"Young children have died or become seriously ill from accidental exposure to a skin patch containing fentanyl, a powerful pain reliever. As a result of this, the Food and Drug Administration (FDA) is issuing a Drug Safety Communication to warn pa"...
(Generic versions may still be available.)
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 events ( ≥ 2%) in the placebo-controlled studies, regardless of relationship to study medication, are listed in Table 5.
Table 5 Adverse Events with Incidence ≥ 2% in Placebo-controlled
Studies 1, 2, and 3 (N=791; 24 Hour Duration), Regardless of Relationship to
|Adverse Event|| IONSYS™
|Body as a Whole|
|Hemic and Lymphatic|
|Application site reaction- Erythema||14%||2%|
|Urinary retention||3%||< 1%|
|* NOTE: Patients reported as having "Nausea and vomiting" are included in "Nausea" and "Vomiting" in Table 5.|
Adverse Events Reported in All Studies in Patients Treated With IONSYS™ (40 mcg/dose: n= 2114 including 3 Placebo-Controlled Trials and 4 Active Comparator Trials vs. IV PCA morphine)
The most common ( > 10%) adverse events reported regardless of relationship to IONSYS™ use were nausea, vomiting, application site reaction-erythema, fever, and headache. Other adverse events reported for IONSYS™ were:
Body as a whole: abdominal pain**, back pain**, extremity pain**, pain**, injection site reaction*, chills*, internal postoperative bleeding*, chest pain*, infection*, injection site edema*, injection site pain*, immune system disorder*, abdomen enlarged*, asthenia*, neck pain*, abscess*, and hypothermia*, Cardiovascular System: hypotension**, tachycardia**, hypertension**, syncope*, postural hypotension*, pulmonary embolus*, atrial fibrillation*, bradycardia*, migraine*, myocardial infarct*, vasodilation*, hemorrhage*, deep thrombophlebitis*, bigeminy*, and arrhythmia*, Digestive System: constipation**, flatulence**, dyspepsia**, ileus**, gastrointestinal disorder*, dry mouth*, diarrhea*, and gastrointestinal hemorrhage*, Hemic and Lymphatic System: anemia**, and leukocytosis*, and Metabolic and Nutritional System: hypokalemia**, peripheral edema*, hypomagnesemia*, hypocalcemia*, hyponatremia*, hyperglycemia*, healing abnormal*, hypoglycemia*, hypophosphatemia*, edema*, and dehydration*, Musculoskeletal System: leg cramps* and myalgia*, Nervous System: dizziness**, insomnia**, anxiety**, hypertonia**, somnolence**, confusion*, paresthesia*, hypesthesia*, nervousness*, agitation*, abnormal dreams*, and tremor*, Respiratory System: hypoxia**, pharyngitis**, hypoventilation*, dyspnea*, apnea*, cough increased*, lung disorder*, asthma*, hiccup*, pneumonia*, atelectasis*, upper respiratory tract infection*, rhinitis*, sinusitis*, and hyperventilation*, Skin System: pruritus**, application site reaction (ASR)-itching**, ASR-vesicles**, ASR-edema**, ASR-other**, sweating**, wound site oozing/bleeding**, wound site inflammation/erythema*, rash*, ASR-dry and flaky*, ASR-papules/pustules*, vesiculobullous rash*, ASR-pain*, ASR-burning*, Special Senses: abnormal vision-blurred vision*, and ear pain*, Urogenital System: urinary retention**, urination impaired*, oliguria*, urogenital disorder*, hematuria*, urinary tract infection*, urinary urgency*, and dysuria*.
The level of current (62 microA/cm2) provided by IONSYS™ is generally imperceptible to the patient.
Scheduled observation of the skin approximately 24 hours after system 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 from another study noted a rectangular mark at the application site, which persisted for up to 3 months after study completion.
Drug Abuse And Dependence
IONSYS™ contains fentanyl, a Schedule II controlled substance.
IONSYS™ contains a high concentration of a potent Schedule II controlled opioid agonist, fentanyl. Schedule II opioid substances, which include fentanyl, morphine, oxycodone, oxymorphone, hydromorphone, and methadone, have the highest potential for abuse. These drugs also have a risk of fatal overdose due to respiratory depression. Fentanyl can be abused and is subject to criminal diversion. The high drug content and concentrated formulation of fentanyl in IONSYS™ may be a particular target for abuse and diversion and may add to the risk of adverse outcomes from abuse. After the maximum dosage administration, a significant amount of fentanyl remains in the device.
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.
Tolerance and physical and psychological dependence may develop upon repeated administration of opioids. latrogenic addiction following opioid administration is relatively rare. Physicians should not let concerns of physical dependence deter them from using adequate amounts of opioids in the management of acute post-operative pain when such use is indicated.
(** indicates 1 to < 10%, * indicates between 0.1 to < 1%).
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 other central nervous system depressants, including other opioids, sedatives, hypnotics, general anesthetics, phenothiazines, tranquilizers, skeletal muscle relaxants, sedating antihistamines, or alcoholic beverages, may produce additive depressant effects. Hypoventilation, hypotension, profound sedation, coma, or death may occur. Therefore, use of concomitant CNS depressants requires individual adjustment of dosage of the concomitant medication and observation of a given patient.
Agents Affecting CYP3A4 Isoenzyme System
Fentanyl is metabolized mainly via the cytochrome P450 3A4 enzyme (CYP3A4). Therefore, drug interactions may occur when IONSYS™ is given concurrently with agents that affect CYP3A4 activity. Coadministration with agents that induce CYP3A4 activity, such as rifampin, carbamazepine, phenytoin, and Saint John's Wort may cause increased clearance of fentanyl and reduce the efficacy of IONSYS™. The concomitant use of fentanyl with CYP3A4 inhibitors such as macrolide antibiotics (e.g. erythromycin), azole antifungal agents (e.g. ketoconazole), or protease inhibitors (e.g. ritonavir) may result in a decrease in fentanyl clearance, which could increase or prolong adverse drug effects including serious respiratory depression. In this situation, special patient care and observation are appropriate.
Last reviewed on RxList: 6/12/2012
This monograph has been modified to include the generic and brand name in many instances.
Additional Ionsys Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Chronic Pain/Back Pain
Find tips and advances in treatment.