Mabelio

Package leaflet: Information for the user

Mabelio 500 mg powder for concentrate for solution for infusion

ceftobiprole
Please read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Mabelio is and what it is used for
2. What you need to know before being given Mabelio
3. How Mabelio is given
4. Possible side effects
5. How to store Mabelio
6. Contents of the pack and other information

1. What Mabelio is and what it is used for

Mabelio is an antibiotic medicine that contains the active substance ceftobiprole medocaril sodium.
It belongs to a class of antibiotic medicines called cephalosporins.
Mabelio is used to treat newborns (full-term), infants, children, adolescents, and adults who have a lung infection called pneumonia.
Mabelio works by killing certain bacteria that can cause serious lung infections.

2. What you should know before using Mabelio

Do not use Mabelio:

• if you are allergic to ceftobiprole medocaril sodium or to any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to other cephalosporins or other beta-lactam antibiotics;
• if you have previously experienced severe allergic reactions to other antibiotics such as penicillins or carbapenems.

Do not use Mabelio if any of the above apply to you. If in doubt, consult your doctor or nurse before Mabelio is administered.
Warnings and precautions
Talk to your doctor or nurse before using Mabelio:

• if you have kidney problems (your doctor may need to reduce the dose of this medicine);
• if you have ever had allergic reactions to other antibiotics such as penicillins or carbapenems;
• if you have ever had seizures (epileptic or otherwise);
• if you have diarrhoea before, during or after treatment with this medicine (you may be suffering from an intestinal inflammation called colitis). Do not take medicines for diarrhoea without first consulting your doctor;
• 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 the lung infection developed more than 48 hours after initiation of mechanical ventilation, Mabelio is not suitable for you (your doctor will prescribe an antibiotic appropriate for you);
• if concomitant administration of calcium-containing solutions, except injectable Ringer's lactate solutions, is required (or may be required) via the same intravenous line, due to the risk of precipitation.

If your doctor considers that you need additional fluids, you will be advised to drink plenty of fluids or you may require intravenous fluids via an infusion during treatment with Mabelio.
If you start treatment with Mabelio and subsequently require mechanical ventilation, your doctor will assess whether Mabelio remains suitable for you.
Laboratory tests
If you undergo a laboratory test to detect certain antibodies in the blood that may act against red blood cells (Coombs test), the results of this test may be abnormal. Mabelio may also interfere with tests for serum creatinine (Jaffé reaction) or with certain tests for detecting glucose in urine. These tests may produce inaccurate results.
If any of the above apply to you (or if you have any doubts), consult your doctor or nurse before using Mabelio.
Children
There are no data available on the use of Mabelio in preterm neonates (babies born prematurely).
Other medicines and Mabelio
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor before using this medicine.
Driving and using machines
Mabelio may cause undesirable effects such as dizziness. This may impair your ability to drive a vehicle or operate machinery.
Mabelio contains sodium
This medicine contains approximately 22 mg of sodium (a main component of table salt) per dose. This corresponds to 1.1% of the maximum daily dietary intake recommended for an adult.

3. How to use Mabelio

Mabelio will be administered to you by a doctor or nurse.
The recommended dose for adults is 500 mg of ceftobiprole every 8 hours, given as an intravenous infusion over 2 hours.
The recommended dose for full-term neonates, 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 (full-term neonates and infants under 3 months of age) as an intravenous infusion lasting 2 hours.
The infusion solution with a ceftobiprole concentration of 2 mg/mL is used for adults and adolescents. For infants and full-term neonates, the infusion solution with a ceftobiprole concentration of 4 mg/mL is used.
Patients with kidney problems
If you have kidney problems, you may need a reduced dose of Mabelio.
If you use more Mabelio than you should
If you think you have been given too much Mabelio, contact your doctor or nurse immediately.
If you forget to use Mabelio
If you think you have missed a dose, contact your doctor or nurse immediately.
If you have any doubts about how to use this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them. The following side effects may occur with this medicine:
Immediately inform your doctor if you experience any of these symptoms, as you may require urgent medical treatment:

• Sudden swelling of the lips, face, throat, or tongue; severe skin rash; difficulty swallowing or breathing. These may be signs of a serious allergic reaction (anaphylaxis) and can be life-threatening.
• Diarrhea that becomes severe or does not go away, or presence of blood or mucus in the stool during or after treatment with Mabelio. In this case, do not take any medicine to stop or slow down intestinal motility.

