TZ-3

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TZ-3 (TZ-3).

How it works

(S)-3-(4-(2-((3-fluorophenyl)amino)-2-oxoethyl)piperazin-1-yl)-N,N-dimethylpropanamide; selectively inhibits the interaction between the PD-1/PD-L1 immune checkpoint, blocking the PD-1/PD-L1 pathway and restoring antitumor T-cell function.

What the body does with it

Metabolism	Metabolized primarily by CYP3A4 and CYP2D6; minor contributions from CYP1A2 and CYP2C9.
Excretion	Primarily renal (60–70% unchanged), with 20–30% biliary/fecal, and <10% metabolized. Dosage adjustment required in renal impairment.
Half-life	12–18 hours (terminal). Steady-state achieved in ~3 days. Extended to ~30 hours in severe renal impairment.
Protein binding	98% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	0.2–0.3 L/kg, indicating limited extravascular distribution (primarily intravascular).
Bioavailability	Oral: 85–90%; IM: 100%; IV: 100%.
Onset of Action	Oral: 30–60 minutes; IV: immediate; IM: 15–30 minutes.
Duration of Action	Oral: 6–8 hours; IV: 4–6 hours; IM: 4–6 hours. May require dose adjustment in hepatic impairment.

Classification & Brands

Dosing & administration

100 mg orally twice daily

Dosage form	CREAM
Renal impairment	GFR 30-59 mL/min: 100 mg once daily; GFR 15-29 mL/min: 100 mg every 48 hours; GFR <15 mL/min: not recommended
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose to 50 mg twice daily; Child-Pugh C: not recommended
Pediatric use	2 mg/kg/dose orally twice daily; maximum 100 mg per dose
Geriatric use	Reduce initial dose to 50 mg twice daily; monitor renal function and adjust accordingly

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for TZ-3 (TZ-3).

Breastfeeding	Excreted into breast milk with milk-to-plasma ratio of 0.8. Oral bioavailability in infants is low (~15%). Use with caution; monitor infant for drowsiness, poor feeding, and lethargy.
Teratogenic Risk	First trimester: Limited human data, animal studies show increased risk of neural tube defects and cardiac malformations at therapeutic doses. Second trimester: Associated with fetal growth restriction and oligohydramnios with prolonged use. Third trimester: Risk of premature closure of ductus arteriosus and persistent pulmonary hypertension of the newborn.

Warnings & precautions

■ FDA Black Box Warning

Immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis, can be severe or fatal. Monitor for signs and symptoms; withhold or permanently discontinue based on severity.

Side Effect Profile

Serious Effects

Absolute Contraindications

Severe hypersensitivity to (S)-3-(4-(2-((3-fluorophenyl)amino)-2-oxoethyl)piperazin-1-yl)-N,N-dimethylpropanamide or any excipients; active autoimmune disease requiring systemic immunosuppressive treatment; history of severe immune-mediated adverse reactions to other PD-1/PD-L1 inhibitors.

Clinical Precautions

Precautions

Immune-mediated adverse reactions (pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, myocarditis); infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation; embryofetal toxicity.

Clinical Tips & Counseling

Drug interactions

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TZ-3

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TZ-3 (TZ-3).

How it works

What the body does with it

Metabolism	Metabolized primarily by CYP3A4 and CYP2D6; minor contributions from CYP1A2 and CYP2C9.
Excretion	Primarily renal (60–70% unchanged), with 20–30% biliary/fecal, and <10% metabolized. Dosage adjustment required in renal impairment.
Half-life	12–18 hours (terminal). Steady-state achieved in ~3 days. Extended to ~30 hours in severe renal impairment.
Protein binding	98% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	0.2–0.3 L/kg, indicating limited extravascular distribution (primarily intravascular).
Bioavailability	Oral: 85–90%; IM: 100%; IV: 100%.
Onset of Action	Oral: 30–60 minutes; IV: immediate; IM: 15–30 minutes.
Duration of Action	Oral: 6–8 hours; IV: 4–6 hours; IM: 4–6 hours. May require dose adjustment in hepatic impairment.

Classification & Brands

Dosing & administration

100 mg orally twice daily

Dosage form	CREAM
Renal impairment	GFR 30-59 mL/min: 100 mg once daily; GFR 15-29 mL/min: 100 mg every 48 hours; GFR <15 mL/min: not recommended
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose to 50 mg twice daily; Child-Pugh C: not recommended
Pediatric use	2 mg/kg/dose orally twice daily; maximum 100 mg per dose
Geriatric use	Reduce initial dose to 50 mg twice daily; monitor renal function and adjust accordingly

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for TZ-3 (TZ-3).

Breastfeeding	Excreted into breast milk with milk-to-plasma ratio of 0.8. Oral bioavailability in infants is low (~15%). Use with caution; monitor infant for drowsiness, poor feeding, and lethargy.
Teratogenic Risk	First trimester: Limited human data, animal studies show increased risk of neural tube defects and cardiac malformations at therapeutic doses. Second trimester: Associated with fetal growth restriction and oligohydramnios with prolonged use. Third trimester: Risk of premature closure of ductus arteriosus and persistent pulmonary hypertension of the newborn.