Fentanyl Transdermal System

Pronunciation

Pronunciation: FEN-ta-nil
Class: Opioid analgesic

Trade Names

Duragesic-12
- Patch, transdermal 12 mcg/h

Duragesic-25
- Patch, transdermal 25 mcg/h

Duragesic-50
- Patch, transdermal 50 mcg/h

Duragesic-75
- Patch, transdermal 75 mcg/h

Duragesic-100
- Patch, transdermal 100 mcg/h

RAN-Fentanyl Transdermal System (Canada)
ratio-Fentanyl (Canada)

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.

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Pharmacokinetics

Absorption

T max is 20 to 72 h. C max is approximately 0.4 to 3.4 ng/mL (dose dependent).

Distribution

Vd is 6 L/kg.

Metabolism

Primarily metabolized by CYP3A4.

Elimination

Half-life is 20 to 27 h after removal. Approximately 75% of an administered dose of fentanyl is excreted in the urine, primarily as metabolites. Approximately 9% of the dose is recovered in the feces, mainly as metabolites.

Special Populations

Elderly

Reduced Cl and terminal half-life is prolonged.

Children

Plasma concentrations were approximately twice as high in pediatric patients 1.5 to 5 y of age compared with adults. Pharmacokinetic parameters in older pediatric patients were similar to those seen in adults.

Indications and Usage

Management of persistent, moderate to severe chronic pain that requires continuous opioid administration for a prolonged period of time and that cannot be managed by other means.

Contraindications

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

Dosage and Administration

Persistent, Moderate to Severe Chronic Pain
Adults and Children 2 y and older

Transdermal Calculate initial 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 based on the daily dose of supplemental opioid analgesics required by the patient in the second or third day of initial application. Further dosage increases should occur at intervals of 6 days or more. Base dose increments on the daily dose of supplementary opioids, using a ratio of 45 mg per 24 h of oral morphine to a 12.5 mcg/h increase in fentanyl transdermal dose. Replace patches every 3 days; some patients require a new patch every 2 days.

Discontinuation of therapy

To convert patient to another opioid, remove patch and titrate the dose of the new analgesic based upon the patient's report of pain until adequate analgesia has been obtained.

General Advice

  • For transdermal use only.
  • Hair at the application site should be clipped (not shaved) prior to application.
  • 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 it 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 agent that might irritate the skin or alter its characteristics); allow skin to dry completely prior to patch application.
  • If problems with adhesion occur, the edges of the patch may be taped with first aid tape. If problems with adhesion persist, the patch may be overlaid with a transparent adhesive film dressing ( Bioclusive or Tegaderm ). If the patch falls off before 72 h, dispose of it and apply a new patch at a different skin site.
  • To dispose of used patch, fold it so that the adhesive side adheres to itself and immediately flush it down the toilet.

Storage/Stability

Store patches in foil packets at or below 77°F. Do not use if seal is broken or the patch is damaged or altered in any way.

Drug Interactions

Amiodarone

Profound bradycardia, sinus arrest, and hypotension may occur. Close cardiac and pulmonary monitoring during and after anesthesia is warranted. Inotropic and vasopressor agents may be needed to maintain cardiac output and hemoperfusion.

Barbiturate anesthetics (eg, thiopurine)

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

Buprenorphine

The analgesic effects of fentanyl may be decreased. Opioid withdrawal symptoms in patients who are opioid dependent may occur if buprenorphine therapy is not initiated properly. Coadminister with caution.

Cimetidine

The actions of opioid analgesics may be enhanced, resulting in toxicity. If excessive CNS or respiratory depression occurs, discontinue both drugs. Administer a narcotic antagonist, if needed.

Crizotinib

Fentanyl plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Avoid coadministration.

CYP3A4 inducers (eg, carbamazepine, phenytoin, rifamycins [eg, rifampin], St. John's wort)

Fentanyl clearance is increased, decreasing fentanyl efficacy. Close clinical monitoring is warranted. Adjust the fentanyl dose as needed.

Droperidol

May cause hypotension and decrease pulmonary arterial pressure. If one of these reactions occurs, the possibility of hypovolemia should also be considered and managed with appropriate parenteral fluid therapy.

Grapefruit juice

Fentanyl clearance may be decreased, which could increase or prolong adverse reactions, including serious respiratory depression. Closely monitor the patient for an extended period of time. Adjust the fentanyl dose as needed.

MAOIs (eg, phenelzine)

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

Naltrexone

The analgesic effects of fentanyl may be decreased or attenuated. Opioid withdrawal symptoms may occur in patients who are opioid dependent. Close clinical monitoring for signs of opioid withdrawal or reduced opioid efficacy is warranted. Patients who are opioid dependent should be detoxified before treatment with naltrexone.

Potent CYP3A4 inhibitors (eg, aprepitant, clarithromycin, diltiazem, erythromycin, fluconazole, itraconazole, ketoconazole, nefazodone, nelfinavir, protease inhibitors [eg, nelfinavir, ritonavir], verapamil, voriconazole), other CNS depressants (eg, alcohol, barbiturates, benzodiazepines [eg, diazepam], general anesthetics, other opioids, phenothiazines, sedating antihistamines, sedatives/hypnotics, skeletal muscle relaxants, tranquilizers)

Increased depressant effects; hypoventilation, hypotension, profound sedation, and life-threatening respiratory depression may occur. Closely monitor patients for an extended period of time. Adjust the dose of one or both agents as needed. Alcohol should be avoided.

Serotonin reuptake inhibitors (eg, fluoxetine)

Toxic effects of serotonin reuptake inhibitor and fentanyl may be additive, increasing the risk of serotonin syndrome. Close clinical monitoring for signs of serotonin syndrome is warranted.

