Zevtera

PATIENT INFORMATION LEAFLET

Leaflet accompanying the packaging: Information for the user

Zevtera, 500 mg, powder for concentrate for solution for infusion

Ceftobiprole

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or nurse.
• If the patient experiences any side effects, including any side effects not listed in the leaflet, they should inform their doctor or nurse. See section 4.

Table of contents of the leaflet

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

1. What is Zevtera and what is it used for

Zevtera is an antibiotic that contains the active substance ceftobiprole medocaril sodium. The medicine belongs to a group of antibiotics called "cephalosporins". Zevtera is used in newborns, infants, children, adolescents, and adults with lung infections, known as "pneumonia". Zevtera works by killing certain strains of bacteria that can cause severe lung infections.

2. Important information before using Zevtera

When not to use Zevtera

• if the patient is allergic to ceftobiprole medocaril sodium or any of the other ingredients of this medicine (listed in section 6),
• if the patient is allergic to other cephalosporins or beta-lactam antibiotics,
• if the patient has previously experienced severe allergic reactions to other antibiotics, such as penicillin or carbapenem.

Do not use Zevtera if any of the above applies to the patient. In case of doubts before taking Zevtera, consult a doctor or nurse.

Warnings and precautions

Before starting treatment with Zevtera, consult a doctor or nurse:

• if the patient has kidney disease (the doctor may reduce the dose of the medicine),
• if the patient has previously experienced any allergic reactions to other antibiotics, such as penicillin or carbapenem,
• if the patient has a history of seizures (epileptic fits),
• if the patient has previously experienced diarrhea during or after treatment with this medicine (the patient may have colitis, also known as pseudomembranous colitis). Do not take anti-diarrheal medicines before consulting a doctor.
• if the patient is HIV positive,
• if the patient's immune system is severely weakened,
• if the patient has a very low white blood cell count or bone marrow depression,
• if the lung infection occurred more than 48 hours after the start of mechanical ventilation, Zevtera is not suitable for the patient (the doctor will prescribe a different antibiotic),
• if the patient requires (or is expected to require) concurrent administration of calcium-containing solutions, except for Ringer's lactate solution for injection, through the same infusion set, due to the risk of precipitation.

If the doctor considers that the patient needs additional fluids, the patient may be asked to drink plenty of fluids or may need to be given fluids through an intravenous infusion during treatment with Zevtera. If the patient starts treatment with Zevtera and then requires mechanical ventilation, the doctor will assess whether continued use of Zevtera is suitable for the patient. Laboratory tests The patient may experience abnormal laboratory test results (Coombs test) related to the presence of certain antibodies against red blood cells in the patient's body. Additionally, Zevtera may interfere with creatinine measurements in serum (Jaffé reaction) or some glucose measurements in urine. The results of these tests may be false. If any of the above applies to the patient (or the patient is unsure), they should consult a doctor or nurse before starting treatment with Zevtera.

Children

There are no available data on the use of Zevtera in premature newborns.

Zevtera and other medicines

Tell the doctor or nurse about all medicines the patient is taking, or has recently taken, including those planned to be taken.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a baby, they should consult a doctor before using this medicine.

Driving and using machines

Zevtera may cause side effects such as dizziness. This may impair the patient's ability to drive or use machines.

Zevtera contains sodium

This medicine contains approximately 22 mg of sodium (the main component of common salt) per vial. This corresponds to 1.1% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to use Zevtera

Zevtera will be administered to the patient by a doctor or nurse. The recommended dose for adults is 500 mg of ceftobiprole every 8 hours, administered as an intravenous infusion over 2 hours. The recommended dose for newborns, infants, children, and adolescents depends on the child's age and weight and is administered every 8 hours (infants aged 3 months or older, children, and adolescents) or every 12 hours (newborns and infants under 3 months) as an intravenous infusion over 2 hours. In adults and adolescents, a solution for infusion with a concentration of 2 mg/mL ceftobiprole is used. In infants and newborns, a solution for infusion with a concentration of 4 mg/mL ceftobiprole is used.

Patients with kidney disease

If the patient has kidney disease, they may need a lower dose of Zevtera.

Overdose of Zevtera

Tell the doctor immediately if the patient thinks they have been given more Zevtera than prescribed.

Missed dose of Zevtera

Tell the doctor immediately if the patient thinks they have missed a dose of Zevtera. In case of any further doubts about using this medicine, consult a doctor or nurse.

4. Possible side effects

Like all medicines, Zevtera can cause side effects, although not everybody gets them. The medicine can cause the following side effects:

Tell the doctor immediately if the patient experiences any of the following symptoms, as they may need urgent medical attention:

• Sudden swelling of the lips, face, throat, or tongue; severe rash and problems with swallowing or breathing. These may be symptoms of a severe allergic reaction (anaphylaxis) that can be life-threatening.
• Diarrhea that becomes severe and does not stop, or stool containing blood or mucus during or after treatment with Zevtera. In this case, do not take medicines that stop or slow down bowel movements.

