Adverse reactions : תופעות לוואי

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are discussed in detail in other sections of the labeling:

•   CNS Depressant Effects and Daytime Impairment [see Warnings and Precautions (5.1)] 
•   Sleep Paralysis, Hypnagogic/Hypnopompic Hallucinations, and Cataplexy-like Symptoms [see Warnings and Precautions (5.2)]

•   Complex Sleep Behaviors [see Warnings and Precautions (5.3)]

•   Patients with Compromised Respiratory Function [see Warnings and Precautions (5.4)] 
•   Worsening of Depression/Suicidal Ideation [see Warnings and Precautions (5.5)] 

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.

The safety of DAYVIGO was evaluated in 1418 adult patients with insomnia disorder (age 18 to 88 years) from two controlled efficacy trials (Study 1 and Study 2). Study 1 was a 6-month placebo- controlled trial assessing DAYVIGO 5 or 10 mg once nightly, followed by a 6-month parallel-group extension period in which patients initially treated with DAYVIGO continued on the same dose, and patients who received placebo were re-randomized to receive DAYVIGO 5 or 10 mg once nightly. In Study 1, 434 patients were treated with DAYVIGO for one year. Study 2 was a 30-day placebo- and active-controlled trial assessing DAYVIGO 5 or 10 mg once nightly.

Adverse Reactions Resulting in Discontinuation of Treatment

The frequencies of discontinuation due to adverse reactions in Study 1 (the first 30 days) and Study 2 were 2.6% and 1.4% for patients treated with 10 mg and 5 mg DAYVIGO, respectively, compared to 1.5% for patients in the placebo group. The most common adverse reactions leading to discontinuation of DAYVIGO were somnolence (1.0% for 10 mg, 0.7% for 5 mg, and 0.4% for placebo) and nightmares (0.3% for 10 mg, 0.3% for 5 mg, and 0% for placebo).

The frequencies of discontinuation due to adverse reactions in the 6-month placebo-controlled period of Study 1 were 8.3% and 4.1% for patients treated with DAYVIGO 10 mg and 5 mg, respectively, compared to 3.8% for patients in the placebo group. The most common reasons for discontinuation of DAYVIGO and occurring in more than one patient within a treatment arm were somnolence (2.9% for 10 mg, 1.0% for 5 mg, and 0.6% for placebo), nightmares (1.3% for 10 mg, 0.3% for 5 mg, and 0% for placebo), and palpitations (0.6% for 10 mg, 0% for 5 mg, and 0% for placebo).

Most Common Adverse Reactions

The most common adverse reaction (reported in 5% or more of patients treated with DAYVIGO and at least twice the rate of placebo) in Study 1 (the first 30 days) and Study 2 was somnolence (10% for DAYVIGO 10 mg, 7% for DAYVIGO 5 mg, and 1% for placebo).

Table 1 presents the adverse reactions based on the pooled data from the first 30 days of Study 1 (6-month controlled efficacy trial) and Study 2 (1-month controlled efficacy trial) where the incidence was ≥2% in DAYVIGO-treated patients and greater than in placebo-treated patients.


Table 1: Adverse Reactions Reported in ≥2% of DAYVIGO-Treated Patients and at a Greater Frequency than Placebo-Treated Patients During the First 30 Days of Study 1 and Study 2

DAYVIGO
Placebo            5 mg                  10 mg n=528            n=580                 n=582
(%)              (%)                   (%)
Somnolence or fatigue *                             1.3              6.9                   9.6 Headache                                            3.4              5.9                   4.5 Nightmare or abnormal dreams                        0.9              0.9                   2.2 *Combines preferred terms somnolence, lethargy, fatigue, sluggishness 

Other Adverse Reactions Observed During Clinical Trials (Studies 1 and 2) 
Other adverse reactions of <2% incidence but greater than placebo are shown below. The following list does not include adverse reactions 1) for which a drug cause was remote, 2) that were so general to be uninformative, or 3) that were not considered to have clinically significant implications.

•   Sleep paralysis was reported in 1.6% and 1.3% of patients receiving DAYVIGO 10 mg and 5 mg, respectively, compared to no reports for placebo. Hypnagogic hallucinations were reported in 0.7% and 0.1% of patients receiving DAYVIGO 10 mg and 5 mg, respectively, compared to no reports for placebo [see Warnings and Precautions (5.2)].

Two events of complex sleep behavior were reported, both in patients receiving DAYVIGO 10 mg [see Warnings and Precautions (5.3)].

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization 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