Zanosar

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Zanosar

Classes

Nitrosoureas

Administration

Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Emetic Risk
High
Administer routine antiemetic prophylaxis prior to treatment.
Extravasation Risk
Irritant
Imported streptozocin from the European Union and United Kingdom is considered a vesicant.

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intravenous Administration

Due to a critical shortage of streptozocin in the United States, non-FDA-approved streptozocin (Zanosar) is being temporarily imported from the European Union and United Kingdom. While dosage schedules are the same for both products, differences in admixture and administration for the imported product are detailed below.
Adequate hydration may decrease nephrotoxic effects. Administration of imported streptozocin requires hyperhydration.
 
Reconstitution and Dilution, FDA-Approved streptozocin:
Add 9.5 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection to each 1g vial to give a pale gold IV solution containing 100 mg/mL streptozocin and 22 mg/mL citric acid.
Discard any unused reconstituted solution left in the vial.
Streptozocin may be further diluted in 5% Dextrose Injection or 0.9% Sodium Chloride Injection if desired.
Storage after reconstitution: The total storage time for streptozocin after being placed in solution should not exceed 12 hours.
 
Reconstitution and Dilution, imported streptozocin:
Add 9.5 mL of 0.9% Sodium Chloride Injection to each 1g vial.
Discard any unused reconstituted solution left in the vial.
Further dilute imported streptozocin in 0.9% Sodium Chloride Injection.
Storage after reconstitution: Immediately dilute reconstituted streptozocin. The resulting solution may be stored below 25 degrees C (77 degrees F) for up to 24 hours in a polyethylene Ecoflac-type bag.
 
Intravenous injection or infusion:
Streptozocin is administered intravenously by rapid injection or short/prolonged infusion.
Imported streptozocin should be infused through a free-flowing line over 30 minutes to 4 hours.
Intra-arterial administration is not recommended as nephrotoxic effects may be evoked more rapidly.

Adverse Reactions
Severe

diabetes insipidus / Delayed / 0-1.0
anuria / Delayed / Incidence not known
azotemia / Delayed / Incidence not known
renal tubular acidosis (RTA) / Delayed / Incidence not known
proteinuria / Delayed / Incidence not known
nephrotoxicity / Delayed / Incidence not known
hepatotoxicity / Delayed / Incidence not known
insulin shock / Delayed / Incidence not known
tissue necrosis / Early / Incidence not known

Moderate

thrombocytopenia / Delayed / 0-1.0
leukopenia / Delayed / 0-1.0
bone marrow suppression / Delayed / 0-1.0
anemia / Delayed / 0-1.0
hypophosphatemia / Delayed / Incidence not known
glycosuria / Early / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
hypoalbuminemia / Delayed / Incidence not known
hypoglycemia / Early / Incidence not known
erythema / Early / Incidence not known
edema / Delayed / Incidence not known
depression / Delayed / Incidence not known
confusion / Early / Incidence not known

Mild

vomiting / Early / 10.0
nausea / Early / 10.0
diarrhea / Early / Incidence not known
injection site reaction / Rapid / Incidence not known
skin irritation / Early / Incidence not known
lethargy / Early / Incidence not known

Boxed Warning
Nephrotoxicity, proteinuria, renal disease, requires a specialized care setting, requires an experienced clinician

Use streptozocin with caution in patients with a history of renal disease. Cumulative, dose-related nephrotoxicity which may be severe or fatal has occurred in patients treated with streptozocin; nephrotoxicity includes azotemia, anuria, proteinuria, hypophosphatemia, glycosuria, and renal tubular acidosis. Treatment with streptozocin requires an experienced clinician experienced in the use of chemotherapy and able to assess the potential benefit versus the known risk of serious renal damage. Adequate hydration may help to reduce the risk of toxicity to the renal tubular epithelium by decreasing the renal and urinary concentrations of streptozocin and it's metabolites. Monitor renal function, urinalysis, and serum electrolytes at baseline and at least weekly during therapy and for 4 weeks after completion of therapy. Quantify any proteinuria with a 24-hour urine collection. A dose reduction may be necessary for patients with significant nephrotoxicity. Administration requires a specialized care setting where patients have access to adequate laboratory and supportive resources.

Hepatic disease, hepatotoxicity

Streptozocin should be used with caution in patients with a history of hepatic disease; hepatotoxicity has been reported with therapy. Monitor liver function tests at least weekly; a dose reduction or discontinuation of therapy may be necessary.

