Streptozocin Keocyt: detailed information

Package leaflet: Information for the patient

Streptozocin Keocyt

Streptozocin
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

What Streptozocin Keocyt is and what it is used for
What you need to know before using Streptozocin Keocyt
How to use Streptozocin Keocyt
Possible side effects
How to store Streptozocin Keocyt
Contents of the pack and other information

1. What Streptozocina Keocyt is and what it is used for

This is a cytostatic medicinal product, which means that it prevents the growth of certain cells.
It is particularly indicated in adults for certain pancreatic tumours (neuroendocrine tumours).
This medicinal product, which is administered by intravenous injection, may be used in combination with 5-fluorouracil (5-FU).

2. What you need to know before using Streptozocin Keocyt

Streptozocin Keocyt must never be used:

if you are allergic to the active substance (streptozocin) or to any of the other ingredients of this medicine (listed in section 6);
if you have severe renal impairment (kidney function failure);
in combination with certain vaccines (so-called live or live attenuated vaccines);
during breastfeeding.

Warnings and precautions
Due to the kidney toxicity of this medicine, you must inform your doctor if you have kidney problems. Renal function will be monitored regularly through blood and urine tests before, during, and after treatment.
This medicine may also be toxic to the liver and blood. Regular liver function tests are necessary to detect any potential liver toxicity.
Streptozocin Keocyt may cause nausea and vomiting. Therefore, your doctor may prescribe antiemetic medicines.
When combined with another medicine from the same class, additional appropriate investigations will be carried out.
Your treatment will be administered under the supervision of a physician experienced in the use of cytostatic medicines. This physician will decide in which setting treatment tolerance monitoring (laboratory tests, etc.) will take place.
Men and women must use an effective method of contraception during and after treatment. See the section “Pregnancy, breastfeeding and fertility” below.
Monitoring during treatment
This medicine may be used only under close medical supervision: medical examinations and blood tests are required during treatment. If in doubt, do not hesitate to consult your doctor or pharmacist.
Children and adolescents
The safety and efficacy of Streptozocin Keocyt have not been studied in children and adolescents under 18 years of age.
Other medicines and Streptozocin Keocyt
Combinations that are contraindicated
This medicine MUST NOT BE USED in the following situations:

In combination with, or sequentially after, other substances that are potentially nephrotoxic (unless otherwise directed by your doctor).
Combination with certain vaccines (so-called live or live attenuated vaccines).

Combinations requiring caution
Inform your doctor:

If you are taking a medicine that reduces or suppresses the body's immune defenses (immunosuppression).
If you are taking oral anticoagulants (vitamin K antagonists).

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Male and female contraception
An effective method of contraception must be used during treatment. A post-treatment contraception period of 90 days is required for men and 30 days for women.
Pregnancy
You must not use this medicine if you are pregnant, planning a pregnancy, or not using a contraceptive method.
Breastfeeding
It is not known whether this medicine passes into breast milk. As a precautionary measure, breastfeeding must be discontinued during treatment.
Fertility
If you are a man undergoing treatment with Streptozocin Keocyt, you are advised not to attempt to father a child for 90 days after treatment, and to seek advice regarding sperm preservation before treatment, as streptozocin may impair male fertility.
If you are a woman, you must continue contraception for 30 days after treatment.
Driving and using machines
Streptozocin Keocyt may cause confusion, fatigue or depression; therefore, if you experience any of these adverse effects, you must not drive or operate machinery.
Streptozocin Keocyt contains sodium:
This medicine contains 30.1 mg of sodium (a main component of table salt) per vial. This corresponds to 1.5% of the maximum daily dietary intake recommended for an adult.

3. How to use Streptozocin Keocyt

This medicine must be prepared and administered only by a healthcare professional.
Your doctor will determine the dose you should receive based on your body surface area and general condition.
The treatment will be administered by intravenous infusion (intravenous use). The infusion will last from 30 minutes to 4 hours.
Two dosing regimens are generally used:

Regimen administered every six weeks: 5 consecutive days every 6 weeks;
Regimen administered every three weeks: 5 consecutive days during the first week, followed by 1 infusion every 3 weeks.

