Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Zevtera 500 mg powder for concentrate for solution for infusion
⚠ This medicine appears to have been discontinued
The electronic medicines compendium (emc) no longer publishes a Summary of Product Characteristics for this product, which usually means it is no longer marketed in the UK. The patient leaflet below is kept for reference, but the product may not be available.
If you were prescribed this medicine, other products containing Ceftobiprole medocaril sodium may still be available. Do not stop your treatment — ask your pharmacist or GP what to use instead.
What it is and what it is used for
for
Zevtera is an antibiotic medicine that contains the active substance ceftobiprole medocaril sodium. It belongs to a group of medicines called 'cephalosporin antibiotics'. Zevtera is used to treat term neonates, infants, children, adolescents, and adults with infections of the lungs called 'pneumonia'. Zevtera works by killing certain bacteria, which can cause serious lung infections. 2.
What you need to know before you take it
e Zevtera
Do not use Zevtera:
- if you are allergic to ceftobiprole medocaril sodium or any of the other ingredients of this medicine (listed in section 6),
- if you are allergic to other cephalosporin or beta-lactam antibiotics,
- if you have had previous severe allergic reactions to other antibiotics like penicillin or carbapenem. Do not use Zevtera if any of the above applies to you. If you are not sure, talk to your doctor or nurse before being given Zevtera. Warnings and precautions Talk to your doctor or nurse before using Zevtera-:
- if you have kidney problems (your doctor may need to lower your dose of this medicine),
- if you have ever had any allergic reactions to other antibiotics like penicillin or carbapenem,
- if you have ever had fits (seizures or convulsions),
- if you have diarrhea before, during or after your treatment with this medicine (you may have an inflammation of the bowel known as 'colitis'). Do not take any medicine to treat diarrhea without first checking with your doctor,
- if you are HIV positive,
- if your immune system is severely weakened,
- if your white blood counts are very low or your bone marrow function is suppressed,
- if your lung infection is developed more than 48 hours after onset of artificial ventilation Zevtera is not suitable for you (your doctor will prescribe a suitable antibiotic for you), 2
–
if you require (or are expected to require) concomitant calcium-containing solutions, except Lactated Ringer's solution for injection, in the same intravenous administration line due to the risk of precipitation.
If your doctor thinks you need more fluids, you may be asked to drink plenty of liquids or you may need to have liquids given as a drip into a vein while you are receiving Zevtera. If you start taking Zevtera and then require ventilation, your doctor will assess whether Zevtera is still suitable for you. Lab tests You may develop an abnormal lab test (called Coombs test) that looks for certain antibodies which may act against your red blood cells. Zevtera may also interact with tests to measure serum creatinine (Jaffé reaction) or with some tests to determine the glucose content in the urine. These tests may provide you with wrong results. If any of the above apply to you (or you are not sure), talk to your doctor or nurse before using Zevtera. Children No data is available for use of Zevtera in preterm 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 breast-feeding If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before using this medicine. Driving and using machines Zevtera may cause side effects such as dizziness.This may impair your ability to drive or operate machinery. Zevtera contains sodium This medicine contains approximately 22 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 1.1% of the recommended maximum daily dietary intake of sodium for an adult. 3.
How to take it
Zevtera
Zevtera will be given to you by a doctor or nurse. The recommended dose for adults is 500 mg ceftobiprole every 8 hours given as a drip into a vein lasting 2 hours. The recommended dose for term neonates, infants, children and adolescents depends on the age and weight of the child and is given every 8 hours (infants aged 3 months or older, children and adolescents) or every 12 hours (term neonates and infants younger than 3 months) as a drip into a vein lasting 2 hours. The infusion solution with a ceftobiprole concentration of 2 mg/mL is used for adults and adolescents. For infants and term neonates, 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, talk to your doctor or nurse straight away. 3
If you forget to use Zevtera If you think you have missed a dose, talk to your doctor or nurse straight away. 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. The following
Possible side effects
may happen with this medicine: 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 lifethreatening.
