ZURZUVAE safety and
tolerability

• ZURZUVAE causes driving impairment due to central nervous system (CNS) depressant effects¹

• Advise patients not to drive a motor vehicle or engage in other potentially hazardous activities requiring complete mental alertness, such as operating machinery, until at least 12 hours after ZURZUVAE administration for the duration of the 14-day treatment course. Inform patients that they may not be able to assess their own driving competence or the degree of driving impairment caused by ZURZUVAE¹

• ZURZUVAE can cause CNS depressant effects such as somnolence and confusion¹

• Somnolence developed in 36% of patients who received ZURZUVAE (50 mg) and in 6% of patients who received placebo daily. Some ZURZUVAE-treated patients developed confusional state. One of these cases was severe, and was also associated with somnolence, dizziness, and gait disturbance¹

• A higher percentage of ZURZUVAE-treated patients, compared to placebo-treated patients, experienced somnolence, dizziness, or confusion that required dosage reduction, interruption, or discontinuation¹

• Because ZURZUVAE can cause CNS depressant effects, patients may be at higher risk of falls¹

• Other CNS depressants such as alcohol, benzodiazepines, opioids, tricyclic antidepressants, or drugs that increase zuranolone concentration, may increase impairment of psychomotor performance or CNS depressant effects such as somnolence, cognitive impairment, and the risk of respiratory depression in ZURZUVAE-treated patients¹

• To reduce the risk of CNS depressant effects and/or mitigate CNS depressant effects that occurs with ZURZUVAE treatment:
  • If patients develop CNS depressant effects, consider dosage reduction or discontinuation of ZURZUVAE¹
  • If use with another CNS depressant is unavoidable, consider dosage reduction¹
  • Reduce the ZURZUVAE dosage in patients taking strong CYP3A4 inhibitors¹

• In pooled analyses of placebo-controlled trials of chronically administered antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with major depressive disorder (MDD)¹

• ZURZUVAE does not directly affect monoaminergic systems. Consider changing the therapeutic regimen, including discontinuing ZURZUVAE, in patients whose depression becomes worse or who experience emergent suicidal thoughts and behaviors¹

• Based on findings from animal studies, ZURZUVAE may cause fetal harm when administered to a pregnant woman¹

• Advise a pregnant woman of the potential risk to an infant exposed to ZURZUVAE in utero. Advise females of reproductive potential to use effective contraception during treatment with ZURZUVAE and for one week after the final dose¹

In a study of another capsule formulation ≈40 mg, the most common adverse reactions (≥5% and greater than placebo) in ZURZUVAE-treated patients were somnolence, nasopharyngitis, dizziness, fatigue, and diarrhea¹

Across PPD clinical studies at all doses studied, serious adverse reactions included confusional state (1%)¹

A higher percentage of patients treated with ZURZUVAE 50 mg vs placebo experienced somnolence, dizziness, or confusion that required dosage reduction, interruption, or discontinuation¹

For additional information, read the entire Warnings and Precautions on Central Nervous System Depressant Effects in Section 5.2 of the
Prescribing Information.

• Individuals with a history of drug abuse or substance use disorders may be at a greater risk of these outcomes with ZURZUVAE¹

• ZURZUVAE demonstrated dose-dependent abuse potential comparable to alprazolam and greater abuse potential vs placebo on positive subjective measures of “drug liking,” “overall drug liking,” “take drug again,” “high,” and “good drug effects”^1||

• Dose-dependent, abuse-related adverse reactions, including euphoric mood, feeling drunk, and somnolence, were reported with ZURZUVAE^1||

• Adverse reactions reported upon discontinuation of ZURZUVAE in healthy subjects who received 50 mg of ZURZUVAE for 5 to 7 days (on the 7th day subjects received 50 mg or 100 mg) included: insomnia, palpitations, decreased appetite, nightmare, nausea, hyperhidrosis, and paranoia. These adverse reactions were mild-to-moderate in severity¹