WARNING: IMPAIRED ABILITY TO DRIVE OR ENGAGE IN OTHER POTENTIALLY HAZARDOUS ACTIVITIES ZURZUVAE causes driving impairment due to central nervous system (CNS) depressant effects [see Warnings and Precautions ( 5.1 , 5.2 )] . Advise patients not to drive or engage in other potentially hazardous activities 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 ZURZUVAE [see Warnings and Precautions ( 5.1 )] . WARNING: IMPAIRED ABILITY TO DRIVE OR ENGAGE IN OTHER POTENTIALLY HAZARDOUS ACTIVITIES See full prescribing information for complete boxed warning. ZURZUVAE causes driving impairment due to central nervous system (CNS) depressant effects. Advise patients not to drive or engage in other potentially hazardous activities until at least 12 hours after administration. Patients may not be able to assess their own driving competence or the degree of impairment caused by ZURZUVAE ( 5.1 , 5.2 ) .
openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 1 · 2 matching rows.
warnings and cautions
5 WARNINGS AND PRECAUTIONS CNS Depressant Effects: ZURZUVAE can cause CNS depressant effects such as somnolence and confusion. If patients develop CNS depression, consider dosage reduction or discontinuation of ZURZUVAE. ( 5.2 ) Suicidal Thoughts and Behavior: Consider changing the therapeutic regimen, including discontinuing ZURZUVAE, in patients whose PPD worsens, or who experience emergent suicidal thoughts and behaviors. ( 5.3 ) Embryo-fetal Toxicity: May cause fetal harm. Advise a pregnant woman of the potential risk to an infant exposed to ZURZUVAE in utero. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during ZURZUVAE treatment and for one week after the final dose. ( 5.4 , 8.1 , 8.2 , 8.3 ) 5.1 Impaired Ability to Drive or Engage in Other Potentially Hazardous Activities ZURZUVAE causes driving impairment due to central nervous system (CNS) depressant effects [see Warnings and Precautions ( 5.2 )] . In two driving simulation studies, the driving ability of healthy adults was impaired in a dose-dependent manner following repeat nighttime administration of 30 mg of ZURZUVAE (0.6 times the recommended dose) for 5 days as well as 50 mg of ZURZUVAE (recommended dose) for 7 days [see Clinical Studies ( 14.2 )] . 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 ZURZUVAE. 5.2 Central Nervous System Depressant Effects ZURZUVAE can cause CNS depressant effects such as somnolence and confusion. In Study 1, 36% of patients who received 50 mg of ZURZUVAE and 6% of patients who received placebo daily developed somnolence. In Study 2, 19% of patients who received another zuranolone capsule formulation (approximately equivalent to 40 mg of ZURZUVAE) and 11% of patients who received placebo daily developed somnolence [see Clinical Studies ( 14 )]. In each clinical study, some ZURZUVAE-treated patients developed confusional state. One of these cases was severe, and was also associated with somnolence, dizziness, and gait disturbance. A higher percentage of ZURZUVAE-treated patients, compared to placebo-treated patients, experienced somnolence, dizziness, or confusion that required dosage reduction, interruption, or discontinuation [see Adverse Reactions ( 6.1 )] . Because ZURZUVAE can cause CNS depressant effects, patients may be at higher risk of falls. 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 patients [see Drug Interactions ( 7 )] . To reduce the risk of CNS depressant effects and/or mitigate CNS depressant effects that occur with ZURZUVAE treatment: If patients develop CNS depressant effects, consider dosage reduction or discontinuation of ZURZUVAE [see Dosage and Administration ( 2.1 )] . If use with another CNS depressant is unavoidable, consider dosage reduction [see Drug Interactions ( 7 )] . Reduce the ZURZUVAE dosage in patients taking strong CYP3A4 inhibitors [see Dosage and Administration ( 2.2 )] . 5.3 Suicidal Thoughts and Behavior 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 24 years of age 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). The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 1 . Table 1. Risk Differences of the Number of Patients with Suicidal Thoughts or Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric * and Adult Patients Age Range (years) Drug-Placebo Difference in Number of Patients with Suicidal Thoughts or Behaviors per 1,000 Patients Treated * ZURZUVAE is not approved in pediatric patients. Increases Compared to Placebo <18 14 additional patients 18-24 5 additional patients Decreases Compared to Placebo 25-64 1 fewer patient 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 behaviors. 5.4 Embryo-fetal Toxicity Based on findings from animal studies, ZURZUVAE may cause fetal harm when administered to a pregnant woman. In rodent studies following exposure during gestation or throughout gestation and lactation, adverse effects on development (fetal malformations, embryofetal and offspring mortality, growth deficits) were observed. In addition, neuronal death was observed in rats exposed to zuranolone during a period of brain development that in humans begins during the third trimester of pregnancy and continues during the first few years after birth [see Use in Specific Populations ( 8.1 , 8.2 )]. 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 1 week after the final dose [see Use in Specific Populations ( 8.1 , 8.3 )].