- Diarrhea that becomes severe or does not go away or stool that contains blood or mucus during or after treatment with Zevtera. In this situation, you should not take medicines that stop or slow bowel movement. Common: may affect up to 1 in 10 people
- Feeling sick (nausea)
- Headache, drowsiness (somnolence)
- Feeling dizzy
- Rash, itching or hives
- Diarrhea, tell your doctor straight away if you get diarrhea
- Being sick (vomiting)
- Stomach pain (abdominal pain), indigestion or heartburn (dyspepsia)
- Unusual taste (dysgeusia)
- Fungal infections in different parts of your body
- Redness, pain or swelling were the injection was given
- Low levels of the mineral sodium in your blood
- Increase in the level of some liver enzymes in your blood
- Hypersensitivity including skin reddening Uncommon: may affect up to 1 in 100 people
- Convulsions, seizures, or fits
- Temporarily decreased or increased numbers of certain types of blood cells
- Blood testing showing decreased levels of potassium
- Sleeplessness and sleep disturbances, maybe including anxiety, panic attacks and nightmares
- Shortness of breath or difficulty breathing, asthma
- Muscle cramps
- Kidney problems
- Swelling, particularly of the ankles and legs
- Blood testing showing temporarily increased levels of triglycerides, blood sugar, or creatinine Not known: frequency cannot be estimated from the available data
- A more severe decrease in a specific type of white blood cells (agranulocytosis) Reporting of side effects If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine. 5.
How to store it
Zevtera 4
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 refers to the last day of that month. Store in a refrigerator (2C-8C). Keep the vial in the outer carton in order to protect from light. For storage of Zevtera reconstituted and diluted infusion solutions, please see the accompanying information for medical or healthcare professionals. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures 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, each mL of concentrate contains 50 mg ceftobiprole, equivalent to 66.7 mg ceftobiprole medocaril sodium. The other ingredients are citric acid monohydrate (E330) and sodium hydroxide (E524), see also section 2.
What Zevtera looks like and contents of the pack Zevtera is a white, yellowish to slightly brownish, cake to broken cake or powder 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: Mercury Pharmaceuticals Ltd, Dashwood House, 69 Old Broad Street, London, EC2M 1QS, UK Manufacturer: ACS Dobfar S.p.A. Via A. Fleming, 2 37135 Verona (VR) Italy This medicine is authorised in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland)under the following names: Austria: Denmark: Finland: France: Germany: Ireland: Italy:
Zevtera 500 mg Pulver für ein Konzentrat zur Herstellung einer Infusionslösung Zevtera Zevtera 500 mg, kuiva-aine välikonsentraatiksi infuusionestettä varten, liuos Mabelio 500 mg, poudre pour solution à diluer pour solution pour perfusion Zevtera 500 mg Pulver für ein Konzentrat zur Herstellung einer Infusionslösung Adaluzis 500 mg powder for concentrate for solution for infusion Mabelio 500 mg, polvere per concentrato per soluzione per infusione 5
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 500mg powder for concentrate for solution for infusion. This leaflet was last revised in January 2025. Detailed information on this medicine is available on the web site of United Kingdom/Medicines and Healthcare Products Regulatory Agency. <—————————————————————————————————————————–> The following information is intended for healthcare professionals only: Each vial is for single use only. Preparation of Zevtera infusion solutions Zevtera must be reconstituted and then diluted prior to infusion. Step 1: Reconstitution For adult and paediatric patients ≥ 12 years who require an infusion solution with a ceftobiprole concentration of 2 mg/mL, the lyophilized powder should be reconstituted with 10 mL of sterile water for injections or dextrose 50 mg/mL (5%) solution for injection. For paediatric patients < 12 years who require an infusion solution with a ceftobiprole concentration of 4 mg/mL, the lyophilized powder must be reconstituted either with 10 mL dextrose 50 mg/mL (5%) solution for injection if further dilution with the same diluent solution (i.e., dextrose 50 mg/mL (5%) solution for injection) is used, or with 10 mL of water for injection if further dilution with sodium chloride 9 mg/mL (0.9%) solution for injection is used (see tables below). The vial should be shaken vigorously until complete dissolution, which in some cases may take up to 10 minutes. The volume of the resulting concentrate is approximately 10.6 mL. Any foam should be allowed to dissipate and the reconstituted solution should be inspected visually to ensure the product is in solution and particulate matter is absent. The reconstituted concentrate contains 50 mg/mL of ceftobiprole (as 66.7 mg/mL of ceftobiprole medocaril sodium) and must be further diluted prior to administration. It is recommended that the reconstituted solution be further diluted immediately. However, if this is not possible the reconstituted solution can be stored at room temperature for up to 1 hour, or in a refrigerator for up to 24 hours. Step 2: Dilution (infusion solution) Use in adult and paediatric patients ≥ 12 years Preparation of 500 mg dose of Zevtera solution for infusion (2 mg/mL ceftobiprole) 10 mL of the reconstituted solution should be withdrawn from the vial and injected into a suitable container (e.g. PVC or PE infusion bags, glass bottles) containing 250 mL of sodium chloride 9 mg/mL (0.9%) solution for injection, dextrose 50 mg/mL (5%) solution for injection, or Lactated Ringer's solution for injection. The infusion solution should be gently inverted 5-10 times to form a homogenous solution. Vigorous agitation should be avoided to prevent foaming. In adults, the entire contents of the infusion bag should be infused to administer a 500 mg dose of ceftobiprole.
