ZANOSAR 1 g POWDER FOR CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

Zanosar 1 g powder for concentrate for solution for infusion

Streptozocin

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.

• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Zanosar and what is it used for
2. What you need to know before you use Zanosar
3. How to use Zanosar
4. Possible side effects
5. Storage of Zanosar
6. Contents of the pack and other information

1. What is Zanosar and what is it used for

This is a cytostatic medicine, which means it prevents the growth of certain cells.

It is especially indicated for the treatment of some pancreatic tumors (neuroendocrine tumors) in adults.

This medicine, which is injected intravenously, can be combined with 5-fluorouracil (5-FU).

2. What you need to know before you use Zanosar

Do not use Zanosar:

• If you are allergic to the active substance (streptozocin) or to any of the other components of this medicine (listed in section 6).
• If you have severe renal impairment (kidney failure).
• In combination with certain vaccines (called live or attenuated live vaccines).
• During breastfeeding.

Warnings and precautions

Due to the renal toxicity of this medicine, you should inform your doctor if you have kidney problems. Your kidney function will be monitored regularly by taking blood and urine samples before, during, and after treatment.

This medicine also has toxicity to the liver and blood. Periodic tests of liver function should be performed to detect the presence of hepatotoxicity.

Zanosar can cause nausea and vomiting. Therefore, your doctor may prescribe you medicines to treat them.

When combined with another medicine belonging to the same class, more adequate evaluations are performed.

Treatment will be administered under the supervision of a doctor with experience in the use of cytostatic medicines, and who will decide how to carry out the evaluation of your tolerance to treatment (analytical tests, etc.).

Men and women should use an effective contraceptive method during and after treatment. See "Pregnancy, breastfeeding, and fertility".

Monitoring during treatment

This medicine can only be used under strict medical supervision: a medical examination and blood tests should be performed during treatment. In case of doubt, ask your doctor or pharmacist for advice.

Children and adolescents

No studies have been conducted on the safety and efficacy of Zanosar in children and adolescents under 18 years of age.

Use of Zanosar with other medicines

Contraindicated combinations

This medicine MUST NOT BE USED in the following situations:

• In combination or successive administration with other substances that are potentially toxic to the kidneys (unless your doctor indicates otherwise).
• In combination with certain vaccines (called live or attenuated live vaccines).

Combinations that require caution

Tell your doctor:

• If you are taking a medicine that reduces or eliminates the body's defenses (immunosuppression),
• If you are taking oral anticoagulants (vitamin K antagonist).

Tell 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 or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Contraceptive methods for men and women

You must use an effective contraceptive method during treatment. A period of contraceptive use after treatment of 90 days, in the case of men, and 30 days, in the case of women, should be applied.

Pregnancy

Do not use this medicine if you are pregnant, plan to conceive, or do not use contraceptive methods.

Breastfeeding

It has not been determined if this medicine is transferred to breast milk. As a precaution, you should interrupt breastfeeding during treatment.

Fertility

Men treated with Zanosar are advised not to attempt to conceive children during the 90 days following treatment and to seek advice on sperm preservation before treatment, as streptozocin may alter male fertility.

Women should continue to use contraceptives during the 30 days following treatment.

Driving and using machines

Zanosar can cause confusion, fatigue, or depression, so you should not drive or use machinery if you experience any of these effects.

Zanosar contains sodium:

This medicine contains 30.1 mg of sodium (the main component of table salt/cooking salt) per vial. This is equivalent to 1.5% of the maximum recommended daily intake of sodium for an adult.

3. How to use Zanosar

This medicine should onlybe prepared and administered by healthcare professionals.

Your doctor will determine the dose you should receive based on your body surface area and general condition.

Treatment will be injected into one of your veins (intravenously) over a period of 30 minutes to 4 hours.

Two dosing regimens are usually used:

• Regimen every 6 weeks: 5 consecutive days every 6 weeks;
• Regimen every 3 weeks: 5 consecutive days during the first week and, subsequently, one infusion every 3 weeks.

If toxicity appears, it may be necessary to adjust the dose or suspend treatment.

Zanosar can cause nausea and vomiting. In this case, your doctor may prescribe you medicines to treat them.

If you take more Zanosar than you should

You will receive appropriate care.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Zanosar can cause side effects, although not everybody gets them.

Very common side effects(may affect more than 1 in 10 people)

On occasion, treatment has had to be suspended due to the appearance of severe nausea and vomiting. Cases of diarrhea have also been described.

Common side effects(may affect up to 1 in 10 people)

Kidney failure (renal insufficiency) that can be severe. Your doctor may prescribe you blood and urine tests before, during, and repeatedly after finishing treatment.

Side effects of unknown frequency(cannot be estimated from the available data)

• Hematological toxicity (toxicity in the blood) that usually involves a drop in hematocrit values (the percentage of red blood cells in relation to the total blood volume), white blood cells, and platelets. It can also increase sensitivity to infections.
• Glucose intolerance, usually mild to moderate and reversible.
• Confusion, apathy, depression.
• Nephrogenic diabetes insipidus (inability of the kidneys to concentrate urine).
• Hepatotoxicity (toxicity in the liver): increased levels of certain liver enzymes, abnormally low levels of albumin in the blood (hypoalbuminemia).
• Reactions at the injection site: tissue necrosis (destruction) when the substance passes outside the vein, burning sensation that spreads from the injection site to the arm.
• Fever.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Zanosar

Keep this medicine out of the sight and reach of children.

