ZANOSAR Powder for concentrate for solution Ref.[8711] Active ingredients: Streptozocin

Zanosar should only be administered under the supervision of a physician experienced in the use of anti-cancer chemotherapeutic agents.

The patient should have access to a facility with a laboratory and supportive resources sufficient to monitor drug tolerance and to protect and maintain a patient compromised by drug toxicity.

Posology

The dose is based on the body surface area (m²).

Two different dosage schedules can be used:

Six-weekly regimen: 500 mg/m²/day, intravenously for 5 consecutive days every 6 weeks until maximum benefit is obtained or until treatment-limiting toxicity is observed. Dose escalation on this schedule is not recommended.

Three-weekly regimen: 500 mg/m²/day, intravenously for 5 consecutive days during cycle 1, followed by 1000 mg/m² every 3rd week during the subsequent cycles.

Other dosing regimens, with similar dose intensity, have been used in clinical studies with comparable efficacy and safety results. However, a single dose of 1500 mg/m² of body surface area should not be exceeded (renal toxicity).

The optimal duration of maintenance therapy with Zanosar has not been established.

For patients with functional tumours, serial monitoring of biological markers allows a determination of biochemical response to therapy. For patients with either functional or nonfunctional tumours, response to therapy can be determined by measurable reductions of tumour size on imaging.

Renal, hepatic and hematological function must be closely monitored before, during and after treatment, as well as blood glucose levels (see section 4.4). Dose adjustment or discontinuation of the drug may be indicated, depending upon the degree of toxicity noted.

Antiemetic premedication is recommended to prevent nausea and vomiting.

Method of administration

Zanosar should be administered intravenously by infusion (See section 6.6). The duration of infusion should be between 30 minutes and 4 hours.

The administration of Zanosar requires hyperhydration (see section 4.4).

This medicinal product is vesicant in nature and as such should be administered with caution through a free-flowing line.

In the event of extravasation, the administration should be discontinued immediately.

Special populations

Patients with renal impairment

Based on clinical practice, the dose of Zanosar should be adapted according to renal function: dose reduction or treatment discontinuation is mandatory in the presence of significant renal toxicity.

If GFR is comprised between 30 and 45 ml/min, the benefit/risk ratio should be thoroughly evaluated in a multidisciplinary approach, which includes soliciting a nephrologist’s opinion and balancing the potential benefit against the known risk of serious renal damage.

Hepatic impairment

Dose reduction should be considered in cases of hepatic impairment (see section 4.4).

Elderly population

The safety and efficacy of Zanosar in patients aged ≥65 years have not been established.

Regimen selection for elderly patients should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapies.

Paediatric population

The safety and efficacy of Zanosar in patients below 18 years have not been established.

For precautions to be taken before handling or administering the medicinal product, see section 6.6.

There is no specific antidote for overdose with Zanosar and treatment of overdose should consist of supportive measures. Overdose should be avoided by carefully calculating the dose to be administered.

Before opening: 36 months

After opening, reconstitution and dilution: The reconstituted solution should be immediately diluted.

The chemical and physical in-use stability of the resulting solution has been demonstrated for 24 hours below 25°C in polyethylene Ecoflac type bag containing a sodium chloride 9 mg/ml (0.9%) solution for injection.

The product does not contain any preservative and is for single use only.

From a microbiological point of view, unless the method of opening/reconstitution/dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use conditions are the responsibility of the user.

Store the vial in a refrigerator (2°C to 8°C); Keep the vial in the outer carton in order to protect from light.

For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

Powder in a 20 mL type I glass vial with a bromobutyl rubber stopper and sealed with an aluminium / plastic flip-off cap.

1 vial.

General precautions

Streptozocin is a cytotoxic agent. Therefore, caution should be used during handling and preparation of Zanosar. Use of gloves and other protective clothing to prevent skin contact is recommended.

Aseptic technique must be strictly observed throughout the handling of Zanosar, since it contains no preservative.

Instructions for reconstitution

Zanosar must be reconstituted by a healthcare professional.

Dose preparation takes into account the patient body surface area (see section 4.2).

Each 20 mL vial of Zanosar must be reconstituted with 9.5 mL of sodium chloride 9 mg/ml (0.9%) solution for injection.

Dissolution of the lyophilised powder is completed in less than 2 minutes. The resulting solution is pale-gold.

The pH value of the reconstituted product is around 4.

After reconstitution, each mL solution contains 100 mg streptozocin per mL.

The correct amount of the reconstituted solution (see section 4.2 for the calculation of the dose based on the body surface area) should then be diluted in 500 mL of the same solution that was used for reconstitution.

In case of co-administration of Zanosar and 5-FU, it is recommended to use an Y-set system.

Precautions to be taken before handling or administering the medicinal product

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.

The preparation of injectable solutions of cytotoxic agents should be done by specialist and trained personnel with knowledge of the medicines used and under conditions guaranteeing the protection of the environment and especially the personnel handling the agents. It requires premises intended solely for preparation. Smoking, eating and drinking in these premises is forbidden. Personnel handling the agents should have at their disposal a set of appropriate handling equipment particularly long sleeved gowns, safety masks, safety cap, safety glasses, sterile single-use PVC gloves, work surface safety sheets, waste-disposal containers and bags. Excreta and vomit should be handled with caution. Pregnant women should be warned and avoid handling cytotoxic agents. Any broken container should be handled with the same precautions and considered contaminated waste. Disposal of contaminated waste should be done by incineration in rigid containers (labelled accordingly i.e. to indicate they contain such contaminated waste).

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.