6
In paediatric patients ≥ 12 years the volume to be administeredshould be calculated based on the patient body weight and must not exceed a maximum of 250 mL (500 mg dose). Preparation of 250 mg dose of Zevtera solution for infusion for adult patients with severe renal impairment 5 mL of the reconstituted solution should be withdrawn from the vial and injected into a suitable container (e.g. PVC or PE infusion bags, glass bottles) containing 125 mL of sodium chloride 9 mg/mL (0.9%) solution for injection, dextrose 50 mg/mL (5%)solution for injection, or Lactated Ringer's solution for injection. The infusion solution should be gently inverted 5-10 times to form a homogenous solution. Vigorous agitation should be avoided to prevent foaming. The entire contents of the infusion bag should be infused to administer a 250 mg dose of ceftobiprole. Use in paediatric patients < 12 years Preparation of Zevtera solution for infusion at a concentration of 4 mg/mL of ceftobiprole Administration via infusion bags, bottles or syringes: The reconstituted solution prepared with 10 mL dextrose 50 mg/mL (5%)solution for injection must be diluted with the same diluent solution (i.e., dextrose 50 mg/mL (5%)solution for injection). The reconstituted solution prepared with 10 mL water for injection solution must be diluted with sodium chloride 9 mg/mL (0.9%) solution for injection. 10 mL should be withdrawn from an infusion container (e.g. PVC or PE infusion bags, glass bottles) containing 125 mL of diluent solution and replaced with 10 mL of the reconstituted solution withdrawn from the vial. The infusion solution should be gently inverted 5-10 times to form a homogenous solution. Vigorous agitation should be avoided to prevent foaming. The volume to be administered should be calculated based on the patient 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 ceftobiprole) prepared with dextrose 50 mg/mL (5%) solution for injection or water for injection should be withdrawn from the vial and diluted with 46 mL of the appropriate infusion solution diluent (see table below). The infusion solution should be gently inverted 5-10 times to form a homogenous solution. Vigorous agitation should be avoided to prevent foaming. The volume to be administered should be calculated based on the patient body weight and must not exceed 50 mL (200 mg dose). Appearance of diluted solution The solution for infusion should be clear to slightly opalescent and yellowish in colour. The solution for infusion should be inspected visually for particulate matter prior to administration, and discarded if particulate matter is visible. See also section 3 for further information. Storage of Zevtera reconstituted and diluted infusion solutions 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 2C-8C. Chemical and physical in-use stability data support the total times for reconstitution and infusion of 2 mg/mL or 4 mg/mL ceftobiprole dilution solutions described in the tables below: Use in adults and adolescents ≥ 12 years (2 mg/mL ceftobiprole): Total time by which reconstitution and infusion (including the period of infusion) must be completed
7
Reconstitution solution diluent
Dextrose 50 mg/mL (5%) solution for injection or Water for injection
Infusion solution diluent
Sodium chloride 9 mg/mL (0.9%) solution for injection Dextrose 50 mg/mL (5%) solution for injection Lactated Ringer's solution for injection
Infusion solutions stored at 25°C
Infusion solutions stored at 2C to 8C Protected from light
Protected from light 24 hours
NOT protected from light 8 hours
12 hours
8 hours
96 hours
24 hours
8 hours
Do not refrigerate
96 hours
Use in children, infants, and neonates (< 12 years) (4 mg/mL ceftobiprole): Total time by which reconstitution and infusion (including the period of infusion) must be completed Reconstitution solution diluent
