Methadone: veterinary dose and monograph

At a glance

Drug class

Analgesic

Also known as

Comfortan, Dolophine, Methadose

Species with doses

Dogs, Cats and Horses

General dose range

0.1–0.5 mg/kg IV q4h — check the species tables for the indication

Routes

IV, IM, PO

Last reviewed

1 October 2026

Indications

• Pre-operative analgesia and sedation
• Post-operative analgesia (soft tissue and orthopaedic)
• Trauma analgesia
• CRI for chronic / refractory pain
• Cancer pain
• Wind-up pain (NMDA antagonism is a unique advantage)

Methadone dose by species

Doses are per administration unless stated. mg/kg doses scale with body weight; per-animal, per-quarter and infusion-rate doses are shown as the reference writes them.

Dogs

• Pre-anaesthetic / analgesia (IV): Papich 5e: 0.1–0.5 mg/kg IV. Plumb’s p.795: pain 0.1–0.25 mg/kg IV/IM/SC, effect 4–6 h (Otero 2006); 0.5 mg/kg IV q6h (Posner & Papich 2009). With acepromazine 0.02–0.05 mg/kg use methadone 0.1–0.3 mg/kg.
• Pre-anaesthetic / analgesia (IM/SC): Plumb’s p.795: pre-anaesthetic 0.2–0.5 mg/kg SC or IM (Cornell 2004); analgesia 0.5–1 mg/kg q6–8h IV, IM or SC (Posner & Papich 2009). Papich 5e lists 0.5–2.2 mg/kg q3–4h SC or IM — start at the low end.

Cats

• Pre-anaesthetic / peri-op: Plumb’s p.795: perioperative pain 0.05–0.5 mg/kg IV, IM or SC q4–6h (Tranquilli); pre-anaesthetic 0.1–0.2 mg/kg SC or IM, or 0.1–0.3 mg/kg with acepromazine (Cornell); for IV use give half the low-end dose titrated over 3–5 min (Mathews). Papich 5e: 0.3–0.6 mg/kg q3–4h IV, SC or IM (up to 0.6 mg/kg IM tolerated, ~4 h effect).
• Oral transmucosal (OTM): Papich 5e: the oral-mucosal dose is about twice the IV dose (IV 0.3–0.6 mg/kg) because less than 50% is absorbed — i.e. about 0.6–1.2 mg/kg of the injectable solution dripped onto the buccal mucosa.

Horses

• Analgesia: Papich 5e: 0.15 mg/kg IV or IM q6–8h; oral absorption appears adequate. Plumb’s p.795 lists only an anecdotal 0.1–0.2 mg/kg PO. Watch for excitement and reduced GI motility.

Contraindications

Hypersensitivity. Severe respiratory depression / airway compromise. Severe hepatic impairment. Concurrent MAO-I (within 14 days). Head trauma with raised ICP (caution). Severe asthma (caution). Animals for human consumption.

Species-specific warnings

Dogs: Standard peri-operative opioid. 0.3–0.5 mg/kg IV/IM provides 4 h analgesia. Less vomiting than morphine.

Cats: Better tolerated than morphine. OTM route (oral mucosa) gives ~80% bioavailability. Watch for hyperthermia at higher doses.

Adverse effects

• Dose-dependent respiratory depression (less than morphine)
• Bradycardia
• Sedation
• Vomiting / hypersalivation (less than morphine)
• Histamine release minimal (advantage over morphine)
• Constipation, urinary retention
• Cats: euphoria, mydriasis, occasional hyperthermia
• Hypothermia or hyperthermia (species-dependent)

Drug interactions

• Naloxone: SPECIFIC REVERSAL agent — 0.04 mg/kg IV titrated to effect (caution: reverses analgesia too)
• Other opioids: additive — reduce doses when combined
• CNS depressants (alpha-2, benzodiazepines, anaesthetics): additive sedation
• MAO-I: CONTRAINDICATED — serotonin syndrome / hypertension
• SSRI (fluoxetine), tramadol: serotonin syndrome risk
• Bezodiazepines: additive respiratory depression
• Acepromazine: synergistic sedation — "neuroleptanalgesia" combo

Pregnancy and lactation

Crosses placenta. Neonatal opioid withdrawal possible if used late pregnancy. Avoid as routine analgesia in pregnant patients near term — but acceptable for emergency / surgical pain control. Excreted in milk.

