ZAVICEFTA 2 g/0.5 g POWDER FOR CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Zavicefta 2 g/0.5 g powder for concentrate for solution for infusion

ceftazidime/avibactam

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 or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Zavicefta and what is it used for
2. What you need to know before you use Zavicefta
3. How to use Zavicefta
4. Possible side effects
   1. Storage of Zavicefta

1. Contents of the pack and other information

1. What is Zavicefta and what is it used for

What is Zavicefta

Zavicefta is an antibiotic that contains the active substances ceftazidime and avibactam.

• Ceftazidime belongs to a group of antibiotics called "cephalosporins". It can kill many types of bacteria.
• Avibactam is a "beta-lactamase inhibitor" that helps ceftazidime kill some bacteria that it cannot kill on its own.

What is Zavicefta used for

Zavicefta is indicated in adults and pediatric patients from birth for the treatment of:

• infections of the stomach and intestines (abdomen)
• infections of the urinary bladder or kidneys, known as "urinary tract infections"
• a lung infection known as "pneumonia"
• infections caused by bacteria that cannot be killed with other antibiotics

Zavicefta is indicated in adults for the treatment of blood infections associated with abdominal, urinary tract, or lung infections.

How Zavicefta works

Zavicefta works by killing certain types of bacteria that can cause serious infections.

2. What you need to know before you use Zavicefta

Do not use Zavicefta if

• you are allergic to ceftazidime, avibactam, or any of the other ingredients of this medicine (listed in section 6)
• you are allergic to other cephalosporins
• you have ever had a severe allergic reaction to other antibiotics belonging to the penicillin or carbapenem groups

Do not use Zavicefta if any of the above applies to you. If you are not sure, consult your doctor or nurse before using Zavicefta.

Warnings and precautions

Consult your doctor or nurse before starting to use Zavicefta if:

• you have ever had an allergic reaction (even if it is just a skin rash) to antibiotics belonging to the penicillin or carbapenem groups
• you have kidney problems - your doctor may need to give you a lower dose to make sure you are not taking too much medicine. This could cause you symptoms such as seizures (see section If you use more Zavicefta than you should)

If any of the above applies to you (or you are not sure), consult your doctor or nurse before using Zavicefta.

Consult your doctor or nurse if you get diarrhea during your treatment.

Other infections

There is a small chance that you may get a different infection caused by another bacterium during or after treatment with Zavicefta. This includes candidiasis (fungal infections of the mouth or genital area).

Lab tests

If you are going to have any tests, tell your doctor that you are being treated with Zavicefta. This is because you may get an abnormal result on a lab test called "Coombs test" or "DAGT". This test detects antibodies that can act against your red blood cells.

Zavicefta may also affect the results of some urine tests for sugar. Tell the person taking the sample that you have been given Zavicefta.

Other medicines and Zavicefta

Tell your doctor or nurse if you are using, have recently used, or might use any other medicines.

Tell your doctor before using Zavicefta if you are taking any of the following medicines:

• an antibiotic called chloramphenicol
• a type of antibiotic called aminoglycoside, such as gentamicin, tobramycin
• a diuretic called furosemide
• a medicine for gout called probenecid

Consult your doctor before using Zavicefta if any of the above applies to you.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before using this medicine.

Driving and using machines

Zavicefta may make you feel dizzy. This may affect your ability to drive or use machines.

Zavicefta contains sodium

This medicine contains approximately 146 mg of sodium (a major component of cooking/table salt) in each vial. This is equivalent to 7.3% of the maximum recommended daily intake of sodium for an adult.

Consult your doctor or pharmacist if you need 3 or more vials per day for a prolonged period, especially if you have been advised to follow a low-salt diet.

3. How to use Zavicefta

Zavicefta will be given to you by a doctor or nurse.

How much to use

The recommended dose for adults is one vial (2 g of ceftazidime and 0.5 g of avibactam) every 8 hours. The doctor will calculate the dose for pediatric patients from birth based on the child's weight and age.

It is given through a drip into a vein - this usually takes about 2 hours.

The duration of treatment is usually 5 to 14 days, depending on the type of infection you have and how you respond to treatment.

People with kidney problems

If you have kidney problems, your doctor may reduce your dose. This is because Zavicefta is removed from your body through your kidneys.

