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. |
| Molecular Weight | 520.5 |
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 | Avoid; limited human data, potential teratogenicity in animal studies. |
| 2nd trimester | Avoid; insufficient data, risk of fetal toxicity outweighs benefits. |
| 3rd trimester | Avoid; may cause fetal harm or neonatal adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for NAVSTEL (NAVSTEL).
| Placental transfer | Crosses placenta extensively; detected in fetal tissues. |
| Breastfeeding | Excreted in breast milk; potential for serious adverse reactions in nursing infants. Not recommended during breastfeeding. |
| Lactation Rating | L5 - Contraindicated |
■ 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 |
Hypersensitivity to navstel or any componentPregnancyBreastfeedingSevere hepatic impairment
| 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 |
| Food/Dietary | Avoid grapefruit juice and grapefruit products as they may increase paclitaxel levels. No other specific dietary restrictions. |
Loading safety data…
| 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. |
| Fertility Effects | Reversible impairment of spermatogenesis and oogenesis observed in animal studies; potential for reduced fertility in both males and females. |
| Clinical Pearls | NAVSTEL is a brand name for paclitaxel. Administer premedication with dexamethasone, diphenhydramine, and H2 antagonist to prevent hypersensitivity reactions. Use non-PVC tubing and in-line filter. Monitor for myelosuppression, neuropathy, and cardiac effects. Dose adjustment required for hepatic impairment. |
| Patient Advice | This drug may cause allergic reactions; report any rash, itching, or difficulty breathing immediately. · You will receive premedication before each infusion to reduce allergic reactions. · Report any numbness, tingling, or burning pain in hands or feet. · Contact your doctor if you develop fever, chills, or signs of infection. · Avoid grapefruit juice during treatment as it may affect drug levels. · Use effective contraception during treatment and for at least 6 months after. |