Fentanyl Citrate

Opioid Analgesic Phenylpiperidine Opioid Rx Controlled Schedule II (US)

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog IV 0.005-0.01 mg/kg (5-10 mcg/kg) As needed (PRN) or continuous rate infusion (CRI) at 0.002-0.005 mg/kg/hour Duration: For acute pain; CRI for 24-72 hours
Notes: Administer slowly to avoid respiratory depression. Titrate to effect.
Dog Transdermal 2-5 mcg/kg/hour (patch size based on body weight) Every 72 hours (replace patch) Duration: For chronic pain; up to 5 days
Notes: Apply to clipped skin on dorsal neck or thorax. Monitor for respiratory depression.
Cat IV 0.005-0.01 mg/kg (5-10 mcg/kg) As needed or CRI at 0.002-0.005 mg/kg/hour Duration: For acute pain; CRI for 24-72 hours
Notes: Cats may be more sensitive to respiratory depression; use lower end of dose range.
Cat Transdermal 2-5 mcg/kg/hour (patch size based on body weight) Every 72 hours (replace patch) Duration: For chronic pain; up to 5 days
Notes: Apply to clipped skin on dorsal neck or thorax. Monitor for respiratory depression.
Horse IV 0.001-0.005 mg/kg (1-5 mcg/kg) As needed or CRI at 0.001-0.002 mg/kg/hour Duration: For acute pain; CRI for 24-48 hours
Notes: Use with caution; may cause excitement. Monitor vital signs.
Cattle IV 0.005-0.01 mg/kg (5-10 mcg/kg) As needed Duration: For acute pain
Notes: Extra-label use; observe withdrawal times. Not commonly used.
Small Ruminants (Sheep/Goats) IV 0.005-0.01 mg/kg (5-10 mcg/kg) As needed Duration: For acute pain
Notes: Limited data; use with caution.
Rabbit IV 0.005-0.01 mg/kg (5-10 mcg/kg) As needed or CRI at 0.002-0.005 mg/kg/hour Duration: For acute pain
Notes: Monitor respiratory rate; may cause respiratory depression.
Bird/Poultry IV/IM 0.02-0.05 mg/kg (20-50 mcg/kg) As needed Duration: For acute pain
Notes: Limited data; use with caution.
Exotic/Other IV/IM 0.01-0.05 mg/kg (10-50 mcg/kg) depending on species As needed Duration: For acute pain
Notes: Species-specific dosing; consult exotic animal references.

Clinical Indications & Species Uses

General Indications
  • Management of acute and chronic pain
  • Anesthetic adjunct for neuroleptanalgesia
  • Sedation and analgesia for diagnostic or therapeutic procedures
Dog (Canine)
  • Analgesia for moderate to severe pain (e.g., postoperative, trauma, cancer)
  • Anesthetic adjunct for balanced anesthesia
  • Sedation and analgesia for minor procedures
  • Transdermal patch for chronic pain management
Cat (Feline)
  • Analgesia for moderate to severe pain (e.g., postoperative, trauma)
  • Anesthetic adjunct for balanced anesthesia
  • Sedation and analgesia for minor procedures
  • Transdermal patch for chronic pain management
Horse (Equine)
  • Analgesia for severe pain (e.g., colic, orthopedic surgery)
  • Anesthetic adjunct for balanced anesthesia
  • Sedation (with caution due to potential excitement)
Cattle (Bovine)
  • Analgesia for severe pain (e.g., surgery, trauma)
  • Anesthetic adjunct for balanced anesthesia
Small Ruminants (Sheep / Goat)
  • Analgesia for severe pain (e.g., surgery, trauma)
  • Anesthetic adjunct for balanced anesthesia
Rabbit & Small Mammals
  • Analgesia for moderate to severe pain (e.g., surgery, dental procedures)
  • Anesthetic adjunct for balanced anesthesia
Avian & Poultry
  • Analgesia for severe pain (e.g., surgery, trauma)
  • Anesthetic adjunct (limited data)
Exotic & Other Species
  • Analgesia for severe pain in various exotic species (e.g., reptiles, small mammals) with caution
  • Anesthetic adjunct

Pharmacology & Mechanism of Action

Drug Class: Opioid Analgesic | Pharmacological Group: Phenylpiperidine Opioid

Mechanism of Action: Fentanyl is a synthetic opioid that primarily acts as a potent agonist at mu-opioid receptors in the central nervous system. Activation of these receptors leads to G-protein coupled inhibition of adenylate cyclase, decreased cAMP production, and modulation of ion channels (increased potassium efflux, decreased calcium influx). This results in reduced neurotransmitter release (e.g., substance P, glutamate) and hyperpolarization of neurons, producing profound analgesia, sedation, and euphoria. Fentanyl also has some activity at delta and kappa receptors but to a lesser extent.

