ZUSDURI

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZUSDURI (ZUSDURI).

How it works

ZUSDURI is a small molecule inhibitor of Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2), reducing signaling of pro-inflammatory cytokines.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ZUSDURI (ZUSDURI).

Breastfeeding	Unknown if excreted in human breast milk. M/P ratio not available. Due to potential for serious adverse reactions in nursing infants, breast-feeding is not recommended during ZUSDURI therapy and for at least 2 weeks after last dose.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

Known hypersensitivity to ZUSDURI or any excipient; active serious infections, including tuberculosis; severe hepatic impairment.

Clinical Precautions

Precautions

Serious infections; tuberculosis; viral reactivation; malignancy; thrombosis; gastrointestinal perforation; laboratory abnormalities (neutropenia, lymphopenia, anemia, elevated liver enzymes, lipid elevations); hypersensitivity reactions; vaccination avoidance.

Clinical Tips & Counseling

Drug interactions

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ZUSDURI

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZUSDURI (ZUSDURI).

How it works

ZUSDURI is a small molecule inhibitor of Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2), reducing signaling of pro-inflammatory cytokines.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ZUSDURI (ZUSDURI).

Breastfeeding	Unknown if excreted in human breast milk. M/P ratio not available. Due to potential for serious adverse reactions in nursing infants, breast-feeding is not recommended during ZUSDURI therapy and for at least 2 weeks after last dose.
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.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

Known hypersensitivity to ZUSDURI or any excipient; active serious infections, including tuberculosis; severe hepatic impairment.