If you use more Zavicefta than you should

Zavicefta will be given to you by a doctor or nurse, so it is unlikely that you will be given an incorrect dose. However, if you experience any side effects or think you may have been given too much Zavicefta, tell your doctor or nurse immediately. If you take too much Zavicefta, you may have an effect on your brain and get seizures or coma.

If you forget to use Zavicefta

If you think you have missed a dose, tell your doctor or nurse immediately.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects may happen with this medicine:

Serious side effects

Tell your doctor immediately if you get any of the following serious side effects - you may need urgent medical treatment:

• severe allergic reactions - the signs may include sudden swelling of your lips, face, throat, or tongue, a severe rash, or other severe skin reactions, difficulty swallowing or breathing, or sudden chest pain (which may be a sign of Kounis syndrome). These reactions can be life-threatening.
• diarrhea that gets worse or does not stop, or stools that contain blood or mucus - this can happen during or after stopping treatment with Zavicefta. In this situation, do not take medicines that stop or slow down bowel movements.

Tell your doctor immediately if you get any of the serious side effects mentioned above.

Other side effects

Tell your doctor or nurse if you get any of the following side effects:

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

• abnormal result on a lab test called "DAGT" or "Coombs test". This test detects antibodies that can act against your red blood cells. You may get anemia (which can make you feel tired) and jaundice (yellowing of the skin and eyes)

Common:(may affect up to 1 in 10 people)

• fungal infections, including infections in the mouth and vagina
• change in the number of some types of blood cells (called "eosinophils" and "platelets") - which can be seen in blood tests
• headache
• feeling dizzy
• feeling sick (nausea) or being sick (vomiting)
• stomach pain
• diarrhea
• increase in the amount of some enzymes produced by the liver - which can be seen in blood tests
• itchy lumps (hives)
• itching
• redness, pain, or swelling at the injection site of Zavicefta
• fever

Uncommon:(may affect up to 1 in 100 people)

• increase in the number of a type of blood cell (called "lymphocytes") - which can be seen in blood tests
• decrease in the number of some types of blood cells (called "leukocytes") - which can be seen in blood tests
• tingling or numbness
• bad taste in the mouth
• increase in the level of some substances in the blood (called "creatinine" and "urea"). These substances indicate how well your kidneys are working.

Rare:(may affect up to 1 in 10,000 people)

• swelling of a part of the kidney that causes a decrease in its normal function

Frequency not known:(frequency cannot be estimated from the available data)

• significant decrease in the type of white blood cells that fight infection, which can be seen in blood tests
• decrease in the number of red blood cells (hemolytic anemia), which can be seen in blood tests
• severe allergic reaction (see serious side effects, above)
• yellowing of the whites of the eyes or skin (jaundice)
• sudden appearance of a severe rash or blistering or peeling of the skin, possibly with high fever or joint pain (these can be signs of more serious medical problems such as toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, or a condition known as DRESS, Drug Reaction with Eosinophilia and Systemic Symptoms)
• swelling under the skin, especially on the lips and around the eyes

Tell your doctor or nurse if you get any of the side effects mentioned above.

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via 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 Zavicefta

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

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.

Store in the original package to protect from light.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Contents and Additional Information

Composition of Zavicefta

• The active substances are ceftazidime and avibactam. Each vial contains ceftazidime pentahydrate equivalent to 2 g of ceftazidime and avibactam sodium equivalent to 0.5 g of avibactam.
• The other excipients are anhydrous sodium carbonate (see section "Zavicefta contains sodium").

Appearance and Container Contents of the Product

Zavicefta is a white to yellow powder for concentrate for solution for infusion contained in a vial. It is marketed in boxes containing 10 vials.

Marketing Authorisation Holder

Pfizer Ireland Pharmaceuticals Unlimited Company

Operations Support Group

Ringaskiddy, County Cork

Ireland

Manufacturer

ACS Dobfar, S.p.A.

Via Alessandro Fleming 2

Verona 37135

Italy

You can request more information about this medicinal product by contacting the local representative of the marketing authorisation holder:

Date of Last Revision of this Leaflet: 02/2025.

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu

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This information is intended only for healthcare professionals:

Important: Please consult the Summary of Product Characteristics before prescribing.

The compatibility of Zavicefta with other medicinal products has not been established. Zavicefta must not be mixed or added to solutions containing other medicinal products.

The powder must be reconstituted with water for injections and the resulting concentrate must then be diluted immediately before use. The reconstituted solution is a pale yellow solution free from particles.

