InfoCons Consumer Protection informs you – Zerbaxa – Package Leaflet

Before anything else

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

• Keep this leaf let. You may need to read it again.
• If you have any f urther questions, ask your doctor or pharmacist.
• If y ou get any side ef f ects, talk to your doctor or pharmacist.

This includes any possible side eff ects not listed in this leaf let. Se e section 4.

ℹ️ 1. What Zerbaxa is and what it is used for

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

• ceftolozane, an antibiotic that belongs to the group of “cephalosporins” and which can kill certain bacteria that can cause inf ection;
• tazobactam, which blocks the action of certain enzymes called beta
• lactamases. These enzymes make bacteria resistant to ceftolozane by breaking down the antibiotic before it can act. By blocking their action, tazobactam makes cef tolozane more ef f ective at killing bacteria.

Zerbaxa is used in all age groups to treat complicated inf ections within the a bdomen, and kidney and urinary system .

Zerbaxa is also used in adults to treat an infection of the lungs called “pneumonia” .

⚠️ 2. What you need to know before you take Zerbaxa

Do not take Zerbaxa

• if you are allergic to cef tolozane, tazobactam or any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to medicines known as “ cephalosporin s”.
• if you have had a severe allergic reaction (e.g., severe skin peeling; swelling of the face, hands, f eet, lips, tongue or throat; or dif fi culty swallowing or breathing) to certain other antibiotics (e.g., penicillins or carbapenems) .

Warnings and precautions

Talk to your doctor or pharmacist bef ore taking 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 diarrhoea while taking Zerbaxa.

Inf ections caused by bacteria that are not sensitive to Zerbaxa or caused by a f ungus can occur during or f ollowing treatment with Zerbaxa . Tell your doctor if you think you may have another inf ection.

Treatment with Zerbaxa sometimes causes production of antibodies that react with your red blood cells. If you are told that you have an abnormal blood test (called Coombs test) tell your doct or that you are having or have recently had Zerbaxa.

Children and adolescents

This medicine should not be given to children under 18 years old to treat pneumonia because there is not enough inf ormation on use in this age group f or the treatment of this inf ection .

Other medicines and Zerbaxa

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

Some medicines may interact with cef tolozane and tazobactam. These include:

• Probe necid (a medicine for gout). This can increase the time it takes f or tazobactam to leave your body.

Pregnancy and breast -feeding If you are pregnant or breast -f eeding, or think you may be pregnant, ask your doctor or pharmacist f or advice bef ore taking th is medicine.

Your doctor will advise if you should receive Zerbaxa during pregnancy.

If you are breast -f eeding , your doctor will advise you on whether you should stop breast -f eeding or stop or avoid Zerbaxa therapy, taking into account the benef it of breast – f eeding f or the child and the benef it of therapy f or you.

Driving and using machines

Zerbaxa may cause dizziness, which can af f ect your ability to drive and use machines.

Zerbaxa contains sodium This medicine contains 230 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 11.5% of the recommended maximum daily dietary intake of sodium f or an adult.

The reconstituted vial with 10 mL of 0.9% sodium chloride (normal saline) f or injection contains 265 mg sodiu m in each vial .

This is equivalent to 13.3% of the recommended maximum daily dietary intake of sodium f or an adult.

💊 3. How to take Zerbaxa

Your doctor or other healthcare prof essional will give you this medicine into one of your veins through an inf usion (a drip) lasting one hour . The dose of medicine given to you depends on whether or not you have kidney problems.

The dose depends on the type of inf ection that you hav e, where the inf ection is in your body and how serious the inf ectio n is. Your doctor will de cide on the dose that you need.

Use in a dults The recommended dose of Zerbaxa is 1 g of cef tolozane and 0.5 g of tazobactam or 2 g of cef tolozane and 1 g of tazobactam every 8 hours, which is given into one of your veins (directly into the bloodstream).