Pharmacodynamics: Fentanyl produces dose-dependent analgesic and sedative effects. It is approximately 100 times more potent than morphine. At therapeutic doses, it provides profound analgesia, sedation, and respiratory depression. It can also cause bradycardia, cough suppression, and miosis in dogs and cats. In horses, it may cause excitement or central nervous system stimulation at higher doses. The onset of action is rapid (within minutes) after IV administration, and the duration is short (20-30 minutes) due to redistribution. Fentanyl also has a ceiling effect on analgesia but not on respiratory depression.

⚡ Pharmacokinetics Summary

Absorption: Fentanyl is well absorbed after oral, transdermal, and transmucosal administration. Oral bioavailability is low (approximately 30-50%) due to first-pass metabolism, but transdermal and transmucosal routes provide more consistent absorption. In dogs, transdermal absorption reaches steady state in 12-24 hours. In cats, absorption is similar but may be more variable.
Distribution: Fentanyl is highly lipophilic, leading to rapid and extensive distribution into tissues, including the brain, lungs, and adipose tissue. It crosses the blood-brain barrier and placenta. The volume of distribution is large (approximately 4-6 L/kg in dogs). Protein binding is approximately 80-85%, primarily to alpha-1-acid glycoprotein and albumin.
Metabolism: Fentanyl is extensively metabolized in the liver via cytochrome P450 enzymes (primarily CYP3A4 in humans, and similar enzymes in animals) to inactive metabolites, mainly norfentanyl. In dogs and cats, hepatic metabolism is rapid, but in cats, glucuronidation is deficient, so metabolism may be slower.
Excretion: Metabolites and a small amount of unchanged drug are excreted primarily in urine (about 75%) and feces (about 9%). Biliary excretion also occurs. The elimination half-life varies by species: dogs ~2-3 hours, cats ~2-4 hours, horses ~1-2 hours, and cattle ~1-2 hours.
Half-Life: Dogs: 2-3 hours; Cats: 2-4 hours; Horses: 1-2 hours; Cattle: 1-2 hours
Bioavailability: Oral: ~30-50%; Transdermal: ~60-80% (dogs); Transmucosal: ~50%
Protein Binding: Approximately 80-85% (primarily to alpha-1-acid glycoprotein)

Available Formulations & Strengths

Injectable Solution 50 mcg/mL (0.05 mg/mL) (IV, IM, SC)
Transdermal Patch 12.5, 25, 50, 75, 100 mcg/hour (Transdermal)
Oral Transmucosal Lozenge 200, 400, 600, 800, 1200, 1600 mcg (Oral transmucosal)
Nasal Spray 50 mcg/spray (Intranasal)

Contraindications & Clinical Warnings

Contraindications:
  • Known hypersensitivity to fentanyl or other opioids
  • Severe respiratory depression or compromised respiratory function
  • Concurrent use of MAO inhibitors (within 14 days)
  • Head trauma or increased intracranial pressure (unless ventilated)
  • Severe hepatic or renal insufficiency (use with caution)
  • Hypovolemia or shock (may exacerbate hypotension)
  • In horses, use with caution in cases of colic due to potential excitement
Warnings & Clinical Precautions:
  • Fentanyl is a potent respiratory depressant; monitor respiratory rate and depth, especially in cats and brachycephalic breeds.
  • May cause bradycardia; have anticholinergics (e.g., atropine) available.
  • Transdermal patches should be handled with gloves; avoid direct skin contact with the gel matrix.
  • In food animals, observe withdrawal times; extra-label use requires veterinary oversight.
  • Use with caution in debilitated, geriatric, or pediatric patients; reduce dose.
  • May cause ileus or constipation; monitor gastrointestinal motility.
  • In horses, may cause central nervous system excitation; use with sedatives if needed.
  • Fentanyl is a controlled substance; store securely and document usage.
  • Do not use transdermal patches in animals with skin lesions or compromised skin integrity.
  • In cats, transdermal absorption may be variable; monitor for adequate analgesia.

