ADVERSE REACTIONS
The following treatment-emergent adverse events are discussed in more detail in other sections of the labeling:
- Respiratory Depression [see Contraindications and Warnings and Precautions]
- CNS Depression [see Warnings and Precautions]
Because clinical studies are conducted under widely varying conditions, adverse event rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. A treatment-emergent adverse event refers to any untoward medical event associated with the use of the drug in humans, whether or not considered drug-related.
Based on data from nine Phase 2/3 studies that administered multiple doses (seven placebo- and/or active-controlled, one noncontrolled and one Phase 3 active-controlled safety study) the most common adverse events (reported by ≥10% in any NUCYNTA™ dose group) were: nausea, dizziness, vomiting and somnolence.
The most common reasons for discontinuation due to adverse events in the studies described above (reported by ≥1% in any NUCYNTA™ dose group) were dizziness (2.6% vs. 0.5%), nausea (2.3% vs. 0.6%), vomiting (1.4% vs. 0.2%), somnolence (1.3% vs. 0.2%) and headache (0.9% vs. 0.2%) for NUCYNTA™- and placebo-treated patients, respectively.
Seventy-six percent of NUCYNTA™-treated patients from the nine studies experienced adverse events.
NUCYNTA™ was studied in multiple-dose, active- or placebo-controlled studies, or noncontrolled studies (n = 2178), in single-dose studies (n = 870), in open-label study extension (n = 483) and in Phase 1 studies (n = 597). Of these, 2034 patients were treated with doses of 50 mg to 100 mg of NUCYNTA™ dosed every 4 to 6 hours.
The data described below reflect exposure to NUCYNTA™ in 3161 patients, including 449 exposed for 45 days. NUCYNTA™ was studied primarily in placebo- and active-controlled studies (n = 2266, and n = 2944, respectively). The population was 18 to 85 years old (mean age 46 years), 68% were female, 75% white and 67% were postoperative. Most patients received NUCYNTA™ doses of 50 mg, 75 mg, or 100 mg every 4 to 6 hours.
Commonly-Observed Treatment-Emergent Adverse Events in Double-Blind Controlled Clinical Trials
Table 1 lists the adverse events reported in ≥1% or more of NUCYNTA™-treated patients with acute moderate to severe pain in the pooled safety data from nine Phase 2/3 studies that administered multiple doses (seven placebo- and/or active-controlled, one noncontrolled, and one Phase 3 active-controlled safety study).
Table 1 Treatment-Emergent Adverse EventsA treatment-emergent adverse event refers to any untoward medical event associated with the use of the drug in humans, whether or not considered drug-related. Reported by ≥1% of NUCYNTA™-Treated Patients In Seven Phase 2/3 Placebo- and/or Oxycodone-Controlled, One Noncontrolled, and One Phase 3 Oxycodone-Controlled Safety, Multiple-Dose Clinical Studies
System/Organ Class
MedDRA Preferred Term |
NUCYNTA™
21 mg — 120 mg
(n=2178)
% |
Placebo
(n=619)
% |
| Gastrointestinal disorders |
|
|
| Nausea |
30 |
13 |
| Vomiting |
18 |
4 |
| Constipation |
8 |
3 |
| Dry mouth |
4 |
<1 |
| Dyspepsia |
2 |
<1 |
| General disorders and administration site conditions |
|
|
| Fatigue |
3 |
<1 |
| Feeling hot |
1 |
<1 |
| Infections and infestations |
|
|
| Nasopharyngitis |
1 |
<1 |
| Upper respiratory tract infection |
1 |
<1 |
| Urinary tract infection |
1 |
<1 |
| Metabolism and nutrition disorders |
|
|
| Decreased appetite |
2 |
0 |
| Musculoskeletal and connective tissue disorders |
|
|
| Arthralgia |
1 |
<1 |
| Nervous system disorders |
|
|
| Dizziness |
24 |
8 |
| Somnolence |
15 |
3 |
| Tremor |
1 |
<1 |
| Lethargy |
1 |
<1 |
| Psychiatric disorders |
|
|
| Insomnia |
2 |
<1 |
| Confusional state |
1 |
0 |
| Abnormal dreams |
1 |
<1 |
| Anxiety |
1 |
<1 |
| Skin and subcutaneous tissue disorders |
|
|
| Pruritus |
5 |
1 |
| Hyperhidrosis |
3 |
<1 |
| Pruritus generalized |
3 |
<1 |
| Rash |
1 |
<1 |
| Vascular disorders |
|
|
| Hot flush |
1 |
<1 |
Other Adverse Reactions Observed During the Premarketing Evaluation of NUCYNTA™
The following adverse drug reactions occurred in <1% of NUCYNTA™-treated patients in the pooled safety data from nine Phase 2/3 studies that administered multiple doses (seven were placebo- and/or active-controlled, one noncontrolled, and one Phase 3 active-controlled safety study):
Cardiac disorders: heart rate increased, heart rate decreased
Eye disorders: visual disturbance
Gastrointestinal disorders: abdominal discomfort, impaired gastric emptying
General disorders and administration site conditions: irritability, edema, drug withdrawal syndrome, feeling drunk
Immune system disorders: hypersensitivity
Investigations: gamma-glutamyltransferase increased, alanine aminotransferase increased, aspartate aminotransferase increased
Musculoskeletal and connective tissue disorders: involuntary muscle contractions, sensation of heaviness
Nervous system disorders: hypoesthesia, paresthesia, disturbance in attention, sedation, dysarthria, depressed level of consciousness, memory impairment, ataxia, presyncope, syncope, coordination abnormal, seizure
Psychiatric disorders: euphoric mood, disorientation, restlessness, agitation, nervousness, thinking abnormal
Renal and urinary disorders: urinary hesitation, pollakiuria
Respiratory, thoracic and mediastinal disorders: oxygen saturation decreased, cough, dyspnea, respiratory depression
Skin and subcutaneous tissue disorders: urticaria
Vascular disorders: blood pressure decreased
In the pooled safety data, the overall incidence of adverse reactions increased with increased dose of NUCYNTA™, as did the percentage of patients with adverse reactions of nausea, dizziness, vomiting, somnolence, and pruritus.
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