ZEVTERA 500 mg POWDER FOR CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you use Zevtera

Do not use Zevtera:

• if you are allergic to ceftobiprole medocaril or any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to other antibiotics such as cephalosporins or beta-lactam antibiotics;
• if you have had a severe allergic reaction to other antibiotics such as penicillin or carbapenem in the past;

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

Warnings and precautions

Consult your doctor or nurse before you start using Zevtera:

• if you have kidney problems (your doctor may reduce the dose of the medicine);
• if you have had an allergic reaction to other antibiotics such as penicillin or carbapenem in the past;
• if you have had seizures (epileptic fits) before;
• if you have had diarrhea before, during, or after treatment with this medicine (you may have an intestinal inflammation called colitis). Do not take any medicine to treat diarrhea without consulting your doctor first;
• if you are HIV-positive;
• if your immune system is severely weakened;
• if your white blood cell count is very low or if your bone marrow function is suppressed;
• if your lung infection developed more than 48 hours after the onset of mechanical ventilation, Zevtera is not suitable for you (your doctor will prescribe a suitable antibiotic for your case);
• if you need (or are expected to need) concomitant solutions containing calcium, except for Ringer's Lactate injection solution, in the same intravenous administration route due to the risk of precipitation.

If your doctor thinks it is necessary, you may be asked to drink plenty of fluids or may need to receive fluids through a drip in a vein while you are being given Zevtera.

If you start taking Zevtera and later require ventilation, your doctor will advise you whether Zevtera is still suitable for you.

Lab tests

You may develop a positive response to a lab test (Coombs test) that looks for the presence of antibodies that can destroy your red blood cells. Zevtera may also interact with tests that measure serum creatinine (Jaffé reaction) or with some tests that determine glucose content in urine. These tests may give false results.

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

Children

There is no data available on the use of Zevtera in premature newborns (born prematurely).

Other medicines and Zevtera

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

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 taking this medicine.

Driving and using machines

Zevtera may cause dizziness as a side effect. This may affect your ability to drive or use machines.

Zevtera contains sodium

This medicine contains approximately 29 mg of sodium (a major component of cooking/table salt) per dose. This is equivalent to 1.45% of the maximum recommended daily sodium intake for an adult.

3. How to use Zevtera

Your doctor or nurse will give you Zevtera.

The recommended dose for adults is 500 mg of ceftobiprole administered every 8 hours by infusion into a vein over a 2-hour period.

The recommended dose for term newborns, infants, children, and adolescents depends on age, child's weight, and is administered every 8 hours (infants 3 months or older, children, and adolescents) or every 12 hours (term newborns and infants less than 3 months) as a 2-hour infusion into a vein.

The infusion solution with a ceftobiprole concentration of 2 mg/ml is used for adults and adolescents. For infants and term newborns, the infusion solution with a ceftobiprole concentration of 4 mg/ml is used.

Patients with kidney problems

You may need a lower dose of Zevtera if you have kidney problems.

If you use more Zevtera than you should

If you think you have been given too much Zevtera, consult your doctor or nurse immediately.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, stating the medicine and the amount ingested.

If you miss a dose of Zevtera

If you think you have missed a dose, consult 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. This medicine can cause the following side effects:

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

• Swelling of the lips, face, throat, or tongue, severe skin rash, or difficulty swallowing or breathing. These can be signs of a severe allergic reaction (anaphylaxis) and can be life-threatening.
• Diarrhea that becomes severe or persistent, or presence of blood or mucus in the stool during or after treatment with Zevtera. In this situation, do not take any medicine that interrupts or slows down bowel movements.

Common: may affect up to 1 in 10 people

• Nausea
• Headache, drowsiness
• Dizziness
• Skin rash, itching, or hives
• Diarrhea (if you have diarrhea, inform your doctor immediately)
• Vomiting
• Stomach pain (abdominal pain), indigestion, or heartburn (dyspepsia)
• Taste disturbances (dysgeusia)
• Fungal infections in different parts of the body
• Redness, pain, and swelling at the injection site
• Low sodium levels in the blood
• Increased levels of some liver enzymes in the blood
• Hypersensitivity, including skin redness

Uncommon: may affect up to 1 in 100 people

• Seizures (epileptic fits)

• Temporary decrease or increase in the number of certain blood cells
• Blood tests showing decreased potassium levels
• Insomnia and sleep disorders, which sometimes include anxiety, panic attacks, and nightmares
• Shortness of breath or difficulty breathing, asthma
• Muscle cramps
• Kidney problems
• Swelling, especially in the ankles and legs
• Blood tests showing temporary increase in triglyceride, sugar, or creatinine levels

Frequency not known: cannot be estimated from the available data

• Severe decrease in a specific type of white blood cell (agranulocytosis)

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if it is possible that they are not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Zevtera

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 and vial after EXP. The expiry date is the last day of the month shown.

