fentanyl iontophoretic transdermal system (Discontinued)

Brand and Other Names:Ionsys
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

iontophoretic transdermal system: Schedule II

  • Discontinued from U.S. market June 19, 2017
  • 40mcg/activation (system provides up to 80 doses [40mcg each]) or up to 24 hours, whichever comes first

Acute Postoperative Pain

Needle-free, patient-controlled analgesia (PCA), preprogrammed fentanyl delivery system for the short-term management of acute postoperative pain in hospitalized adults

After titrating to acceptable level of analgesia using another opioid analgesic, apply one Ionsys system transdermally to healthy, unbroken/intact, nonirritated, and nonirradiated skin on the chest or upper outer arm only

Each activation provides a 40-mcg dose of fentanyl

It is important to instruct patients how to operate Ionsys to self-administer doses of fentanyl as needed to manage their postoperative pain

Allow only the patient to self-administer doses

Each on-demand dose is delivered over a 10-minute period

One fentanyl transdermal patch may be applied at a time

May be used for a maximum of 3 days (72 hours) of therapy for acute postoperative pain, with each subsequent patch applied to a different skin site

Also see Administration

Dosing Considerations

Limitations of use

  • Only for use in patients who are alert enough and have adequate cognitive ability to understand the directions for use
  • Not for home use; for use only in patients in the hospital
  • Discontinue treatment with PCA with Ionsys before patients leave the hospital
  • Use after patients have been titrated to an acceptable level of analgesia using alternate opioid analgesics

<18 years: Safety and efficacy not established

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Interactions

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            Adverse Effects

            >10%

            Nausea (39%)

            Application site reaction, erythema (14%)

            Vomiting (12%)

            1-10%

            Headache (9%)

            Pruritus (6%)

            Urinary retention (3%)

            Anemia (3%)

            Dizziness (3%)

            Hypotension (2%)

            Frequency Not Defined

            Body as a whole: Abdominal pain, back pain, extremity pain, chest pain, chills, abdomen enlarged, asthenia, abscess, hypothermia

            Cardiovascular system: Syncope, postural hypotension, vasodilation, hypertension, atrial fibrillation, bradycardia, tachycardia, bigeminy, arrhythmia, myocardial infarct

            Digestive system: Constipation, flatulence, dyspepsia, ileus, dry mouth, diarrhea

            Metabolic and nutritional system: Peripheral edema, healing abnormal, edema, dehydration

            Musculoskeletal system: Leg cramps, myalgia

            Nervous system: Insomnia, anxiety, somnolence, confusion, paresthesia, hypoesthesia, nervousness, agitation, abnormal dreams, tremor

            Respiratory system: Hypoxia, hypoventilation, dyspnea, apnea, cough increased, asthma, hiccup, atelectasis, rhinitis, hyperventilation

            Skin system: Application site reactions, including itching, vesicles, papules/pustules, edema, pain, burning, dry and flaky skin, vesiculobullous rash, oozing/bleeding, inflammation/erythema, and general rash and general sweating

            Special senses: Abnormal vision; blurred vision

            Urogenital system: Impaired urination, hematuria, urinary tract infection, urinary urgency, dysuria

            Postmarketing Reports

            Application site reactions: Urticaria, application site discharge, erosion, hyperesthesia, pustules, rash and scab, application site bleeding, application site infection, necrosis

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            Warnings

            Black Box Warnings

            Because of potentially life-threatening respiratory depression resulting from accidental exposure, the system is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the IONSYS REMS Program

            Exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death; assess each patient’s risk before prescribing, and monitor regularly for development of these behaviors or conditions

            Life-threatening respiratory depression

            • Use may result in potentially life-threatening respiratory depression and death as a result of the active drug, fentanyl
            • Only the patient should activate dosing
            • Accidental exposure to an intact system or to the hydrogel component, especially by children, through contact with skin or contact with mucous membranes can result in a fatal overdose of fentanyl
            • Use only in patients in the hospital
            • Discontinue PCA with Ionsys before patients leave the hospital
            • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to minimum required; follow patients for signs and symptoms of respiratory depression and sedation

            CYP3A4 interactions

            • The concomitant use with all CYP3A4 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 CYP3A4 inducer may result in an increase in fentanyl plasma concentration
            • Monitor patients receiving fentanyl and any CYP3A4 inhibitor or inducer

            Contraindications

            Significant respiratory depression

            Acute or severe bronchial asthma

            Known or suspected paralytic ileus and GI obstruction

            Hypersensitivity to fentanyl or cetylpyridinium chloride (eg, Cepacol) or any component of fentanyl iontophoretic transdermal system

            Cautions

            Profound sedation, respiratory depression, coma, and death may result from concomitant administration with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol); because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate

            Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients; monitor such patients closely when iontophoretic transdermal system is coadministered with other drugs that depress respiration

            Remove before MRI procedure, cardioversion or defibrillation, or radiographic imaging; system contains metal parts that may interfere with MRI or cardiovascular procedures, and it contains radiopaque components that may interfere with radiography or CT scanning

            Avoid contact with synthetic materials (eg, carpeted flooring) to reduce the possibility of electrostatic discharge and damage to Ionsys

