Zanosar


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Zanosar

 [zan´o-sahr]
trademark for preparations of streptozocin, an antitumor antibiotic.

streptozocin

(strep-toe-zoe-sin) ,

Zanosar

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: antitumor antibiotics
Pregnancy Category: C

Indications

Metastatic islet cell carcinoma of the pancreas.
  • Metastatic carcinoid tumor,
  • Hodgkin’s disease,
  • Pancreatic adenocarcinoma,
  • Colorectal cancer.

Action

Inhibits DNA synthesis by cross-linking DNA strands (cell-cycle phase–nonspecific).

Therapeutic effects

Death of rapidly replicating cells, particularly malignant ones.

Pharmacokinetics

Absorption: Administered IV only, resulting in complete bioavailability.
Distribution: Rapidly distributed. High concentrations in liver, pancreas, kidneys, and intestine. Probably crosses the placenta. Active metabolite enters the CSF.
Metabolism and Excretion: Highly metabolized in liver and kidneys. 10–20% excreted unchanged by the kidneys. Small amounts excreted in expired air (5%) and feces (1%).
Half-life: 35–40 min.

Time/action profile

ROUTEONSETPEAKDURATION
IV (effects on blood counts)unknown1–2 wkunknown
IV (tumor response)17 days35 daysunknown

Contraindications/Precautions

Contraindicated in: Hypersensitivity.
Use Cautiously in: Underlying or pre-existing renal disease (dose reduction recommended); Liver disease; Geriatric patients (consider↓ body mass, age-related ↓ in renal/hepatic/cardiac function as well as concurrent illness and drug therapies; Patients with childbearing potential; Active infections; ↓ bone marrow reserve; Other chronic debilitating illnesses; Obstetric / Lactation / Pediatric: Pregnancy, lactation, or children (safety not established).

Adverse Reactions/Side Effects

Central nervous system

  • confusion
  • lethargy
  • mental depression

Gastrointestinal

  • drug-induced hepatitis (life-threatening)
  • nausea (most frequent)
  • vomiting (most frequent)
  • diarrhea
  • duodenal ulcer

Genitourinary

  • nephrotoxicity (most frequent)
  • gonadal suppression
  • proteinuria

Fluid and Electrolyte

  • hypophosphatemia

Hematologic

  • anemia
  • leukopenia
  • thrombocytopenia
  • eosinophilia

Local

  • phlebitis at IV site (most frequent)
  • injection site reactions

Metabolic

  • hypoglycemia (first dose) (life-threatening)
  • hyperglycemia

Miscellaneous

  • fever

Interactions

Drug-Drug interaction

↑ myelosuppression with other antineoplastics.↑ risk of nephrotoxicity with other nephrotoxic agents (aminoglycoside antibiotics).Toxicity may be ↑ by concurrent phenytoin therapy.May ↑ toxicity of doxorubicin.May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions.

Route/Dosage

Intravenous (Adults) 500 mg/m2/day for 5 days every 4–6 wk or 1 g/m2/wk for 2 wk; then may be increased (not to exceed 1.5 g/m2/dose) and given weekly for 4–6 doses.

Availability

Powder for injection: 1 g/vial

Nursing implications

Nursing assessment

  • Monitor vital signs prior to and periodically during therapy.
  • Monitor intake and output and daily weight. Report significant discrepancies or dependent edema; may indicate nephrotoxicity. Encourage fluids to 3000 mL/day to reduce risk of renal damage.
  • Monitor IV site carefully and ensure patency. Discontinue infusion immediately if severe discomfort, erythema along vein, or infiltration occurs. Apply cool packs above injection site. Tissue ulceration and necrosis may result from infiltration. Resume infusion in another vein and notify physician or other health care professional.
  • Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
  • Monitor hydration status, appetite, and nutritional intake. Adequate hydration may decrease the risk of nephrotoxicity by decreasing urine/renal concentration of the drug and its metabolites. Severe, protracted nausea and vomiting may occur 1–4 hr after beginning infusion. Nausea and vomiting may worsen with subsequent doses. Administration of an antiemetic and adjustment of diet as tolerated may help maintain fluid and electrolyte balance and nutritional status.
  • Lab Test Considerations: Monitor renal status prior to and frequently during therapy and for 4 wk after course of therapy. Nephrotoxicity is common and may be manifested by ↑ BUN and creatinine, decreased CCr, and presence of protein in urine. Reduction or discontinuation of streptozocin may allow reversal of renal damage.
    • Monitor for hepatotoxicity, evidenced by ↑ AST, ALT, LDH, serum bilirubin, and alkaline phosphatase or ↓ serum albumin, at least weekly.
    • May cause hypoglycemia. Monitor serum glucose prior to and after initial dose and periodically during therapy.
    • Monitor serum uric acid prior to and periodically during therapy.
    • Monitor CBC and differential prior to and weekly during therapy. Report significant ↓.
    • Serial fasting insulin concentrations may be used to determine response to therapy.