Store in a refrigerator (between 2°C and 8°C).

Keep the vial in the outer packaging to protect it from light.

For information on the storage of reconstituted and diluted Zevtera infusion solutions, consult the information intended for healthcare professionals.

Medicines should not be disposed of via wastewater or household waste. Return the containers and any unused medicines to the pharmacy for proper disposal. Ask your pharmacist how to dispose of the containers and any unused medicines. This will help protect the environment.

6. Container Contents and Additional Information

Zevtera Composition

• The active substance is ceftobiprol. Each vial contains 500 mg of ceftobiprol, equivalent to 666.6 mg of ceftobiprol medocaril sodium. After reconstitution, each ml of concentrate contains 50 mg of ceftobiprol, equivalent to 66.7 mg of ceftobiprol medocaril sodium.
• The other ingredients are citric acid monohydrate (E330) and sodium hydroxide (E524); see section 2.

Product Appearance and Container Contents

Zevtera is a compact or loose powder, white, yellowish, or slightly brownish in color, for concentrate for solution for infusion in a 20 ml vial. It is available in packs containing 10 vials.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Advanz Pharma Limited

Unit 17, Northwood House,

Northwood Crescent,

Dublin 9,

D09 V504,

Ireland

Manufacturer:

ACS DOBFAR S.P.A.

Via A. Fleming, 2

37135 Verona (VR)

Italy

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Advanz Pharma Spain S.L.U.

Paseo de la Castellana 135, 7th floor

28046 Madrid (Spain)

Tel. +34 900 834 889

[email protected]

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

Austria: Zevtera 500 mg powder for concentrate for solution for infusion

Denmark: Zevtera

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

France: Mabelio 500 mg, powder for solution to be diluted for infusion solution

Germany: Zevtera 500 mg powder for concentrate for solution for infusion

Ireland: Adaluzis 500 mg powder for concentrate for solution for infusion

Italy: Mabelio 500 mg, powder for concentrate for solution for infusion

Luxembourg: Mabelio 500 mg, powder for solution to be diluted for infusion solution

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

Poland: Zevtera, 500 mg, powder for solution for infusion

Portugal: Zevtera 500 mg powder for concentrate for solution for infusion

Spain: Zevtera 500 mg powder for concentrate for solution for infusion

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

United Kingdom (Northern Ireland): Zevtera 500 mg powder for concentrate for solution for infusion

Date of Last Revision of this Leaflet:January 2025

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.es/

____________________________________________________________________________

This information is intended only for healthcare professionals:

All vials are for single use.

Preparation of Zevtera Infusion Solutions

Prior to infusion, Zevtera must be reconstituted and then diluted.

Step 1: Reconstitution

For adult and paediatric patients ≥ 12 years of age who require an infusion solution with a ceftobiprol concentration of 2 mg/ml, the lyophilised powder must be reconstituted with 10 ml of water for injections or with dextrose 50 mg/ml (5%) solution for injection.

For paediatric patients <12 years of age who require an infusion solution with a ceftobiprol concentration 4 mg ml, the lyophilised powder must be reconstituted 10 ml dextrose 50 (5%) for injection if additional dilution is used same diluent (i.e., injection), or sterile water injections sodium chloride 9 (0.9%) injection.< p>

Vigorously shake the vial until complete dissolution, which may take up to 10 minutes. The resulting concentrate volume is approximately 10.6 ml. Allow the foam to dissipate and visually inspect the reconstituted solution to ensure the product is in solution and free of particles. The reconstituted concentrate contains 50 mg/ml of ceftobiprol (66.7 mg/ml of ceftobiprol medocaril sodium) and must be further diluted prior to administration. It is recommended that the reconstituted solution be diluted immediately. However, if this is not possible, the reconstituted solution may be stored at room temperature for up to 1 hour or in the refrigerator for up to 24 hours.

