fentanyl transdermal (Duragesic)

Dosing and uses of Duragesic (fentanyl transdermal)

• Adult
• Pediatric

 

Adult dosage forms and strengths

transdermal patch: Schedule II

• 12.5mcg/hr
• 25mcg/hr
• 50mcg/hr
• 75mcg/hr
• 100mcg/hr

 

Chronic Severe Pain

Indicated for chronic pain in opioid-tolerant patients, severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate

25-100 mcg/hr, reapplied q72hr until adequate analgesia is achieved

Refer to opioid conversion table in prescribing information

Opioid-tolerant definition

• Patients who are opioid tolerant are those receiving, for 1 week or longer, at least 60 mg/day PO morphine, 30 mg/day PO oxycodone, 8 mg/day PO hydromorphone, 25 mg/day PO oxymorphone, or an equianalgesic dose of another opioid

Limitations of use

• Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve for patients whom alternative treatment options (eg, nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain

 

Dosing Considerations

Not for use in acute pain or as PRN analgesic

Conversion to transdermal patch: Estimate daily PO morphine equivalent, then decrease by 25-50% to select initial patch; also supply PO opioid for breakthrough pain during transition to patch and titration

Discontinue all other around-the-clock opioid drugs when initiating the fentanyl patch

Initial dose may be approximated from the 24 hr morphine dosage equivalent; titrate to minimize effects; replace patch every 3 days

Patients with adequate relief with a fentanyl infusion may be converted  to transdermal dosing at a rate equivalent to intravenous rate

Dosage should not be titrated more frequently than 3 days after the initial dose or every 6 days thereafter; patient should wear a consistent fentanyl dosage patch through two applications (6 days) before dosage increase based on supplemental opioid dosages can be estimated

Most patients may be controlled on every 72 hr administration; a minority of patients may require every 48hr administration

 

Pediatric dosage forms and strengths

transdermal patch: Schedule II

• 12.5mcg/hr
• 25mcg/hr
• 50mcg/hr
• 75mcg/hr
• 100mcg/hr

 

Chronic Pain (Off-label)

Treatment of chronic pain in children who are opioid-tolerant and receiving ≥60 mg/day PO of morphine or equivalent

<2 years: Safety not established

≥2 years: 25-100 mcg/hr, reapplied q72hr until adequate analgesia is achieved

Dosing considerations

• Not for use in acute pain or as PRN analgesic
• Conversion to transdermal patch: Estimate daily PO morphine equivalent, then decrease by 25-50% to select initial patch; also supply PO opioid for breakthrough pain during transition to patch and titration
• Discontinue all other around-the-clock opioid drugs when initiating the fentanyl patch
• Initial dose may be approximated from the 24 hr morphine dosage equivalent; titrate to minimize effects; replace patch every 3 days
• Patients with adequate relief with a fentanyl infusion may be converted to transdermal dosing at a rate equivalent to intravenous rate
• Dosage should not be titrated more frequently than 3 days after the initial dose or every 6 days thereafter; patient should wear a consistent fentanyl dosage patch through two applications (6 days) before dosage increase based on supplemental opioid dosages can be estimated
• Most patients may be controlled on every 72 hr administration; a minority of patients may require every 48hr administration

 

Duragesic (fentanyl transdermal) adverse (side) effects

Frequency not defined

Asthenia

Confusion

Constipation

Dry mouth

Nausea

Somnolence

Sweating

Vomiting

Abdominal pain

Anorexia

Anxiety

Apnea

Depression

Diarrhea

Dizziness

Dyspepsia

Dyspnea

Euphoria

Fatigue

Hallucinations

Headache

Hemoptysis

Hypoventilation

Influenzalike symptoms

Nervousness

Pharyngitis

Pruritus

Upper respiratory tract infection Urinary retention

Abnormal coordination, thinking, gait, dreams

Accidental injury

Agitation

Amnesia

Angina pectoris

Application-site reaction

Back pain

Bradycardia

Bronchitis

Cardiac arrest, ST-segment elevation

Coma

Dysphoria

Faintness

Fever

Flatulence

Flushing

Hiccups

Mental clouding

Micturition disorder

Myocardial infarction

Oliguria

Paranoid reaction

Paresthesia

Rash

Respiratory arrest

Respiratory/circulatory depression

Rhinitis

Sedation

Seizures

Severe cardiac arrhythmias

Shock

Sinusitis

Speech disorder

Syncope

Tremor

Urinary retention

Ventricular tachycardia

Visual disturbances

Warmness of face/neck/upper thorax, urticaria

Weakness

 

