Package Insert: Information for the User

Zevtera 500 mg Powder for Concentrate for Solution for Infusion

Ceftobiprol

Read this package insert carefully before starting to use this medication, as it contains important information for you.

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

Zevtera is an antibiotic that contains ceftobiprol sodium medocaril as the active ingredient. It belongs to a group of antibiotic medications called cephalosporins.

Zevtera is used to treat pneumonia in term newborns, infants, children, adolescents, and adults.

Zevtera works by destroying certain bacteria that can cause severe lung infections.

Do not use Zevtera:

• if you are allergic to ceftobiprol sodium or any of the other components of this medication (listed in section 6);
• if you are allergic to other antibiotics such as cephalosporins or beta-lactamics;
• if you have had a severe allergic reaction to other antibiotics such as penicillin or carbapenem before;

Do not use Zevtera if any of the above circumstances apply. If you are unsure, consult your doctor or nurse before Zevtera is administered to you.

Warnings and precautions

Consult your doctor or nurse before starting to use Zevtera:

• if you have kidney problems (your doctor may reduce the medication dose);
• if you have ever had an allergic reaction to other antibiotics such as penicillin or carbapenem;
• if you have ever had seizures (epileptic attacks);
• if you have had diarrhea before, during, or after treatment with this medication (you may have an intestinal inflammation called colitis).Do not take any medication to treat diarrhea without consulting your doctor first;
• if you test positive for HIV,
• 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 has developed more than 48 hours after the onset of mechanical ventilation, Zevtera is not suitable for you (your doctor will prescribe an appropriate antibiotic for your case);
• if you need (or are expected to need) solutions that contain calcium, except for sodium lactate solution, in the same intravenous administration route due to the risk of precipitation.

If your doctor thinks you need to, you may be asked to drink plenty of fluids, or you may need to receive fluids through a vein while Zevtera is administered to you.

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

Laboratory tests

You may develop a positive result on a laboratory 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 the glucose content in your urine. These tests may give incorrect results.

If any of the above circumstances apply (or you are unsure), consult your doctor or nurse before starting to use Zevtera.

Children

Zevtera is not recommended for premature newborns since the safety and efficacy of Zevtera have not been established in this age group.

Use of Zevtera with other medications

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, or plan to become pregnant, consult your doctor before using this medication.

Driving and operating machinery

Zevtera may cause dizziness as a side effect, which may affect your ability to drive or operate machinery.

Patients with low-sodium diets should note that this medication contains 29 mg (1.3 mmol) of sodium per dose.

Your doctor or nurse will administer Zevtera.

The recommended dose for adults is 500 mg of ceftobiprol administered every 8 hours through a drip in a vein over a period of 2 hours.

The recommended dose for full-term newborns, infants, children, and adolescents depends on the age, weight of the child and is administered every 8 hours (infants ≥ 3 months) or every 12 hours (full-term newborns and infants < 3 months).

The infusion solution with a ceftobiprol concentration of 2 mg/ml is used for adults and adolescents. For infants and full-term newborns, the infusion solution with a ceftobiprol 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 Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forgot to use Zevtera

If you think you have forgotten a dose, consult your doctor or nurse immediately.

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

Like all medicines, this medicine may cause side effects, although not everyone will experience them. This medicine may cause the following side effects:

Talk to 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 may be signs of a severe allergic reaction (anaphylaxis) and can be potentially life-threatening.
• Diarrhea that becomes severe or persistent, or the presence of blood or mucus in the stool during or after treatment with Zevtera. In this situation, do not take medications that slow down or stop intestinal movement.

Frequent: may affect between 1 and 10 in 100 people

• Discomfort (nausea)
• Headache, drowsiness
• Sensation of dizziness
• Skin rash, itching, or urticaria
• Diarrhea (if you have diarrhea, inform your doctor immediately)
• Desire to vomit (vomiting)
• Abdominal pain (abdominal pain), indigestion, or stomach acid (heartburn)
• Alterations in taste (distaste)
• Fungal infections in various parts of the body
• Redness, pain, and swelling at the injection site
• Low sodium levels in the blood
• Increased levels of certain liver enzymes in the blood
• Hypersensitivity, including skin redness

Rare: may affect between 1 and 10 in 1,000 people

• Seizures (epileptic attacks)

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

Unknown frequency: cannot be estimated from available data

• Seizures (epileptic attacks)

Reporting of side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es. 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. The expiration date is the last day of the month indicated.

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

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

To obtain information about the conservation of Zevtera reconstituted and diluted infusion solutions, consult the attached information for healthcare professionals.

Medicines should not be disposed of through drains or in the trash. Deposit the containers and unused medications at the SIGRE point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and unused medications. By doing so, you will help protect the environment.

Composition of Zevtera

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

Appearance of the product and contents of the package

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

Marketing authorization holder and responsible manufacturer

Marketing authorization holder:

Advanz Pharma Limited

Unit 17, Northwood House,

Northwood Crescent,

Dublin 9,

D09 V504,

Ireland

Responsible manufacturer:

ACS DOBFAR S.P.A.

Via A. Fleming, 2

37135 Verona (VR)

Italy

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Advanz Pharma Spain S.L.U.

