ZURZUVAE

Posology Treatment should be initiated under the supervision of a specialist prescriber. The recommended dose of zuranolone is 50 mg (two 25 mg capsules) for 14 days as a single course of treatment. 4). Treatment duration beyond 14 days has not been evaluated.

If a patient forgets to take zuranolone, the patient should be instructed to skip the missed dose and take the next dose at their regular time the next day. The patient should not take additional capsules on the same day to make up for the missed dose.

Zuranolone may be used alone or as an adjunct to oral antidepressant therapy. If dose discontinuation is required, treatment may be stopped without down-titration. Special populations Renal impairment The recommended dose in patients with moderate (estimated glomerular filtration rate [eGFR] 30 to 59 mL/min) or severe renal impairment (eGFR < 30 mL/min not requiring dialysis) is 30 mg.

2). Hepatic impairment The recommended dose in patients with severe hepatic impairment (Child-Pugh class C) is 30 mg. 2). 5). g. fluoxetine. 5). Paediatric population The safety and efficacy of zuranolone in postpubertal females less than 18 years old have not been established.

No data are available. There is no relevant use of zuranolone in prepubertal females. 2). Zuranolone capsules are swallowed whole.

1). Adverse drug reactions (ADRs) with onset up to 3 days after treatment discontinuation are reported at the highest frequency from either study. Serious adverse reaction (SAR) in 1 subject was confusional state. 3% in zuranolone-treated subjects.

0%). Most ADRs in subjects receiving zuranolone were mild to moderate in intensity. The most frequently reported (≥ 10% in zuranolone 50 mg and greater than placebo) adverse reactions were somnolence, dizziness, and sedation. Tabulated list of adverse reactions ADRs are presented in the Table 1.

The ADRs are listed by system organ class (SOC) and frequency. Frequency categories were defined according to very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000), and not known (cannot be estimated from the available data).

Table 1. Adverse drug reactions occurring in patients with PND treated with zuranolone System organ class (SOC) Adverse drug reaction Frequency Memory impairment Common Psychiatric disorders Confusional state Common Somnolence1 Very Common Dizziness2 Very Common Sedation Very Common Nervous system disorders Tremor Common Gastrointestinal disorders Diarrhoea Common General disorders and administration site conditions Fatigue3 Common 1 Include the following preferred terms (PTs): somnolence and hypersomnia.

2 Include the following PTs: dizziness and vertigo. 3 Include the following PTs: fatigue and asthenia. Description of selected adverse reactions Somnolence and sedation These ADRs were generally mild to moderate in severity; most appeared within the first two days of treatment, were limited to the on-treatment period, and improved during the treatment course.

Most somnolence and sedation ADRs resolved without intervention. In cases where dose reduction due to these ADRs was needed, most subjects completed the treatment course at the reduced dose. Confusional state Across the two clinical studies, two subjects experienced confusional state.

Impaired ability to drive or engage in potentially hazardous activities Zuranolone impairs the ability to drive due to central nervous system (CNS) depressant effects. Patients should be counselled not to drive or engage in other potentially hazardous activities until at least 12 hours after taking each dose of zuranolone.

7). 8). 5). The zuranolone dose should be reduced to 40 mg or permanently discontinued based on the severity of the adverse reaction and the individual sensitivity of the patient to these effects. 5). Abuse potential and dependence Zuranolone has potential for abuse.

5 mg, 3 mg) on positive subjective measures of “drug liking”, “overall drug liking”, “take drug again”, “high” and “good drug effects”. Zuranolone may produce physical dependence. In a driving simulation study (N=67), healthy subjects who received 50 mg of zuranolone for up to 7 days (on the 7th day subjects received 50 mg or 100 mg) experienced mild or moderate symptoms of possible withdrawal syndrome.

2), has not been evaluated in clinical studies. 3). Caution should be used in individuals with a history of abuse or addiction to alcohol or other substances.

Suicide/suicidal thoughts or clinical worsening:

Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events). This risk persists until significant remission occurs therefore, patients should be closely monitored. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

Patients with a history of suicide-related events or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts and should receive careful monitoring during treatment.

1, • During pregnancy.