Chemicals / Complex Chemical Agents/ Chemical:

Fentanyl (with special reference to Ruminants, Hedgehogs, Bears, Lagomorphs and Great Apes)

INFORMATION AVAILABLE

GENERAL CHEMICAL INFORMATION THERAPEUTIC INFORMATION [DOSE, FREQUENCY & ROUTE]

NUTRITIONAL INFORMATION

TOXICITY INFORMATION ENVIRONMENTAL INFORMATION
Information in this page has been entered to support the current volumes of Wildpro and further information will be added as new volumes are completed. This page is not intended to substitute for the manufacturer's data sheet and the information is not yet complete for all species, or for all contra-indications etc.

CAUTION: Before any pharmaceutical product is used, the manufacturer's data sheet, containing information on uses, dosage and administration, contra-indications, warnings etc., should always be consulted. It is important to remember that licensing of pharmaceutical products for use in a particular species/condition, as well as mandatory meat and milk withdrawal times for food-producing animals, varies between countries and changes with time. Withdrawal times also may vary between different pharmaceutical formulations and depending on route of administration. In the EU, the prescription cascade must be followed (see LCofC1.2H and W564.Apr05.w1); note that specific restrictions apply for food-producing animals. In the USA, FARAD may be consulted regarding residues and meat and milk withdrawal times.

General Chemical Information

Summary 
An opiate analgesic. (B263)

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Names and Formulae
Type A Class-II opiate analgesic. (B263)
Alternative Names 1-Phenethyl-4-(phenylproprionylamino)piperidine; Duragesic; N-(1-Phenethyl-4-piperidyl)proprionanilide. (W324)
Chemical Formula C22H28N2O (W324)
Chemical Structure --
Molecular Weight 336.476 (W324)
Related Chemicals --

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Physical Properties / Chemistry
Appearance
  • White crystalline powder. (B263)

Melting point
  • 147 - 152 C
Boiling point --
Density --
Water solubility
  • Sparingly soluble. (B263)
Other solubility
  • Highly lipid soluble. (B322.3.w3)
  • Soluble in alcohol. (B263)
Acid/Base

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Pharmacology & General Information
Pharmacology
  • A mu opiate agonist. (B263)
Storage / Stability
  • Transdermal patches should be stored below 25C.  The injectable form should be protected from light. (B263)
Legal Category (In UK)
  • Schedule 2 Controlled Drug; POM. (B350)

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References

Associated Techniques

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ORGANISATIONS

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ELECTRONIC LIBRARY
(Further Reading)
Click image for full contents list of ELECTRONIC LIBRARY

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Authors Debra Bourne (V.w5); Penny Cusdin (V.w60)
Referees Suzanne I. Boardman (V.w6)

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Therapeutic Information

Uses/Indications
Activity
  • Highly potent selective mu opioid receptor agonist. (B322.3.w3)
  • Short duration of activity (5 to 20 minutes) depending on dose. (B322.3.w3)
  • Fentanyl in sheep was more effective against a noxious heat stimulus than against a noxious mechanical stimulus; even at high doses the analgesic effect lasted less than two hours. (J290.17.w1, P61.62.w1)
Appropriate Use
  • Analgesic for use intraoperatively due to short time to onset of activity, short duration and high potency. (B322.3.w3)
  • For the adjunctive control of postoperative pain and in the control of severe pain associated with chronic conditions. (B263)

In goats:

  • Short half-life limits the usefulness of intravenously administered fentanyl for pain management in goats. While transdermal patches may result in plasma concentrations in excess of those expected on the basis of a theoretical delivery rate, the drug may not achieve stable plasma concentrations. (J13.60.w1)
Limitations
  • Potent respiratory depressant. (B322.3.w3)
  • Induces bradycardia, which may be prevented by pre-medication with an antimuscarinic agent. (B322.3.w3)
  • At high doses in humans produces muscle rigidity; doses used in animals are generally lower. (B322.3.w3)
  • There have been varying responses to the transdermal product between species, both in time taken to achieve therapeutic levels, and the levels achieved. (B263)
Notes Laboratory interactions: 
  • Plasma amylase and lipase values may be increased for up to 24 hours after administration of fentanyl, since they increase biliary tract pressure. (B263)