Potential Nursing Diagnoses

Risk for infection (Side Effects)
Risk for deficient fluid volume (Side Effects)

Implementation

  • IV dextrose should be immediately available, because hypoglycemia may occur in response to initial dose.
    • Solution is pale gold. Do not use if dark brown. Stable for 12 hr at room temperature, for 96 hr at 2–8°C.
    • Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in designated containers (see ).
  • Intravenous Administration
  • Intermittent Infusion: Diluent: Reconstitute vial with 9.5 mL of D5W or 0.9% NaCl. May be further diluted in 10–200 mL of D5W or 0.9% NaCl. Do not admix. Concentration: 100 mg/mL.
  • Rate: Infuse over 10–15 min. Slower infusion rates (45–60 min) have been used to decrease venous irritation. May also be infused over 6 hr.
    • May be administered via rapid IV injection.
  • Y-Site Compatibility: amifostine, anidulafungin, bivalirudin, caspofungin, codeine, diltiazem, ertapenem, etoposide phosphate, fenoldopam, filgrastim, gemcitabine, granisetron, hydromorphone, linezolid, lorazepam, melphalan, meperidine, metronidazole, milrinone, nesiritide, octreotide, ondansetron, paclitaxel, palonosetron, pancuronium, rituximab, sodium acetate, tacrolimus, teniposide, thiotepa, tigecycline, tirofiban, vasopressin, vecuronium, vinorelbine, voriconazole, zoledronic acidY-Site Incompatibility: allopurinol, amphotericin B lipid complex, aztreonam, cefepime, daptomycin, levofloxacin, pantoprazole, piperacillin/tazobactam, trastuzumab

Patient/Family Teaching

  • Instruct patient to notify nurse immediately if pain or redness develops at IV site.
  • Instruct patient to notify nurse immediately if symptoms of hypoglycemia occur (anxiety; chills; cold sweats; confusion; cool, pale skin; difficulty in concentration; drowsiness; excessive hunger; headache; irritability; nausea; nervousness; shakiness; unusual tiredness; or weakness).
  • Instruct patient to notify health care professional if decreased urine output; swelling of lower extremities; yellowing of skin; fever; chills; sore throat; signs of infection; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor. Caution patient not to drink alcoholic beverages or take products containing aspirin or NSAIDs.
  • This drug may cause gonadal suppression; however, patient should still practice birth control. Advise patient to inform health care professional immediately if pregnancy is suspected or if breastfeeding.
  • Instruct patient not to receive any vaccinations without advice of health care professional.
  • Advise patient of need for medical follow-up and frequent lab tests.

Evaluation/Desired Outcomes

  • Decrease in size and spread of tumor.
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References in periodicals archive ?
The typical cyclic voltammogram is shown in Figure 2 and cyclicevoltammtric data of zanosar has been reported in Table 2.
The differential pulse polarography measurements have been carried out in the present investigation for the analysis of zanosar in pharmaceutical formulation and spiked human urine samples with supporting electrolyte of BR buffer as shown in Figure 3.
Under the experimental conditions described above, the polarographic reduction of zanosar gave a single well-defined two-electron reduction peak at pH 2.0-12.0 with all the techniques, corresponding to the reduction of carbonyl groups.
The total number of electrons involved during the electrode reduction of zanosar was determined by millicoulometry [19].
Zanosar in pharmaceutical formulation namely streptozotocin should be administered intravenously by rapid injection or short/prolonged infusion.
The applicability of the method for the estimation of zanosar in urine was checked by using different spiked human urine samples coupled with a standard addition method.
The Differential pulse polarography well-defined wave/peak obtained at pH 4.0 is used in the analytical estimation of zanosar. Both standard addition and calibration methods are used for the analysis of zanosar in pharmaceutical formulations and urine samples.
The electrochemical behaviour of zanosar at hanging mercury drop electrode was examined in BR buffer over a pH range from 2.0 to 12.0 by D.C polarography, differential pulse polarography, and cyclic voltammetric methods.