Sibutramine

The risk of serotonin syndrome may be increased. Avoid coadministration.

Sodium oxybate

Concurrent use of sodium oxybate with fentanyl may result in an increase in sleep duration and CNS depression due to additive pharmacologic effects. Coadministration is contraindicated.

Adverse Reactions

Cardiovascular

Arrhythmias, chest pain, hypertension, syncope, tachycardia (1% to less than 3%).

CNS

Asthenia, confusion, somnolence (at least 10%); anxiety, depression, dizziness, euphoria, fatigue, hallucinations, headache, insomnia, nervousness (3% to 10%); abnormal coordination, abnormal dreams, abnormal gait, abnormal thinking, agitation, amnesia, convulsions, paranoid reaction, paresthesia, speech disorder, stupor, tremor (1% to less than 3%).

Dermatologic

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

EENT

Pharyngitis, rhinitis (1% to less than 3%); blurred vision (postmarketing).

GI

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

Genitourinary

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

Metabolic

Weight loss (postmarketing).

Musculoskeletal

Back pain, rigors (1% to less than 3%).

Respiratory

Apnea, dyspnea, hypoventilation, respiratory tract infection (3% to 10%); bronchitis, coughing, hemoptysis, hiccups, respiratory depression, sinusitis (1% to less than 3%).

Miscellaneous

Influenza-like symptoms, pain (3% to 10%); allergic reaction, fever (1% to less than 3%); edema (postmarketing).

Precautions

Warnings

Fentanyl transdermal should only be used for chronic pain in patients who are already receiving continuous opioid therapy, are opioid tolerant, require a total daily dose at least equivalent to fentanyl 25 mcg/h transdermal, and cannot be managed by lesser means. Risk of potentially fatal hypoventilation contraindicates use in patients who are not opioid tolerant or who have acute, mild, intermittent, or postoperative pain. Because peak fentanyl levels occur between 20 and 72 h of treatment, be aware that serious or life-threatening hypoventilation may occur, even in patients who are opioid tolerant during the initial application period.

Concomitant use of fentanyl and potent CYP3A4 inhibitors may result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse drug effects and cause fatal respiratory depression.

Fentanyl transdermal should only be used in children 2 y and older who are opioid tolerant.

Fentanyl patches can be abused in a manner similar to other legal or illicit opioid agonists. Assess patients for clinical risk of opioid abuse or addiction.

Do not use a patch if the pouch seal is broken or the patch is cut, damaged, or changed in any way.

There is potential for temperature-dependent increases in fentanyl released from the system, resulting in possible overdose and death. Exposure of the patch application site and surrounding area to direct external heat sources should be avoided. Patients should also avoid taking hot baths or sunbathing while using fentanyl.


Monitor

Routinely monitor patients for signs of misuse, abuse, and addiction. Monitor the use of fentanyl by clinical evaluation, especially within the initial 24 to 72 h when serum concentrations from the initial patch will peak, and following increases in dosage. Monitor patients who have experienced a serious adverse reaction, including overdose, for at least 24 h. Monitor patients wearing fentanyl transdermal who develop fever or increased core body temperature caused by strenuous exertion for opioid adverse effects and adjust the dose if necessary. Carefully observe patients with hypoventilation for degree of sedation and monitor their respiratory rates until respiration has stabilized.


Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy have not been established in children younger than 2 y.

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 cachectic patients or patients with increased intracranial pressure, impaired consciousness, coma, brain tumors, biliary tract disease, or acute pancreatitis.

Hazardous Tasks

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

Accidental exposure

Death and other serious medical problems have occurred after accidental exposure, including transfer of a patch from an adult to a child while hugging, sitting on a patch, and exposure of a caregiver during application or removal of the patch.

Cardiac effects

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

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.

Overdosage

Symptoms

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

Patient Information

  • Instruct patients to read the Medication Guide prior to first use and to reread with each refill.
  • Caution patients or caregivers 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 patients or caregivers to avoid alcohol and other depressants (eg, sleep medications, tranquilizers) because dangerous additive effects may occur, resulting in serious injury or death.
  • Remind patients or caregivers 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 patients or caregivers 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 patients or caregivers that medication can cause severe constipation and to use stool softeners, dietary fiber, and adequate fluids. Advise patients or caregivers to notify their health care provider if severe constipation develops.
  • Caution patients or caregivers to notify their 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.
  • Advise patients that patches contain fentanyl, a potent opioid pain medicine similar to morphine, hydromorphone, methadone, oxycodone, and oxymorphone.
  • Advise patients or caregivers that each patch may be worn continuously for 72 h before removal and to apply the replacement patch to a different skin site.
  • Ensure patients or caregivers understand 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 skin 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 it firmly in place with the palm of the hand for 30 seconds, making sure the contact is complete, especially around the edges. Caution patients not to fold the patch so that only part of the patch is exposed.
  • Advise patients that if they experience problems with adhesion of the patch, they may tape the edges with first aid tape. If problems persist, patients may overlay the patch with a transparent adhesive film dressing ( Bioclusive or Tegaderm ).
  • Advise patients if a patch falls off before 72 h, a new patch may be applied to a different skin site.
  • Inform patients that if a patch dislodges and accidentally sticks to the skin of another person, to immediately remove the patch, wash the exposed area with water, and seek medical attention for the accidentally exposed individual.
  • Caution patients or caregivers not to apply the patch if the seal is broken, or if the patch is altered, cut, or damaged in any way.
  • Caution patients or caregivers 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.
  • Caution patients or caregivers not to change the dose or stop using unless advised by their health care provider. Advise patients 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 patients or caregivers to keep patches in a safe place out of the reach of children because of the high risk of fatal respiratory depression.
  • Instruct patients or caregivers that when patches are 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.

Copyright © 2009 Wolters Kluwer Health.

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