NAVSTEL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NAVSTEL (NAVSTEL).
NAVSTEL is a vascular disrupting agent that selectively targets and disrupts tumor vasculature by binding to tubulin at the colchicine-binding site, leading to microtubule depolymerization, cytoskeletal disruption, and subsequent endothelial cell apoptosis and necrosis in tumors.
| Metabolism | Hepatic via CYP3A4 and CYP2C8; also metabolized by non-CYP pathways including hydrolysis and glucuronidation. |
| Excretion | Renal excretion of unchanged drug accounts for 70% of clearance; biliary/fecal elimination accounts for 25%; 5% metabolized. |
| Half-life | Terminal half-life is 12 hours (range 10–14 h). With normal renal function, steady-state is reached after 2–3 days. Half-life extends to 24 hours in moderate renal impairment. |
| Protein binding | 98% bound, primarily to albumin. |
| Volume of Distribution | Vd = 0.35 L/kg (range 0.3–0.4 L/kg), indicating distribution primarily into extracellular fluid. |
| Bioavailability | Oral: 75% (range 70–80%) due to first-pass metabolism; not administered via other enteral routes. |
| Onset of Action | Oral: 1–2 hours; Intravenous: 5–10 minutes. |
| Duration of Action | Oral: 8–12 hours; Intravenous: 4–6 hours. Duration may be prolonged with high doses or renal impairment. |
400 mg orally once daily
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended for severe renal impairment (CrCl <30 mL/min) due to lack of data. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). For moderate to severe (Child-Pugh B or C), reduce dose to 200 mg once daily. |
| Pediatric use | Safety and efficacy not established in pediatric patients <18 years; not recommended. |
| Geriatric use | No specific dose adjustment required; monitor renal function and potential for adverse effects due to age-related renal decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NAVSTEL (NAVSTEL).
| Breastfeeding | Contraindicated in breastfeeding. M/P ratio not available; drug is lipophilic and likely excreted in breast milk. |
| Teratogenic Risk | Teratogenic in animal studies; avoid in pregnancy unless benefit outweighs risk. First trimester: increased risk of major malformations. Second/third trimester: risk of fetal growth restriction and preterm labor. |
| Fetal Monitoring | Monitor maternal complete blood count, liver function tests, and renal function. Fetal monitoring includes ultrasound for growth and anatomy, and nonstress test or biophysical profile in third trimester. |
■ FDA Black Box Warning
NAVSTEL is associated with severe neutropenia, infections, and sepsis, which may be fatal. Monitor blood counts frequently. Granulocyte colony-stimulating factor (G-CSF) is recommended for neutropenia management.
| Serious Effects |
["Known hypersensitivity to the active substance or any excipients"]
| Precautions | ["Neutropenia and febrile neutropenia: monitor absolute neutrophil counts (ANC) regularly","Cardiotoxicity: QT prolongation, cardiac failure, and myocardial ischemia; assess cardiac function before and during treatment","Hemorrhage: tumor hemorrhage may occur, especially in the tumor bed","Hepatotoxicity: monitor liver function tests","Infusion reactions: premedicate with corticosteroids and antihistamines"] |
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| Fertility Effects | Reversible impairment of spermatogenesis and oogenesis observed in animal studies; potential for reduced fertility in both males and females. |