Very common: may affect up to 1 in 10 people

• Nausea (feeling sick)
• Headache, drowsiness
• Dizziness
• Rash, itching, or hives
• Diarrhea, if diarrhea occurs, tell the doctor immediately
• Vomiting
• Abdominal pain, indigestion, or "heartburn" (dyspepsia)
• Taste disturbances
• Fungal infections in different parts of the body
• Redness, pain, or swelling at the injection site
• Low sodium levels in the blood
• Increased activity of certain liver enzymes in the blood
• Hypersensitivity, including skin redness

Uncommon: may affect up to 1 in 100 people

• Seizures, convulsions, or epileptic fits
• Temporary decrease or increase in certain blood cell counts
• Blood tests showing low potassium levels
• Insomnia and sleep disturbances, sometimes including anxiety, panic attacks, and nightmares
• Shortness of breath or difficulty breathing, asthma
• Muscle cramps
• Kidney disease
• Swelling, especially of the ankles and feet
• Blood tests showing temporary increases in triglycerides, blood sugar, or creatinine

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

• Severe decrease in the number of a certain type of white blood cell (agranulocytosis)

Reporting side effects

If the patient experiences any side effects, including those not listed in the leaflet, they should tell their doctor or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products; Jerozolimskie 181C; PL-02 222 Warsaw; Tel.: +48 22 49 21 301; Fax: +48 22 49 21 309; Website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, more information can be gathered on the safety of the medicine.

5. How to store Zevtera

Keep the 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 EXP. The expiry date refers to the last day of the month. Store in a refrigerator (2°C–8°C). Store the vial in the outer packaging to protect from light. Information on the storage of reconstituted and diluted solutions for infusion of Zevtera is given in the information intended for healthcare professionals. Medicines should not be disposed of via wastewater or household waste. Ask a pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Zevtera contains

• The active substance is ceftobiprole. Each vial contains 500 mg of ceftobiprole (as 666.6 mg of ceftobiprole medocaril sodium). After reconstitution, 1 mL of concentrate contains 50 mg of ceftobiprole (as 66.7 mg of ceftobiprole medocaril sodium). The other ingredients are citric acid monohydrate and sodium hydroxide (for pH adjustment) (see also section 2).

What Zevtera looks like and contents of the pack

Zevtera is a white, yellowish, or light brown disk or broken disk of compressed powder or powder for concentrate for solution for infusion in a 20 mL vial. The medicine is available in packs containing 10 vials.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Advanz Pharma Limited; Unit 17, Northwood House; Northwood Crescent; Dublin 9; D09 V504; Ireland; e-mail: medicalinformation@advanzpharma

Manufacturer:

ACS Dobfar S.p.A.; Via A. Fleming, 2; 37135 Verona (VR); Italy

This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Austria: Zevtera 500 mg Pulver für ein Konzentrat zur Herstellung einer Infusionslösung; Denmark: Zevtera; Finland: Zevtera 500 mg, kuiva-aine välikonsentraatiksi infuusionestettä varten, liuos; France: Mabelio 500 mg, poudre pour solution à diluer pour solution pour perfusion; Ireland: Adaluzis 500 mg powder for concentrate for solution for infusion; Germany: Zevtera 500 mg Pulver für ein Konzentrat zur Herstellung einer Infusionslösung; Italy: Mabelio 500 mg, polvere per concentrato per soluzione per infusione; Luxembourg: Mabelio 500 mg, poudre pour solution à diluer pour solution pour perfusion; Norway: Zevtera 500 mg, pulver til konsentrat til infusjonsvæske, oppløsning; Poland: Zevtera 500 mg, proszek do sporządzania koncentratu roztworu do infuzji; Portugal: Zevtera 500 mg pó para concentrado para solução para perfusão; Spain: Zevtera 500 mg, polvo para concentrado para solución para perfusión; Sweden: Zevtera 500 mg pulver till koncentrat till infusionsvätska, lösning; United Kingdom (Northern Ireland): Zevtera 500 mg powder for concentrate for solution for infusion. Date of last revision of the leaflet:01/2025. Detailed information on this medicine is available on the website: Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, www.urpl.gov.pl. _______________________________________________________________________
Information intended for healthcare professionals only::
Each vial is for single use only.

