TZ-3
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TZ-3 (TZ-3).
(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.
| 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. |
| Molecular Weight | 350.43 |
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 |
| 1st trimester | Insufficient human data; animal studies show fetotoxicity at high doses. Avoid use in first trimester unless benefits outweigh risks. |
| 2nd trimester | Limited human data; possible risk of fetal growth restriction. Use only if clearly needed. |
| 3rd trimester | May cause neonatal withdrawal; avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for TZ-3 (TZ-3).
| Placental transfer | Crosses placenta extensively; cord blood levels approximately 50-70% of maternal plasma levels. |
| Breastfeeding | Excreted in breast milk in small amounts; monitor infant for sedation and poor feeding. Consider alternative therapy during breastfeeding. |
| Lactation Rating |
■ 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.
| Serious Effects |
Hypersensitivity to TZ-3 or any componentSevere hepatic impairment (Child-Pugh class C)Concurrent use with strong CYP3A4 inducersBreastfeeding women unless infant monitored
| 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. |
| Food/Dietary | Take TZ-3 with a meal to reduce the risk of nausea. Avoid high-fat meals as they may delay absorption and increase gastrointestinal discomfort. No known significant food-drug interactions; however, alcohol should be limited as it may increase the risk of hypoglycemia when combined with other antidiabetic agents. |
Loading safety data…
| L3 - Moderately Safe |
| 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. |
| Fetal Monitoring | Maternal: Renal function, hepatic enzymes, complete blood count, and drug levels every 2 weeks. Fetal: Ultrasound for growth and amniotic fluid index monthly after 24 weeks; fetal echocardiography at 24-28 weeks. |
| Fertility Effects | Reversible impairment of spermatogenesis in males; females may experience anovulation and menstrual irregularities. Fertility generally returns 3-6 months after discontinuation. |
| Clinical Pearls | TZ-3 is a novel oral hypoglycemic agent that potentiates GLP-1 receptor signaling. Use with caution in patients with severe renal impairment (eGFR <30 mL/min). May cause transient nausea; titrate dose slowly to improve tolerability. Monitor for acute pancreatitis if abdominal pain persists. Discontinue before elective surgery with prolonged fasting. |
| Patient Advice | Take TZ-3 exactly as prescribed, usually once daily with the first meal of the day to reduce gastrointestinal side effects. · If you miss a dose, skip it and take the next dose at the usual time. Do not double the dose. · Contact your healthcare provider immediately if you develop severe abdominal pain that may radiate to your back, as this could be a sign of pancreatitis. · This drug may cause nausea, vomiting, or diarrhea, especially when starting treatment. These symptoms often improve over time. · Do not share your medication with others. Keep it out of reach of children. · Tell your doctor about all other medications you are taking, including over-the-counter drugs and herbal supplements. |