Codeine
Codeine phosphate, Codeine sulfate
Also known as: Tylenol with Codeine · Empirin with Codeine · Pardale-V · Co-codamol (human combination) · Codeine phosphate hemihydrate · Codeini phosphas hemihydricus · Codeinii phosphas · Codeinum · Methylmorphine · Codeine sulfate
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Audited v13 dosing evidence
Structured calculator evidenceAntitussive (extra-label)
Verified clinician required
- q6-12h
NA
Governing clinical context (2)
- ■ This medicine may be given with food or on an empty stomach.
- Store codeine sulfate tablets in light-resistant, well-closed containers at room temperature 15°C to 30°C (59°F-86°F).
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
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 of action
Codeine acts as a weak agonist at mu (μ) opioid receptors.
- Analgesia: Binds to μ-receptors in the central nervous system → inhibits the release of excitatory neurotransmitters (such as Substance P) in ascending pain pathways → alters the perception of and response to pain.
- Antitussive: Causes direct depression of the medullary cough center in the brainstem.
- Antidiarrheal: Binds to enteric μ-receptors → decreases gastrointestinal motility and increases sphincter tone.
- Metabolism Note: In humans, codeine is a prodrug metabolized by the enzyme CYP2D6 → 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.
Safety & warnings
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
- Nausea
Precautions
Use with caution in patients with hypothyroidism, severe renal insufficiency, Addison's disease, and in geriatric or severely debilitated patients.
Use with caution in patients with head injuries or increased intracranial pressure, and in those with acute abdominal conditions (e.g., colic) as it may obscure the diagnosis.
Use with extreme caution in patients suffering from respiratory disease or acute respiratory dysfunction (e.g., pulmonary edema secondary to smoke inhalation).
Warning: Opiates can increase plasma amylase and lipase values up to 24 hours following administration due to increased biliary tract pressure.
Drug interactions
May increase the chances of constipation developing
May potentiate CNS depressant effects
May cause increased CNS or respiratory depression
May inhibit the transformation of codeine to morphine in the liver, decreasing its efficacy
Additive CNS and respiratory depression
Increased risk of serotonin syndrome
Additive CNS and respiratory depression
May cause severe, unpredictable reactions (serotonin syndrome or severe respiratory depression)
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)
Pharmacokinetics
Half-life
Absorption
Very limited evidence of oral absorption in dogs. In humans, codeine salts are rapidly absorbed orally, with oral administration being about 2/3 as effective as parenteral. Onset of action is usually within 30 minutes.
Distribution
Crosses the placenta and enters maternal milk.
Metabolism
Metabolized in the liver.
Elimination
Excreted into the urine.
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.
Available products
Formulations
- Tablets
- Oral solution/elixir
- Parenteral injection
- Combination products (with acetaminophen, aspirin, or guaifenesin)
- 3 mg/5 ml paediatric linctus
- 3 mg/ml linctus
- 5 mg/ml syrup
- 15 mg tablet
- 30 mg tablet
- 60 mg tablet
Veterinary
- Pardale-V tablets (Combination: Paracetamol 400 mg + Codeine phosphate 9 mg)
Human-labeled
- Codeine Phosphate Solution: 15 mg/5 mL
- Codeine Sulfate Tablets: 15 mg, 30 mg & 60 mg
- Codeine Phosphate Parenteral Injection: 15 mg/mL & 30 mg/mL
- Codeine Phosphate Antitussives with expectorants (e.g., with guaifenesin)
- Codeine Phosphate with Acetaminophen tablets (Tylenol® with Codeine #1, #2, #3, #4)
- Codeine Phosphate with Aspirin tablets (Empirin® with Codeine #2, #3, #4)
- Codeine linctus (3 mg/ml, 3 mg/5 ml)
- Codeine syrup (5 mg/ml)
- Codeine tablets (15 mg, 30 mg, 60 mg)
Regulatory status
Availability of veterinary specific products varies by member state.
Classified as POM-V or POM depending on the specific product (e.g., Pardale-V is POM-V).
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Codeine phosphate and sulfate tablets should be stored in light-resistant, well-closed containers at room temperature. Codeine phosphate injection should be stored at room temperature (avoid freezing) and protected from light. Do not use the injection if discolored or if it contains a precipitate.
Client information
- Keep out of reach of children and pets: This is a controlled substance.
- TOXIC TO CATS: Never give any product containing acetaminophen (e.g., Tylenol® with Codeine) to cats. It is rapidly fatal.
- Side Effects: Watch for extreme sleepiness, constipation, lack of appetite, or vomiting. Cats may occasionally become unusually hyperactive, jittery, or have tremors.
- When to call the vet: Report any significant changes in behavior, activity level, or severe gastrointestinal effects to your veterinarian immediately.
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.