ADVERSE REACTIONS
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 Study Medication |
* NOTE: Patients reported as having “Nausea and vomiting” are included in “Nausea” and “Vomiting” in Table 5.
|
| Adverse Event | IONSYS™
(n=475) | Placebo
(n=316) |
| Body as a Whole |
| Headache | 9% | 7 % |
| Fever | 9% | 10 % |
| Back Pain | 2% | 3 % |
| Cardiovascular |
| Hypotension | 2% | <1 % |
| Digestive * |
| Nausea | 39 % | 22 % |
| Vomiting | 12 % | 6 % |
| Hemic and Lymphatic |
| Anemia | 3 % | <1 % |
| Nervous system |
| Insomnia | 3 % | 5 % |
| Dizziness | 3 % | 1 % |
| Skin system |
| Application site reaction- Erythema | 14% | 2% |
| Pruritus | 6% | <1% |
| Urogenital |
| Urinary retention | 3% | <1% |
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:
(** indicates 1 to <10%, * indicates between 0.1 to <1%).
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.
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