Dosing and uses of Zanosar (streptozocin)
Adult dosage forms and strengths
powder for injection
- 1g/vial
Metastatic Islet Cell Cancer of Pancreas
Single agent therapy
- 1000 mg/m² IV qWeek, may increase to no more than 1500 mg/m²
- Risk of azotemia increase with >1500 mg/m²
- Monitor: CBC, LFTs, renal function
Combination therapy
- 500 mg/m²/day IV for 5 days q4-6Weeks
- Monitor: CBC, LFTs, renal function
Renal Impairment
CrCl >50 mL/min: May administer full dose
CrCl: 10-50 mL/min: 75% of regular dose
CrCl: <10 mL/min: 50% of regular dose
Other Indications & Uses
Metastatic islet cell cancer of pancreas
Off-label: carcinoid syndrome
Pediatric dosage forms and strengths
Not recommended
Geriatric dosage forms and strengths
Metastatic islet cell cancer of pancreas
Single agent therapy
1000 mg/m² IV qWeek, may increase to no more than 1500 mg/m²
Risk of azotemia increase with >1500 mg/m²
Monitor: CBC, LFTs, renal function
Combination therapy
500 mg/m²/day IV for 5 days q4-6Weeks
Risk of azotemia increase with >1500 mg/m²
Monitor: CBC, LFTs, renal function
Zanosar (streptozocin) adverse (side) effects
>10%
Nephrotoxicity (up to 75%)
Vomiting (up to 90% if no antiemetic)
Metabolic changes, including elevated LFTs, increased LDH (25%)
Hypoglycemia (20%)
Myelosuppression (10-20%)
Frequency not defined
Confusion Lethargy Depression
Nausea
Fever
Chills
Hematologic toxicity (fatal reported)
Injection site reactions
Decreased liver function
Jaundice
Nail changes
Nephrogenic diabetes insipidus (rare)
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy physician in a facility equipped to monitor drug tolerance and to protect and maintain a patient compromised by drug toxicity
Renal toxicity is dose-related and cumulative and may be severe or fataL
Nausea and vomiting may be severe and treatment limiting at times
Liver dysfunction, diarrhea, and hematologic changes reported
Parenteral streptozocin is mutagenic and found to be tumorigenic in some rodents
The physician must weigh risks versus benefits to the patient
Contraindications
Hypersensitivity; pregnancy
Cautions
Risk of severe nephrotoxicity, dose-related & cumulative (ie, >1500 mg/m²/dose may cause azotemia)
Risk of severe nausea/vomiting
Rapid infusion may cause burning sensation
May alter glucose metabolism in some patients
Avoid pregnancy
Pregnancy and lactation
Pregnancy category: d
Lactation: not known if excreted in breast milk, do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Zanosar (streptozocin)
Mechanism of action
Nitrosurea agent that contains a glucose moiety and interferes with DNA function; alkylates DNA, crosslinks DNA strands, may modify proteins and inhibit enzymes involved in DNA synthesis.
Pharmacokinetics
Half-Life: 35-40 min
Bioavailability: 17-25%
Onset: 17 days (with dose schedule of 1500 mg/m²)
Peak Response: 35 days (with dose schedule of 1500 mg/m²)
Vd: 43.8 L
Metabolism: Liver
Clearance: 478 mcg/min (range 173-718 mcg/min)
Excretion: Urine (60-70%)
Administration
IV Incompatibilities
Y-site: allopurinol, aztreonam, cefepime, piperacillin/tazobactam
IV Compatibilities
Solution: D5W, Ns
Y-site: amifostine, etoposide PO4, filgrastim, gemcitabine, granisetron, melphalan, ondansetron, teniposide, thiotepa, vinorelbine
IV Preparation
Reconstitute in 9.5 mL D5W or NS to obtain a 100 mg/mL pale gold solution
Stable for 48 hr at room temp & 96 hr under refrigeration, BUT mfr recommends use within 12 hr because no preservatives
IV Administration
Vesicant
IV infusion in >100 mL D5W or NS over 15 min-6 hr
Continous infusion over 5 days have been given, but may be associated with increased CNS toxicity
Storage
Refrigerate vials
Protect from light