Step 2: Dilution (Infusion Solution)

Use in Adult and Paediatric Patients ≥ 12 Years of Age

Preparation of 500 mg Zevtera Infusion Solution(2 mg/ml of ceftobiprol)

The 10 ml of reconstituted solution must be withdrawn from the vial and injected into a suitable container (e.g., PVC or PE infusion bags, glass bottles) with 250 ml of solution of one of the following solutions: sodium chloride 9 mg/ml (0.9%) solution for injection, dextrose 50 mg/ml (5%) solution for injection, or Ringer's Lactate solution for injection. The infusion solution must be gently inverted 5-10 times to form a homogeneous solution. Avoid vigorous shaking to prevent foam formation.

In adults, the entire contents of the infusion bag must be administered to deliver the 500 mg dose of ceftobiprol.

In paediatric patients ≥ 12 years of age, the volume to be administered must be calculated based on the patient's body weight and must not exceed a maximum of 250 ml (500 mg dose).

Preparation of 250 mg Zevtera Infusion Solution for Adult Patients with Severe Renal Impairment

The 5 ml of reconstituted solution must be withdrawn from the vial and injected into a suitable container (e.g., PVC or PE infusion bags, glass bottles) with 125 ml of sodium chloride 9 mg/ml (0.9%) solution for injection, dextrose 50 mg/ml (5%) solution for injection, or Ringer's Lactate solution for injection. The infusion solution must be gently inverted 5-10 times to form a homogeneous solution. Avoid vigorous shaking to prevent foam formation. The entire contents of the infusion bag must be administered to deliver the 250 mg dose of ceftobiprol.

Use in Paediatric Patients <12 years of age< strong>

Preparation of Zevtera Infusion Solution at a Concentration of 4 mg/ml of Ceftobiprol

Administration via Infusion Bags, Bottles, or Syringes:

The reconstituted solution prepared with 10 ml of dextrose 50 mg/ml (5%) solution for injection must be diluted with the same diluent (i.e., dextrose 50 mg/ml (5%) solution for injection). The reconstituted solution prepared with 10 ml of water for injections must be diluted with sodium chloride 9 mg/ml (0.9%) solution for injection.

10 ml must be withdrawn from an infusion container (e.g., PVC or PE infusion bags, glass bottles) containing 125 ml of diluent and replaced with 10 ml of the reconstituted solution withdrawn from the vial. The infusion solution must be gently inverted 5-10 times to form a homogeneous solution. Avoid vigorous shaking to prevent foam formation. The volume to be administered must be calculated based on the patient's body weight and must not exceed a maximum of 125 ml (500 mg dose).

For administration via a 50 ml syringe, if the calculated dose does not exceed 200 mg, 4 ml of the reconstituted solution (equivalent to 200 mg of ceftobiprol) prepared with dextrose 50 mg/ml (5%) solution for injection or with water for injections must be withdrawn from the vial and diluted with 46 ml of the appropriate diluent for the infusion solution (see table below). The infusion solution must be gently inverted 5-10 times to form a homogeneous solution. Avoid vigorous shaking to prevent foam formation. The volume to be administered must be calculated based on the patient's body weight and must not exceed a maximum of 50 ml (200 mg dose).

Appearance of the Diluted Solution

The infusion solution must be clear or slightly opalescent and yellowish in color. Before administration, the infusion solution must be visually inspected for the absence of particles and discarded if visible particles are observed.

See section 3 for further information.

Storage of Reconstituted and Diluted Zevtera Infusion Solutions

Chemical and physical stability during use has been demonstrated for the reconstituted solution for 1 hour at 25°C and up to 24 hours at 2°C-8°C.

The chemical and physical stability data during use are compatible with the total reconstitution and infusion times of the ceftobiprol dilution solutions of 2 mg/ml or 4 mg/ml described in the following tables:

Use in Adults and Adolescents ≥ 12 Years of Age (2 mg/ml of Ceftobiprol): Total Time for Reconstitution and Infusion (Including Infusion Period)

Use in Children, Infants, and Neonates (<12 years of age) (4 mg ml ceftobiprol): total time for reconstitution and infusion (including period)< strong>

From a microbiological point of view, unless the method of reconstitution/dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user.

The reconstituted and infusion solutions must not be frozen or exposed to direct sunlight.

If the infusion solution is stored in the refrigerator, it must be brought to room temperature before administration. It is not necessary to protect the infusion solution from light during administration.

See section 5 for further information.