Fentanyl Transdermal System
(for transdermal administration)
ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL EXPOSURE; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; and EXPOSURE TO HEAT
Addiction, Abuse, and Misuse
Fentanyl transdermal system exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing fentanyl transdermal system, and monitor all patients regularly for the development of these behaviors or conditions [see WARNINGS AND PRECAUTIONS].
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of fentanyl transdermal system, even when used as recommended. Monitor for respiratory depression, especially during initiation of fentanyl transdermal system or following a dose increase. Because of the risk of respiratory depression, fentanyl transdermal system is contraindicated for use as an as-needed analgesic, in non-opioid tolerant patients, in acute pain, and in postoperative pain [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].
Deaths due to a fatal overdose of fentanyl have occurred when children and adults were accidentally exposed to fentanyl transdermal system. Strict adherence to the recommended handling and disposal instructions is of the utmost importance to prevent accidental exposure [see WARNINGS AND PRECAUTIONS].
Neonatal Opioid Withdrawal Syndrome
Prolonged use of fentanyl transdermal system during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see WARNINGS AND PRECAUTIONS].
Cytochrome P450 3A4 Interaction
The concomitant use of fentanyl transdermal system with all cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in fentanyl plasma concentration. Monitor patients receiving fentanyl transdermal system and any CYP3A4 inhibitor or inducer [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].
Exposure To Heat
Exposure of the fentanyl transdermal system application site and surrounding area to direct external heat credits, such as heating pads or electric blankets, heat or tanning lamps, sunbathing, hot baths, saunas, hot tubs, and heated water beds may increase fentanyl absorption and has resulted in fatal overdose of fentanyl and death [see WARNINGS AND PRECAUTIONS]. Patients wearing fentanyl transdermal systems who develop fever or increased core body temperature due to strenuous exertion are also at risk for increased fentanyl exposure and may require an adjustment in the dose of fentanyl transdermal system to avoid overdose and death [see WARNINGS AND PRECAUTIONS].
Fentanyl transdermal system is a transdermal system containing fentanyl. The chemical name is N-Phenyl-N-(1-(2-phenylethyl)-4-piperidinyl) propanamide. The structural formula is:
The n-octanol: water partition coefficient is 860:1. The pKa is 8.4.
System Components And Structure
The amount of fentanyl released from each system per hour is proportional to the surface area (25 mcg/hr per 7.8 cm²). The composition per unit area of all system sizes is identical.
|Dose* (mcg/hr)||Size (cm²)||Fentanyl Content (mg)||Color of Printing on Back of Patch|
|*Nominal delivery rate per hour
†Nominal delivery rate is 12.5 mcg/hr
Fentanyl transdermal system is a rectangular transparent unit comprising a protective liner and four functional layers. Proceeding from the outer surface toward the surface adhering to skin, these layers are:
- a backing layer of PET foil;
- a drug containing layer of fentanyl and dipropylene glycol with hydroxypropyl cellulose;
- an ethylene vinyl-acetate copolymer membrane that controls the rate of fentanyl delivery to the skin surface; and
- a silicone adhesive. Before use, a protective liner covering the adhesive layer is removed and discarded.