SIDE EFFECTS

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 activecontrolled 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 Events* 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

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.

Post-marketing Experience

The following additional adverse reactions have been identified during post-approval use of NUCYNTA®. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably.

Gastrointestinal disorders: diarrhea

Immune system disorders: angioedema

Nervous system disorders: headache

Psychiatric disorders: hallucination

Cardiac disorders: palpitations

Read the entire FDA prescribing information for Nucynta (Tapentadol Immediate-Release Oral Tablets) »