If toxicity develops, dose adjustment or treatment discontinuation may be necessary.
Streptozocin Keocyt may cause nausea and vomiting. Therefore, your doctor may prescribe antiemetic medicines.
If you receive more Streptozocin Keocyt than you should
Appropriate supportive measures will be provided.
If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Very common side effects (may affect more than 1 in 10 people)
Severe nausea and vomiting, which occasionally required discontinuation of treatment.
Cases of diarrhoea have also been reported.
Common side effects (may affect up to 1 in 10 people)
Kidney damage (impaired kidney function), which can be severe. Your doctor may prescribe blood and urine tests before, during, and repeatedly after completion of treatment.
Side effects of unknown frequency (frequency cannot be estimated from the available data)

Haematological toxicity (blood toxicity), which usually involves a decrease in haematocrit values (the percentage volume of red blood cells in total blood volume), white blood cells, and platelets. This may also increase susceptibility to infections.
Abnormalities in glucose tolerance, usually mild to moderate and generally reversible.
Confusion, lethargy, depression.
Nephrogenic diabetes insipidus (inability of the kidneys to concentrate urine).
Hepatotoxicity (liver toxicity): increase in certain liver enzymes, abnormally low levels of albumin in the blood (hypoalbuminaemia).
Reactions at the injection site: tissue necrosis (tissue destruction) when the substance leaks outside the vein, burning sensations spreading from the injection site up the arm.
Fever.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Streptozocin Keocyt

Keep this medicine out of the sight and reach of children.
Do not use Streptozocin Keocyt after the expiry date stated on the vial after Exp.:.
The expiry date refers to the last day of that month.
Before opening: store the vial in a refrigerator (2°C – 8°C); keep the vial in the outer packaging to protect the medicine from light.
After opening, reconstitution, and dilution: the reconstituted solution must be diluted immediately. Chemical and physical in-use stability of the resulting solution has been demonstrated for 24 hours at a temperature below 25 °C.
The product does not contain preservatives and is for single use only.
From a microbiological standpoint, unless the method of opening/reconstitution/dilution excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the user is responsible for the storage conditions and duration of use.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Streptozocina Keocyt contains:
The active substance is:
Streptozocin 1 g (per vial of powder).
The other components are:
Anhydrous citric acid
Sodium hydroxide to adjust pH

Description of the appearance of Streptozocina Keocyt and package contents
This medicine is a sterile powder, white to pale yellow in colour, for infusion concentrate.
Pack: 1 vial per carton.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
ESTEVE PHARMACEUTICALS S.A.S.
Immeuble Cap Sud
106, avenue Marx-Dormoy
92120 Montrouge
France

Manufacturer:
VALDEPHARM
Parc Industriel d’Incarville
Parc de la Fringale – CS10606
27106 Val de Reuil
France

This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

België/Belgique/Belgien Danmark
Streptozocine Esteve 1g, powder for Zanosar
concentrate for solution for infusion

Deutschland Nederland
Zanosar 1g, powder for concentrate for Zanosar 1g, powder for concentrate for
preparation of infusion solution solution for infusion

España Norge
Zanosar 1g, powder for concentrate for Zanosar 1g, powder for concentrate for
infusion solution infusion solution, solution

France Italia
Zanosar 1g, powder for solution to be diluted Streptozocina Keocyt
for infusion

Suomi/Finland Sverige
Zanosar 1g, dry substance for intermediate Zanosar 1g, powder for concentrate for
concentrate for infusion, solution infusion solution, solution

United Kingdom (Northern Ireland)
Zanosar 1g, powder for concentrate for
solution for infusion

Further sources of information
More detailed information on this medicinal product is available on the website of the AIFA (Agenzia Italiana del Farmaco, Italy).

