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“The following serious adverse reactions are described below and elsewhere in the labeling:

  • Serious Rash, including Stevens-Johnson Syndrome [see WARNINGS AND PRECAUTIONS]
  • Angioedema and Anaphylactoid Reactions [see WARNINGS AND PRECAUTIONS]
  • Multi-organ Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
  • Persistent Sleepiness [see WARNINGS AND PRECAUTIONS]
  • Psychiatric Symptoms [see WARNINGS AND PRECAUTIONS]
  • Diagnosis of Sleep Disorders [see WARNINGS AND PRECAUTIONS]
  • CPAP Use in Patients with OSA [see WARNINGS AND PRECAUTIONS]
  • Effects on Ability to Drive and Use Machinery [see WARNINGS AND PRECAUTIONS]
  • Cardiovascular System [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.

OSA, SWD, and Narcolepsy

NUVIGIL has been evaluated for safety in over 1100 patients with excessive sleepiness associated with OSA, SWD, and narcolepsy.

In the pre-approval controlled clinical trials, the most commonly observed adverse events ( ≥ 5%) associated with the use of NUVIGIL occurring more frequently than in the placebo-treated patients were headache, nausea, dizziness, and insomnia. The adverse event profile was similar across the studies.

In the pre-approval controlled clinical trials, 44 of the 645 patients (7%) who received NUVIGIL discontinued due to an adverse experience compared to 16 of the 445 (4%) of patients that received placebo. The most frequent reason for discontinuation was headache (1%).

Incidence in Controlled Trials

The following table (Table 1) presents the adverse experiences that occurred at a rate of 1% or more and were more frequent in patients treated with NUVIGIL than in placebo group patients in the pre-approval controlled clinical trials.

The prescriber should be aware that the figures provided below cannot be used to predict the frequency of adverse experiences in the course of usual medical practice, where patient characteristics and other factors may differ from those occurring during clinical studies. Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigations involving different treatments, uses, or investigators. Review of these frequencies, however, provides prescribers with a basis to estimate the relative contribution of drug and non-drug factors to the incidence of adverse events in the population studied.

Table 1: Incidence 1% or Greater Of Treatment-Emergent Adverse Experiences In Parallel-Group, Placebo-Controlled Clinical Trials* In OSA, Narcolepsy and SWD With NUVIGIL (150 mg and 250 mg)

System Organ Class MedDRA preferred term NUVIGIL
(%)
N=645
Placebo
(%)
N=445
Cardiac Disorders
  Palpitations 2 1
Gastrointestinal Disorders
  Nausea 7 3
  Diarrhea 4 2
  Dry Mouth 4 1
  Dyspepsia 2 0
  Abdominal Pain Upper 2 1
  Constipation 1 0
  Vomiting 1 0
  Loose Stools 1 0
General Disorders And Administration Site Conditions
  Fatigue 2 1
  Thirst 1 0
  Influenza-Like Illness 1 0
  Pain 1 0
  Pyrexia 1 0
Immune System Disorders
  Seasonal Allergy 1 0
Investigations
  Gamma-Glutamyltransferase Increased 1 0
  Heart Rate Increased 1 0
Metabolism And Nutrition Disorders
  Anorexia 1 0
  Decreased Appetite 1 0
Nervous System Disorders
  Headache 17 9
  Dizziness 5 2
  Disturbance In Attention 1 0
  Tremor 1 0
  Migraine 1 0
  Paresthesia 1 0
Psychiatric Disorders
  Insomnia 5 1
  Anxiety 4 1
  Depression    2 0
  Agitation 1 0
  Nervousness    1 0
  Depressed Mood 1 0
Renal And Urinary Disorders
  Polyuria 1 0
Respiratory, Thoracic And Mediastinal Disorders  
  Dyspnea 1 0
Skin And Subcutaneous Tissue Disorders
  Rash 2 0
  Contact Dermatitis 1 0
  Hyperhydrosis 1 0
* Four double-blind, placebo-controlled clinical studies in SWD, OSA, and narcolepsy; incidence is rounded to the nearest whole percent. Included are only those events for which NUVIGIL incidence is greater than that of placebo.

Dose Dependency of Adverse Events

In the pre-approval controlled clinical trials which compared doses of 150 mg/day and 250 mg/day of NUVIGIL and placebo, the only adverse events that appeared to be dose-related were headache, rash, depression, dry mouth, insomnia, and nausea. See Table 2 for additional information.

Table 2: Incidence Of Dose-Dependent, Treatment-Emergent Adverse Experiences By Dose and By Treatment In Parallel-Group, Placebo-Controlled Clinical Trials* In OSA, Narcolepsy and SWD With NUVIGIL (150 mg and 250 mg)

System Organ Class MedDRA preferred term NUVIGIL 250 mg
(%)
N=198
NUVIGIL 150 mg
(%)
N=447
NUVIGIL Combined
(%)
N=645
Placebo
(%)
N=445
Gastrointestinal Disorders
  Nausea 9 6 7 3
  Dry Mouth 7 2 4 < 1
Nervous System Disorders
  Headache 23 14 17 9
Psychiatric Disorders
  Insomnia 6 4 5 1
  Depression 3 1 2 < 1
Skin And Subcutaneous Tissue Disorders
  Rash 4 1 2 < 1
* Four double-blind, placebo-controlled clinical studies in SWD, OSA, and narcolepsy.

Laboratory Changes

Clinical chemistry, hematology, and urinalysis parameters were monitored in the studies. Mean plasma levels of gamma glutamyltransferase (GGT) and alkaline phosphatase (AP) were found to be higher following administration of NUVIGIL, but not placebo. Few subjects, however, had GGT or AP elevations outside of the normal range. No differences were apparent in alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, or total bilirubin, although there were rare cases of isolated elevations of AST and/or ALT. A single case of mild pancytopenia was observed after 35 days of treatment and resolved with drug discontinuation. A small mean decrease from baseline in serum uric acid compared to placebo was seen in clinical trials. The clinical significance of this finding is unknown.

Vital Sign Changes

Blood pressure monitoring in pre-approval controlled trials of OSA, SWD, and narcolepsy showed small average increases in mean systolic and diastolic blood pressure in patients receiving NUVIGIL as compared to placebo (1.2 to 4.3 mmHg in the various experimental groups). There was also a slightly greater proportion of patients on NUVIGIL requiring new or increased use of antihypertensive medications (2.9%) compared to patients on placebo (1.8%). There was a small, but consistent, average increase in pulse rate over placebo in pre-approval controlled trials. This increase varied from 0.9 to 3.5 BPM. [see WARNINGS AND PRECAUTIONS]