Label: information for the patient

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

ceftolozano / tazobactam

Read this label carefully before starting to use this medication, because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience adverse effects, consult your doctor or pharmacist,even if they are not listed in this label. See section 4.

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

• ceftolozano, an antibiotic thatbelongs to the group of “cephalosporins” and can kill certain bacteria that may cause infection;
• tazobactam, which blocks the action of certain enzymes called beta-lactamases. These enzymes make the bacteria resistant to ceftolozano by destroying the antibiotic before it can act. By blocking the action of the enzymes, tazobactam makes ceftolozano more effective at killing the bacteria.

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

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

Do not use Zerbaxa

• if you are allergic toceftolozane, tazobactamor any of the other ingredients in this medication (listed in section6).
• if you are allergic to medications called “cephalosporins”.
• if you have had a severe allergic reaction (for example, severe skin peeling; facial, hand, foot, lip, tongue, or throat inflammation; or difficulty swallowing or breathing) to other antibiotics (such as penicillins or carbapenems).

Warnings and precautions

Consult your doctor or pharmacistbefore starting to useZerbaxa if you know that you are, or have been in the past, allergic to cephalosporins, penicillins, or other antibiotics.

Consult your doctor or pharmacistif diarrhea appears while taking Zerbaxa.

During or after treatment with Zerbaxa, infections caused by bacteria that are not sensitive to Zerbaxa or caused by a fungus may appear. Inform your doctor if you think you may have another infection.

Occasionally, treatment with Zerbaxa may cause 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 using or have recently used Zerbaxa.

Children and adolescents

This medication should not be administered to children under 18years to treat pneumonia, as there is not enough information available for this age group for the treatment of this infection.

Other medications and Zerbaxa

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

Some medications may interact withceftolozaneand tazobactam, including:

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, consult your doctor or pharmacist before using this medication. Your doctorwill advise you if you should useZerbaxa during pregnancy.

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

Driving and operating machines

Zerbaxa may cause dizziness, which may affect your ability to drive and operate machines.

Zerbaxa contains sodium

This medication contains 230mg of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 11.5% of the maximum daily sodium intake recommended for an adult. Thevialreconstituted with 10ml of 0.9% sodium chloride solution (physiological saline solution) for injectable preparations contains 265mg of sodium in each vial. This is equivalent to 13.3% of the maximum daily sodium intake recommended for an adult

Your doctor or other healthcare professional will administer this medication through a vein via an infusion (drip) for 1 hour.The dose of medication you receive will depend on whether you have any kidney problems.

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

Use in Adults

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

The 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 the treatment.

Use in Children and Adolescents

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

The 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 the treatment.

Patients with Kidney Problems

Your doctor may reduce your dose of Zerbaxa or decide on the frequency of Zerbaxa administration. Your doctor may also perform blood tests to ensure you receive an appropriate dose, especially if you need to receive this treatment for a long time.

If You Take More Zerbaxa Than You Should

Since this medication is administered by a doctor or other healthcare professional, it is very unlikely that you will receive more than you should. However, if you have any doubts, inform your doctor, nurse, or pharmacist immediately.

If You Stop Treatment with Zerbaxa

If you think you have not received a dose of Zerbaxa, inform your doctor or healthcare professional immediately.

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

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

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

• Sudden inflammation 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 can be life-threatening
• Diarrhea that may be severe or persistent, or stools that contain blood or mucus during or after treatment with Zerbaxa. In this situation, do not take medications that slow down or stop intestinal movement

Adults treatedfor complicated infections within the abdomen and kidney and urinary tract infections

Side effectscommon(may affect up to 1 in 10people):

Headache, stomach pain, constipation, diarrhea, nausea, vomiting, elevated liver enzymes (in blood tests), rash, high temperature (fever), decreased blood pressure, decreased potassium (in blood tests), increased platelet count, dizziness, anxiety, difficulty sleeping, reactions at the infusion site

Side effectsuncommon(may affect up to 1 in 100people):

Inflammatory bowel disease due to bacteriaC.difficile, stomach inflammation, abdominal distension, indigestion, excessive gas in the stomach or intestines, intestinal obstruction, fungal infection of the mouth (candidiasis), vaginal yeast infection, urinary tract fungal infection, elevated blood sugar (glucose) (in blood tests), decreased magnesium (in blood tests), decreased phosphate (in blood tests), ischemic stroke (stroke caused by reduced blood flow to the brain), vein irritation or inflammation at the injection site, venous thrombosis (blood clot in a vein), low red blood cell count, atrial fibrillation (rapid or irregular heart rhythm), rapid heart rate, angina (chest pain or sensation of tightness, pressure, or heaviness in the chest), itchy or swollen skin rash, hives, positive Coombs test (blood test that looks for antibodies against your red blood cells), kidney problems, kidney disease, difficult breathing