Preparation of Zevtera solutions for infusion

Zevtera must be reconstituted and then diluted before administration. Step 1: Reconstitution For adults and adolescents aged ≥ 12 years, requiring a solution for infusion with a concentration of 2 mg/mL ceftobiprole, the lyophilized powder should be reconstituted in 10 mL of sterile water for injection or glucose 50 mg/mL (5%) solution for injection. For children under 12 years of age, requiring a solution for infusion with a concentration of 4 mg/mL ceftobiprole, the lyophilized powder should be reconstituted in 10 mL of glucose 50 mg/mL (5%) solution for injection, sterile water for injection, or glucose 50 mg/mL (5%) solution for injection, if the same diluent (i.e., glucose 50 mg/mL (5%) solution for injection) is used for further dilution, or in 10 mL of sterile water for injection, if sodium chloride 9 mg/mL (0.9%) solution for injection is used for further dilution (see tables below). Shake the vial vigorously to achieve complete dissolution. In some cases, this may take up to 10 minutes. The volume of the resulting concentrate is approximately 10.6 mL. If foam appears, let it disappear and inspect the reconstituted solution visually to ensure that the product has dissolved and that there are no particles. The reconstituted concentrate contains 50 mg/mL of ceftobiprole (as 66.7 mg of ceftobiprole medocaril sodium) and must be further diluted before administration. It is recommended to proceed with the further dilution immediately. If this is not possible, the reconstituted solution should be stored at room temperature for a maximum of 1 hour or in a refrigerator for a maximum of 24 hours. Step 2: Dilution (solution for infusion) Administration in adults and adolescents aged ≥ 12 years Preparation of a 500 mg dose of Zevtera solution for infusion (2 mg/mL ceftobiprole)Take 10 mL of the reconstituted solution from the vial and inject it into an appropriate container (e.g., an infusion bag made of PVC or PE, a glass bottle) containing 250 mL of sodium chloride 9 mg/mL (0.9%) solution for injection, glucose 50 mg/mL (5%) solution for injection, or Ringer's lactate solution for injection. The solution for infusion should be gently inverted 5-10 times to achieve a homogeneous solution. Avoid vigorous shaking, as this may cause foam formation. For adults, to administer a dose of 500 mg of ceftobiprole, the entire contents of the infusion bag should be administered. For adolescents aged ≥ 12 years, the volume to be administered should be calculated based on the patient's body weight and should not exceed a maximum volume of 250 mL (dose of 500 mg). Preparation of a 250 mg dose of Zevtera solution for infusion in adult patients with severe renal impairmentTake 5 mL of the reconstituted solution from the vial and inject it into an appropriate container (e.g., an infusion bag made of PVC or PE, a glass bottle) containing 125 mL of sodium chloride 9 mg/mL (0.9%) solution for injection, glucose 50 mg/mL (5%) solution for injection, or Ringer's lactate solution for injection. The solution for infusion should be gently inverted 5-10 times to achieve a homogeneous solution. Avoid vigorous shaking, as this may cause foam formation. To administer a dose of 250 mg of ceftobiprole, the entire contents of the infusion bag should be administered. Administration in children under 12 years of agePreparation of Zevtera solution for infusion with a concentration of 4 mg/mL ceftobiproleAdministration using infusion bags, bottles, or syringes: The reconstituted solution in 10 mL of glucose 50 mg/mL (5%) solution for injection should be diluted with the same diluent (i.e., glucose 50 mg/mL (5%) solution for injection). The reconstituted solution in 10 mL of sterile water for injection should be diluted with sodium chloride 9 mg/mL (0.9%) solution for injection. Take 10 mL of the solution from the infusion container (e.g., an infusion bag made of PVC or PE, a glass bottle) containing 125 mL of the diluent and replace it with 10 mL of the reconstituted solution taken from the vial. The solution for infusion should be gently inverted 5-10 times to achieve a homogeneous solution. Avoid vigorous shaking, as this may cause foam formation. The volume to be administered should be calculated based on the patient's body weight and should not exceed a maximum volume of 125 mL (dose of 500 mg). If the calculated dose does not exceed 200 mg, to administer the dose using a 50 mL syringe, take 4 mL of the solution (corresponding to 200 mg of ceftobiprole) reconstituted in glucose 50 mg/mL (5%) solution for injection or sterile water for injection and dilute it with 46 mL of the appropriate diluent for infusion (see section 6.3). The solution for infusion should be gently inverted 5-10 times to achieve a homogeneous solution. Avoid vigorous shaking, as this may cause foam formation. The volume to be administered should be calculated based on the patient's body weight and should not exceed 50 mL (dose of 200 mg). Appearance of the diluted solution The solution for infusion should be clear or slightly opalescent and yellowish. Before administration, the solution for infusion should be inspected visually for the presence of particles and, if present, the solution should be discarded. Additional information is also given in section 3.

Storage of reconstituted and diluted Zevtera solutions for infusion

Chemical and physical stability has been demonstrated for the reconstituted solution stored for 1 hour at 25°C and for 24 hours at 2°C-8°C. Data on chemical and physical stability during storage support the combined time for reconstitution and infusion of 2 mg/mL or 4 mg/mL diluted ceftobiprole solution and are described in the tables below:

Administration in adults and adolescents aged ≥ 12 years (2 mg/mL ceftobiprole): Combined time for reconstitution and infusion (including infusion time)

Administration in children, infants, and newborns (under 12 years of age) (4 mg/mL ceftobiprole):

Combined time for reconstitution and infusion (including infusion time)

From a microbiological point of view, as long as the method of reconstitution/dilution does not eliminate the risk of microbial contamination, the product should be used immediately. If the product is not used immediately, the user is responsible for the subsequent storage conditions. Do not freeze or expose reconstituted solutions and infusion solutions to direct sunlight. If the infusion solution is stored in a refrigerator, its temperature should be allowed to reach room temperature before administration. During infusion, the infusion solution does not need to be protected from light. Additional information is also given in section 5.