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Streptozocin

Pronunciation: STREP-toe-ZOE-sin
Class: Nitrosourea

Trade Names

Zanosar
- Powder for injection 1 g

Pharmacology

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).

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Pharmacokinetics

Absorption

Streptozocin disappears from blood very quickly.

Distribution

Streptozocin concentrates in liver and kidneys

Metabolism

As much as 20% of the drug (or metabolites containing an N-nitrosourea group) is metabolized and/or excreted by the kidney.

Elimination

As much as 20% of the drug (or metabolites containing an N-nitrosourea group) is metabolized and/or excreted by the kidney.

Indications and Usage

Adult/Pediatric

Symptomatic or progressive metastatic islet cell carcinoma of the pancreas.

Contraindications

Standard considerations.

Dosage and Administration

Pancreatic Islet Cell Carcinoma
Adult

IV 500 mg/m 2 /day for 5 days every 4 to 6 wk; or 1,000 mg/m 2 once a week for the first 2 wk, increased to a max of 1,500 mg/m 2 if necessary. Do not give more than 1,500 mg/m 2 in a single dose because of dose-related nephrotoxicity. Median total dose to maximal response is 4,000 mg/m 2 .

Pediatric

IV No pediatric dosing information is available.

Adjustment in Renal Insufficiency
Adult

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

Drug Interactions

Nephrotoxic agents

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

Laboratory Test Interactions

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

Warnings

GI

Nausea and vomiting usually begin 1 to 4 hr after administration and last for 24 hr; occasionally requiring discontinuation of drug therapy.

Liver dysfunction, hematological changes

Have been observed.

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.


Pregnancy

Category C .

Lactation

Undetermined.

Extravasation risk

Local irritation or phlebitis may occur. Refer to your institution specific protocol.

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.

Topical exposure

May pose a carcinogenic hazard following topical exposure if not properly handled.

Patient Information

  • 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.
  • Caution women of childbearing potential to avoid becoming pregnant during therapy.

Copyright © 2009 Wolters Kluwer Health.

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