Zerbaxa 1 g/0.5 g powder for concentrate for solution for infusion

Package leaflet: Information for the patient

Introduction

Package leaflet: information for the patient

Zerbaxa 1 g / 0.5 g powder for concentrate for solution for infusion

ceftolozane / tazobactam

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor or pharmacist, even if it is a side effect not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Zerbaxa is and what it is used for

Zerbaxa is a medicine used to treat a range of bacterial infections. It contains two active substances:

• ceftolozane, an antibiotic belonging to the "cephalosporin" group that can kill certain bacteria that may cause infection;
• tazobactam, which blocks the action of certain enzymes called beta-lactamases. These enzymes make bacteria resistant to ceftolozane by destroying the antibiotic before it can act. By blocking the action of these enzymes, tazobactam makes ceftolozane more effective at killing bacteria.

Zerbaxa is used in all age groups to treat complicated infections within the abdomen, kidney, and urinary tract.

Zerbaxa is also used in adults to treat a lung infection called "pneumonia."

2. What you need to know before using Zerbaxa

Do not use Zerbaxa

• if you are allergic to ceftolozane, tazobactam, or any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to medicines called "cephalosporins".
• if you have had a severe allergic reaction (for example, severe skin peeling; swelling of the face, hands, feet, lips, tongue, or throat; or difficulty swallowing or breathing) to other antibiotics (for example, penicillins or carbapenems).

Warnings and precautions

Talk to your doctor or pharmacist before starting Zerbaxa if you know you are, or have previously been, allergic to cephalosporins, penicillins, or other antibiotics.

Talk to your doctor or pharmacist if you develop diarrhea while taking Zerbaxa.

Infections caused by bacteria that are not sensitive to Zerbaxa or infections caused by fungi may occur during or after treatment with Zerbaxa. Inform your doctor if you think you may have another infection.

Sometimes treatment with Zerbaxa causes the production of antibodies that react with your red blood cells. If you are told that you have an abnormal blood test (called a Coombs test), inform your doctor that you are currently using or have recently used Zerbaxa.

Children and adolescents

This medicine should not be given to children under 18 years of age for the treatment of pneumonia, as there is insufficient information on its use in this age group for treating this infection.

Other medicines and Zerbaxa

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Some medicines may interact with ceftolozane and tazobactam, including:

• Probenecid (a medicine for gout). This may increase the time it takes for tazobactam to leave your body.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medicine. Your doctor will advise you whether you should use Zerbaxa during pregnancy.

If you are breastfeeding, your doctor will advise whether you should discontinue breastfeeding or stop using or avoid treatment with Zerbaxa, after considering the benefit of breastfeeding for the child and the benefit of treatment for you.

Driving and using machines

Zerbaxa may cause dizziness, which may affect your ability to drive or operate machinery.

Zerbaxa contains sodium

This medicine contains 230 mg of sodium (the main component of table/cooking salt) per vial. This corresponds to 11.5% of the maximum daily recommended sodium intake for an adult. The reconstituted vial with 10 ml of 0.9% sodium chloride (physiological saline) for injectable preparations contains 265 mg of sodium per vial. This corresponds to 13.3% of the maximum daily recommended sodium intake for an adult.

3. How to use Zerbaxa

Your doctor or other healthcare professional will administer this medicine into a vein by infusion (drip) over 1 hour. The dose of medicine you will receive depends on whether or not you have any kidney problems.

The dose depends on the type of infection you have, where in your body the infection is located, and how severe the infection is. Your doctor will decide the dose you need.

Use in adults

The recommended dose of Zerbaxa is 1 g of ceftolozano and 0.5 g of tazobactam or 2 g of ceftolozano and 1 g of tazobactam every 8 hours, administered into a vein (directly into the bloodstream).

Treatment with Zerbaxa usually lasts between 4 and 14 days, depending on the severity and location of the infection and how your body responds to treatment.

Use in children and adolescents

The recommended dose of Zerbaxa is 20 mg/kg of ceftolozano and 10 mg/kg of tazobactam every 8 hours, administered into a vein (directly into the bloodstream). The dose should not exceed 1 g of ceftolozano and 0.5 g of tazobactam.

Treatment with Zerbaxa usually lasts between 5 and 14 days, depending on the severity and location of the infection and how your body responds to treatment.

Patients with kidney problems

Your doctor may reduce your dose of Zerbaxa or adjust the frequency of administration. Your doctor may also perform blood tests to ensure you are receiving an appropriate dose, especially if you need to receive this treatment for a prolonged period.

If you use more Zerbaxa than you should

Since this medicine is given by a doctor or other healthcare professional, it is very unlikely that you will be given too much. However, if you have any concerns, you should immediately inform your doctor, nurse, or pharmacist.