            Avoid exposing Ionsys to electronic security systems to reduce the possibility of damage to Ionsys

            Use near communications equipment (eg, base stations for radiotelephones and land mobile radios, amateur radio, AM and FM radio broadcast and TV broadcast radio) and radio frequency identification (RFID) transmitters can damage Ionsys; depending on the rated maximum output power and frequency of the transmitter, recommended separation distance ranges between 0.12 and 23 meters

            Topical skin reactions may occur and are typically limited to the site application area and generally resolve without treatment; if observed, remove iontophoretic transdermal system and discontinue further use

            Monitor patients with significant COPD or cor pulmonale and patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression for respiratory depression, particularly when initiating therapy; consider the use of alternative nonopioid analgesics if possible

            May aggravate convulsions in patients with convulsive disorders and may induce or aggravate seizures in some clinical settings

            May produce bradycardia; monitor patients with bradyarrhythmias closely for changes in heart rate, particularly when initiating therapy

            Hepatic impairment: Insufficient data are available; monitor for signs of sedation and respiratory depression

            Renal impairment: A clinical pharmacology study with intravenous fentanyl in patients undergoing kidney transplantation has shown that patients with high blood urea nitrogen levels had low fentanyl clearance; monitor for signs of sedation and respiratory depression

            Risk of addiction, abuse, and misuse

            Concomitant use with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of fentanyl and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of fentanyl injection is achieved; similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in fentanyl-injection treated patients may increase fentanyl plasma concentrations and prolong opioid adverse reactions; when using fentanyl Injection with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in fentanyl-Injection treated patients, monitor patients closely at frequent intervals and consider dosage reduction of fentanyl injection until stable drug effects are achieved

            Concomitant use of fentanyl injection with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease fentanyl plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to fentanyl; when using fentanyl injection with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur

            Profound sedation, respiratory depression, coma, and death may result from concomitant administration with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol); because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate

            Monoamine oxidase inhibitors (MAOIs) may potentiate effects of opioid, opioid’s active metabolite, including respiratory depression, coma, and confusion; therapy should not be administered within 14 days of initiating or stopping MAOIs

            Cases of serotonin syndrome, a potentially life-threatening condition, reported with concomitant use of serotonergic drugs; this may occur within the recommended dosage range; the onset of symptoms generally occur within several hours to a few days of concomitant use, but may occur later than that; discontinue therapy immediately if serotonin syndrome is suspected

            Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean patient off of opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers; other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency

            Use caution when selecting dosage for an elderly patient, usually starting at low end of dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy; because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and may be useful to monitor renal function

            Avoid use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic; mixed agonist/antagonist and partial agonist analgesics may reduce analgesic effect and/or precipitate withdrawal symptoms; when discontinuing therapy in physically-dependent patient, gradually taper dosage; do not abruptly discontinue therapy in these patients

            Severe hypotension

            • May cause severe hypotension, including orthostatic hypotension and syncope, in ambulatory patients
            • Risk increased in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines, general anesthetics); monitor these patients after initiating
            • Avoid use in patients with circulatory shock; may cause vasodilation in patients with circulatory shock that can further reduce cardiac output and blood pressure

            Patients with head injury or increased ICP

            • Not suitable for use in patients who are not alert and able to follow directions (eg, head injury, increased ICP)
            • Avoid use in patients with impaired consciousness or coma susceptible to intracranial effects of CO2 retention
            • May reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure
            • Opioids may obscure the clinical course of patients with head injury
            • Use with caution in patients with brain tumors

            Patients with GI disorders

            • Contraindicated in patients with GI obstruction, including paralytic ileus
            • May cause spasm of the sphincter of Oddi
            • Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms
            • Opioids may cause increases in serum amylase
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            Pregnancy & Lactation

            Pregnancy

            There are no studies of Ionsys in pregnant women

            Limited published data on fentanyl use during pregnancy are insufficient to establish any drug-associated risks

            Labor or delivery: Opioids cross the placenta and may produce respiratory depression and psychophysiologic effects in neonates; Ionsys is not recommended for use in women during or immediately prior to labor, when other analgesic techniques are more appropriate

            Lactation

            Distributed in human breast milk at low levels, which resulted in an estimated infant dose of 0.38% of the maternal weight-adjusted dosage

            There are no reports of adverse effects on the breastfed infant and no information on the effects on milk production

            The developmental and health benefits from breastfeeding should be considered along with the mother’s need for Ionsys and any potential effects on the breastfed infant

            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.