Adverse Effects & Reactions

Common:

  • Respiratory depression
  • Bradycardia
  • Sedation
  • Miosis (dogs and cats)
  • Constipation
  • Nausea and vomiting (especially in dogs)
  • Urinary retention

Serious / Severe:

  • Severe respiratory depression or apnea
  • Cardiac arrest
  • Hypotension
  • Seizures (rare, especially with high doses)
  • Serotonin syndrome (if combined with serotonergic drugs)
  • Anaphylaxis (rare)

Rare:

  • Muscle rigidity (especially with rapid IV administration)
  • Pruritus
  • Hyperalgesia (paradoxical pain)
  • CNS excitement (horses)
  • Ileus

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Benzodiazepines (e.g., diazepam, midazolam) Additive sedation and respiratory depression High
Barbiturates (e.g., phenobarbital) Additive CNS depression and respiratory depression High
Other opioids (e.g., morphine, butorphanol) Additive respiratory depression and sedation; may cause withdrawal if mixed agonist-antagonist used High
MAO inhibitors (e.g., selegiline) Risk of serotonin syndrome or hypertensive crisis High
Tricyclic antidepressants (e.g., amitriptyline) Increased risk of serotonin syndrome and cardiac effects Moderate
SSRIs (e.g., fluoxetine) Increased risk of serotonin syndrome Moderate
Alpha-2 agonists (e.g., xylazine, dexmedetomidine) Additive bradycardia, sedation, and respiratory depression High
Phenothiazines (e.g., acepromazine) Additive hypotension and sedation Moderate
CYP3A4 inhibitors (e.g., ketoconazole, erythromycin) Increased fentanyl levels and toxicity Moderate
CYP3A4 inducers (e.g., rifampin, phenytoin) Decreased fentanyl efficacy Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Severe respiratory depression (bradypnea, apnea)
  • Cyanosis
  • Bradycardia
  • Hypotension
  • Muscle rigidity
  • Coma
  • Miosis (pinpoint pupils)
  • Seizures (in some species)

Emergency Treatment Protocol: Immediately discontinue fentanyl. Provide respiratory support: intubation and mechanical ventilation if necessary. Administer naloxone (opioid antagonist) at a dose of 0.01-0.04 mg/kg IV (dogs and cats) or 0.01-0.02 mg/kg IV (horses), titrated to effect. Naloxone may need to be repeated due to fentanyl's longer duration. Supportive care: maintain body temperature, blood pressure (fluids, vasopressors if needed), and monitor cardiac function. In cases of muscle rigidity, administer a neuromuscular blocker if ventilated. For transdermal patch overdose, remove the patch and wash the area with soap and water.

Food Animal Withdrawal Times

Fentanyl is not approved for use in food animals in the US. Extra-label use requires extended withdrawal times; consult FARAD (Food Animal Residue Avoidance Databank) for specific recommendations. As a general guideline, a withdrawal time of at least 7 days for meat and 72 hours for milk is often suggested, but this is not official and must be based on residue studies.

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).

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

Handling & Special Conditions: Protect from light. Store in a secure, locked cabinet as a controlled substance. Do not freeze. Keep out of reach of children and animals.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Fentanyl citrate is FDA-approved for human use, but not specifically for veterinary use. However, it is commonly used in veterinary medicine as an extra-label drug. Transdermal patches are approved for human use and used extra-label in animals.

Extra-Label (Off-Label) Use: Fentanyl is a Schedule II controlled substance. Extra-label use in animals is permitted under the Animal Medicinal Drug Use Clarification Act (AMDUCA) in the US, but requires a valid veterinarian-client-patient relationship. For food animals, extra-label use is prohibited if an approved animal drug exists that is labeled for the condition and species, and if the drug is not used in a manner that results in violative residues. Withdrawal times must be extended and determined by FARAD.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Fentanyl is a potent opioid analgesic used in veterinary medicine for managing moderate to severe pain. It is particularly useful for perioperative analgesia, as an anesthetic adjunct, and for chronic pain management via transdermal patches. Due to its high potency and rapid onset, it requires careful dosing and monitoring. Respiratory depression is the most significant adverse effect, especially in cats and small patients. Transdermal patches provide sustained analgesia but have a delayed onset (12-24 hours) and should be used for chronic pain, not acute pain. In horses, fentanyl can cause excitement and should be used with caution, often combined with sedatives. For food animals, extra-label use is limited due to withdrawal time concerns. Always have naloxone available when using fentanyl. Monitor patients closely for respiratory rate, heart rate, and sedation level. Adjust doses based on individual response and pain scores. Fentanyl is a controlled substance; proper storage and documentation are required.

References & Literature

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