Special Warning : אזהרת שימוש

5 WARNINGS AND PRECAUTIONS

5.1    CNS Depressant Effects and Daytime Impairment
DAYVIGO is a central nervous system (CNS) depressant that can impair daytime wakefulness even when used as prescribed. CNS depressant effects may persist in some patients for up to several days after discontinuing DAYVIGO. Prescribers should advise patients about the potential for next- day somnolence.

Driving ability was impaired in some subjects taking DAYVIGO 10 mg [see Clinical Studies (14.2)].
The risk of daytime impairment is increased if DAYVIGO is taken with less than a full night of sleep remaining or if a higher than recommended dose is taken [see Dosage and Administration (2.1)]. If DAYVIGO is taken in these circumstances, patients should be cautioned against driving and other activities requiring complete mental alertness.

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression, which can cause daytime impairment. Dosage adjustments of DAYVIGO and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of DAYVIGO with other drugs to treat insomnia is not recommended. Patients should be advised not to consume alcohol in combination with DAYVIGO because of additive effects [see Drug Interactions (7.1)].



Because DAYVIGO can cause drowsiness, patients, particularly the elderly, are at a higher risk of falls.

5.2  Sleep Paralysis, Hypnagogic/Hypnopompic Hallucinations, and Cataplexy-like Symptoms

Sleep paralysis, an inability to move or speak for up to several minutes during sleep-wake transitions, and hypnagogic/hypnopompic hallucinations, including vivid and disturbing perceptions, can occur with the use of DAYVIGO. Prescribers should explain the nature of these events to patients when prescribing DAYVIGO.

Symptoms similar to mild cataplexy can occur with DAYVIGO. Such symptoms can include periods of leg weakness lasting from seconds to a few minutes, can occur either at night or during the day, and may not be associated with an identified triggering event (e.g., laughter or surprise).

5.3   Complex Sleep Behaviors

Complex sleep behaviors, including sleep-walking, sleep-driving, and engaging in other activities while not fully awake (e.g., preparing and eating food, making phone calls, having sex), have been reported to occur with the use of hypnotics such as DAYVIGO. These events can occur in hypnotic- naïve as well as in hypnotic-experienced persons. Patients usually do not remember these events.
Complex sleep behaviors may occur following the first or any subsequent use of DAYVIGO, with or without the concomitant use of alcohol and other CNS depressants [see Drug Interactions (7.1)].
Discontinue DAYVIGO immediately if a patient experiences a complex sleep behavior.

5.4   Patients with Compromised Respiratory Function

DAYVIGO has been studied in mild to severe Obstructive Sleep Apnea (OSA) and moderate to severe Chronic Obstructive Pulmonary Disease (COPD) in short-term clinical trials. The effect of DAYVIGO on respiratory function should be considered if prescribed to patients with compromised respiratory function.) [see Use in Specific Populations (8.8)].

5.5   Worsening of Depression/Suicidal Ideation

In clinical studies of DAYVIGO in patients with insomnia, the incidence of suicidal ideation or any suicidal behavior, as assessed by questionnaire, was higher in patients receiving DAYVIGO than in those receiving placebo (0.3% for DAYVIGO 10 mg, 0.4% for DAYVIGO 5 mg, and 0.2% for placebo).

In primarily depressed patients treated with hypnotics, worsening of depression and suicidal thoughts and actions (including completed suicides) have been reported. Suicidal tendencies may be present in such patients and protective measures may be required. Intentional overdose is more common in this group of patients; therefore, the lowest number of tablets that is feasible should be prescribed at any one time.

The emergence of any new behavioral sign or symptom of concern requires careful and immediate evaluation.

5.6   Need to Evaluate for Co-morbid Diagnoses

Because sleep disturbances may be the presenting manifestation of a medical and/or psychiatric disorder, treatment of insomnia should be initiated only after careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Worsening of insomnia or the emergence of new cognitive or behavioral abnormalities may be the result of an unrecognized underlying psychiatric or medical disorder and can emerge during the course of treatment with sleep-promoting drugs such as DAYVIGO.

Lactose

Dayvigo contains lactose, patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

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

Effects on Driving