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Trade Names:
Duragesic-12
- Transdermal System 1.25 mg

Trade Names:
Duragesic-25
- Transdermal System 2.5 mg

Trade Names:
Duragesic-50
- Transdermal System 5 mg

Trade Names:
Duragesic-75
- Transdermal System 7.5 mg

Trade Names:
Duragesic-100
- Transdermal System 10 mg

Trade Names:
Ionsys
- Iontophoretic Transdermal System 10.8 mg

Mechanism of Action

Pharmacology

A potent opiate agonist that relieves pain by stimulating opiate receptors in CNS; also causes respiratory depression and peripheral vasodilation; inhibits intestinal peristalsis and sphincter of Oddi spasm; stimulates chemoreceptors that cause vomiting; increases bladder tone.

Pharmacokinetics

Absorption

T _max is 24 to 72 h. C _max is about 0.3 to 2.5 ng/mL (dose dependent).

On-demand dosing with Ionsys results in absorption of a fentanyl 40 mcg dose by about 10 h posttreatment initiation; thereafter, fentanyl 40 mcg is delivered with each activation. When placed on the lower inner arm, fentanyl delivery from Ionsys is 20% lower than when applied on the upper outer arm or chest.

Distribution

Vd is 6 L/kg.

Metabolism

Primarily metabolized by CYP-450 3A4.

Elimination

Mean t _½ is 17 h after removal ( Duragesic ).

The mean t _½ of Ionsys is 11 h. Approximately 75% of an administered dose of fentanyl is excreted in the urine, primarily as metabolites. About 9% of the dose is recovered in the feces, mainly as metabolites.

Special Populations

Reduced Cl and terminal t _½ is prolonged.

Indications and Usage

Management of persistent moderate to severe chronic pain that requires continuous opioid administration for a prolonged period of time and cannot be managed by other means ( Duragesic ); short-term management of acute postoperative pain in adult patients during hospitalization ( Ionsys ).

Contraindications

Patients who are not opioid-tolerant; management of acute pain or in patients requiring opioid analgesia for short periods of time; management of postoperative pain (including out-patient or day surgeries); management of mild pain; management of intermittent pain; situations of considerable respiratory depression, especially in unmonitored settings without resuscitative equipment; patients with acute or severe bronchial asthma; patient with paralytic ileus; hypersensitivity to fentanyl or any component of the product; hypersensitivity to cetylpyridium chloride (eg, Cepacol ) ( Ionsys ).

Dosage and Administration

Transdermal Calculate dose based on previous day's opiate requirements using manufacturer's conversion charts. Max pain relief does not occur until 24 h or more after application; a short-acting opiate may be needed for breakthrough pain. Initial dose can be increased after 3 days. Further dosage increases should occur at intervals of 6 days or more. Replace patches every 3 days; some patients require new patch every 2 days.

Transdermal Titrate patient to comfort before initiating Ionsys . Ionsys provides a fentanyl 40 mcg dose per on-demand activation. Each dose is delivered over a 10-min period. To activate administration, patient must press the button twice firmly within 3 sec. A max of six 40 mcg doses can be administered by Ionsys . The max amount of fentanyl that can be administered from a single Ionsys system over 24 h is 3.2 mg.

General Advice

• Hair at the application site should be clipped (not shaved) prior to application.

• Duragesic
• Apply only to intact, nonirritated, and nonirradiated skin on a flat surface (eg, chest, back, flank, upper arm; in young children or people with cognitive impairment, place patch on the upper back to lower the chance that the patch will be removed and placed in the mouth).
• Apply patch immediately upon removal from the sealed package and after removal of the protective liner by pressing firmly in place with the palm of the hand for 30 sec, making sure the contact is complete, especially around the edges. After removal of the patch, apply the next patch to a different skin site.
• If the site of application must be cleansed prior to application, use clear water only (do not use soaps, oils, lotions, alcohol, or any other agents that might irritate the skin or alter its characteristics); allow to dry completely prior to patch application.
• To dispose of used patch, fold (so that the adhesive side adheres to itself) and immediately flush down the toilet.
• If accidental skin contact with the gel from the patch occurs, wash the area clean with clear water (do not use soap, alcohol, or other chemicals).

