Brands, Medical Use, Clinical Data
- Opiate Agonists
- Disc (sustained-release)
Brands / Synonyms
Actiq; Duragesic; Duragesic-100; Durogesic; Fentanest; Fentanil; Fentanil [DCIT]; Fentanila; Fentanila [Inn-Spanish]; Fentanyl; Fentanyl citrate; Fentanylum; Fentanylum [Inn-Latin]; Fentora; Pentanyl; Phentanyl; Sentonil; Sublimaze; Sublimaze
For the treatment of cancer patients with severe pain that breaks through their regular narcotic therapy.
Fentanyl is an opioid analgesic. Fentanyl interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, Fentanyl exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Fentanyl may increase the patient's tolerance for pain and decrease the perception of suffering, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Fentanyl depresses the respiratory centers, depresses the cough reflex, and constricts the pupils.
Mechanism of Action
Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Fentanyl's analgesic activity is, most likely, due to its conversion to morphine. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability.
Biotrnasformation / Drug Metabolism
Fentanyl is metabolized primarily via human cytochrome P450 3A4 isoenzyme system.
Because serious or life-threatening hypoventilation could occur, DURAGESIC® (fentanyl
transdermal system) is contraindicated:
· in patients who are not opioid-tolerant
· in the management of acute pain or in patients who require opioid
analgesia for a short period of time
· in the management of post-operative pain, including use after
out-patient or day surgeries, (e.g., tonsillectomies)
· in the management of mild pain
· in the management of intermittent pain (e.g., use on an as needed
· in situations of significant respiratory depression, especially in
unmonitored settings where there is a lack of resuscitative equipment
· in patients who have acute or severe bronchial asthma
DURAGESIC® (fentanyl transdermal system) is contraindicated in patients who have or are suspected
of having paralytic ileus.
DURAGESIC® (fentanyl transdermal system) is contraindicated in patients with known
hypersensitivity to fentanyl or any components of this product.
Agents Affecting Cytochrome P450 3A4 Isoenzyme System
Fentanyl is metabolized mainly via the human cytochrome P450 3A4 isoenzyme system (CYP3A4), therefore potential
interactions may occur when DURAGESIC® is given concurrently with agents that affect CYP3A4 activity.
Coadminstration with agents that induce 3A4 activity may reduce the efficacy of DURAGESIC®. The concomitant use
of transdermal fentanyl with ritonavir or other potent 3A4 inhibitors such as ketoconazole, itraconazole,
troleandomycin, clarithromycin, nelfinavir, and nefazadone may result in an increase in fentanyl plasma
concentrations. The concomitant use of other CYP3A4 inhibitors such as diltiazem and erythromycin with transdermal
fentanyl may also result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse
drug effects and may cause serious respiratory depression. In this situation, special patient care and observation
Central Nervous System Depressants
The concomitant use of DURAGESIC® (fentanyl transdermal system) with other central nervous system depressants,
including but not limited to other opioids, sedatives, hypnotics, tranquilizers (e.g., benzodiazepines), general
anesthetics, phenothiazines, skeletal muscle relaxants, and alcohol, may cause respiratory depression, hypotension,
and profound sedation, or potentially result in coma or death. When such combined therapy is contemplated, the dose
of one or both agents should be significantly reduced.
DURAGESIC® is not recommended for use in patients who have received MAOI within 14 days because severe and
unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.