warnings and cautions table
<table ID="t1" width="100%"><caption>Table 1. Risk Differences of the Number of Patients with Suicidal Thoughts or Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric<sup>*</sup> and Adult Patients </caption><col width="25.900%" align="left"/><col width="74.100%" align="left"/><thead><tr><th align="center" valign="top" styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">Age Range (years)</content></th><th align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">Drug-Placebo Difference in Number of Patients with Suicidal Thoughts or Behaviors per 1,000 Patients Treated</content></th></tr></thead><tfoot><tr><td colspan="2" align="left" valign="top"><paragraph styleCode="footnote"><sup>*</sup>ZURZUVAE is not approved in pediatric patients. </paragraph></td></tr></tfoot><tbody><tr><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"><content styleCode="bold">Increases Compared to Placebo</content></td></tr><tr><td align="center" valign="top" styleCode="Botrule Lrule Rrule"><18 </td><td align="center" valign="top" styleCode="Botrule Rrule">14 additional patients </td></tr><tr><td align="center" valign="top" styleCode="Botrule Lrule Rrule">18-24 </td><td align="center" valign="top" styleCode="Botrule Rrule">5 additional patients </td></tr><tr><td align="center" valign="top" styleCode="Botrule Lrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"><content styleCode="bold">Decreases Compared to Placebo</content></td></tr><tr><td align="center" valign="top" styleCode="Botrule Lrule Rrule">25-64 </td><td align="center" valign="top" styleCode="Botrule Rrule">1 fewer patient </td></tr></tbody></table>
6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Impaired Ability to Drive or Engage in Other Potentially Hazardous Activities [see Warnings and Precautions ( 5.1 )] Central Nervous System Depressant Effects [see Warnings and Precautions ( 5.2 )] Suicidal Thoughts and Behavior [see Warnings and Precautions ( 5.3 )] Most common adverse reactions (incidence ≥5% and greater than placebo) were somnolence, dizziness, diarrhea, fatigue, nasopharyngitis, and urinary tract infection. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Biogen at 1-844-987-9882 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial 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 ZURZUVAE for the treatment of postpartum depression (PPD) was evaluated in two placebo-controlled clinical studies in 347 women with PPD treated with 50 mg of ZURZUVAE (Study 1), or with another zuranolone capsule formulation approximately equivalent to 40 mg of ZURZUVAE (Study 2) once daily for 14 days [see Clinical Studies ( 14.1 )]. The studies included adult patients 18 to 44 years of age diagnosed with PPD. Across PPD clinical studies at all doses studied (Studies 1 and 2), serious adverse reactions included confusional state (1%) [see Clinical Studies ( 14.1 )]. In Study 1, the incidence of adverse reactions that led to discontinuation in patients treated with 50 mg of ZURZUVAE and placebo was 2% and 1%, respectively. The most common adverse reaction leading to treatment discontinuation in ZURZUVAE-treated patients was somnolence. Dosage reduction due to an adverse reaction occurred in 16% of ZURZUVAE-treated patients. The most common adverse reactions leading to dosage reduction in ZURZUVAE-treated patients were somnolence (10%) and dizziness (6%). The most common adverse reactions (≥5% and greater than placebo) in ZURZUVAE-treated patients were somnolence, dizziness, diarrhea, fatigue, and urinary tract infection. Table 2 summarizes the adverse reactions that occurred in ≥2% of patients with PPD treated with 50 mg of ZURZUVAE and at a higher incidence than in patients who received placebo in Study 1. Table 2. Adverse Reactions that Occurred in ≥2% of Patients with PPD Treated with 50 mg of ZURZUVAE and Greater than in Patients Treated with Placebo (Study 1) Adverse Reaction Placebo (N=98) (%) 50 mg of ZURZUVAE (N=98) (%) 1 Somnolence includes sedation and hypersomnia 2 Dizziness includes vertigo 3 Fatigue includes asthenia 4 Abdominal pain includes upper abdominal pain Somnolence 1 6 36 Dizziness 2 9 13 Diarrhea 2 6 Fatigue 3 2 5 Urinary tract infection 4 5 Memory impairment 0 3 Abdominal pain 4 0 3 Tremor 0 2 Hypoesthesia 0 2 Muscle twitching 0 2 Myalgia 0 2 COVID-19 0 2 Anxiety 1 2 Rash 1 2 In Study 2, the incidence of adverse reactions that led to discontinuation in patients who received another zuranolone capsule formulation (approximately equivalent to 40 mg of ZURZUVAE) and placebo was 1% and 0%, respectively. The adverse reaction that led to treatment discontinuation was somnolence. Dosage reduction due to an adverse reaction occurred in 4% of zuranolone-treated patients. The adverse reactions that led to dosage reduction were somnolence and confusional state. The most common (≥5% and greater than placebo) adverse reactions in zuranolone-treated patients were somnolence, nasopharyngitis, dizziness, fatigue, and diarrhea. Table 3 summarizes the adverse reactions that occurred in ≥2% of zuranolone-treated patients with PPD and at a higher incidence than in placebo-treated patients in Study 2. Table 3. Adverse Reactions that Occurred in ≥2% of Patients with PPD Treated with Another Zuranolone Capsule Formulation * and Greater than in Patients Treated with Placebo (Study 2) Adverse Reaction Placebo (N=73) (%) Another Zuranolone Capsule Formulation * (N=78) (%) 1 Somnolence includes sedation 2 Nasopharyngitis includes upper respiratory tract infection 3 Fatigue includes lethargy * This capsule formulation of zuranolone is approximately equivalent to 40 mg of ZURZUVAE. Somnolence 1 11 19 Nasopharyngitis 2 3 9 Dizziness 6 8 Fatigue 3 1 5 Diarrhea 3 5 Dry mouth 0 4 Sinus congestion 0 3 Toothache 0 3