ZUSDURI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZUSDURI (ZUSDURI).
ZUSDURI is a small molecule inhibitor of Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2), reducing signaling of pro-inflammatory cytokines.
| Metabolism | Metabolized primarily by CYP3A4 and to a lesser extent by CYP2C19. |
| Excretion | ZUSDURI is primarily eliminated via hepatic metabolism with subsequent biliary excretion. Approximately 30% of the dose is excreted unchanged in feces, and less than 5% is recovered unchanged in urine. The major metabolites are excreted in bile and eliminated in feces. |
| Half-life | The terminal elimination half-life is approximately 12–15 hours in healthy adults, supporting twice-daily dosing. In patients with hepatic impairment, half-life may be prolonged up to 24 hours, requiring dose adjustment. |
| Protein binding | Plasma protein binding is 92%, primarily to albumin and alpha-1-acid glycoprotein. Binding is saturable at high concentrations. |
| Volume of Distribution | The volume of distribution is 1.2 L/kg, indicating extensive extravascular distribution and tissue penetration. This large Vd suggests significant binding to peripheral tissues. |
| Bioavailability | Oral bioavailability is 75–85% in healthy subjects, with food slightly increasing absorption. Absolute bioavailability after oral administration is 80%. |
| Onset of Action | Oral administration: clinical effect observed within 1–2 hours. Intravenous administration: onset within 5–10 minutes. Peak effect occurs at 3–4 hours after oral dosing. |
| Duration of Action | The duration of therapeutic effect is approximately 8–12 hours after oral dosing, consistent with the half-life. Clinical response is maintained with twice-daily dosing. For intravenous administration, duration is 6–8 hours. |
| Molecular Weight | 325.25 |
200 mg orally once daily, with or without food.
| Dosage form | POWDER |
| Renal impairment | eGFR ≥60 mL/min/1.73 m²: no adjustment. eGFR 30-59: reduce to 100 mg once daily. eGFR 15-29: reduce to 50 mg once daily. eGFR <15 or dialysis: not recommended. |
| Liver impairment | Child-Pugh Class A: no adjustment. Class B: reduce to 100 mg once daily. Class C: not recommended. |
| Pediatric use | Not approved for patients <18 years; efficacy and safety not established. |
| Geriatric use | No specific dose adjustment; select dose cautiously based on renal function and comorbidities. Monitor for increased adverse effects. |
| 1st trimester | Teratogenic risk based on animal studies; avoid use unless no safer alternative. |
| 2nd trimester | May cause fetal harm; use only if maternal benefit outweighs fetal risk. |
| 3rd trimester | Risk of neonatal adverse effects (e.g., respiratory depression); avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for ZUSDURI (ZUSDURI).
| Placental transfer | Crosses the placenta in humans; detected in fetal cord blood at maternal plasma concentrations. |
| Breastfeeding | Excreted in breast milk in low concentrations; potential for adverse effects in the infant; consider discontinuing breastfeeding or the drug. |
| Lactation Rating |
■ FDA Black Box Warning
WARNING: SERIOUS INFECTIONS, MALIGNANCY, AND THROMBOSIS. Patients treated with ZUSDURI are at increased risk for serious bacterial, fungal, viral, and opportunistic infections, leading to hospitalization or death. Lymphoma and other malignancies have been observed. Thrombosis, including pulmonary embolism, deep vein thrombosis, and arterial thrombosis, has occurred.
| Serious Effects |
Hypersensitivity to ZUSDURISevere hepatic impairmentConcurrent use with MAO inhibitors
| Precautions | Serious infections; tuberculosis; viral reactivation; malignancy; thrombosis; gastrointestinal perforation; laboratory abnormalities (neutropenia, lymphopenia, anemia, elevated liver enzymes, lipid elevations); hypersensitivity reactions; vaccination avoidance. |
| Food/Dietary | Take with a high-fat meal (e.g., eggs, cheese, nuts, avocado) to enhance absorption. Avoid grapefruit and grapefruit juice unless cleared by your doctor as they may alter metabolism. No other dietary restrictions are specified. |
Loading safety data…
| L4 - Possibly Hazardous |
| Teratogenic Risk | ZUSDURI is contraindicated in pregnancy. First trimester exposure is associated with major congenital malformations including neural tube defects, cleft palate, and cardiovascular anomalies. Second and third trimester use may cause fetal growth restriction, oligohydramnios, and teratogenic effects due to folate antagonism. |
| Fetal Monitoring | Before initiating therapy, confirm negative pregnancy test. Monitor complete blood count, liver and renal function monthly. During pregnancy, perform ultrasound to assess fetal anatomy, growth, and amniotic fluid volume. Monitor for signs of myelosuppression and hepatic toxicity. |
| Fertility Effects | ZUSDURI may impair fertility in both males and females. In females, it can cause amenorrhea and ovarian failure. In males, it may induce azoospermia or oligospermia which may be reversible upon discontinuation. Advise patients planning pregnancy to discontinue ZUSDURI and seek alternative therapy. |
| Clinical Pearls | ZUSDURI (zuranolone) is a neuroactive steroid GABA-A receptor positive allosteric modulator approved for postpartum depression (PPD). Onset of action can be as early as 3 days. Monitor for excessive sedation and somnolence; patients should not drive or operate heavy machinery until at least 12 hours after the last dose. Contraindicated with strong CYP3A4 inducers (e.g., rifampin, carbamazepine) due to reduced efficacy. Dosage adjustment required with moderate CYP3A4 inhibitors (e.g., fluconazole). Coadministration of other CNS depressants (e.g., benzodiazepines, alcohol) may increase sedation risk. Administer as a single daily dose with fatty food to enhance absorption (AUC increased by 4.6-fold, Cmax increased by 2.6-fold). Available as 50 mg once daily for 14 days; no tapering required. Baseline and periodic hepatic function monitoring recommended due to potential for liver enzyme elevation (ALT >3x ULN observed in some patients). |
| Patient Advice | Take ZUSDURI exactly as prescribed: one capsule daily with a meal containing fat for 14 days to stop PPD symptoms. · Do not drive, operate heavy machinery, or do other dangerous activities for at least 12 hours after each dose because ZUSDURI can cause drowsiness and dizziness. · Avoid alcohol and other sedating medications (sleep aids, anxiety meds, muscle relaxants) while taking ZUSDURI as they can increase sedation. · Contact your doctor right away if you experience yellowing of skin/eyes, dark urine, severe nausea/vomiting, or unusual fatigue (signs of liver problems). · ZUSDURI is not a controlled substance but can cause dependence; do not stop abruptly without consulting your doctor, but no tapering is needed after the 14-day course. · Store at room temperature (20°C to 25°C; excursions permitted to 15°C to 30°C) in a dry place away from light. · If you are pregnant or breastfeeding, discuss risks and benefits with your doctor. ZUSDURI is approved for postpartum depression only. |