Dextrose 50 mg/mL (5%) solution for injection Water for injection
Infusion solution diluent
Infusion solutions stored at 25°C NOT protected from light 12 hours
Dextrose 50 mg/mL (5%) solution for injection Sodium chloride 9 mg/mL (0.9%) solution for injection
Infusion solutions stored at 2°C to 8°C Protected from light
8 hours
24 hours 8 hours
From a microbiological point of view, unless the method of reconstitution/dilution precludes the risk of microbiological contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user. The reconstituted and infusion solutions should not be frozen or exposed to direct sunlight. If the infusion solution is stored in the refrigerator, it should be equilibrated to room temperature prior to administration. The infusion solution does not need to be protected from light during administration. See also section 5 for further information.
8
Frequently asked questions about Zevtera 500 mg powder for concentrate for solution for infusion
How do I take Zevtera 500 mg powder for concentrate for solution for infusion?
Zevtera 500 mg powder for concentrate for solution for infusion comes as infusion containing 500mg. Always follow the dose your doctor or pharmacist has given you, and read the leaflet that comes with the medicine.
What is the active substance in Zevtera 500 mg powder for concentrate for solution for infusion?
The active substance in Zevtera 500 mg powder for concentrate for solution for infusion is ceftobiprole medocaril sodium.
Where does this information come from?
This leaflet reproduces the patient information leaflet approved for Zevtera 500 mg powder for concentrate for solution for infusion, as published on the electronic medicines compendium (emc). The version printed inside your medicine’s packaging is the one that applies to you.
Can I get Zevtera 500 mg powder for concentrate for solution for infusion without a prescription?
Whether a medicine is available over the counter or on prescription only depends on its licence. Check the leaflet, or ask your pharmacist — they can tell you straight away.
About this leaflet
The text above reproduces the patient information leaflet approved for this medicine, restructured for easier reading.
- Source: electronic medicines compendium (emc), Datapharm
- Active substance: ceftobiprole medocaril sodium
- Official document: view the original leaflet on emc →
⚕For healthcare professionals — Summary of Product Characteristics (SmPC)Full SmPC: dosage, interactions, contraindications, warnings+
4.1. Therapeutic indications
Zevtera is indicated for the treatment of the following infections in adults, term neonates, infants, children and adolescents (see sections 4.4 and 5.1):
- Hospital-acquired pneumonia (HAP), excluding ventilator-associated pneumonia (VAP)
- Community-acquired pneumonia (CAP)
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
4.2. Posology and method of administration
Posology
The recommended regimen for adult and paediatric patients with normal renal function is shown in Table 1.
Table 1 Dosage in adult and paediatric patients with normal renal function or mild renal impairment (i.e., creatinine clearance [CLCR] ≥ 50 mL/min)
Age group
Body weight (kg)
Ceftobiprole dose
Concentration of infusion solutiona
Infusion time/ Frequency
Adults
-
500 mg
2 mg/mL
2 h infusion / every 8 hours
Adolescents aged 12 to < 18 years
≥ 50 kg
500 mg
< 50 kg
10 mg/kg
Infants aged ≥ 3 months and children < 12 years
≥ 33 kg
500 mg
4 mg/mL
2 h infusion / every 8 hours
< 33 kg
15 mg/kg
Term neonates and infants < 3 months
≥ 4 kg
15 mg/kg
2 h infusion / every 12 hours
< 4 kg
10 mg/kg
a See section 6.6.
For CAP, a switch to an appropriate oral antibiotic may be considered after completion of at least 3 days of intravenous ceftobiprole treatment, depending on the patient's clinical response.