Treatment with Zerbaxa normally lasts between 4 and days, depending on the severity and location of the inf ection and on 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 given into one of your veins (directly into the bloodstream).

The dose should not exceed 1 g of cef tolozane and 0.5 g of tazobactam .

Treatment with Zerbaxa normally lasts betwee n 5 and 14 days, depending on the severity and location of the inf ection and on how your body responds to the treatment.

Patients with kidney problems Your doctor may need to reduce the dose of Zerbaxa or decide how of ten Zerbaxa is give n to you.

Your doctor may also want to test your blood to make sure you receive an appropriate dose, especially if you have to take this medicine f or a long time.

If you take more Zerbaxa than you should

As this product is given by a doctor or other healthcare pr of essional, it is very unlikely that you will be given too much Zerbaxa. However, if you have any concerns you should let your doctor, nurse or pharmacist know immediately.

If you stop taking Zerbaxa

If you think you have not been given a dose of Zerbaxa , tell your doctor or other healthcare prof essional immediately.

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

❗ 4. Possible side effects

Like all medicines, this medicine can cause side ef f ects, although not everybody gets them.

Tell your doctor straight away if you get these symptoms as you may need urgent medical treatment:

• Sudden swelling of your lips, face, throat or tongue; a severe rash; and, swallowing or breathing problems. These may be signs of a severe allergic reaction (anaphylaxis) and may be lif e
• threatening

Diarrhoea that becomes severe or does not go away or stool that contains blood or mucus during or af ter treatment with Zerbaxa. In this situation, you should not take medicines that stop o r slow bowel movement Adults treated f or complicated inf ections within the abdomen, and kid ney and urinary system

Common

side ef f ects (may af f ect up to 1 in 10 people):

Headache, stomach ache, constipation, diarrhoea, nausea, vomiting, increase in liver enzymes (f rom blood tests), rash, f ever (high temperature), decrease in blood pressure, decrease in potassium (f rom blood tests), increase in the number of certain types of blood cells known as platelets, dizziness, anxiety, dif f iculty sleeping, inf usion s ite reactions

Uncommon

side eff ects (may aff ect up to 1 in 100 people):

Inf lammation of the large intestine due to C. difficile bacteria, inf lammation of the stomach, abdominal distension, indigestion, excessive gas in stomach or bowel, obstruction of the intestine, yeast inf ection in the mouth (thrush), yeast inf ection of f emale genitalia, f ungal urinary tract inf ection, increase in sugar (glucose) levels (f rom blood tests), decrease in magnesium levels (f rom blood tests), decrease in phosphate levels (f r om blood tests), ischemic stroke (stroke caused by reduced blood f low in brain ), irritation or inf lammation of a vein at injection site, venous thrombosis (blood clot in a vein), low red blood cell counts, atrial f ibrillation (rapid or irregular heartbeat) , f ast heartbeat, angina pectoris (chest pain or f eeling of tightness, pressure or heaviness in chest), itchy rash or swellings on the skin, hives, Coombs test positive (a blood test that looks for antibodies that may f ight against your red blood cells), k idney problems, kidney disease, shortness of breath Additional side ef f ects observed in children and adolescents treated f or complicated inf ections within the abdomen, and kidney and urinary system

Common

side ef f ects (may af f ect up to 1 in 10 people):

I ncreased appetite, low white blood cell counts, altered taste Adults treated for an infection of the lungs called “pneumonia”

Common

side ef f ects (may af f ect up to 1 in 10 people):

Inf lammation of the large intestine due to C. difficile bacteria , diarrhoea, vomiting, increase in liver enzymes (f rom blood tests )

Uncommon

side eff ects (may aff ect up to 1 in 100 people):

Inf ection due to C. difficile bacteria , C. difficile test positive (f rom stool test), Coombs test positive ( a blood test that looks f or antibodies that may f ight against your red blood cells )

Reporting of side effects

If you get any side ef f ects, talk to your doctor or pharmacist.