Monitoring

• Respiratory rate, depth — supplemental oxygen if RR <8 (dogs) or <12 (cats)
• Heart rate — bradycardia common, anticholinergic if symptomatic
• Sedation depth — naloxone titrated reversal if oversedated
• Pain scoring at 30 min, 2 h, 4 h post-dose
• Body temperature — hypothermia (dogs) or hyperthermia (cats) possible
• Pupil size — miosis confirms opioid effect
• Schedule II logbook — record every dose, vial wastage, signatures

Toxicity and overdose

Respiratory depression (less than morphine but real), bradycardia, sedation, hypothermia. Overdose: severe respiratory depression, coma, miosis (mu effect). Cats: dose carefully — hyperthermia and dysphoria at high doses. Dogs: panting, bradycardia common. QT prolongation reported in humans — rare cardiac arrhythmias.

Management: NALOXONE 0.04 mg/kg IV is the specific antagonist — titrate to restore respirations without fully reversing analgesia (start at 0.01 mg/kg, increase if needed). Support airway / ventilation. Atropine for bradycardia. Naloxone half-life shorter than methadone — RE-DOSE every 30 min as needed or use naloxone CRI 0.1 mg/kg/h.

Clinical pearls

• Dogs pre-op: 0.3–0.5 mg/kg IV/IM — 4 h analgesia + sedation; pair with dexmedetomidine for excellent restraint
• Cats pre-op: 0.2–0.4 mg/kg IV/IM — better tolerated than morphine, less vomiting
• NMDA antagonism is the unique advantage — for chronic / wind-up pain better than morphine or hydromorphone
• CRI 0.05–0.1 mg/kg/h after loading — gentler than repeated bolus
• OTM in cats: 0.3–0.6 mg/kg drip onto oral mucosa — non-invasive and effective
• Less histamine release than morphine — better choice in cardiac patients or those needing rapid IV
• Naloxone reversal: titrate slowly (0.01 mg/kg IV, repeat to effect) — full reversal eliminates analgesia
• Schedule II logbook — record every dose

Mechanism of action

Pure mu-opioid receptor agonist + non-competitive NMDA receptor antagonist. The dual mechanism is unique: mu agonism provides classic opioid analgesia (G-protein-coupled receptor → decreased cAMP → reduced neuronal excitability), while NMDA antagonism prevents central sensitisation ("wind-up pain"). Less histamine release than morphine — useful in cardiac patients. Long duration (~4 h) due to slow receptor dissociation.

Formulations and products

• Comfortan 10 mg/mL veterinary injection
• Methadose 10 mg/mL human injection
• Methadone 5 / 10 mg human tablet
• Comfortan (Dechra) — 10 mg/mL, Injection (dogs/cats)
• Methadose — 10 mg/mL, Injection (human-label)
• Methadone HCl — 5 / 10 mg, Tablet (human-label)

Storage

Injectable: 15–25 °C, protect from light. Schedule II controlled substance — LOCKED storage, controlled-substance log. Multidose vial: discard 28 days after broaching.

Before you use this dose

Reference doses for veterinary professionals. Confirm the dose against the product label, the patient’s condition, current guidance and local regulations before use; the attending veterinarian remains responsible for every clinical decision.

Other analgesics

• Fentanyl
• Gabapentin
• Hydromorphone
• Lidocaine HCl
• Morphine Sulfate
• Nalbuphine
• Paracetamol (Acetaminophen)
• Pethidine (Meperidine)

Frequently asked questions