Paediatric population
No data are available for use of ceftobiprole in preterm neonates.
Special populations
Elderly patients
No dose adjustment is necessary in elderly patients, except in cases of moderate to severe renal impairment (see below and section 5.2).
Renal impairment
In adult and paediatric patients with mild renal impairment (i.e., CLCR 50 to 80 mL/min), no dosage adjustment is necessary.
In adult and paediatric patients with moderate renal impairment (CLCR 30 to < 50 mL/min), adult and paediatric patients with severe renal impairment (CLCR 10 mL/min to < 30 mL/min), and adult patients with end-stage renal disease (ESRD) requiring dialysis, the dosage of ceftobiprole should be adjusted as shown in Table 2. There is insufficient information to recommend dosage adjustments in paediatrics with ESRD.
Table 2 Dosage in adult and paediatric patients with moderate renal impairment (CLCR 30 to <50 mL/min), severe renal impairment (CLCR <30 mL/min), or patients with ESRD requiring dialysis
Age group
Creatinine clearance, CLCR (mL/min)a
Ceftobiprole dose
Concentration of infusion solutiond
Infusion time (hours)/ Frequency
Adults
30 to < 50
500 mg
2 mg/mL
2 h infusion / every 12 hours
10 to < 30
250 mg
ESRD, including haemodialysisb
250 mg
2 h infusion / every 24 hours
Adolescents
Aged 12 to < 18 years
30 to < 50
7.5 mg/kg
2 h infusion / every 12 hours
10 to < 30
7.5 mg/kgc
Children aged 6 to < 12 years
30 to < 50
7.5 mg/kg
4 mg/mL
2 h infusion / every 12 hours
10 to < 30
7.5 mg/kgc
2 h infusion / every 24 hours
Infants aged ≥ 3 months and children < 6 years
30 to < 50
10 mg/kg
2 h infusion / every 12 hours
10 to < 30
10 mg/kg
2 h infusion / every 24 hours
Term neonates and infants < 3 months, bodyweight ≥ 4 kg
30 to < 50
15 mg/kg
2 h infusion / every 12 hours
10 to < 30
15 mg/kg
2 h infusion / every 24 hours
Term neonates and infants < 3 months, bodyweight < 4 kg
30 to < 50
10 mg/kg
2 h infusion / every 12 hours
10 to < 30
10 mg/kg
2 h infusion / every 24 hours
Note: All regimen administered as a 2 h infusion with a maximum allowable dose of 500 mg regardless of patient's weight unless otherwise specified.
a Calculated in mL/min/1.73 m2 using the Schwartz formula for paediatric patients. CLCR should be closely monitored and the dose adjusted according to changing renal function.
b Ceftobiprole medocaril sodium is haemodialysable; thus ceftobiprole should be administered after haemodialysis on haemodialysis days.
c Up to a maximum dose of 250 mg.
d See section 6.6.
Dose recommendations for paediatric patients are based on pharmacokinetic modelling.
Due to limited clinical data and an expected increased exposure of ceftobiprole and its metabolite, ceftobiprole should be used with caution in patients with severe renal impairment (see section 5.2).
Patients with creatinine clearance > 150 mL/min
At start of treatment the prescribing physician should assess the renal function of the patient based on creatinine clearance expressed in mL/minute.
In patients with a supra-normal creatinine clearance (> 150 mL/min), based on pharmacokinetic/pharmacodynamic considerations, prolongation of the infusion duration to 4 hours is recommended (see section 5.2).
Hepatic impairment
There is limited experience in patients with hepatic impairment. As ceftobiprole undergoes minimal hepatic metabolism and is eliminated predominantly by the kidneys, no dosage adjustment is considered necessary in patients with hepatic impairment.
Method of administration
Zevtera must be reconstituted and then further diluted (see section 6.6) prior to administration by intravenous infusion over a period of 2 hours. For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.
For adult and paediatric patients aged ≥ 12 years, ceftobiprole concentration of the infusion solution is 2 mg/mL. To limit the infusion volume in paediatric patients < 12 years of age, ceftobiprole concentration of the infusion solution for these patients is 4 mg/mL.