Chemotherapy-induced nausea/vomiting, diarrhea

Severe chemotherapy-induced nausea/vomiting which may be treatment-limiting occurs in most patients treated with streptozocin; discontinuation of therapy may be necessary. Diarrhea has also been observed in some patients.

Bone marrow suppression, leukopenia, thrombocytopenia

While bone marrow suppression is rare with streptozocin therapy, fatal hematologic toxicity with significant leukopenia and thrombocytopenia has been reported. Monitor complete blood counts at least weekly during treatment; a dose reduction or discontinuation of therapy may be necessary.

Common Brand Names

Zanosar

Dea Class

Rx

Description

Alkylating agent
Used for the treatment of metastatic islet cell carcinoma of the pancreas
May cause severe dose-related and cumulative nephrotoxicity; nausea and vomiting may also be severe and treatment-limiting

Dosage And Indications
For the treatment of pancreatic cancer. For the treatment of symptomatic or progressive metastatic islet cell pancreatic cancer. Intravenous dosage, EVERY-6-WEEKS Adults

500 mg/m2 IV once daily, every 6 weeks until maximum benefit or treatment-limiting toxicity is observed; the ideal duration of therapy has not been clearly established. Dose escalation is not recommended. Responses have been obtained with both functional and nonfunctional carcinomas.

Intravenous dosage, WEEKLY Adults

1,000 mg/m2 IV once weekly; after the first 2 weeks, the dose may be escalated (maximum, 1,500 mg/m2) in patients who have not achieved a therapeutic response and who have not experienced significant toxicity. Continue until maximum benefit or treatment-limiting toxicity is observed; the ideal duration of therapy has not been clearly established. Responses have been obtained with both functional and nonfunctional carcinomas. The median time to onset of response with a weekly schedule of administration is approximately 17 days and the median time to maximum response is approximately 35 days.

For the treatment of advanced carcinoid†. Intravenous dosage Adults

500 mg/m2/day IV on days 1—5 every 10 weeks has been studied in combination with 5-fluorouracil (5-FU) 400 mg/m2/day IV on days 1—5 and 36—40, every 10 weeks. In a phase II/III clinical trial of 249 patients with unresectable advanced carcinoid tumor, streptozocin/5-FU improved overall survival compared to 5-FU/doxorubicin (24.3 months vs 15.7 months, p = 0.0267). The overall response rate (ORR) and progression-free survival were not significantly different. In clinical trials of various designs, ORR of 16—33% have been observed with streptozocin/5-FU.

For the treatment of colorectal cancer†. Intravenous dosage Adults

Dosage is not established. 500 mg/m2 IV weekly from day 1 in combination with methyl-CCNU 30 mg/m2/day on days 2—6, 5-fluorouracil (5-FU) 300 mg/m2/day IV on days 1—5 and 36—40, and vincristine 1 mg/m2 IV on days 1 and 36, repeated every 10 weeks, has been studied. Response rates in clinical trials of previously treated and previously untreated patients ranged from 10—34% with streptozocin based therapy. Significant nausea/vomiting and myelosuppression was observed in clinical trials.

†Indicates off-label use

Dosing Considerations
Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available.

Renal Impairment

Significant nephrotoxicity: A dose reduction or discontinuation of therapy is recommended.