Gently mix to reconstitute and check that the contents have dissolved completely. Parenteral medicinal products must be inspected visually for particulate matter before administration.

Infusion Bags

If the intravenous solution is prepared with the diluents listed in section 6.6 (ceftazidime concentration of 8 mg/ml), chemical and physical stability in use (from initial vial puncture) has been demonstrated for a period of up to 12 hours at 2°C – 8°C, followed by up to 4 hours at not more than 25°C.

If the intravenous solution is prepared with the diluents listed in section 6.6 (ceftazidime concentration of > 8 mg/ml to 40 mg/ml), chemical and physical stability in use (from initial vial puncture) has been demonstrated for a period of up to 4 hours at not more than 25°C.

From a microbiological point of view, the product must be used immediately, unless reconstitution and dilution are performed under aseptic conditions and validated. If not used immediately, the periods and conditions of storage before use are the responsibility of the user and should not exceed those mentioned above.

Infusion Syringes

If the intravenous solution is prepared with the diluents listed in section 6.6 (ceftazidime concentration ≥ 8 mg/ml to 40 mg/ml), chemical and physical stability in use (from initial vial puncture) has been demonstrated for a period of up to 6 hours at not more than 25°C.

From a microbiological point of view, the product must be used immediately, unless reconstitution/dilution is performed under aseptic conditions and validated. If not used immediately, the periods and conditions of storage before use are the responsibility of the user and should not exceed 6 hours at not more than 25°C.

Zavicefta (ceftazidime/avibactam) is a combination medicinal product; each vial contains 2 g of ceftazidime and 0.5 g of avibactam in a fixed ratio of 4:1. Dosing recommendations are based solely on the ceftazidime component.

For preparation and administration of the solution, standard aseptic techniques should be employed. Paediatric doses can be prepared in an infusion bag or a syringe of suitable size.

The resulting solution should be administered over 120 minutes.

Each vial is for single use.

Disposal of unused medicinal product and all materials that have come into contact with it should be done in accordance with local regulations.

The total time between the start of reconstitution and completion of preparation of the intravenous infusion should not exceed 30 minutes.

Instructions for preparing doses for adults and paediatric patients in an INFUSION BAG or an INFUSION SYRINGE:

NOTE: The following procedure describes the steps to prepare an infusion solution with a final concentration of 8-40 mg/ml of ceftazidime. All calculations should be completed before starting these steps.

• For paediatric patients from 3 to 12 months of age, the following detailed steps are provided to prepare a concentration of 20 mg/ml (sufficient for most situations).
• For paediatric patients from birth (including premature infants) to <3 months of age< strong>, the following detailed steps are provided to prepare a concentration of 10 mg/ml (sufficient for most situations).

1. Prepare the reconstituted solution(167.3 mg/mlof ceftazidime):

1. Insert the needle of the syringe through the vial stopper and inject 10 ml of sterile water for injections.
2. Remove the needle and shake the vial until a clear solution is obtained.
3. Insert a needle to release the gas through the vial stopper afterthe product has dissolved to release the internal pressure (this is important to preserve the sterility of the product).

1. Prepare the final solutionfor infusion (the final concentration should be 8 to 40 mg/mlof ceftazidime):

1. Infusion bag: prepare additional dilutions of the reconstituted solution by transferring a correctly calculated volume of the reconstituted solution to an infusion bag containing one of the following solutions: sodium chloride 9 mg/ml (0.9%) solution for injection, glucose 50 mg/ml (5%) solution for injection, or Lactated Ringer's solution. Refer to the table below.
2. Infusion syringe: prepare additional dilutions of the reconstituted solution by transferring a correctly calculated volume of the reconstituted solution combined with a sufficient volume of diluent (sodium chloride 9 mg/ml (0.9%) solution for injection or glucose 50 mg/ml (5%) solution for injection) to an infusion syringe.

Refer to the table below.

1 Based solely on the ceftazidime component.

2 Dilute to a final concentration of ceftazidime of 8 mg/ml for stability in use during a period of up to 12 hours at 2°C – 8°C, followed by up to 4 hours at not more than 25°C (i.e., dilute a dose of 2 g of ceftazidime in 250 ml, a dose of 1 g of ceftazidime in 125 ml, a dose of 0.75 g of ceftazidime in 93 ml, etc.). All other concentrations of ceftazidime (> 8 mg/ml to 40 mg/ml) have stability in use during a period of up to 4 hours at not more than 25°C.