Precipitation can occur when Zevtera is mixed with calcium-containing solutions in the same intravenous administration line. Therefore, Zevtera and calcium-containing solutions, except Lactated Ringer's solution for injection, must not be mixed or administered simultaneously in the same intravenous line (see sections 4.4, 6.2).
4.3. Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Hypersensitivity to the cephalosporin class of antibacterials.
Immediate and severe hypersensitivity (e.g. anaphylactic reaction) to any other type of beta-lactam antibacterial agent (e.g. penicillins or carbapenems).
4.4. Special warnings and precautions for use
Hypersensitivity reactions
As with all beta-lactam antibacterial agents, serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported. In case of severe hypersensitivity reactions, treatment with ceftobiprole must be discontinued immediately and adequate emergency measures must be initiated.
Before beginning treatment, it should be established whether the patient has a history of severe hypersensitivity reactions to ceftobiprole, to other cephalosporins or to any other type of beta-lactam agent. Caution should be used if ceftobiprole is given to patients with a history of non-severe hypersensitivity to other beta-lactam agents.
Dosing above the recommended dose range
There is no clinical experience with ceftobiprole doses higher than the recommended 500 mg administered every eight hours.
Patients with pre-existing seizure disorders
Seizures have been associated with the use of ceftobiprole. Seizures occurred most commonly in patients with pre-existing CNS/seizure disorders during treatment with ceftobiprole. Therefore, caution is advised when treating these patients.
Clostridioides difficile-associated diarrhea
Antibacterial agent-associated colitis and pseudomembranous colitis have been reported with the use of ceftobiprole and may range in severity from mild to life-threatening. This diagnosis should be considered in patients with diarrhea during or subsequent to the administration of ceftobiprole (see section 4.8). Discontinuation of therapy with ceftobiprole and the administration of specific treatment for Clostridioides difficile should be considered. Medicinal products that inhibit peristalsis should not be given.
Superinfection with non-susceptible organisms
The use of ceftobiprole may result in overgrowth of non-susceptible organisms, including fungi.
Appropriate measures should be taken if evidence of superinfection occurs during therapy.
Renal toxicity
In animals, reversible renal toxicity was observed at high doses of ceftobiprole and was associated with precipitation of drug-like material in the distal tubules (see section 5.3). Although the clinical significance of this observation is unknown, it is advisable to correct hypovolaemia to maintain normal urinary output in patients receiving ceftobiprole.
Precipitation with calcium-containing solutions
Precipitation can occur when Zevtera is mixed with calcium-containing solutions in the same intravenous administration line. Therefore, Zevtera and calcium-containing solutions, except Lactated Ringer's solution for injection, must not be mixed or administered simultaneously in the same intravenous line (see section 6.2).
Limitations of clinical data
Standard indications
There is limited experience with ceftobiprole in the treatment of HAP (excluding VAP) and CAP in HIV-positive patients, patients with neutropenia, immunocompromised patients, and patients with myelosuppression. Caution is advised when treating such patients.
Patients with ventilator-associated pneumonia (VAP)
Ceftobiprole has not been shown to be effective in the treatment of patients with VAP. Ceftobiprole should not be initiated in patients with VAP (see section 5.1). In addition, on the basis of a post-hoc analysis showing a trend in favour of ceftobiprole, it is recommended that in patients with hospital-acquired pneumonia (HAP) who subsequently require ventilation, ceftobiprole should be used with caution.
Interference with serological testing
Direct antiglobulin test (Coombs test) seroconversion and potential risk of haemolytic anaemia
The development of a positive direct antiglobulin test may occur during treatment with a cephalosporin. In clinical studies there was no evidence of haemolytic anaemia. However, the possibility that haemolytic anaemia may occur in association with ceftobiprole treatment cannot be ruled out. Patients experiencing anaemia during or after treatment with ceftobiprole should be investigated for this possibility.
Potential interference with serum creatinine test
It is not known whether ceftobiprole, like some other cephalosprins, interferes with the alkaline picrate assay to measure serum creatinine (Jaffé reaction), which may lead to erroneously high creatinine measurements. During treatment with ceftobiprole it is recommended that an enzymatic method of measuring serum creatinine be used.