If you interrupt treatment with Zerbaxa

If you think you have missed a dose of Zerbaxa, inform your doctor or healthcare professional immediately.

If you have any other questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Tell your doctor immediately if you have any of these symptoms, as you may need urgent medical treatment:

• Sudden swelling of your lips, face, throat or tongue; widespread rash; and difficulty swallowing or breathing. These may be signs of a severe allergic reaction (anaphylaxis) and could be life-threatening
• Diarrhea that may become severe or does not go away, or blood or mucus in your stools during or after treatment with Zerbaxa. In this case, you should not take medicines that stop or slow down intestinal movement

Adults treated for complicated intra-abdominal infections and kidney and urinary tract infections

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

Headache, stomach pain, constipation, diarrhea, nausea, vomiting, increased liver enzymes (in blood tests), rash, fever (high temperature), low blood pressure, decreased potassium (in blood tests), increased number of certain types of blood cells known as platelets, dizziness, anxiety, difficulty sleeping, infusion site reactions

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

Inflammation of the large intestine due to C. difficile bacteria, stomach inflammation, abdominal distension, indigestion, excessive gas in the stomach or intestine, intestinal obstruction, fungal infection in the mouth (candidiasis), fungal infection of the female genital tract, fungal (yeast) infection of the urinary tract, increased blood sugar (glucose) levels (in blood tests), decreased magnesium levels (in blood tests), decreased phosphate levels (in blood tests), ischaemic stroke (stroke caused by reduced blood flow to the brain), irritation or inflammation of a vein at the injection site, venous thrombosis (blood clot in a vein), low red blood cell count, atrial fibrillation (fast or irregular heartbeat), rapid heartbeat, angina (chest pain or sensation of tightness, pressure or heaviness in the chest), itchy rash or skin swelling, hives, positive Coombs test (a blood test that detects antibodies against your red blood cells), kidney problems, kidney disease, difficulty breathing

Additional adverse effects observed in children and adolescents treated for complicated intra-abdominal infections and kidney and urinary tract infections

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

Increased appetite, low white blood cell count, altered taste

Adults treated for a lung infection called "pneumonia"

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

Inflammation of the large intestine due to C. difficile bacteria, diarrhea, vomiting, increased liver enzymes (in blood tests)

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

Infection due to C. difficile bacteria, positive C. difficile test (in stool tests), positive Coombs test (a blood test that detects antibodies against your red blood cells)

Reporting of adverse effects

If you experience any adverse effects, talk to your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Zerbaxa

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

Do not use this medicine after the expiry date stated on the carton and vial after “CAD” or “EXP”. The expiry date refers to the last day of the month indicated.

Unopened vials: Store in a refrigerator (between 2 ºC and 8 ºC).

Keep in the original packaging to protect from light.

Medicines should not be disposed of via wastewater. Disposal of unused medicine and all materials that have come into contact with it must be carried out in accordance with local regulations. This will help protect the environment.

6. Contents of the pack and other information

Composition of Zerbaxa

• The active substances are ceftolozane and tazobactam.
• Each vial contains ceftolozane sulfate equivalent to 1 g of ceftolozane and sodium tazobactam equivalent to 0.5 g of tazobactam. Two vials are used for doses exceeding 1 g of ceftolozane and 0.5 g of tazobactam.
• The other excipients are sodium chloride, arginine, and anhydrous citric acid.

Nature and contents of the container

Zerbaxa is a white to slightly yellow powder for concentrate for solution for infusion (powder for concentrate) supplied in a vial.

Zerbaxa is available in packs containing 20 ml clear type I glass vials with a stopper (bromobutyl rubber) and a seal.

Packs containing 10 vials.

Marketing Authorization Holder

Merck Sharp & Dohme B.V.

Waarderweg 39

2031 BN Haarlem

The Netherlands

Manufacturer responsible for production

FAREVA Mirabel

Route de Marsat

Riom

63963, Clermont-Ferrand Cedex 9

France

Further information on this medicinal product is available from the local representative of the Marketing Authorization Holder:

Date of the most recent review of this summary: {month YYYY}.

Other sources of information

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

This information is intended for healthcare professionals only:

Preparation of solutions

Each vial is for single use only.

Aseptic technique must be used when preparing the infusion solution.

Preparation of doses

Each vial of powder for concentrate for solution for infusion is reconstituted with 10 ml of water for injections or 9 mg/ml sodium chloride (0.9%) solution for injections per vial; after reconstitution, the vial should be gently shaken to dissolve the powder. The final volume is approximately 11.4 ml per vial. The resulting concentration is approximately 132 mg/ml (88 mg/ml ceftolozane and 44 mg/ml tazobactam) per vial.

WARNING: THE RECONSTITUTED SOLUTION MUST NOT BE INJECTED DIRECTLY.

The Zerbaxa infusion solution is clear and colourless to slightly yellow.