This includes any possible side ef f ects not listed in this leaf let. You can also report side ef f ects directly via the national reporting system listed in Appendix V .

By reporting side ef f ects you can help provide more inf ormation on the safety of this medicine.

🌡️ 5. How to store Zerbaxa

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

Do not use this medicine af ter the expiry date which

is stated on the carton and vial af ter “EXP.” The expiry date ref ers to the last day of that month.

Unopened vials:

Store in a ref rigerator (2 ºC – 8 ºC).

Store in the original package in order to protect f rom light.

Do not throw away any medicines via wastewater.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

These measures will help protect the environment.

📦 6. Contents of the pack and other information

What Zerbaxa contains

• The active substances are ceftolozane and tazobactam.

Each vial contains cef tolozane sulf ate equivalent to 1

g ceftolozane and tazobactam sodium equivalent to 0.5 g tazobactam. For doses above 1 g cef tolozane and 0.5 g tazobactam, two vials are used.

• The other excipi ents are sodium chloride, arginine, and citric acid, anhydrous.

What Zerbaxa looks like and contents of the pack

Zerbaxa is a white to slightly yellow powder f or concentrate for solution f or inf usion (powder f or concentrate) supplied in a vial.

Zerbaxa is available in packs containing 20 mL Type I clear glass vial with stopper (bromobutyl rubber) and f lip -of f seal.

Pack size of 10 vials.

Marketing Authorisation Holder

Merck Sharp & Dohme B.V.

Waarderweg 39 2031 BN Haarlem The Netherlands

Manufacturer

FAREVA Mirabel Route de Marsat Riom 63963, Clermont

• Ferrand Cedex 9 France For any inf ormation about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien MSD Belgium Tél/Tel: +32(0)27766211 [email protected] Lietuva UAB Merck Sharp & Dohme Tel.: +370 5 278 02 47 [email protected] България Мерк Шарп и Доум България ЕООД Тел.: +359 2 819 3737 inf o- [email protected] Luxembourg/Luxemburg MSD Belgium Tél/Tel: +32(0)27766211 [email protected] Česká republika Merck Sharp & Dohme s.r.o.

Tel.: +420 233 010 111 [email protected] Magyarország MSD Pharma Hungary Kf t.

Tel.: +361 888 53 00 [email protected] Danmark MSD Danmark ApS Tlf : +45 4482 4000 [email protected] Malta Merck Sharp & Dohme Cyprus Limited Tel: 8007 4433 (+356 99917558) malta_inf [email protected] Deutschland MSD S harp & Dohme GmbH Tel: 0800 673 673 673 (+49 (0) 89 4561 0) e- [email protected] Nederland Merck Sharp & Dohme B .V.

Tel: 0800 9999000 (+31 23 5153153) medicalinf [email protected] Eesti Merck Sharp & Dohme OÜ Tel.: +372 6144 200 [email protected] Norge MSD (Norge) AS Tlf : +47 32 20 73 00 [email protected] Ελλάδα MSD Α.Φ.Β.Ε.Ε.

Τηλ: +30 210 98 97 300 [email protected] Österreich Merck Sharp & Dohme Ges.m.b.H.

Tel: +43 (0) 1 26 044 dpoc_austria @merck.com España Merck Sharp & Dohme de España, S.A.

Tel: +34 91 321 06 00 msd_inf [email protected] Polska MSD Polska Sp.z o.o.

Tel.: +48 22 549 51 00 [email protected] 32France MSD France Tél: + 33 (0) 1 80 46 40 40 Portugal Merck Sharp & Dohme, Lda Tel: +351 21 4465700 inf [email protected] Hrvatska Merck Sharp & Dohme d.o.o.

Tel: + 385 1 6611 333 croatia_inf [email protected] România Merck Sharp & Dohme Romania S.R.L.