Warnings

Black box warnings

Addiction, abuse, and misuse

• Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death
• Assess each patient’s risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions

Life-threatening respiratory depression

• Serious, life-threatening, or fatal respiratory depression may occur
• Monitor for respiratory depression, especially during initiation or following a dose increase
• Instruct patients to swallow tablet/capsule whole; crushing, chewing, or dissolving can cause rapid release and absorption of a potentially fatal dose

Accidental exposure

• Accidental of even 1 dose, especially by children, can result in a fatal overdose

Neonatal opioid withdrawal syndrome

• Prolonged use 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
• Syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight
• Onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn
• 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

CYP3A4 inhibitors

• Concomitant use of transdermal fentanyl with all cytochrome CYP450 3A4 inhibitors (ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, nefazodone, amiodarone, amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, verapamil) may result in increased fentanyl plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression
• Patients receiving fentanyl transdermally and any CYP34A inhibitors should be carefully monitored for extended period, and dosage adjustments should be made if warranted

Exposure to heat

• Exposure of the application site and surrounding area to direct external heat sources (eg, 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
• Patients wearing a fentanyl patch 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 to avoid overdose and death

 

Contraindications

Hypersensitivity

Toxin-mediated diarrhea (until toxins are cleared), paralytic ileus, respiratory depression, acute or severe bronchial asthma

Within 2 weeks of monoamine oxidase inhibitor (MAOI) therapy

Management of postoperative, mild, or intermittent pain

Opioid-naive or non-opioid-tolerant patients

 

Cautions

Use caution in acute pancreatitis, Addison disease, benign prostatic hyperplasia, cardiac arrhythmias, central nervpous system (CNS) depression, drug abuse or dependence, emotional lability, gallbladder disease, gastrointestinal (GI) disorder, pseudomembranous colitis, GI surgery, head injury, hypothyroidism or untreated myxedema, intracranial hypertension, brain tumor, toxic psychosis, urethral stricture, urinary tract surgery, seizures, acute alcoholism, delirium tremens, shock, cor pulmonale, chronic pulmonary disease, emphysema, hypercapnia, kyphoscoliosis, severe obesity, renal or hepatic impairment, elderly or debilitated patients

Increased risk of potentially fatal respiratory depression, pruritus (despite little histamine release), and abuse or addiction

May impair physical or mental abilities; use caution when operating machinery or driving

Not recommended wihtin 14 days of MAO inhibitor intake

Only apply to intact skin

Schedule II opioid analgesics expose users to the risks of addiction, abuse, and misuse; there is a greater risk for overdose and death with extended-release opioids due to the larger amount of active opioid present (see Black box warnings)

Addiction, abuse, and misuse risks are increased in patients with a personal or family history of substance abuse or mental illness (eg, major depression); the potential for these risks should not, however, prevent the prescribing of proper pain management in any given patient; intensive monitoring is necessary (see Black box warnings)

Serious, life-threatening, or fatal respiratory depression reported (see Black box warnings)

Accidental exposure reported, including fatalities (see Black box warnings)

Neonatal opioid withdrawal syndrome reported with long-term use during pregnancy (see Black box warnings)

Interactions with CNS depressants (eg, alcohol, sedatives, anxiolytics, hypnotics, neuroleptics, other opioids) can cause additive effects and increase risk for respiratory depression, profound sedation, and hypotension

Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients

 

Pregnancy and lactation

Pregnancy category: C

Lactation: Drug distributed in breast milk; breastfeeding not recommended

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Duragesic (fentanyl transdermal)

Mechanism of action

Narcotic agonist-analgesic of opiate receptors; inhibits ascending pain pathways; alters pain perception, thus altering response to pain; produces analgesia, respiratory depression, and sedation

 

Absorption

After patch removal, continued systemic absorption occurs from residual fentanyl in skin, so that serum concentrations fall by average of 50% in ~20-27 hr

Onset: 6 hr

Duration: 72-96 hr

Peak plasma time: 28.8-35.8 hr (dose dependent; following first application)

Peak plasma concentration: 0.38-3.36 ng/mL (dose dependent; following first application)

 

Distribution

Vd: 4-6 L/kg

Protein binding: 80-85%

 

Metabolism

Metabolized in liver by CYP3A4

 

Elimination

Half-life: 20-27 hr

Excretion: Urine (75% mostly as metabolites), feces (9% as metabolites)