Adverse reactions : תופעות לוואי

6. ADVERSE REACTIONS

The following serious adverse reactions are described below and elsewhere in the labeling: • Serious Dermatologic Reactions [see Warnings and Precautions (5.1)] • Drug Reaction with Eosinophilia and System Symptoms (DRESS)/Multiorgan Hypersensitivity [see Warnings and Precautions (5.2)]
• Angioedema and Anaphylaxis Reactions [see Warnings and Precautions (5.3)] • Persistent Sleepiness [see Warnings and Precautions (5.4)]
• Psychiatric Symptoms [see Warnings and Precautions (5.5)]
• Effects on Ability to Drive and Use Machinery [see Warnings and Precautions (5.6)] • Cardiovascular Events [see Warnings and Precautions (5.7)]

6.1 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.


NUVIGIL has been evaluated for safety in over 1,100 patients with excessive sleepiness associated with OSA, SWD, and narcolepsy.

Most Common Adverse Reactions
In the placebo-controlled clinical trials, the most common adverse reactions (≥ 5%) associated with the use of NUVIGIL more frequently than in placebo-treated patients were headache, nausea, dizziness, and insomnia. The adverse reaction profile was similar across the studies.

Table 1 presents the adverse reactions that occurred at a rate of 1% or more and were more frequent in NUVIGIL-treated patients than in placebo-treated patients in the placebo- controlled clinical trials.

Table 1: Adverse Reactions in Pooled Placebo-Controlled Clinical Trials* in OSA, Narcolepsy, and SWD with NUVIGIL (150 mg and 250 mg)
NUVIGIL           Placebo
(%)              (%)
N=645            N=445
Headache                                   17                9
Nausea                                      7                3
Dizziness                                   5                2
Insomnia                                    5                1
Anxiety                                     4                1
Diarrhea                                    4                2
Dry Mouth                                   4                1
Depression                                  2                0
Dyspepsia                                   2                0
Fatigue                                     2                1
Palpitations                                2                1
Rash                                        2                0
Upper Abdominal Pain                        2                1
Agitation                                   1                0
Anorexia                                    1                0
Constipation                                1                0
Contact Dermatitis                          1                0
Decreased Appetite                          1                0
Depressed Mood                              1                0
Disturbance In Attention                    1                0
Dyspnea                                     1                0
Hyperhydrosis                               1                0
Increased Gamma-Glutamyltransferase         1                0
Increased Heart Rate                        1                0
Influenza-Like Illness                      1                0
Loose Stools                                1                0
Migraine                                    1                0
Nervousness                                 1                0
Pain                                        1                0
Paresthesia                                 1                0


                                                        NUVIGIL          Placebo
(%)             (%)
N=645           N=445
Polyuria                                       1                0
Pyrexia                                        1                0
Seasonal Allergy                               1                0
Thirst                                         1                0
Tremor                                         1                0
Vomiting                                       1                0
* Adverse reactions that occurred in > 1% of NUVIGIL-treated patients and greater incidence than that of placebo.

Dose-Dependent Adverse Reactions
In the placebo-controlled clinical trials which compared doses of 150 mg/day and 250 mg/day of NUVIGIL and placebo, the following adverse reactions were dose-related: headache, rash, depression, dry mouth, insomnia, and nausea. See Table 2 for additional information.

Table 2. Dose-Dependent Adverse Reactions in Pooled Placebo-Controlled Clinical Trials in OSA, Narcolepsy and SWD

NUVIGIL      NUVIGIL NUVIGIL
250 mg       150 mg Combined              Placebo
(%)          (%)     (%)                   (%)
N=198        N=447   N=645                N=445

Headache                        23         14            17            9 Nausea                           9          6            7             3 Insomnia                         6          4            5             1 Dry Mouth                        7          2            4             <1 Rash                             4          1            2             <1 Depression                       3          1            2             <1 

Adverse Reactions Resulting in Discontinuation of Treatment
In placebo-controlled clinical trials, 44 of the 645 patients (7%) who received NUVIGIL discontinued due to an adverse reaction compared to 16 of the 445 (4%) of patients that received placebo. The most frequent reason for discontinuation was headache (1%).

Laboratory Abnormalities
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 patients, 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.


6.2 Postmarketing Experience
The following adverse reactions have been identified during post approval use of NUVIGIL.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal Disorders: Mouth Sores (including mouth blistering and ulceration).

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form (https://sideeffects.health.gov.il/)