Tel: +40 21 529 29 00 [email protected] Ireland Merck Sharp & Dohme Ireland (Human Health) Limited Tel: +353 (0)1 299 8700 medinf [email protected] Slovenija Merck Sharp & Dohme, inovativna zdravila d.o.o.

Tel: + 386 1 5204 201 msd. [email protected] Ísland Vistor hf .

Sími: +354 535 7000 Slovenská republika Merck Sharp & Dohme, s. r. o.

Tel.: +421 2 58282010 [email protected] Ιtalia MSD Italia S.r.l.

Tel:

800 23 99 89 (+39 06 361911 ) medicalinf ormation.it@ msd.com Suomi/Finland MSD Finland Oy Puh/Tel: +358 (0) 9 804650 inf [email protected] Κύπρος Merck Sharp & Dohme Cyprus Limited Τηλ: 800 00 673 (+357 22866700) cyprus_inf [email protected] Sverige Merck Sharp & Dohme (Sweden) AB Tel: +46 77 5700488 medicinskinf [email protected] Latvija SIA Merck Sharp & Dohme Latvija Tel: +371 67364224 [email protected].

United Kingdom (Northern Ireland) Merck Sharp & Dohme Ireland (Human Health) Limited Tel: + 353 (0)1 2998700 medinf [email protected] This leaflet was last revised in { month YYYY}.

Other sources of information Detailed inf ormation on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu . —————————————————————- —————————— —————————– The following inf ormation is intended f or healthcare prof essionals only:

Preparation of solutions Each vial is for single use only.

Aseptic technique must be f ollowed in preparing the inf usion solution.

Preparation of doses The powder f or concentrate for solution f or inf usion f or each vial is reconstituted with 10 mL of water f or injections or sodium chloride 9 mg/mL (0.9%) solution f or injection per vial; f ollowing reconstitution the vial should be shaken gently to dissolve the powder. The final volume is approximately 11.4 mL per vial . Th e resultant concentration is approximately 132 mg/mL (88 mg/mL of ceftolozane and 44 mg/mL of tazobactam) per vial .

CAUTION: THE RECONSTITUTED SOLUTION IS NOT FOR DIRECT INJECTION.

Zerbaxa solution f or inf usion is clear and colourless to slightly yellow .

Variations in colour within this range do not af f ect the potency of the product.

Af ter reconstitution and dilution , chemical and physical in

• use stability has been demonstrated f or hours at room temperature or days at 2 to 8 ºC.

The medicinal prod uct is photosensitive and should be protected f rom light when not stored in the original carton.

See section 4.2 of the Summary of Product Characteristics f or r ecommended dose regimens f or Zerbaxa based on indication and renal function.

The preparation f o r each dose is shown below.

Instructions f or preparing adult doses in INFUSION BAG:

For preparation of the 2 g cef tolozane / 1 g tazobactam dose: Withdraw the entire contents f rom two reconstituted vials (approximately 11.4 mL per vial) using a syringe and add it to an inf usion bag containing 100 mL of 0.9% sodium chloride f or injection (normal saline) or 5% glucose injection.

For preparation of the 1.5 g cef tolozane / 0.75 g tazobactam dose: Withdraw the entire contents f rom one reconstituted vial (app roximately 11.4 mL per vial) and 5.7 mL f rom a second reconstituted vial using a syringe and add it to an inf usion bag containing 100 mL of 0.9% sodium chloride for injection (normal saline) or 5% glucose injection.

For preparation of the 1 g cef tolozane / 0.5 g tazobactam dose: Withdraw the entire contents (approximately 11.4 mL) of the reconstituted vial using a syringe and add it to an inf usion bag containing 100 mL of 0.9% sodium chloride f or injection (normal saline) or 5% glucose injection.

For preparation of the 500 mg cef tolozane / 250 mg tazobactam dose: Withdraw 5.7 mL of the contents of the reconstituted vial and add it to an inf usion bag containing 100 mL of 0.9% sodium chloride for injection (normal saline) or 5% glucose injection.