The following information is intended for healthcare professionals only:

Dosage:
The dose is based on body surface area (m²).
Two different dosage regimens may be used:
Six-weekly regimen – 500 mg/m²/day, administered intravenously for 5 consecutive days every six weeks, until maximum benefit is achieved or until treatment-limiting toxicity is observed.
Three-weekly regimen – 500 mg/m²/day, administered intravenously for 5 consecutive days during the first cycle, followed by 1000 mg/m² every three weeks in subsequent cycles.
Other dosage regimens with similar dose intensity have been used in clinical studies, yielding comparable efficacy and safety results.
The optimal duration of maintenance therapy with Streptozocin Keocyt has not been established.
For patients with functional tumors, serial monitoring of biochemical markers allows assessment of biochemical response to therapy. For patients with either functional or non-functional tumors, response to therapy may be determined by measurable tumor reduction on diagnostic imaging.
Careful monitoring of renal, hepatic, and hematological function must be performed before, during, and after treatment, along with blood glucose determination. Dose adjustment or drug discontinuation may be required based on the degree of observed toxicity.
Anti-emetic premedication is recommended to prevent nausea and vomiting.

Precautions to be taken before handling or administering the medicinal product
Exercise caution when handling and preparing the powder and solution; the use of gloves is recommended. If sterile Streptozocin Keocyt powder or a prepared Streptozocin Keocyt solution comes into contact with skin or mucous membranes, immediately wash the affected area with soap and water.
Appropriate procedures for the safe handling and disposal of antineoplastic drugs should be followed.
Preparation of injectable cytotoxic solutions must be carried out by specialists and trained personnel familiar with these medicinal products, under conditions ensuring environmental protection, particularly for personnel handling the agents. This procedure requires dedicated preparation areas. Eating, drinking, and smoking in these areas are strictly prohibited. Personnel handling cytotoxic agents must have access to appropriate protective equipment, including long-sleeved gowns, safety masks, safety head covers, safety goggles, sterile disposable PVC gloves, protective surface coverings, and waste containers and bags for disposal. Excreta and vomit must be handled with caution. Pregnant women should be advised to avoid handling cytotoxic agents. Any broken container must be handled with the same precautions and considered contaminated waste. Disposal of contaminated waste must be carried out in an incinerator using rigid containers (properly labeled to indicate the presence of such contaminated waste).

Overdose
There are no specific antidotes for Streptozocin Keocyt overdose, and treatment of overdose should consist of supportive measures. Overdose must be avoided by careful calculation of the administered dose.

Method of administration
Streptozocin Keocyt must be administered intravenously by infusion. The infusion should last between 30 minutes and 4 hours.
Administration of Streptozocin Keocyt requires hyperhydration.
This medicinal product is vesicant in nature and must therefore be administered with caution via a free-flowing line.
In case of extravasation, administration must be stopped immediately. Healthcare providers must take appropriate protective measures. The initial goal is to minimize the volume of extravasated product in surrounding tissues and to aspirate as much of the product as possible from the cannula using a syringe. Cold compresses should be applied and adequate medical monitoring initiated.

Reconstitution instructions
Streptozocin Keocyt must be reconstituted by a healthcare professional.
Dose preparation must take into account the patient’s body surface area (see Dosage section above).
Each 20 mL vial of Streptozocin Keocyt must be reconstituted with 9.5 mL of 0.9% (9 mg/mL) sodium chloride injectable solution. Complete dissolution of the lyophilized powder occurs in less than 2 minutes.
The resulting solution is pale golden in color.
The pH of the reconstituted product is 4.
After reconstitution, each mL of solution contains 100 mg of streptozocin.
The appropriate volume of reconstituted solution (see section 4.2 of the SmPC for dose calculation based on body surface area) should then be diluted in 500 mL of the same solution used for reconstitution.
In case of co-administration of Streptozocin Keocyt and 5-FU, a Y-site infusion set system is recommended.