• Ionsys
• To ensure the patient understands how to operate Ionsys and that the system is working properly, a health care professional should observe administration of the first dose.
• Apply to intact, nonirritated, and nonirradiated skin on the chest or upper outer arm. Do not apply to abnormal skin sites (eg, scars, burns, tattoos).
• Doses should only be administered by the patient.
• Before applying, wipe the application site with a standard alcohol swab and allow to dry completely.
• To avoid irritating the skin or altering absorption characteristics, do not use soaps, oils, lotions, or any other agent. Press system firmly in place, with sticky side down, on the skin for at least 15 sec, using fingers around the outer edge to ensure system sticks to the skin.
• Each system may be used for 24 h from completion of the first on-demand dose or until 80 doses have been administered, whichever occurs first. After this, Ionsys is inactivated and cannot deliver any additional doses.
• Ionsys may be removed at any time; however, once removed, the same system should not be reapplied.
• If the hydrogel becomes separated from the system, gloves or tweezers should be used to remove the hydrogel from the skin.
• Care should be taken not to touch the exposed hydrogel compartments or the adhesive of the system. If a hydrogel drug reservoir is touched accidentally, rinse area thoroughly with water (do not use soap).

Storage/Stability

Store Duragesic patches in foil packets at or below 77°F. Apply immediately after removal from sealed package. Do not use if seal is broken or the patch is damaged or altered in any way.

Store Ionsys at 59° to 86°F. Apply to skin immediately after removal from sealed package. Do not use if foil pouch is broken.

Drug Interactions

Possible additive CNS depressant effects.

Profound bradycardia, sinus arrest, and hypotension may occur.

May have additive effects. Reduce dosage of 1 or both agents.

Not recommended for use in patients who have received MAOIs within 14 days.

Increased depressant effects; hypoventilation, hypotension, profound sedation, and life-threatening respiratory depression may occur.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Arrhythmias, chest pain (at least 1%); tachycardia (postmarketing).

Hypertension, syncope, tachycardia (at least 1%).

Hypotension (2%); hypertension, tachycardia (1% to less than 10%).

CNS

Fatigue, headache (3% to 10%).

Asthenia, headache, insomnia, nervousness, somnolence (3% to 10%); agitation, anxiety, confusion, convulsions, depression, dizziness, hallucinations, paranoid reaction, speech disorder, stupor, tremor (at least 10%).

Headache (9%); dizziness, insomnia (3%); anxiety, hypertonia, somnolence (1% to less than 10%).

Dermatologic

Sweating (at least 10%); pruritus (3% to 10%); rash (at least 1%).

Application-site reaction, pruritus (3% to 10%); erythematous rash, increased sweating, localized skin reaction, rash (at least 1%).

EENT

Blurred vision (postmarketing).

Rhinitis (at least 10%).

Pharyngitis (1% to less than 10%).

GI

Constipation, dry mouth, nausea, vomiting (at least 10%); anorexia, diarrhea, dyspepsia (3% to 10%); flatulence (at least 1%).

Nausea, vomiting (at least 10%); constipation (3% to 10%); diarrhea, dry mouth, (at least 1%).

Nausea (39%); vomiting (12%); constipation, dyspepsia, flatulence, ileus (1% to less than 10%).

Genitourinary

Urinary retention (3% to 10%); micturition disorder (at least 1%); anorgasmia, decreased libido, ejaculatory difficulty (postmarketing).

Urinary retention (at least 1%).

Urinary retention (3%).

Hematologic-Lymphatic

Anemia (3%).

Local

Application-site reaction including edema, erythema, itching, papules (at least 1%).

Application-site erythema (14%); pruritus (6%); application-site edema, itching, and vesicles, sweating, wound oozing/bleeding (1% to less than 10%).

Metabolic

Weight loss (postmarketing).

Metabolic-Nutritional

Hypokalemia (1% to less than 10%).

Musculoskeletal

Back pain, rigors (at least 1%).

Back pain (2%).

Respiratory

Apnea, dyspnea, hypoventilation (3% to 10%); bronchitis, hiccups, rhinitis, sinusitis, upper respiratory tract infection (at least 1%).

Coughing, dyspnea, respiratory depression (at least 10%).

Hypoxia (1% to less than 10%).

Miscellaneous

Abdominal pain (3% to 10%); accidental injury, fever, influenza-like symptoms (at least 1%); edema (postmarketing).

Pain (3% to 10%); abdominal pain, allergic reaction, fever, flushing (at least 1%).

Fever (9%); abdominal pain, extremity pain, pain (1% to less than 10%).

Precautions

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established in children younger than 2 yr of age ( Duragesic ). Safety and efficacy not established in patients younger than 18 yr of age ( Ionsys ).

Renal Function

Fentanyl is renally excreted. Use with caution.

Hepatic Function

Fentanyl is hepatically metabolized. Use with caution.

