ZURZUVAE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZURZUVAE (ZURZUVAE).
Zurzuvae (zuranolone) is a neuroactive steroid that acts as a positive allosteric modulator of GABA-A receptors, enhancing the inhibitory effects of GABA in the central nervous system.
| Metabolism | Primarily metabolized by CYP3A4, and to a lesser extent by CYP2C19 and CYP2D6. |
| Excretion | Zuranolone is primarily eliminated via hepatic metabolism, with negligible renal excretion. Approximately 90% of a radiolabeled dose is recovered in feces (as metabolites), and less than 1% in urine as unchanged drug. |
| Half-life | The terminal elimination half-life is approximately 16–23 hours in healthy subjects, supporting once-daily dosing. The half-life may be prolonged in patients with hepatic impairment. |
| Protein binding | Zuranolone is highly protein bound (>99%), primarily to albumin, with minor binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | The apparent volume of distribution is approximately 1.1–1.7 L/kg, suggesting extensive distribution into tissues, including the central nervous system. |
| Bioavailability | The absolute oral bioavailability is approximately 50%, due to first-pass metabolism. Food does not significantly affect bioavailability. |
| Onset of Action | Following oral administration, clinical effect (improvement in depressive symptoms) is observed as early as Day 3 of treatment, with peak plasma concentrations achieved around 1–2 hours post-dose. |
| Duration of Action | The therapeutic effect following a 14-day course of zuranolone persists beyond the dosing period, with symptom improvement maintained for up to several weeks post-treatment. The duration of action is supported by sustained plasma levels above therapeutically relevant thresholds. |
50 mg orally once daily at bedtime, with or without food, for 14 days.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not recommended for severe renal impairment (eGFR <30 mL/min/1.73m²). |
| Liver impairment | Child-Pugh A (mild): no adjustment. Child-Pugh B (moderate): reduce dose to 25 mg once daily. Child-Pugh C (severe): not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). |
| Geriatric use | No specific dose adjustment recommended; clinical trials included patients ≥65 years, but experience limited. Monitor for adverse reactions. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZURZUVAE (ZURZUVAE).
| Breastfeeding | Present in breast milk in rats; human data unavailable. M/P ratio unknown. Consider developmental benefits of breastfeeding versus potential for infant exposure. |
| Teratogenic Risk | Insufficient human data; animal studies show no teratogenic effects at clinically relevant doses. First trimester: theoretical risk, no observed increase in malformations. Second/third trimester: no adverse fetal effects reported. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Concomitant use with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin).","Hypersensitivity to zuranolone or any excipients."]
| Precautions | ["Somnolence/sedation: May impair driving or operating machinery; avoid driving within 12 hours of administration.","Suicidal thoughts and behaviors: Monitor for worsening depression or suicidality.","Dosage adjustment required with moderate or strong CYP3A4 inhibitors."] |
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| Monitor maternal mood, suicidality, and sedation. Fetal monitoring not routinely required; assess if maternal toxicity occurs. |
| Fertility Effects | No human data; animal studies show no impairment of fertility at therapeutic doses. |