Drug Interactions

Aliskiren; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Amikacin: (Moderate) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents, including aminoglycosides, could exacerbate the renal insult.
Amiloride: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Amiloride; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Aminoglycosides: (Moderate) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents, including aminoglycosides, could exacerbate the renal insult.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Atenolol; Chlorthalidone: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Azilsartan; Chlorthalidone: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Benazepril; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Bumetanide: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Candesartan; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Captopril; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Chlorothiazide: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Chlorthalidone: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Chlorthalidone; Clonidine: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cisplatin: (Moderate) Other nephrotoxic drugs, such as streptozocin, can aggravate the nephrotoxicity and electrolyte loss seen with cisplatin if given concurrently or shortly after cisplatin therapy.
Clindamycin: (Moderate) Concomitant use of streptozocin and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Clofarabine: (Major) Avoid the concomitant use of clofarabine and streptozocin due to the risk of additive hepatotoxicity. Coadministration may also increase the risk of additive nephrotoxicity.
Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Enalapril; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Eprosartan; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Ethacrynic Acid: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Febuxostat: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi.
Foscarnet: (Moderate) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents, such as foscarnet, could exacerbate the renal insult.
Fosinopril; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Furosemide: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Gentamicin: (Moderate) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents, including aminoglycosides, could exacerbate the renal insult.
Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like streptozocin. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Hydrochlorothiazide, HCTZ; Methyldopa: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Hydrochlorothiazide, HCTZ; Moexipril: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like streptozocin. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Irbesartan; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Lisinopril; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Live Vaccines: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Loop diuretics: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Losartan; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Methyclothiazide: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Metolazone: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Metoprolol; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Olmesartan; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Paromomycin: (Moderate) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents, including aminoglycosides, could exacerbate the renal insult.
Plazomicin: (Moderate) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents, including aminoglycosides, could exacerbate the renal insult.
Potassium-sparing diuretics: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Propranolol; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Quinapril; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Spironolactone: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Spironolactone; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Streptomycin: (Moderate) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents, including aminoglycosides, could exacerbate the renal insult.
Telavancin: (Moderate) Concurrent or sequential use of telavancin with other potentially nephrotoxic drugs such as streptozocin may lead to additive nephrotoxicity. Closely monitor renal function and adjust telavancin doses based on calculated creatinine clearance.
Telmisartan; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Thiazide diuretics: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Tobramycin: (Moderate) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents, including aminoglycosides, could exacerbate the renal insult.
Torsemide: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Triamterene: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Triamterene; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Valsartan; Hydrochlorothiazide, HCTZ: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Vancomycin: (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drug, such as streptozocin, can lead to additive nephrotoxicity.
Voclosporin: (Moderate) Concomitant use of voclosporin and streptozocin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.

How Supplied

Streptozocin/Zanosar Intravenous Inj Pwd F/Sol: 1g

Maximum Dosage
Adults

1,500 mg/m2 IV.

Geriatric

1,500 mg/m2 IV.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Mechanism Of Action

Streptozocin is a cell cycle non-specific alkylating agent. The biochemical mechanism leading to mammalian cell death has not been definitely established; streptozocin inhibits cell proliferation at a considerably lower level than that needed to inhibit precursor incorporation into DNA or to inhibit several of the enzymes involved in DNA synthesis. It undergoes rapid decomposition to form methylcarbonium ions which alkylate DNA, causing DNA strand breakage and interstrand crosslinking. In mammalian cells, this leads to impaired DNA synthesis as well as DNA mismatches, impaired DNA repair, and eventually apoptosis; in bacterial cells, a specific interaction with cytosine moieties leads to DNA degradation. The presence of a sugar moiety on streptozocin increases its specificity for pancreatic neuroendocrine tumors through the glucose GLUT2 transporter on beta cells. Streptozocin is active in the L1210 leukemic mouse over a fairly wide range of parenteral dose schedules. In animal experiments, streptozocin induces diabetes that resembles hyperglycemic nonketotic diabetes in humans which appears to be mediated by lowering beta cell nicotinamide adenine dinucleotide (NAD) and consequent histopathologic alteration of pancreatic islet beta cells.

Pharmacokinetics

Streptozocin is administered intravenously; pharmacokinetics are both linear and predictable. After IV administration, the unchanged drug was cleared from plasma within a few minutes (initial half-life, 5 to 6 minutes; terminal half-life, 35 minutes); the half-life of metabolites was more than 24 hours. While no parent drug was found in the cerebrospinal fluid, metabolites of streptozocin did enter the central nervous system. After IV administration of radioactive isotope-labeled forms, streptozocin accumulates first in the liver and is then cleared by the kidneys. Excretion is largely urinary, especially in the first hour after administration, after which only trace amounts appear in the bile. Approximately 30% of a dose is excreted in the urine as nitrosourea-containing metabolites during the first 24 hours after administration; parent drug accounts for 10% to 20% of renal excretion with less than 1% of a radiolabeled dose recovered in the feces.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None
In vitro, CYP isoenzymes are not involved in the degradation or metabolism of streptozocin; additionally, streptozocin does not inhibit CYP450 isoenzymes.

Pregnancy And Lactation
Pregnancy

Pregnancy should be avoided by females of reproductive potential during streptozocin treatment unless the potential benefit justifies the potential risk to the fetus. Although there are no studies in pregnant women, streptozocin can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving streptozocin should be apprised of the potential hazard to the fetus.

Due to the potential for serious adverse reactions in nursing infants from streptozocin, advise women to discontinue breast-feeding during treatment. It is not known whether streptozocin is present in human milk, although many drugs are excreted in human milk.