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            Pharmacology

            Mechanism of Action

            Mu-opioid receptor agonist with the principle effect resulting in analgesia

            In addition to analgesia, undesirable pharmacodynamic effects from opioid agonists include CNS depression (eg, sedation, respiratory depression/hypoventilation); orthostatic hypotension; alterations in mood, euphoria and dysphoria, and drowsiness; increased tone and decreased propulsive contractions of smooth muscle of the GI tract; and urinary retention or urgency

            Absorption

            Compared to IV fentanyl, fentanyl concentrations in blood increase slowly with Ionsys activation and continue to increase for approximately 5 minutes after the completion of each 10-minute dose

            The systemic absorption of fentanyl from Ionsys increases as a function of time, and this increase appears to be independent of frequency of dosing

            At treatment initiation, the amount of fentanyl absorbed is expected to be approximately 16 mcg

            Absorption is similar whether applied on the upper outer arm or the chest; when placed on the lower inner arm, the delivery of fentanyl is approximately 20% lower

            AUC per dose: 0.51-0.57 ng/mL

            Peak plasma concentration: 1.3-1.94 ng/mL

            Distribution

            Distribution half-life (IV, 3-compartment model): 6 min, 1 hr, 16 hr (terminal half-life)

            Protein bound: 79-87%; binds to erythrocytes, alpha-1-acid glycoproteins, and plasma albumin; ionization of drug and blood pH affect binding

            Vd (IV, steady-state): 833 L

            Metabolism

            Metabolized by CYP3A4 to norfentanyl and other inactive metabolites

            Elimination

            Clearance (IV): 53 L/hr

            Excretion (IV within 72 hr): 75% urine (>10% representing unchanged drug); 9% feces (primarily as metabolites)

            A decline in fentanyl concentration after termination of treatment and the terminal half-life is similar to that following IV administration; This suggests a negligible continued absorption of fentanyl remaining on the skin

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            Administration

            Instructions

            After titrating to acceptable level of analgesia using another opioid analgesic, apply one Ionsys system transdermally to healthy, unbroken/intact, nonirritated, and nonirradiated skin on the chest or upper outer arm only

            Each activation provides a 40-mcg dose of fentanyl

            It is important to instruct patients how to operate Ionsys to self-administer doses of fentanyl as needed to manage their postoperative pain

            Allow only the patient to self-administer doses

            Each on-demand dose is delivered over a 10-minute period

            Each system operates up to 24 hr or 80 doses, whichever comes first

            Preparation of application site

            Choose healthy, unbroken skin on the upper outer arm of chest only

            Clip excessive hair if necessary; do not shave as this may irritate skin

            Clean site with alcohol and let it dry

            Do not use soaps, lotions, or other agents

            Wear gloves when handling Ionsys

            Assembly and application of Ionsys

            See prescribing information for diagrams for assembly

            Apply by peeling of clear plastic liner covering the adhesive and hydrogels

            Take care not to pull on the red tab while removing the clear plastic liner when preparing to apply the system to the patient; the red tab is only to be used when separating Ionsys for disposal

            Press and hold Ionsys firmly in place, with the sticky side down, onto patient’s skin for at least 15 seconds; press with your fingers around the edges to be sure it adheres to the skin, but do not press the dosing button

            Occasionally, the system may loosen from the skin; if this occurs, secure it to patient’s skin by pressing the edges with fingers or securing with a nonallergenic tape to be sure that all edges make complete contact with the skin

            After taping, if Ionsys beeps again, remove and dispose; place a new system on a different skin site

            Operation of Ionsys

            A recessed button is located on the top; to initiate administration of a fentanyl dose, the patient must press and release the button twice within 3 seconds

            System should only be activated by the patient

            One single audible beep indicates the start of delivery of each dose; the green light will start blinking rapidly and the digital display will alternate between a rotating circle and the number of doses delivered

            Each dose will be delivered over 10-minutes

            During this time, Ionsys is locked-out and will not respond to additional button presses

            When the 10-minute dose is complete, the green light will return to a slow rate of blinking and the display will show the number of doses delivered

            The system is now ready to be used again by the patient

            The next dose cannot begin until the previous 10-minute delivery cycle is complete

            Pressing the button during delivery of a dose will not result in additional drug being administered

            A healthcare professional must observe the first dose administered to ensure that the patient understands how to operate Ionsys and that the system is working properly

            Each Ionsys will cease functioning at the end of 24 hr of use or after 80 doses have been administered, whichever comes first

            The green light will turn off and the number of doses delivered will flash on and off

            The flashing digital display may be turned off by pressing and holding the dosing button for 6 seconds

            Removal

            May be removed at any time

            Once Ionsys has been removed, the same system must not be reapplied

            At the end of 24 hr of use or after 80 doses have been delivered, Ionsys will deactivate and should be removed from the patient’s skin

            With gloves on, remove the system from the patient

            Disposal

            Contact with the hydrogels contained can result in a fatal overdose of fentanyl

            Using gloves, handle the used Ionsys by the sides and top while avoiding contact with the hydrogel

            Dispose in accordance with state and federal regulations for controlled substances

            The used red bottom housing of Ionsys contains a significant amount of fentanyl that could cause a fatal overdose of fentanyl

            To dispose of a used Ionsys

            • 1. With gloves on, pull the red tab to separate the red bottom housing containing fentanyl from Ionsys
            • 2. Fold the red housing in half with the sticky side facing in
            • 3. Dispose of the folded over red housing containing the residual fentanyl per the institution’s procedures for disposal of Schedule II drugs or by flushing it down the toilet
            • 4. Hold down dosing button until the display goes blank and then dispose of the remaining part of Ionsys containing electronics in waste designated for batteries

            Storage

            Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)

            Assemble and use immediately after removal from the individually sealed package

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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.