibitors (MAOIs) ยท May cause severe, unpredictable reactions (serotonin syndrome or severe respiratory depression) ยท major
Monitoring
- Efficacy (pain relief, reduction in coughing, or resolution of diarrhea)
- Adverse effects (sedation, respiratory rate, GI signs)
- Respiratory rate and depth
- Level of sedation
- Pain score or coughing frequency
- Bowel movements (monitor for constipation)
Overdose
Opiate overdosage may produce profound **respiratory and/or CNS depression**. Other effects can include cardiovascular collapse, hypothermia, and skeletal muscle hypotonia. * **Decontamination**: Oral ingestions should be removed using standard gut removal protocols. Inducing vomiting should be attempted with caution due to rapid changes in CNS status. * **Antidote**: **Naloxone** is the agent of choice for treating respiratory depression. In massive overdoses, naloxone doses may need to be repeated, as its effects may diminish before subtoxic levels of codeine are attained. * **Supportive Care**: Mechanical respiratory support should be considered in cases of severe respiratory depression. Contact an animal poison control center for further guidance.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.