"Two US Food and Drug Administration (FDA) panels â€” the Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) and Drug Safety and Risk Management Advisory Committee (DSaRM) â€” voted 18 to 1 in favor of recommending approval of the abus"...
(Generic versions may still be available.)
The following serious adverse reactions are described elsewhere in the labeling:
- Life-threatening respiratory depression [see WARNINGS AND PRECAUTIONS]
- Addiction, abuse, and misuse [see WARNINGS AND PRECAUTIONS]
- Interactions with other CNS depressants [see WARNINGS AND PRECAUTIONS]
- Hypotensive effects [see WARNINGS AND PRECAUTIONS]
- Gastrointestinal effects [see WARNINGS AND PRECAUTIONS]
- Seizures [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In controlled and uncontrolled studies, the safety of IONSYS 40 mcg was evaluated in a total of 2114 patients with acute postoperative pain requiring opioid analgesia.
The most common adverse reactions ( ≥ 2%) in the placebo-controlled studies, regardless of relationship to study medication, are listed in Table 3.
Table 3: Adverse Reactions with Incidence ≥ 2%
in Placebo-controlled Studies 1, 2, and 3 (N=791; 24 Hour Duration)
|Body as a Whole|
|Hemic and Lymphatic System|
|Application site reaction- Erythema||14%||2%|
|NOTE: Patients reported as having “Nausea and vomiting” are included in “Nausea” and Vomiting” in Table 3.|
Other Adverse Reactions
Other adverse reactions that were reported (excluding adverse reactions listed in Table 3) in 4 active comparator trials vs. IV PCA morphine in patients treated with IONSYS (n=1288), are described below:
Metabolic and Nutritional System: peripheral edema, healing abnormal, edema, dehydration
Musculoskeletal System: leg cramps and myalgia
Skin System: application site reactions including: itching, vesicles, papules/pustules, edema, pain, burning, dry and flaky skin, and vesiculobullous rash wound site oozing/bleeding, wound site inflammation/erythema, rash, sweating
Special Senses: abnormal vision-blurred vision
Scheduled observation of the skin approximately 24 hours after IONSYS removal was included in several studies. Some redness at the skin sites was observed in approximately 60% of patients at this observation. The skin findings included erythema, edema, and papules. The majority of these events were categorized as mild. Two patients were noted to have hyperpigmentation lasting 2 - 3 weeks at the application site. Three patients noted a rectangular mark at the application site, which persisted for up to 3 months after study completion.
The following adverse reactions have been identified during post approval use of IONSYS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The most commonly observed events were related to application site reactions which included urticaria, application site discharge, erosion, hyperesthesia, pustules, rash and scab, application site bleeding, application site infection, and necrosis.
Read the Ionsys (fentanyl iontophoretic transdermal system) Side Effects Center for a complete guide to possible side effects
Central Nervous System Depressants
The concomitant use of IONSYS with other central nervous system depressants including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, general anesthetics, other opioids, and alcohol can increase the risk of respiratory depression, profound sedation, coma, and death. Monitor patients receiving concomitant CNS depressants and IONSYS for signs of respiratory depression, sedation, and hypotension [see WARNINGS AND PRECAUTIONS].
IONSYS may enhance the neuromuscular blocking action of true skeletal muscle relaxants and produce an increased degree of respiratory depression. Monitor patients receiving muscle relaxants and IONSYS for signs of respiratory depression that may be greater than otherwise expected.
Drugs Affecting CYP3A4 Isoenzyme System
Inhibitors of CYP3A4
Because the CYP3A4 isoenzyme plays a major role in the metabolism of fentanyl, drugs that inhibit CYP3A4 activity may cause decreased clearance of fentanyl which could lead to an increase in fentanyl plasma concentrations and result in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of 3A4 inhibitors. If coadministration with IONSYS is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider dose adjustments until stable drug effects are achieved [see CLINICAL PHARMACOLOGY].
Inducers of CYP3A4
CYP450 3A4 inducers may induce the metabolism of fentanyl and, therefore, may cause increased clearance of the drug which could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. If co-administration with IONSYS is necessary, monitor for signs of opioid withdrawal and consider dose adjustments until stable drug effects are achieved [see CLINICAL PHARMACOLOGY].
After stopping the treatment of a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects, and may cause serious respiratory depression or death [see CLINICAL PHARMACOLOGY
Monoamine Oxidase (MAO) Inhibitors
Avoid use of IONSYS in patients who would require the concomitant administration of a monoamine oxidase (MAO) inhibitor, or within 14 days of stopping such a treatment because severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.
Mixed Agonist/Antagonist And Partial Agonist Opioid Analgesics
Mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) and partial agonist (buprenorphine) analgesics may reduce the analgesic effect of IONSYS or may precipitate withdrawal symptoms. Avoid the use of agonist/antagonist and partial agonist analgesics in patients receiving IONSYS.
IONSYS can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. IONSYS may also lead to acute retention of urine by causing spasm of the sphincter of the bladder, particularly in men with enlarged prostates.
Anticholinergics or other medications with anticholinergic activity when used concurrently with IONSYS may result in increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor patients for signs of urinary retention or reduced gastrointestinal motility when IONSYS is used concurrently with anticholinergic drugs.
Drug Abuse And Dependence
IONSYS contains fentanyl, a Schedule II controlled substance with a high potential for abuse similar to other opioids including morphine, hydromorphone, methadone, oxycodone, and oxymorphone. IONSYS can be abused and is subject to misuse, addiction, and criminal diversion [see WARNINGS AND PRECAUTIONS].
All patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use.
Drug abuse is the intentional non-therapeutic use of an over-the-counter or prescription drug, even once, for its rewarding psychological or physiological effects. Drug abuse includes, but is not limited to, the following examples: the use of a prescription or over-the-counter drug to get “high”, or the use of steroids for performance enhancement and muscle build up.
Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and include: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.
“Drug-seeking” behavior is very common in addicts and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction.
Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.
IONSYS, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity and frequency is strongly advised.
Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.
Risks Specific to Abuse of IONSYS IONSYS is for transdermal use only for patients in the hospital. Abuse of IONSYS poses a risk of overdose and death. This risk is increased with concurrent abuse of IONSYS and alcohol and other central nervous system depressants [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS]. Contact with residual fentanyl in hydrogel of the device can result in fatal overdose.
Access to abusable drugs such as IONSYS presents a risk for abuse and diversion in the health care community. Implementation of effective accounting procedures in addition to routine procedures for handling controlled substances may minimize these risks.
Healthcare professionals should contact their State Professional Licensing Board or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product.
Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.
Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dose reduction of a drug. Withdrawal may also be precipitated through the administration of drugs with opioid antagonist activity, e.g., naloxone, nalmefene, mixed agonist/antagonist analgesics (pentazocine, butorphanol, malbuphine), or partial agonists (buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.
Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms [see Use in Specific Populations].This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 9/8/2015
Additional Ionsys Information
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