F or preparation of the 300 mg cef tolozane / 150 mg tazobactam dose: Withdraw 3.5 mL of the contents of the reconstituted vial and add it to an inf usion bag containing 100 mL of 0.9% sodium chloride for injection (normal saline) or 5% glucose injection.

For preparation of the 250 mg cef tolozane / 125 mg tazobactam dose: Withdraw 2.9 mL of the contents of the reconstituted vial and add it to an inf usion bag containing 100 mL of 0.9% sodium chloride for injection (normal saline) or 5% glucose injection.

For preparation of the 100 mg cef tolozane / 50 mg tazobactam dose: Withdraw 1.2 mL of the contents of the reconstituted vial and add it to an inf usion bag containing 100 mL of 0.9% sodium chloride for injection (normal saline) or 5% glucose injection.

Instru ctions f or preparing paediatric doses in INFUSION BAG or in INFUSION SYRINGE:

NOTE: The following procedure describes the steps to prepare 100 mL of stock solution with a f inal concentration of mg/mL cef tolozane / 5 mg/mL tazobactam . The volume of this stock solution to be administered to the paediatric patient will be based on calculating the appropriate dose based on the 34patient’s weight (see section 4.2 of the Summary of Product Characteristics ) . Detailed steps and calculations are provided.

1. Prepa ring 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 it to an inf usion bag containing 89 mL of 0.9% sodium chloride for injecti on (normal saline) or 5% glucose injection.

2.

Preparing the required volume of stock solution f or inf usion: a.

Calculate the appropriate amount of Zerbaxa (in mg) to deliver the required dose to the paediatric patient. Based on this dose in mg, calculate the a ppropriate volume of the 10 mg/mL ceftolozane / 5 mg/mL tazobactam stock solution to be administered.

Refer to Table below to conf irm the calculations. Note that the table is NOT inclusive of all possible calculated doses but may be utili s ed to estimate the approximate volume to verif y the calculation. b.

Transfer an appropriately calculated volume of stock solution to an adequately sized inf usion bag or inf usion syringe. Values shown in Table are approximate, and it may be necessary to round to the nearest graduation mark of an appropriately sized syringe f or smaller volumes.

Table 1 : Preparation of Zerbaxa for paediatric patients ( from birth * to below 18 years of age) from the 100 mL stock s olution of 10 mg/mL ceftolozane / 5 mg/mL tazobactam Zerbaxa dose (mg/kg) Weight (kg) Calculated amount of ceftolozane (mg)Calculated amount of tazobactam (mg)Volume of stock solution to administer to patient (mL) mg/kg ceftolozane / 10 mg/kg tazobactam ** 50 and greater 1 000 500 100 40 800 400 80 30 600 300 60 20 400 200 40 15 300 150 30 10 200 100 20 5 100 50 10 3 60 30 6 1.5 30 15 3 * Defined as > 32 weeks gestational age and ≥ 7 days postnatal. ** Children weighing > 50 kg and with eGFR > mL/min/1.73 m2 should not exceed the maximum dose of 1 g cef tolozane / 0.5 g tazobactam.

From a microbiological point of view, the medicinal product should be used immediately upon reconstitution. If not used immediately, in -use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8 ºC, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.

One of the active ingredients, ceftolozane, may have harmful effects if it reaches the aquatic environment. Do not throw away any unused medicinal product or waste material via wastewater. Any unused medicinal product or waste material should be disposed of in accordance wi th local requirements. These measures will help protect the environment.

📄 Package Leaflet – official source

This article reproduces the information in the official package leaflet, as authorised in the European Union. You can consult the original document here: Product information Zerbaxa (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/15/1032).

⚠️ Important: This article is for information purposes only and does not replace medical advice or the package leaflet inside the medicine box. Read the leaflet carefully before use. For any questions about your treatment, talk to your doctor or pharmacist. If you experience side effects, tell your doctor or pharmacist and report them through your national reporting system.