Streptozocin

A to Z Drug Facts

Streptozocin

	Actions
	Indications
	Contraindications
	Route/Dosage
	Interactions
	Lab Test Interferences
	Adverse Reactions
	Precautions
Patient Care Considerations
	Administration/Storage
	Assessment/Interventions
	Patient/Family Education

(STREP-toe-ZOE-sin)

Zanosar

Powder for injection

1 g

Class: Alkylating agent

Nitrosoureas

Actions Streptozocin is a naturally occurring nitrosourea that contains a glucose moiety not present in the other compounds. The glucose moiety is believed to contribute to reduced myelotoxicity. Streptozocin inhibits DNA synthesis without significantly affecting RNA or protein synthesis in bacterial and mammalian cells. The biochemical mechanism leading to mammalian cell death has not been established but is at least partially caused by DNA alkylation causing intrastrand crosslinks. After rapid IV injection, unchanged drug is rapidly cleared from the plasma (half-life, 35 min). Two hours after administration, metabolites are detected in spinal fluid in equivalent concentration to plasma. Metabolites persist in plasma over 24 hr and concentrate in the liver and kidney. Most excretion is completed in 24 hr.

Indications

Adult/Pediatric

Symptomatic or progressive metastatic islet cell carcinoma of the pancreas.

Contraindications Standard considerations.

Route/Dosage

Pancreatic Islet Cell Carcinoma

ADULT: IV 500 mg/m²/day for 5 days q 4 to 6 wk; or 1000 mg/m² once a week for the first 2 wk, increased to a max of 1500 mg/m² if necessary. Do not give more than 1500 mg/m² in a single dose because of dose related nephrotoxicity. Median total dose to maximal response is 4000 mg/m².

PEDIATRIC: IV No pediatric dosing information is available.

Adjustment in Renal Insufficiency

ADULT: IV If Ccr is more than 50 mL/min, administer 100% of usual dose. If Ccr is 10 to 50 mL/min, administer 75% of usual dose. If Ccr is less than 10 mL/min, administer 50% of usual dose.

Interactions

Nephrotoxic agents

Because streptozocin is nephrotoxic, do not use in combination with other nephrotoxic agents.

Lab Test Interferences None well documented.

Adverse Reactions

CNS: Confusion, lethargy, depression (observed with 5 day continuous infusion). GI: Very high potential for nausea and vomiting, diarrhea, jaundice, transient elevation of LFTs, hypoalbuminemia. HEMATOLOGIC: Bone marrow suppression, nadir at 7 to 14 days. METABOLIC: Hypoglycemia, usually within 24 hr of the dose. RENAL: Dose-related and cumulative renal tubular damage in 25% to 75% of patients, renal failure, reversible if streptozocin stopped early.

Precautions

Pregnancy: Category C. Lactation: Undetermined. Hematologic: Hematologic toxicity has been rare, most often involving mild decreases in hematocrit. However, fatal hematologic toxicity with substantial reductions in leukocyte and platelet counts has been observed. Extravasation risk: Local irritation or phlebitits may occur. Refer to your institution specific protocol. GI: Nausea and vomiting usually begins 1 to 4 hr after administration and lasts 24 hr; occasionally requiring discontinuation of drug therapy. Hypoglycemia: Mild to moderate abnormalities of glucose tolerance have generally been reversible, but insulin shock with hypoglycemia has occurred. Hydration: Because of renal toxicity, keep the patient well hydrated. Renal toxicity: Renal toxicity occurs in up to 2/3 of all patients treated with streptozocin, as evidenced by azotemia, anuria, hypophosphatemia, glycosuria, and renal tubular acidosis. Such toxicity is dose-related and cumulative and may be severe or fatal. Topical exposure: May pose a carcinogenic hazard following topical exposure if not properly handled.

PATIENT CARE CONSIDERATIONS

Administration/Storage

Refrigerate. Protect from light.
Add 9.5 mL of 5% Dextrose injection or 0.9% Sodium Chloride to the vial producing a clear, pale-gold solution (concentration is 100 mg/mL). Dilute further for IV infusion with 5% Dextrose or 0.9% Sodium Chloride.
Reconstituted solutions are stable for up to 48 hr at room temperature and for up to 96 hr under refrigeration. Use streptozocin solutions within 24 hr because they are preservative-free. The manufacturer recommends disposal within 12 hr of reconstitution. A color change from pale-gold to dark brown indicates decomposition.
Diluted 2 mg/mL solutions prepared with 5% Dextrose or 0.9% Sodium Chloride are stable for up to 48 hr at room temperature and for up to 96 hr under refrigeration.
Rapid IV injection, or IV infusion over 15 min to 6 hr. Bolus administration may cause intense venous pain.

Assessment/Interventions

Monitor renal function before and after each course of therapy. Obtain serial urinalysis, BUN, plasma creatinine, serum electrolytes, and Ccr prior to, at least weekly during, and for 4 wk after drug administration. Serial urinalysis is particularly important for the early detection of proteinuria; quantitate with a 24-hr collection when proteinuria is detected. Mild proteinuria is one of the first signs of renal toxicity. Reduce the dose or discontinue treatment in the presence of significant renal toxicity. In patients with preexisting renal disease, judge potential benefit of streptozocin against known risk of serious renal damage. Do not use in combination or concomitantly with other potential nephrotoxins.
Have 50% Dextrose injection on hand, especially when the first dose is administered, because of the risk of hypoglycemia.
Assess renal function prior to, weekly during, and for 4 wk after streptozocin therapy. Ample fluid intake and subsequent increase in urine output may aid excretion and reduce renal toxicity.
Closely monitor for evidence of renal, hepatic, and hematopoietic toxicity. Perform CBCs and LFTs at least weekly. Dosage adjustments or discontinuance of the drug may be indicated, depending upon the degree of toxicity.

Patient/Family Education

Explain name, action, and potential side effects of drug.
Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
Review dosing schedule (daily or weekly dose) with patient, family, or caregiver.
Advise patient, family, or caregiver to immediately report any of the following to the health care provider: decreased urination; fever, chills, or other signs of infection; unusual bleeding or bruising; pain, redness, or swelling at injection site.
Advise patient, family, or caregiver to report any of the following to the health care provider: persistent nausea, vomiting, diarrhea, or appetite loss; persistent or worsening general body weakness.
Caution patient that medication may cause confusion, drowsiness, and depression and to use caution when driving or performing other tasks that require mental alertness or coordination.
Instruct patient not to take any prescription or OTC medications or dietary supplements unless advised to do so by health care provider.
Caution women of childbearing potential to avoid becoming pregnant during therapy.
Instruct women of childbearing potential to notify health care provider if pregnant, planning to become pregnant, or breastfeeding.
Advise patient, family, or caregiver that frequent follow-up visits and laboratory tests will be required to monitor therapy and to keep appointments.