FENTANYL, TRANSDERMAL

Note: A separate monograph for fentanyl/droperidol (Innovar®) follows this one.
Chemistry - Fentanyl citrate, a very potent opiate agonist, occurs as a white, crystalline powder. Itis sparingly soluble in water and soluble in alcohol. It is odorless and tasteless (not recommendedfor taste test because of extreme potency) with a pKa of 8.3 and a melting point between 147°-152°C.

Storage, Stability, Compatibility

Fentanyl transdermal patches should be stored at temperaturesless than 25°C and applied immediately after removing from the individually sealed package.

Pharmacology - FENTANYL, TRANSDERMAL

Fentanyl is a mu opiate agonist. The pharmacology of the opiate agonists arediscussed in more detail in the monograph, Narcotic (opiate) Agonist Analgesics.
Uses, Indications - In veterinary medicine, fentanyl transdermal patches are used primarily in dogsand cats and have been shown to be useful for the adjunctive control of postoperative pain and inthe control of severe pain associated with chronic pain, dull pain and non-specific, widespread pain(e.g., associated with cancer, pancreatitis, aortic thromboemboli, peritonitis, etc.). Although clinicaluse in dogs and cats has been limited, thus far transdermal fentanyl has overall been clinical yeffective and has not had substantial adverse effect problems.
In humans, significant respiratory depression with use of the patches after surgery has precludedfrom using them post-operatively, but this has not been a significant problem in veterinarymedicine.

Pharmacokinetics - FENTANYL, TRANSDERMAL

There have been limited pharmacokinetic studies performed with transdermalfentanyl patches in dogs and cats. While therapeutic levels of fentanyl are attained, there is asignificant interpatient variability with both the time to achieve therapeutic levels and the levelsthemselves. Cats tend to achieve therapeutic levels faster than do dogs and in dogs, the patch shouldbe applied 24 hours in advance of need if possible, minimum of 12 hours pre-need. Most cats attaintherapeutic benefit in about 6 hours after application. While applied, duration of action persists forat least 72 hours (usually for at least 104 hours). Duration of action is generally longer in cats thanin dogs.
Contraindications/Precautions - Use cautiously with other CNS depressants, dosages of otheropiates may need to be reduced when given with fentanyl transdermal, particularly several hoursafter application of the patch. Transdermal fentanyl should be used cautiously in geriatric, very ill ordebilitated patients and those with a preexisting respiratory problem. Febrile patients may haveincreased absorption of fentanyl and will require increased monitoring should application be made.
Safe use in pregnancy has not been established.

Adverse Effects, Warnings

Respiratory depression and bradycardia associated with fentanylpatches are the most concerning adverse effects, but incidence of these effects have not beenwidespread thus far when used alone (without other opiates or other respiratory and cardiodepressant medications). Rashes at the patch site have been reported and should they occur, the patch should be removed. If an additional patch is warranted, a different site should be chosen. Urine retention and constipation may occur. Consider removing patch in patients developing a fever afterapplication, as fentanyl absorption may increase. Some patients exhibit dysphoria after application;acepromazine or other mild tranquilizer may alleviate dysphoria.
Overdosage - Overdosage may produce profound respiratory and/or CNS depression in mostspecies. Newborns may be more susceptible to these effects than adult animals. Other toxic effectsmay include cardiovascular collapse, tremors, neck rigidity, and seizures. Naloxone is the agent ofchoice in treating respiratory depression. In massive overdoses, naloxone doses may need to berepeated, animals should be closely observed as naloxone's effects may diminish before sub-toxiclevels of fentanyl are attained. Mechanical respiratory support should also be considered in cases ofsevere respiratory depression.

Drug Interactions

For opiates (fentanyl): Other CNS depressants (e.g., anesthetic agents, antihistamines, phenothiazines, barbiturates, tranquilizers, alcohol, etc.) may cause increased CNS or respiratory depression when used with opiates. Opiate analgesics are contraindicated in patients receiving monamine oxidase (MOA) inhibitors (rarely used in veterinary medicine) for at least 14 days after receiving MOA inhibitors (in humans).
Laboratory Interactions - Plasma amylase and lipase values may be increased for up to 24hours following administration of opiate analgesics as they may increase biliary tract pressure.