3 Dilute to a final concentration of ceftazidime of ≥ 8 mg/ml to 40 mg/ml for stability in use during a period of up to 6 hours at not more than 25°C.

Paediatric patients from 3 to 12 months of age

NOTE: The following procedure describes the steps to prepare an infusion solution with a final concentration of 20 mg/ml of ceftazidime (sufficient for most situations). Alternative concentrations can be prepared, but they should have a final concentration range of 8 to 40 mg/ml of ceftazidime.

1. Prepare the reconstituted solution(167.3 mg/mlof ceftazidime):

1. Insert the needle of the syringe through the vial stopper and inject 10 ml of sterile water for injections.
2. Remove the needle and shake the vial until a clear solution is obtained.
3. Insert a needle to release the gas through the vial stopper afterthe product has dissolved to release the internal pressure (this is important to preserve the sterility of the product).

1. Prepare the final solutionfor infusion at a final concentration of 20 mg/mlof ceftazidime:

1. Prepare additional dilutions of the reconstituted solution by transferring a correctly calculated volume of the reconstituted solution combined with a sufficient volume of diluent (sodium chloride 9 mg/ml (0.9%) solution for injection or glucose 50 mg/ml (5%) solution for injection) to an infusion syringe.
2. Refer to the tables below to confirm calculations. The values shown are approximate, as it may be necessary to round to the nearest graduation mark on a syringe of suitable size. Note that the tables do NOT include all possible calculated doses, but can be used to estimate the approximate volume for verification of the calculation.

Preparation of Zavicefta (final concentration of 20 mg/ml of ceftazidime) for paediatric patients from 3 to 12 months of age with creatinine clearance (CrCL) > 50 ml/min/1.73 m2

1 Based solely on the ceftazidime component.

Preparation of Zavicefta (final concentration of 20 mg/ml of ceftazidime) for paediatric patients from 3 to 12 months of age with creatinine clearance (CrCL) of 31 to 50 ml/min/1.73 m2

Content of ceftazidime.

Preparation of Zavicefta (final concentration of 20 mg/ml of ceftazidime) for pediatric patients from 3 to 12 months of age with creatinine clearance (CrCL) of 16 to 30 ml/min/1.73 m2

1 Based solely on the ceftazidime component.

Pediatric patients from birth (including preterm infants) to < 3 months of age:

NOTE: The following procedure describes the steps to prepare a parenteral solution for infusion with a final concentration of 10 mg/ml of ceftazidime suitable for administration of doses less than 250 mg to pediatric patients from birth (including preterm infants) to < 3 months of age. Alternative concentrations can be prepared, but they should have a final concentration range of 8 to 40 mg/ml of ceftazidime.

1. Prepare the reconstituted solution(167.3mg/mlof ceftazidime):

1. Insert the needle of the syringe through the vial stopper and inject 10 ml of sterile water for injectable preparations.
2. Remove the needle and shake the vial until a clear solution is obtained.
3. Insert a needle to release the gas through the vial stopper afterthe product has dissolved to release the internal pressure (this is important to preserve the sterility of the product).

1. Prepare the final parenteral solutionfor infusion at a final concentration of 10mg/mlof ceftazidime:

1. Prepare additional dilutions of the reconstituted solution by transferring 3 ml of the reconstituted solution to an infusion bag or syringe containing 47 ml of diluent (sodium chloride 9 mg/ml [0.9%] injectable solution or dextrose 50 mg/ml [5%] injectable solution) to obtain a final volume of 50 ml.
2. Mix well (e.g., gently invert the infusion bag or, using a syringe connector, slowly pass the solution from one side to the other at least 5 times between 2 syringes).
3. Transfer an appropriate volume of 10mg/mlceftazidime parenteral solution to an infusion syringe. Refer to the table below for the volume of parenteral solution to be transferred to the infusion syringe to be administered. The values shown are approximate, as it may be necessary to round to the nearest graduation mark of a syringe of suitable size.

Note that the tables DO NOT include all possible calculated doses, but can be used to estimate the approximate volume for verification of the calculation.

Administration of Zavicefta in pediatric patients from birth (including preterm infants) to < 3 months of age using a 50 ml Zavicefta parenteral solution (final concentration of 10 mg/ml of ceftazidime) prepared with 3 ml of reconstituted solution extracted from the vial and added to 47 ml of diluent.

1 Based solely on the ceftazidime component.