Dosing and uses of Ionsys (fentanyl iontophoretic transdermal system)
Adult dosage forms and strengths
iontophoretic transdermal system: Schedule II
- 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
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Ionsys (fentanyl iontophoretic transdermal system) adverse (side) 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
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
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
Coadministration with alcohol or other CNS depressants (eg, sedatives, anxiolytics, hypnotics, neuroleptics, other opioids) may cause hypotension, profound sedation, respiratory depression, coma, and death; monitor patients closely if coadministration is required
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
Caution if coadministered with CYP3A4 inhibitors or inducers (see Black box warnings)
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
Pregnancy and 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.
Pharmacology of Ionsys (fentanyl iontophoretic transdermal system)
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
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