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Pharmacokinetics and Drug Interactions
Absorption /Bioavailability Rapid onset of action (2-5 minutes). (B322.3.w3)

In sheep:

  • Fentanyl does not have any significant antinociceptive effect when administered intrathecally in sheep at doses from 5 to 100 g. (J13.54.w2)

In goats: 

  • Absorption is rapid. (J215.25A.w1)
  • Following intravenous administration of 2.5 g/kg fentanyl in healthy two-year-old goats, the terminal elimination half life (t1/2β) was 1.20 +/- 0.78 h (mean +/- SD)(range 0.84-3.13 h) and clearance was 2.09 +/- 0.62 L/kg/h (range 1.45-3.18 L/kg/h). (J13.60.w1)
  • Following application of a transdermal patch (50g/h) of fentanyl to shaved skin in six healthy two-year-old goats, the drug was first detectable in plasma after an interval as short as one hour (two goats) to as long as eight hours (one goat). Peak plasma concentrations varied from 1.12 to 16.69 ng/mL (mean 6.99 ng/mL. SD 6.03 ng/mL) and mean plasma concentrations were in excess of 0.2 ng/mL from four to 36 hours after patch application. Consistent concentrations were not achieved at any time during the 72 hour study period. The calculated actual dose delivery rate ranged from 0.95-6.00 g/kg/h (mean +/-SD 3.03 +/- 2.15 g/kg/h. (J13.60.w1)

Transdermal patches: 

  • Cats - therapeutic benefit achieved approximately 6 hours after application. (B263)
  • Dogs - the patch should be applied a minimum of 12 hours before the effects of the drug are required. (B263)
Distribution In dogs:
  • Large volume of distribution. (B322.3.w3)

In goats:

Plasma Protein binding / Storage --
Elimination Route --
Elimination half-life / Clearance Rate High clearance but a relatively long elimination half-life due to penetration into poorly perfused body compartments (such as fat) from which it is released only slowly. (B322.3.w3)

In goats:

  • Rapid clearance. (J215.25A.w1)
  • Following intravenous administration of 2.5 g/kg fentanyl in healthy two-year-old goats, the terminal elimination half life (t1/2β) was 1.20 +/- 0.78 h (mean +/- SD) (range 0.84-3.13 h) and clearance was 2.09 +/- 0.62 L/kg/h (range 1.45-3.18 L/kg/h). (J13.60.w1)
  • Following application of a transdermal patch (50g/h) fentanyl to shaved skin in six healthy two-year-old goats, after removal of the patch at 72 hours after application, the mean terminal half-life (for four goats) was 5.34 +/- 5.34 h (range1.69-14.56h). Fentanyl was detectable in plasma in all the goats at 76 hours, at 80 hours in two goats and at 84 hours (last sample taken) in one goat. (J13.60.w1)
Drug Interactions
  • When used concurrently with fentanyl, other CNS depressants such as anaesthetics, antihistamines, phenothiazines, barbiturates, tranquillisers or alcohol may cause increased CNS or respiratory depression. (B263)
  • Contraindicated in animals receiving MAO inhibitors (rarely used in animals). (B263)

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Administration
Formulations available UK:

Veterinary licensed product with fluanisone:

  • Hypnorm (Janssen Animal Health): Injection, fentanyl citrate 0.315 mg/mL and fluanisone 10mg, 5 x 10mL vials. For mice, rabbits and guinea pigs. (B350)

Human preparations

  • Actiq, Durogesic, Sublimaze. (N14.Jan2004.w1)
Doses / Administration Routes / Frequencies
  • May be administered as an intravenous bolus, intermittent intravenous injection or a short term intravenous infusion. (B322.3.w3)
  • Transdermal administration via skin patches has been used in dogs and cats; there is considerable variation between individual animals in the resultant plasma levels of drug. (B322.3.w3)
  • Plasma concentrations of fentanyl achieved with transdermal patches show considerable intra- and inter-specific variation. (J13.60.w1)

