ZANOSAR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZANOSAR (ZANOSAR).
Streptozocin, a nitrosourea compound, is a DNA alkylating agent that inhibits DNA synthesis and is selectively toxic to pancreatic beta cells due to preferential uptake via the GLUT2 transporter.
| Metabolism | Primarily metabolized by the liver via microsomal enzymes (possibly CYP450); extensive first-pass metabolism. |
| Excretion | Primarily renal (70-80% as unchanged drug). Minor biliary/fecal excretion (<10%). |
| Half-life | Terminal elimination half-life is approximately 5-7 hours; prolonged in renal impairment. |
| Protein binding | Approximately 50-60% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution (Vd) is 0.5-1.0 L/kg, suggesting distribution into total body water. |
| Bioavailability | Not applicable; administered intravenously only. Oral bioavailability is negligible due to first-pass metabolism. |
| Onset of Action | Onset of clinical effect occurs within 1-2 hours after intravenous administration. |
| Duration of Action | Duration of action is approximately 12-24 hours, with sustained effects due to prolonged alkylation. |
500 mg/m² IV on days 1-5 and 8-12 of a 28-day cycle; or 2-4 mg/kg IV on days 1-5 and 8-12 of a 28-day cycle.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 50-90 mL/min: 75% of normal dose. GFR 25-50 mL/min: 50% of normal dose. GFR <25 mL/min: Consider alternative therapy. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: 75% of normal dose. Child-Pugh C: Avoid use or reduce dose by 50% with close monitoring. |
| Pediatric use | 300 mg/m² IV on days 1-5 and 8-12 of a 28-day cycle; or 1.5-3 mg/kg IV on days 1-5 and 8-12 of a 28-day cycle (max dose 500 mg/m²). |
| Geriatric use | Start at 400 mg/m² IV on days 1-5 and 8-12 of a 28-day cycle; increase to 500 mg/m² if tolerated. Monitor renal function closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZANOSAR (ZANOSAR).
| Breastfeeding | Contraindicated during breastfeeding. ZANOSAR is excreted into human milk; M/P ratio not established. Potential for serious adverse reactions in nursing infants (e.g., immunosuppression, growth retardation). |
| Teratogenic Risk | Pregnancy Category D. First trimester: High risk of teratogenicity including CNS, skeletal, and visceral anomalies. Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and neonatal toxicity (e.g., myelosuppression). |
| Fetal Monitoring |
■ FDA Black Box Warning
ZANOSAR (streptozocin) should be administered under the supervision of a qualified physician experienced in cancer chemotherapy. Severe renal toxicity, including renal failure, has been reported. Renal function should be closely monitored. May cause severe myelosuppression, including fatal neutropenia and thrombocytopenia. Not recommended for use in patients with pre-existing renal impairment.
| Serious Effects |
["Hypersensitivity to streptozocin or any component of the formulation.","Severe renal impairment (creatinine clearance <20 mL/min)."]
| Precautions | ["Renal toxicity: dose-dependent and cumulative; monitor BUN, serum creatinine, and creatinine clearance before and during therapy.","Myelosuppression: leukopenia, thrombocytopenia, and anemia; monitor blood counts.","Hepatotoxicity: elevations in liver enzymes may occur.","Gastrointestinal toxicity: severe nausea and vomiting may require antiemetics.","Carcinogenicity: mutagenic and potentially carcinogenic.","Fertility: may cause gonadal suppression and infertility."] |
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| Monitor maternal CBC, renal and hepatic function, and fetal growth by ultrasound. Assess amniotic fluid volume. Postnatal monitoring of neonate for myelosuppression and infection. |
| Fertility Effects | ZANOSAR may cause gonadotoxicity leading to amenorrhea in females and oligospermia or azoospermia in males, potentially irreversible. Fertility preservation counseling recommended. |