Common: may affect up to 1 in 10 people

• Nausea
• Headache, drowsiness
• Dizziness
• Rash, itching, or hives
• Diarrhea (if you have diarrhea, inform your doctor immediately)
• Vomiting
• Stomach ache ( abdominal pain ), indigestion, or  heartburn  ( dyspepsia )
• Unusual taste in the mouth ( dysgeusia )
• Fungal infections in various parts of the body
• Redness, pain, or swelling at the injection site
• Low levels of  sodium  , a mineral in the blood
• Increased levels of certain liver enzymes in the blood
• Hypersensitivity, including skin redness

Uncommon: may affect up to 1 in 100 people

• Seizures, epileptic fits
• Temporary decrease or temporary increase in certain blood cells
• Decreased potassium levels in blood tests
• Insomnia and sleep disturbances, possibly with anxiety, panic attacks, and nightmares
• Shortness of breath or difficulty breathing, asthma
• Muscle cramps
• Kidney problems
• Swelling, particularly of the ankles and legs
• Temporary increase in blood levels of triglycerides, blood sugar, and creatinine

Not known: frequency cannot be estimated from the available data

• A more severe reduction in a particular type of white blood cells ( agranulocytosis )

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system at the following website:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Mabelio

Keep this 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 that month.
Store in a refrigerator (2 °C–8 °C).
Keep the vial in the outer packaging to protect the medicine from light.
For information on the storage of reconstituted and diluted Mabelio infusion solutions, refer to the package leaflet intended for healthcare professionals.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Mabelio contains