Variation in colour within this range does not affect the potency of the medicine.

After reconstitution and dilution, chemical and physical in-use stability has been demonstrated for 24 hours at room temperature or 4 days at 2 to 8 °C. The medicine is photosensitive and must be protected from light when not stored in the original container.

See section 4.2 of the Summary of Product Characteristics for recommended dosing regimens for Zerbaxa according to indication and renal function. Preparation of each dose is described below.

Instructions for preparing adult doses in an INFUSION BAG:

Preparation of the 2 g ceftolozane/1 g tazobactam dose: Withdraw the entire contents of two reconstituted vials (approximately 11.4 ml per vial) using a syringe and add to an infusion bag containing 100 ml of 0.9% sodium chloride for injections (normal saline) or 5% glucose for injections.

Preparation of the 1.5 g ceftolozane/0.75 g tazobactam dose: Withdraw the entire contents of one reconstituted vial (approximately 11.4 ml per vial) and 5.7 ml from a second reconstituted vial using a syringe and add to an infusion bag containing 100 ml of 0.9% sodium chloride for injections (normal saline) or 5% glucose for injections.

Preparation of the 1 g ceftolozane/0.5 g tazobactam dose: Withdraw the entire contents (approximately 11.4 ml) of the reconstituted vial using a syringe and add to an infusion bag containing 100 ml of 0.9% sodium chloride for injections (normal saline) or 5% glucose for injections.

Preparation of the 500 mg ceftolozane/250 mg tazobactam dose: Withdraw 5.7 ml of the contents from the reconstituted vial and add to an infusion bag containing 100 ml of 0.9% sodium chloride for injections (normal saline) or 5% glucose for injections.

Preparation of the 300 mg ceftolozane/150 mg tazobactam dose: Withdraw 3.5 ml of the contents from the reconstituted vial and add to an infusion bag containing 100 ml of 0.9% sodium chloride for injections (normal saline) or 5% glucose for injections.

Preparation of the 250 mg ceftolozane/125 mg tazobactam dose: Withdraw 2.9 ml of the contents from the reconstituted vial and add to an infusion bag containing 100 ml of 0.9% sodium chloride for injections (normal saline) or 5% glucose for injections.

Preparation of the 100 mg ceftolozane/50 mg tazobactam dose: Withdraw 1.2 ml of the contents from the reconstituted vial and add to an infusion bag containing 100 ml of 0.9% sodium chloride for injections (normal saline) or 5% glucose for injections.

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

NOTE: The following procedure describes the steps to prepare 100 ml of a stock solution with a final concentration of 10 mg/ml ceftolozane / 5 mg/ml tazobactam. The volume to be administered to the paediatric patient from this stock solution will be based on the appropriate dose calculation according to the patient's body weight (see section 4.2 of the Summary of Product Characteristics). Detailed steps and calculations are provided.

1. Preparation of the stock solution (100 ml of 10 mg/ml ceftolozane / 5 mg/ml tazobactam): Withdraw the entire contents (approximately 11.4 ml) of the reconstituted vial using a syringe and add to an infusion bag containing 89 ml of 0.9% sodium chloride for injections (normal saline) or 5% glucose for injections.
2. Preparation of the required volume of stock solution for infusion solution:
   1. Calculate the appropriate amount of Zerbaxa (in mg) required to administer the necessary dose to the paediatric patient. Based on this dose in mg, calculate the appropriate volume of the 10 mg/ml ceftolozane / 5 mg/ml tazobactam stock solution to administer. Refer to Table 1 below to verify calculations. Note that the table does not include all possible calculated doses, but may be used to estimate the volume to verify the calculation.
   2. Transfer the appropriately calculated volume of stock solution to a suitable-sized infusion bag or infusion syringe. The values shown in Table 1 are approximate and may need to be rounded to the nearest graduation mark on an appropriately sized syringe for smaller volumes.

Table 1: Preparation of Zerbaxa for paediatric patients (from birth* up to 18 years of age) from a 100 ml stock solution of 10 mg/ml ceftolozane / 5 mg/ml tazobactam

*Defined as > 32 weeks gestational age and ≥ 7 days after birth.

**Children weighing > 50 kg with an eGFR > 50 ml/min/1.73 m² must not exceed the maximum dose of 1 g ceftolozane / 0.5 g tazobactam.

From a microbiological standpoint, the medicinal product should be used immediately after reconstitution. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and will normally not exceed 24 hours at a temperature of 2 to 8 °C, unless reconstitution/dilution took place under controlled and validated aseptic conditions.

One of the active substances, ceftolozane, may have harmful effects if it reaches the aquatic environment. Unused medicine and all materials that have come into contact with it must not be disposed of via wastewater. Disposal of unused medicine and all materials that have been in contact with it must be carried out in accordance with local regulations. This will help protect the environment.