Special Risk Patients

Use with caution in elderly, debilitated, or cachetic patients or patients with myxedema, acute alcoholism, acute abdominal conditions, biliary tract disease (including acute pancreatitis), ulcerative colitis, head injury or increased intracranial pressure, brain tumors, supraventricular tachycardia, depleted blood volume, or circulatory shock.

Hazardous Tasks

May impair physical or mental abilities required to perform potentially dangerous tasks.

Cardiac disease

May cause bradycardia. Use with caution in patients with bradyarrhythmias.

Drug dependence

Fentanyl has abuse potential.

Exposure to external heat

Direct contact with heating pads, electric blankets, saunas, or hot tubs could increase fentanyl absorption.

Fever

May increase absorption of fentanyl; monitor for adverse reactions.

Respiratory depression

Serious or life-threatening hypoventilation may occur, especially during the initial 24 to 72 h and following increases in dose. Use with extreme caution in patients with COPD or cor pulmonale, or in patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression.

Tolerance

May occur.

Topical skin reactions

After removal of Ionsys , topical skin reactions (eg, erythema, sweating, vesicles, papules/pustules) may occur at the application site.

Overdosage

Symptoms

Cardiopulmonary arrest, circulatory collapse, CNS depression, death, hypoventilation, miosis, respiratory depression, seizures.

Patient Information

• Caution patient or caregiver that medication may impair mental and/or physical abilities required for the performance of potentially hazardous tasks (eg, driving, operating machinery) and to use caution until tolerance is determined.
• Caution patient or caregiver to avoid alcohol and other depressants (eg, sleep medications, tranquilizers) because dangerous additive effects may occur, resulting in serious injury or death.
• Remind patient or caregiver that fentanyl is a medication with high potential for abuse and to protect the systems from theft or misuse in the work or home environment.
• Warn patient or caregiver that transdermal system should never be used by anyone other than the individual for whom it was prescribed because of the risk of death or other serious medical problems.
• Caution patient or caregiver that medication can cause severe constipation and to use stool softeners, dietary fiber, and adequate fluids. Advise patient or caregiver to notify health care provider if severe constipation develops.
• Caution patient or caregiver to notify health care provider if a high fever develops because there is a potential for temperature-dependent increase in fentanyl release from the system that could result in fentanyl overdose.

• Duragesic
• Advise patient that patches contain fentanyl, a potent opioid pain medicine similar to morphine, hydromorphone, methadone, oxycodone, and oxymorphone.
• Advise patient or caregiver that each patch may be worn continuously for 72 h before removal and to apply the replacement patch to a different skin site.
• Ensure patient or caregiver understands how to apply patch: apply only to intact, nonirritated, and nonirradiated skin on a flat surface (eg, back, chest, flank, upper arm). In young children or people with cognitive impairment, secure the patch on the upper back to lower the chance that it will be removed and placed in the mouth. Hair at the application site should be clipped (not shaved) prior to patch application; if the site of application must be cleansed prior to application of the patch, do so with clear water (do not use soaps, oils, lotions, alcohol, or any other agents that might irritate the skin or alter its characteristics) and allow to dry completely prior to patch application; apply patch immediately upon removal from the sealed package and after removal of the protective liner by pressing firmly in place with the palm of the hand for 30 sec, making sure the contact is complete, especially around the edges. Caution patient not to fold the patch so that only part of the patch is exposed.
• Caution patient or caregiver not to apply the patch if the seal is broken, or if the patch is altered, cut, or damaged in any way. Advise patient that this could lead to the rapid release and absorption of the contents of the patch resulting in serious side effects or death.
• Caution patient or caregiver to avoid exposing the application site to direct external heat sources (eg, heating pads, electric blankets, heat lamps, saunas, hot tubs, heated water beds) while wearing the patch.
• Instruct patient or caregiver that if the gel from the patch accidentally contacts the skin, to wash the area with clear water. Soap, alcohol, or other chemicals should not be used because these products may increase the ability of fentanyl to go through the skin.
• Caution patient or caregiver not to change the dose or stop using unless advised by health care provider. Advise patient that suddenly stopping therapy after long-term use could cause narcotic withdrawal symptoms and that the dose will usually be slowly reduced if therapy needs to be discontinued.
• Caution patient or caregiver to keep patches in a safe place out of the reach of children because of the high risk of fatal respiratory depression.
• Instruct patient or caregiver that when patches are either used or no longer needed, to remove the used patch from the skin or the unused patches from their pouches, fold so that the adhesive side of the patch adheres to itself, and flush down the toilet.

• Ionsys
• Review the patient information leaflet with the patient before use.
• Advise patient not to let anyone else activate the dosing button on the Ionsys system.
• Instruct patient not to touch the sticky side of the system or the gels.