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

Description of the appearance of Mabelio and contents of the pack
Mabelio is a compact or crushed solid or a powder, white to yellowish or slightly brown in colour, for concentrate for solution for infusion in a 20 mL vial.
It is available in packs containing 10 vials each.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Advanz Pharma Limited
Unit 17, Northwood House
Northwood Crescent
Dublin 9
D09 V504
Ireland
National contacts of the Marketing Authorisation Holder for medical information:
Tel.: 02 600 63037
Email: [email protected]
Manufacturer:
ACS DOBFAR S.p.A.
Via A. Fleming, 2
37135 Verona (VR)
Italy
This medicinal product is authorised in 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
Germany: Zevtera 500 mg Pulver für ein Konzentrat zur Herstellung einer Infusionslösung
Italy: Mabelio 500 mg, polvere per concentrato per soluzione per infusione
Ireland: Adaluzis 500 mg powder for concentrate for solution for infusion
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.
More detailed information on this medicinal product is available on the website of the Italian Medicines Agency https://www.aifa.gov.it/.
___________________________________________________________________________
The following information is intended exclusively for physicians or healthcare professionals:
Each vial is for single use only.
Preparation of Mabelio infusion solutions
Mabelio must be reconstituted and then diluted before infusion.
Step 1: Reconstitution
For adult and pediatric patients aged ≥ 12 years requiring an infusion solution with a ceftobiprole concentration of 2 mg/mL, the lyophilized powder must be reconstituted with 10 mL of sterile water for injections or with 50 mg/mL (5%) dextrose solution for injection.
For pediatric patients aged < 12 years requiring an infusion solution with a ceftobiprole concentration of 4 mg/mL, the lyophilized powder must be reconstituted with 10 mL of 50 mg/mL (5%) dextrose solution for injection if further dilution will be performed with the same diluent (i.e., 50 mg/mL (5%) dextrose solution for injection), or with 10 mL of water for injections if further dilution will be performed with 9 mg/mL (0.9%) sodium chloride solution for injection (see tables below).
The vial must be shaken vigorously until the powder is completely dissolved, which may take up to 10 minutes in some cases. The resulting concentrate volume is approximately 10.6 mL. Allow any foam to dissipate and visually inspect the reconstituted solution to ensure complete dissolution of the medicinal product and absence of particles. The reconstituted concentrate contains 50 mg/mL of ceftobiprole (i.e., 66.7 mg/mL of ceftobiprole medocaril sodium) and must be further diluted before administration. Immediate dilution of the reconstituted solution is recommended. However, if this is not possible, the reconstituted solution may be stored at room temperature for up to 1 hour or refrigerated at 2°C–8°C for up to 24 hours.
Step 2: Dilution (infusion solution)
Use in adult and pediatric patients aged ≥ 12 years
Preparation of 500 mg Mabelio infusion solution (2 mg/mL ceftobiprole)
Withdraw 10 mL of reconstituted solution from the vial and inject it into a suitable container (e.g., PVC or PE infusion bags, glass bottles) containing 250 mL of 9 mg/mL (0.9%) sodium chloride solution for injection, 50 mg/mL (5%) dextrose solution for injection, or Ringer's lactate solution for injection. Gently invert the infusion solution 5–10 times to obtain a homogeneous mixture. Avoid vigorous shaking to prevent foaming.
In adults, the entire contents of the infusion bag must be infused to deliver a dose of 500 mg of ceftobiprole.
In pediatric patients aged ≥ 12 years, the volume to be administered must be calculated based on body weight and must not exceed a maximum of 250 mL (500 mg dose).
Preparation of a 250 mg Mabelio infusion solution for adult patients with severe renal impairment
Withdraw 5 mL of reconstituted solution from the vial and inject it into a suitable container (e.g., PVC or PE infusion bags, glass bottles) containing 125 mL of 9 mg/mL (0.9%) sodium chloride solution for injection, 50 mg/mL (5%) dextrose solution for injection, or Ringer's lactate solution for injection. Gently invert the infusion solution 5–10 times to obtain a homogeneous mixture. Avoid vigorous shaking to prevent foaming. The entire contents of the infusion bag must be infused to deliver a dose of 250 mg of ceftobiprole.
Use in pediatric patients aged < 12 years
Preparation of Mabelio infusion solution at a concentration of 4 mg/mL ceftobiprole
Administration via infusion bags, bottles, or syringes:
The reconstituted solution prepared with 10 mL of 50 mg/mL (5%) dextrose solution for injection must be diluted with the same diluent (i.e., 50 mg/mL (5%) dextrose solution for injection). The reconstituted solution prepared with 10 mL of water for injections must be diluted with 9 mg/mL (0.9%) sodium chloride solution for injection.
10 mL must be withdrawn from a container for infusion (e.g., PVC or PE infusion bags, glass bottles) containing 125 mL of diluent and replaced with 10 mL of 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 foaming. The volume to be administered must be calculated based on 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 reconstituted solution (equivalent to 200 mg of ceftobiprole), prepared with either 50 mg/mL (5%) dextrose solution for injection or water for injections, must be withdrawn from the vial and diluted with 46 mL of the appropriate diluent for 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 foaming. The volume to be administered must be calculated based on body weight and must not exceed 50 mL (200 mg dose).
Appearance of the diluted solution
The infusion solution should be clear to slightly opalescent and yellowish in colour. The infusion solution must be visually inspected for the presence of particles before administration and discarded if particles are visible.
See also section 3 for further information.
Storage of reconstituted and diluted Mabelio infusion solutions
The chemical and physical in-use stability of the reconstituted solution has been demonstrated for 1 hour at 25°C and up to 24 hours at 2°C–8°C.
Chemical and physical in-use stability data confirm the total times within which reconstitution and infusion of ceftobiprole solutions diluted to 2 mg/mL or 4 mg/mL must be completed, as described in the tables below:
Use in adults and adolescents aged ≥ 12 years (2 mg/mL ceftobiprole): Total time within which reconstitution and infusion of the medicinal product (including infusion period) must be completed

Use in children, infants and neonates (< 12 years) (4 mg/mL ceftobiprole): Total time
within which reconstitution and infusion (including infusion period) must be completed.

From a microbiological standpoint, the medicinal product should be used immediately unless the method of reconstitution/dilution excludes the risk of microbiological contamination. If the product is not used immediately, the times and conditions of storage prior to use are the responsibility of the user.
The reconstituted solution and the infusion solution must not be frozen or exposed to direct sunlight.
If the infusion solution is stored in a refrigerator, it must be brought to room temperature before administration. It is not necessary to protect the infusion solution from light during administration.
See also section 5 for further information.