ZANOSAR is indicated in the treatment of metastatic islet
cell carcinoma of the pancreas. Responses have been obtained with both
functional and nonfunctional carcinomas. Because of its inherent renal toxicity,
therapy with this drug should be limited to patients with symptomatic or
progressive metastatic disease.
DOSAGE AND ADMINISTRATION
ZANOSAR sterile powder should be administered
intravenously by rapid injection or short/prolonged infusion. It is not active
orally. Although it has been administered intra arterially, this is not recommended
pending further evaluation of the possibility that adverse renal effects may be
evoked more rapidly by this route of administration.
Two different dosage schedules have been employed
successfully with ZANOSAR.
The recommended dose for daily intravenous administration
is 500 mg/m² of body surface area for five consecutive days every six weeks
until maximum benefit or until treatment-limiting toxicity is observed. Dose
escalation on this schedule is not recommended.
The recommended initial dose for weekly intravenous
administration is 1000 mg/m² of body surface area at weekly intervals for the
first two courses (weeks). In subsequent courses, drug doses may be escalated
in patients who have not achieved a therapeutic response and who have not
experienced significant toxicity with the previous course of treatment.
However, A SINGLE DOSE OF 1500 mg/m² BODY SURFACE AREA SHOULD NOT BE EXCEEDED
as a greater dose may cause azotemia. When administered on this schedule, the
median time to onset of response is about 17 days and the median time to maximum
response is about 35 days. The median total dose to onset of response is about
2000 mg/m² body surface area and the median total dose to maximum response is about
4000 mg/m² body surface area.
The ideal duration of maintenance therapy with ZANOSAR
has not yet been clearly established for either of the above schedules.
For patients with functional tumors, serial monitoring of
fasting insulin levels allows a determination of biochemical response to
therapy. For patients with either functional or nonfunctional tumors, response to
therapy can be determined by measurable reductions of tumor size (reduction of
organomegaly, masses, or lymph nodes).
Reconstitute ZANOSAR with 9.5 mL of dextrose injection,
USP, or 0.9% sodium chloride injection, USP. The resulting pale-gold solution
will contain 100 mg of streptozocin and 22 mg of citric acid per mL. Where more
dilute infusion solutions are desirable, further dilution in the above vehicles
is recommended. The total storage time for streptozocin after it has been
placed in solution should not exceed 12 hours. This product contains no
preservatives and is not intended as a multiple-dose vial.
Caution in the handling and preparation of the powder and
solution should be exercised, and the use of gloves is recommended. If the
sterile powder of ZANOSAR or a solution prepared from ZANOSAR contacts the skin
or mucosae, immediately wash the affected area with soap and water.
Procedures for proper handling and disposal of anticancer
drugs should be considered. Several guidelines on this subject have been
published.1-7 There is no general agreement that all of the procedures
recommended in the guidelines are necessary or appropriate.
ZANOSAR is supplied as follows:
||1 gram vials
Unopened vials of ZANOSAR should be stored at
refrigeration temperatures (2° to 8°C) and protected from light (preferably
stored in carton).
1. Recommendations for the Safe Handling of Parenteral
Antineoplastic Drugs, NIH Publication No. 83-2621. For sale by the
Superintendent of Documents, U. S. Government Printing Office, Washington, DC
2. AMA Council Report. Guidelines for Handling Parenteral
Antineoplastics. JAMA. 1985; 2.53(11):1590–1592.
3. National Study Commission on Cytotoxic
Exposure-Recommendations for Handling Cytotoxic Agents. Available from Louis P.
Jeffrey, ScD. , Chairman, National Study Commission on Cytotoxic Exposure,
Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue,
Boston, Massachusetts 02115.
4. Clinical Oncological Society of Australia, Guidelines
and Recommendations for Safe Handling of Antineoplastic Agents. Med J Australia,
5. Jones RB, et al: Safe Handling of Chemotherapeutic
Agents: A Report from the Mount Sinai Medical Center. CA—A Cancer Journal for
Clinicians, 1983; (Sept/Oct) 258–263.
6. American Society of Hospital Pharmacists Technical
Assistance Bulletin on Handling Cytotoxic and Hazardous Drugs. AM J. Hosp Pharm,
7. Controlling Occupational Exposure to Hazardous Drugs.
(OSHA Work-Practice Guidelines), Am J Health-Syst Pharm, 1996; 53:1669–1685.
Manufactured by: Teva Parenteral Medicines, Inc. Irvine,
CA 92618. Revised: 9/2012