Paseo de la Castellana 135, 7ª

28046 Madrid (Spain)

Tel. +34 900 834 889

[email protected]

This medication is authorized in the member states of the European Economic Area with the following names:

Austria: Zevtera500 mg Powder for a Concentrate for Solution for Infusion

Denmark: Zevtera

Finland: Zevtera500 mg, dry substance for a concentrate for solution for infusion, solution

France: Mabelio500 mg, powder for a solution to be diluted for a solution for infusion

Germany: Zevtera500 mg Powder for a Concentrate for Solution for Infusion

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

Italy: Mabelio500 mg, powder for a concentrate for solution for infusion

Luxembourg: Mabelio500 mg, powder for a solution to be diluted for a solution for infusion

Norway: Zevtera500 mg, powder for a concentrate for infusion solution, solution

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

Portugal: Zevtera 500 mg powder for a concentrate for solution for perfusion

Spain: Zevevtera500 mg powder for a concentrate for solution for infusion

Sweden: Zevtera500 mg powder for a concentrate for infusion solution, solution

United Kingdom(Northern Ireland): Zevtera500mg powder for concentrate for solution for infusion.

Last review date of this leaflet:February 2023

For detailed and updated information about this medication, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.es/

____________________________________________________________________________

This information is intended solely for healthcare professionals:

All vials are for single use.

Preparation of Zevtera infusion solutions

Before infusion, Zevtera must be reconstituted and then diluted.

Step 1: Reconstitution

For adult and pediatric patients ≥ 12 years requiring an infusion solution with a ceftobiprol concentration of 2 mg/mL, the lyophilized powder must be reconstituted with 10 ml of water for injection or with dextrose 50 mg/ml (5%) injection solution.

For pediatric patients <12 years old, the reconstitution must be performed with 10 ml of dextrose 50 mg/ml (5%) injection solution. The vial must be shaken vigorously until the complete dissolution is achieved, which in some cases may take up to 10 minutes. The resulting concentrate volume is approximately 10.6 ml. The reconstituted solution must be allowed to dissipate any foam and visually inspected to ensure that the product is in solution and free of particles. The reconstituted concentrate contains 50 mg/ml of ceftobiprol (66.7 mg/ml of medocaril sodium ceftobiprol) and must be further diluted before 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 pediatric patients ≥ 12 years

Preparation of the 500 mg Zevtera infusion solution (2 mg/mL ceftobiprol)(2 mg/mL ceftobiprol)

The 10 ml of reconstituted solution must be extracted from the vial and injected into an appropriate container (e.g., PVC or PE infusion bags, glass containers) with 250 ml of one of the following solutions: sodium chloride 9 mg/ml (0.9%) injection solution, dextrose 50 mg/ml (5%) injection solution, or lactated Ringer's injection solution. The infusion solution must be gently inverted 5-10 times to form a homogeneous solution. Agitation of the mixture should be avoided to prevent foam formation.

In adults, agitation of the mixture should be avoided to prevent foam formation. The entire contents of the infusion bag must be administered to administer the 500 mg ceftobiprol dose.

In pediatric patients ≥ 12 years, the volume to be administered is equivalent to the calculated dose in mg/kg but not exceeding a maximum of 500 mg of Zevtera.

Preparation of the 250 mg Zevtera infusion solution for adult patients with severe renal impairment

The 5 ml of reconstituted solution must be extracted from the vial and injected into an appropriate container (e.g., PVC or PE infusion bags, glass containers) with 125 ml of sodium chloride 0.9% injection solution, dextrose 5% injection solution, or lactated Ringer's injection solution. The infusion solution must be gently inverted 5-10 times to form a homogeneous solution. Agitation of the mixture should be avoided to prevent foam formation. The entire contents of the infusion bag must be administered to administer the 250 mg ceftobiprol dose.

Use in pediatric patients <12 years

Preparation of Zevtera infusion solution at a ceftobiprol concentration of 4 mg/mL

Administration via infusion bags, containers, or syringes:

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

10 ml of a container for infusion (e.g., PVC or PE infusion bags, glass containers) containing 125 ml of diluent solution must be extracted and replaced with 10 ml of the reconstituted solution extracted from the vial. The infusion solution must be gently inverted 5-10 times to form a homogeneous solution. Agitation of the mixture should be avoided to prevent foam formation. The volume to be administered is equivalent to the calculated dose in mg/kg but not exceeding a maximum of 500 mg of Zevtera.

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%) injection solution or with water for injection must be extracted from the vial and diluted with 46 ml of the appropriate diluent solution for the infusion solution (see section 6.3). The infusion solution must be gently inverted 5-10 times to form a homogeneous solution. Agitation of the mixture should be avoided to prevent foam formation. The volume to be administered is equivalent to the calculated dose in mg/kg but not exceeding a maximum of 500 mg of Zevtera.

Appearance of the diluted solution

The infusion solution must be between transparent and slightly opalescent and yellowish in color. Before administration, the infusion solution must be visually inspected to check for the absence of particles and discarded if particles are visible.

See section 3 for more information.

Storage of Zevtera reconstituted and diluted infusion solutions

Chemical and physical stability has been demonstrated during the use of 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 times for reconstitution and infusion 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 (2 mg/mL ceftobiprol): Total time to complete reconstitution and infusion (including a 2-hour infusion period, see Section 4.2)

Use in children, infants, and neonates (<12 years)

From a microbiological point of view, unless the reconstitution/dilution method eliminates the risk of microbiological contamination, the product must be used immediately. If not used immediately, the storage periods during use and the conditions before this will be the responsibility of the user.

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

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

See section 5 for more information.