Do not use Zanosar after the expiry date that appears on the packaging after EXP. The expiry date refers to the last day of the month indicated.

Before opening: store the vial in the refrigerator (2°C to 8°C); keep the vial in the outer packaging to protect it from light.

After opening, reconstitution, and dilution: the reconstituted solution should be diluted immediately. Physical and chemical stability has been demonstrated for the resulting reconstituted solution for 24 hours below 25°C.

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

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

Medicines should not be disposed of via wastewater or household waste. Dispose of the packaging and any unused medicine in the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Contents of the pack and other information

Composition of Zanosar:

The active substance is:

Streptozocin 1 g (per vial of powder).

The other ingredients are:

Anhydrous citric acid

Sodium hydroxide for pH adjustment

Appearance of the product and pack contents

This medicine is presented as a sterile powder, white to light yellow in color, intended for preparation for infusion.

Box of 1 vial.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Esteve Pharmaceuticals, S.A.

Passeig de la Zona Franca, 109

08038 Barcelona

Spain

Manufacturer:

VALDEPHARM

Parc Industriel d’Incarville

Parc de la Fringale – CS10606

27106 Val de Reuil

France

This medicine is authorized in the EEA member states with the following names:

Date of last revision of this leaflet:May 2021

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

The following information is intended for healthcare professionals only:

Posology:

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

Two different dosing regimens can be used:

Regimen every 6 weeks- 500 mg/m2/day intravenously for 5 consecutive days every 6 weeks until maximum benefit is achieved or limiting toxicity is observed.

Regimen every 3 weeks- 500 mg/m2/day intravenously for 5 consecutive days in cycle 1, followed by 1000 mg/m2 every 3 weeks in subsequent cycles.

Dosing regimens with similar dose intensity have been used in clinical trials with comparable safety and efficacy results.

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

In patients with functional tumors, serial monitoring of biological markers allows determination of the biochemical response to treatment. In patients with functional or non-functional tumors, response to treatment can be determined by observing measurable reductions in tumor size on imaging.

Close monitoring of renal, hepatic, and hematological functions, as well as blood glucose levels, should be performed before, during, and after treatment. The degree of toxicity observed may require dose adjustment or suspension of the medicine.

Anti-emetic premedication is recommended to prevent nausea and vomiting.

Precautions to be taken before handling or administering the medicine

The powder and solution should be handled and prepared with care, and the use of gloves is recommended. If the sterile powder of Zanosar or a solution prepared from Zanosar comes into contact with the skin or mucous membranes, the affected area should be washed immediately with soap and water.

Adequate procedures for handling and disposal of anticancer medicines should be taken into account.

Preparation of injectable solutions of cytotoxic agents should be performed by specialized personnel with training who are familiar with the medicines used, and under conditions that ensure protection of the environment and, in particular, the personnel handling the agents. Dedicated facilities are required for preparation. Smoking, eating, and drinking are prohibited in these facilities. Personnel handling the agents should have adequate handling equipment, including long-sleeved gowns, safety masks, safety hats, safety glasses, sterile PVC gloves for single use, safety sheets for the work surface, waste containers, and bags. Excreta and vomit should be handled with caution. Pregnant women should be warned of the danger and avoid handling cytotoxic agents. Broken containers should be handled with the same precautions and considered contaminated waste. Disposal of contaminated waste should be performed by incineration in rigid containers (labeled accordingly, i.e., indicating that they contain contaminated waste).

Overdose

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

Method of administration

Zanosar should be administered intravenously by infusion. The duration of intravenous infusion should be between 30 minutes and 4 hours.

Administration of Zanosar requires hyperhydration.

This medicine has a vesicant nature and, as such, should be administered with caution through a free-flowing vein.

In case of extravasation, administration should be stopped immediately. Healthcare professionals should apply adequate protective measures. The initial goal is to minimize the volume of product extravasated to the surrounding tissues and aspirate as much product as possible from the cannula with a syringe. Cold compresses should be applied, and adequate medical supervision will be necessary.

Instructions for reconstitution

Reconstitution of Zanosar should be performed by a healthcare professional.

Preparation of doses should take into account the patient's body surface area (see the "Posology" section above).

Each 20 mL vial of Zanosar should be reconstituted with 9.5 mL of sodium chloride 9 mg/mL (0.9%) injectable solution. Dissolution of the lyophilized powder is complete in less than 2 minutes.

The resulting solution has a light yellow color.

The pH value of the reconstituted product is 4.

After reconstitution, each milliliter of solution contains 100 mg of streptozocin.

The correct amount of reconstituted solution (see section 4.2 of the SmPC to determine how to calculate the dose 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 Zanosar and 5-FU, a Y-system is recommended.