Sheep:

Experimental data:

  • Fentanyl administered at 5 g/kg five minutes prior to the application of a tourniquet in adult male neutered Suffolk-cross sheep increased the threshold to noxious mechanical stimulation with thresholds being significantly higher than control values (3.4 +/- 0.3 N) at five minutes (6.6 +/- 0.88 N, P<0.01) and ten minutes after application of the tourniquet (5.5 +/- 0.49, P<0.05) i.e. at 10 and 15 minutes after administration of fentanyl, with final recorded thresholds at 30 minutes, before the tourniquet was removed which were also higher (P<0.07) than control values. In sheep not given any analgesic, by contrast, the threshold to noxious mechanical stimulation was significantly reduced at 10, 15 and 20 minutes after application of the tourniquet. (J21.57.w1)
  • Peripherally administered fentanyl at 11.2 g/kg in sheep, injected intravenously and restricted to the periphery via a forelimb tourniquet, failed to increase nociceptive thresholds to mechanical (blunt pin) stimulation. (J289.20.w1)
  • Fentanyl at 5 g/kg intravenously in sheep did not provide any significant increase in the mechanical antinociceptive threshhold (measured by blunt pin force). When the same dose was administered in combination with the neuroleptic drug droperidol at 5 g/kg intravenously (which did not, alone, have any effect on the mechanical nociceptive threshold), a profound increase in nociceptive threshold was observed (from 0.8 +/- 0.12 Newtons to a maximum of 15.1 +/- 1.9 N), this being significant (p<0.05) from 10 to 35 minutes post injection with the maximum effect at 25 minutes post injection. However, the combination (but not either drug alone at these dose rates) also caused agitation in the sheep, particularly on approach and handling, including increased locomotor activity, attempts to turn around and climb out of the crate and compulsive chewing. When fentanyl was administered intravenously 30 minutes after intrathecal administration of 5 g/kg droperidol, there was also a significant increase in the nociceptive threshold, from 2.2 +/- 0.39 N to a maximum of 7.7 +/- 1.35 N by ten minutes post injection and remaining significantly raised between five and 25 minutes after the fentanyl administration; no behavioural changes were apparent with this combination. When fentanyl at 5 g/kg intravenously was combined with zuclopenthixol (100 g/kg intravenously, which did not, alone, have any effect on the mechanical nociceptive threshold) there was an increase in the nociceptive threshold, from 3.4 +/- 0.08 N to a maximum of 7.0 +/- 0.55 N by fifteen minutes post injection, the threshold being significantly raised (p<0.05) from 5-35 minutes post administration. (J13.54.w2)
  • Fentanyl in sheep was more effective against a noxious heat stimulus than against a noxious mechanical stimulus; even at high doses the analgesic effect lasted less than two hours. (P61.62.w1, J290.17.w1)

Erinaceus europaeus - West European Hedgehog:

  • Fentanyl/fluanisone (Hypnorm) 1-2 mL/kg intramuscularly. For prolonged anaesthesia. (B156.7.w7)
  • Fentanyl/fluanisone (Hypnorm, Janssen). 0.5-1.0 mL/kg intramuscularly. Sedation and anaesthesia for minor procedures such as suturing. (B284.6.w6)
  • Fentanyl/fluanisone (Hypnorm) 1 mg/kg intramuscularly or subcutaneously. (D107)

Dogs

Fentanyl injectable

  • For perioperative pain: 5 g/kg intravenously plus 3 to 6 g/kg/hour by intravenous infusion. (B263)
  • For initial management of acute moderate to severe pain: 0.004 to 0.01+ mg/kg (4-10 g/kg) intravenous bolus, then 0.001 to 0.004 mg/kg/hour (4-10 g/kg/hour) constant rate intravenous infusion. (B263)