Additional side effects observed in children and adolescents treated for complicated infections within the abdomen and kidney and urinary tract infections

Side effectscommon(may affect up to 1 in 10people):

Increased appetite, low white blood cell count, altered taste

Adults treated for a lung infection called “pneumonia”

Side effectscommon(may affect up to 1 in 10people):

Colitis due to bacteriaC.difficile, diarrhea, vomiting, elevated liver enzymes (in blood tests)

Side effectsuncommon(may affect up to 1 in 100people):

Colitis due to bacteriaC.difficile, positive C. difficile test (in stool tests), positive Coombs test (blood test that looks for antibodies against your red blood cells)

Reporting side effects

If you experienceany type of side effect, consult your doctor or pharmacist, even if it is apossibleside effect that does not appear in this leaflet.You can also report them directly through the national reporting system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box and vial after“CAD” or “EXP”.The expiration date is the last day of the month indicated.

Unopened vials: Store in refrigerator (between 2°C and 8°C).

Store in the original packagingto protect it from light.

Medicines should not be disposed of through drains.The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations. This will help protect the environment.

Composition of Zerbaxa

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

Appearance of the product and contents of the package

Zerbaxa is a white to slightly yellowish powder for concentrate for solution for infusion (powder for concentrate) that is presented in a vial.

Zerbaxa is available in packages containing 20ml of transparent type I glass vials with a bromobutyl rubber stopper and crimp.

Packages containing 10vials.

Marketing Authorization Holder

Merck Sharp & Dohme B.V.

Waarderweg 39

2031 BN Haarlem

Netherlands

Responsible for manufacturing

FAREVA Mirabel

Route de Marsat

Riom

63963, Clermont-Ferrand Cedex 9

France

For more information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last date of revision of the summary of product characteristics:{month YYYY}.

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

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This information is intended for healthcare professionals only:

Preparation of the solutions

Each vial is for single use only.

Aseptic technique should be followed to prepare the infusion solution.

Preparation of the doses

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

WARNING: THE RECONSTITUTED SOLUTION SHOULD NOT BE INJECTED DIRECTLY.

The infusion solution of Zerbaxa is transparent and colorless to slightly yellowish.

The color difference within this range does not affect the potency of the drug.

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

See section4.2 of the SmPC for recommended dosing regimens for Zerbaxa based on indication and renal function. The preparation of each dose is shown below.

Instructions for preparing adult doses in INFUSION BAG:

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

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

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

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

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

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

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

Instructions for preparing pediatric doses in INFUSION BAG or SYRINGE FOR INFUSION:

NOTE: The following procedure describes the steps to prepare 100ml of mother solution with a final concentration of 10mg/ml of ceftolozane/5mg/ml of tazobactam. The volume to be administered to the pediatric patient will be based on the calculation of the appropriate dose based on the patient's weight (see section4.2 of the SmPC). Detailed steps and calculations are provided.

1. Preparation of the mother solution (100ml of 10mg/ml of ceftolozane/5mg/ml of tazobactam): Extract all the contents (approximately 11.4ml) of the reconstituted vial using a syringe and add it to an infusion bag containing 89ml of sodium chloride 0.9%) for injections (physiological saline solution) or 5%) glucose for injections.
2. Preparation of the necessary volume of mother solution for infusion:
   1. Calculate the appropriate amount of Zerbaxa (in mg) to administer the necessary dose to the pediatric patient. Based on this dose in mg, calculate the appropriate volume of the mother solution of 10mg/ml of ceftolozane/5mg/ml of tazobactam to administer. Consult Table1 below to confirm the calculations. Note that the table does not include all possible calculated doses, but it can be used to calculate the approximate volume to check the calculation.
   2. Transfer an appropriately calculated volume of mother solution to an infusion bag or a syringe for infusion of suitable sizes. The values shown in Table1 are approximate and may need to be rounded to the nearest graduation mark of a syringe of suitable size for smaller volumes.

Table1: Preparation of Zerbaxa for pediatric patients (from birth* to 18years of age) from the mother solution of 100ml of 10mg/ml of ceftolozane/5mg/ml of tazobactam

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

**The children who weigh ≥50kg and with a TFGe ≥50ml/min/1.73m2, should not exceed the maximum dose of 1g of ceftolozane/0.5g of tazobactam.

From a microbiological point of view, the drug should be used immediately after reconstitution. If not used immediately, the times and conditions of conservation before use are the responsibility of the user, and will normally not exceed 24hours at a temperature of 2to 8°C, unless the reconstitution/dilution has taken place in controlled and validated aseptic conditions.

One of the active ingredients, ceftolozane, may have harmful effects if it reaches aquatic environments. The unused drug and all materials that have come into contact with it should not be disposed of through the drains. The disposal of unused drug and all materials that have come into contact with it will be carried out in accordance with local regulations. In this way, it will help to protect the environment.