Cats

Fentanyl injectable

  • For perioperative pain: 2 to 3 g/kg intravenously plus 2-3 g/kg/hour by intravenous infusion. (B263)
  • For initial management of acute moderate to severe pain: 0.004 to 0.1+ mg/kg (4-10 g/kg) intravenous bolus and then 0.001 to 0.004 mg/kg/hour (4 to 10 g/kg/hour) constant rate intravenous infusion. (B263)

Cats and Dogs

Fentanyl transdermal

  • Small dogs/cats 5-10 kg bodyweight: dose 25 g/hr - 2.5 mg fentanyl content. (B263)
  • Dogs 10-20 kg bodyweight: dose 50 g/hr - 5 mg fentanyl content. (B263)
  • Dogs 20-30 kg bodyweight: dose 75 g/hour - 7.5 mg fentanyl content. (B263)
  • Dogs >30 kg bodyweight: dose 10 g/hour - 10 mg fentanyl content. (B263)

Patches should be applied to a clean, dry, clipped area of skin of the neck, thorax or inguinal area. For small animals, half patches may be used by covering one half of the patch membrane with tape - patches should not be cut in half. Padded bandages or adhesive dressings should be used to hold the patch in place. Therapeutic dose levels are obtained in approximately 6 hours after application in cats, and a minimum of 12 hours after application in dogs. (B263)

Bears:

As an anaesthetic agent:

  • 0.34-0.68 mg/kg in captive Ursus maritimus - Polar bear, giving smooth induction in 5-8 minutes. Injection of antagonist (naloxone, 25 mg naloxone per 10 mg of fentanyl given) gave arousal in 1-11 minutes, but one bear, on its feet six minutes after injection of the antagonist, relapsed and was recumbent overnight. (J4.175.w2)
  • Fentanyl plus azaperone has been used (15 mg fentanyl plus 60 mg azaperone in a 150 kg two-year-old female American black bear and 5 mg fentanyl plus 10 mg azaperone in a 47 kg male six-month old black bear). There was severe respiratory depression. The female was revived using 1.25 mg naloxone. (P1.1976.w2)
  • Fentanyl-droperidol (Innovar Vet, 0.4 mg/mL fentanyl + 20 mg/mL droperidol) (B121) has been used at 1.0 mL Innovar vet per 18.2 kg bodyweight, with an induction time of 10-15 minutes. (B16.9.w9)
    • Neuroleptanalgesia with Innovar Vet produces deep sedation with profound analgesia, appropriate for minor procedures such as lancing an abscess or carrying out diagnostic procedures (e.g. endoscopic examination), but not sufficient for major surgery. (B121)
  • Note: Fentanyl may severely depress respiration. (B407.w18)
Lagomorphs - Oryctolagus cuniculus domesticus - Domestic rabbit:
  • Fentanyl 0.0074 mg/kg intravenously. For analgesia. (B548.w8)
  • Fentanyl/fluanisone 0.5 mL/kg intramuscularly. (B373.Guide.w41)
  • Fentanyl/fluanisone, (Hypnorm, Janssen) 0.2 - 0.3 mL/kg intramuscularly or subcutaneously for premedication, analgesia and anaesthesia. Used in combination with midazolam or diazepam at 0.5 - 2.0 mg/kg See Fentanyl-Fluanisone - Midazolam Anaesthesia in Rabbits (Techniques). (B600.4.w4)
  • Fentanyl/fluanisone 0.2 mL/kg intramuscularly for moderate sedation plus excellent analgesia. (B603.5.w5)
  • Fentanyl/fluanisone 0.5 mL/kg intramuscularly. (B546)
    • (Fluanisone is a butyrophenone tranquillizer). (B546)

Ferrets - Mustela putorius furo - Ferret:

  • Fentanyl/fluanisone: 0.3 mL/kg intramuscularly. (B631.22.w22, J29.7.w1)
  • Fentanyl/droperidol 0.15 mL/kg intramuscularly. (B631.22.w22)
  • Microdosing for perioperative analgesia:
    • Fentanyl can be used intraoperatively together with Ketamine, in micro-doses via a constant rate infusor (CRI). Use of this combination reduces the concentration of anaesthetic inhalant (gaseous) anaesthetic agent required and reduces  hypotension associated with gaseous anaesthesia. Following a 0.1 mg/kg loading dose of ketamine, ketamine is given intra-operatively via CRI at 0.3 - 0.4 mg/kg/hour with fentanyl at 10-20 g/kg/hour, then post-operatively ketamine at 0.3 - 0.4 mg/kg/hour with fentanyl at 5 - 10 g/kg/hour. (J513.7.w3)

Great Apes

  • Adult Pan troglodytes - Chimpanzee:
    • 5 - 10 g/kg/hour intravenously by constant rate infusion. As an analgesic. (W768.Jun2012.w1)
    • Fentanyl/Droperidol 0.3 mL/kg intramuscularly. As an anaesthetic agent. (W768.Jun2012.w1)
  • Primates: 0.05 - 0.15 mg/kg intramuscularly. (D425.3.15.w3o)
Monitoring parameters
  • Analgesic efficacy. (B263)
  • Heart rate and respiratory rate. (B263)

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Withdrawal period / Withholding time
Notes Opioid drugs are not licensed for use in food producing animals in the UK unless a guarantee can be given that the animal in which the drug is used will not enter the food chain. (B322.3.w3)

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Toxic Information

Toxic effects of Pharmaceutical Products
Contraindications / Precautions
  • Use with caution with other CNS depressants. Dosages of other opiates may need to be reduced when given with fentanyl transdermal particularly several hours after application of the patch. (B263)
  • Use transdermal patches with caution in geriatric, very ill or debilitated animals, or those with preexisting respiratory problems. (B263)
  • Febrile patients may have increased absorption of fentanyl. (B263)
  • Safety in pregnancy is not established. (B263)
In sheep:
  • Fentanyl administered at 5 g/kg five minutes prior to the application of a tourniquet in adult male neutered Suffolk-cross sheep resulted in marked behavioural changes: chewing frantically at ropes, snatching at hay, nystagmus in some individuals, ataxia in some individuals and pacing back and forth within the available space in other individuals. (J21.57.w1)
Adverse Effects / Side Effects / Warnings
  • Respiratory depression and bradycardia associated with the transdermal product is the adverse effect of most concern. (B263)
  • Rash may develop at patch site. (B263)
  • Urine retention and constipation may occur. (B263)
  • Some patients may experience agitation or dysphoria after application, which can be treated with acepromazine. (B263)
Operator Warnings --
Overdose / Acute Toxicity
  • Overdose may produce profound respiratory and/or CNS depression. Newborn animals are more susceptible than adults. (B263)
  • Other toxic effects include cardiovascular collapse, tremors, neck rigidity and seizures. (B263)
  • Respiratory depression caused by fentanyl overdose may be treated with naloxone. Repeated doses may be required. (B263)

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Detailed Toxicological Information
Classification --
Acute Toxicity --
Chronic Toxicity --
Reproductive effects --
Teratogenic effects --
Mutagenic effects --
Carcinogenic effects

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Organ toxicity --
Bird Toxicity --
Aquatic organism activity --
Other organism toxicity --

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Nutrient Information

Nutritional Data
Sources --
Biological Use --
Recommended Daily Allowance / Recommended level in food --
Stability in food (Storage time) --
Interactions --

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External / Environmental Information

External / Environmental Uses
Use --
Formulation --
Application method --
Application Concentration --
Persistence of Effect / Frequency of Application --

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Sources in the Environment
Natural sources --
Human-associated sources --

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Effects on the Environment
Effects in the aquatic environment

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Effects on land --

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Persistence in the Environment
Breakdown in soil and groundwater

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Breakdown in water --
Breakdown in vegetation --

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