Potential interference with urine glucose test
During treatment with ceftobiprole it is recommended that an enzymatic method to detect glucosuria be used, because of potential interference with tests using the copper reduction technique.
Sodium content
This medicinal product contains approximately 0.95 mmol (22 mg) sodium per vial, equivalent to 1.1 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.
4.5. Interaction with other medicinal products and other forms of interaction
In vitro studies have been carried out to investigate potential interactions at the level of CYP enzymes. However, as the concentrations of ceftobiprole used in these studies were limited by solubility, the potential for CYP drug interactions cannot be ruled out.
In vitro studies showed that ceftobiprole inhibits OATP1B1 and OATP1B3 with IC50s of 67.6 µM and 44.1 µM, respectively. ceftobiprole may increase concentrations of drugs eliminated by OATP1B1 and OATP1B3, such as statins (pitavastin, pravastatin, rosuvastatin), glyburide, and bosentan.
No clinical interaction studies have been performed. Caution is advised when ceftobiprole is administered together with drugs with narrow therapeutic index.
4.6. Fertility, pregnancy and lactation
Pregnancy
There are no adequate and well-controlled studies with ceftobiprole in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3).
As no data in exposed human pregnancies are available, ceftobiprole should not be used during pregnancy unless strictly necessary.
Breastfeeding
Animal studies have shown the excretion of ceftobiprole/metabolites in milk at low concentrations. It is unknown whether ceftobiprole is excreted in human milk and the risk of diarrhea and fungal infection of the mucous membranes in the breast-fed infant cannot be excluded. The possibility of sensitisation should be taken into account. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from ceftobiprole therapy, taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.
Fertility
The effects of ceftobiprole medocaril on fertility in humans have not been studied. Animal studies with ceftobiprole medocaril do not indicate harmful effects with respect to fertility.
4.7. Effects on ability to drive and use machines
Ceftobiprole could have an influence on the ability to drive and use machines based on dizziness as a common undesirable effect.
4.8. Undesirable effects
Summary of the safety profile
In therapeutic clinical studies in adults, 1,668 subjects received ceftobiprole. Within these trials there were a total of 1,239 subjects (696 subjects in community-acquired pneumonia and nosocomial pneumonia, and 543 subjects in complicated skin and soft tissue infections, cSSTIs) who received 500 mg three times daily, 389 subjects (cSSTIs) who received 500 mg twice daily and 40 subjects (cSSTIs) who received 750 mg twice daily.
The most common adverse reactions occurring in ≥ 3% of patients treated with ceftobiprole were nausea, vomiting, diarrhea, infusion site reactions, hypersensitivity (including urticaria, pruritic rash and drug hypersensitivity) and dysgeusia.
Less frequently reported, but more serious, adverse reactions include thrombocytopenia, agranulocytosis, anaphylaxis, Clostridioides difficile, colitis, convulsion, agitation (including anxiety, panic attacks and nightmares), and renal failure.
Tabulated list of adverse reactions
The following adverse reactions were reported during therapy and during follow-up with frequencies corresponding to very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).
Table 3 Adverse reactions from clinical studies and post-marketing reports
System Organ Class
Frequency: adverse events
Infections and infestations
Common: Fungal infection (including vulvovaginal, oral and cutaneous fungal infections)
Uncommon: Clostridioides difficile colitis (including pseudomembranous colitis)
Blood and lymphatic system disorders
Uncommon: Eosinophilia, leukopenia, anaemia, thrombocytosis, thrombocytopenia
Not known: Agranulocytosis
Immune system disorders
Common: Hypersensitivity reactions (including urticaria, pruritic rash and drug hypersensitivity)
Uncommon: Anaphylactic reactions
Metabolism and nutrition disorders
Common: Hyponatraemia
Uncommon: Hypokalaemia
Psychiatric disorders
Uncommon: Insomnia, agitation (including anxiety, panic attacks and nightmares)
Nervous system disorders
Common: Dysgeusia, headache, dizziness, somnolence
Uncommon: Convulsions (including seizure, epilepsy, generalized tonic-clonic seizure, myoclonic epilepsy, myoclonus, seizure like phenomena and status epilepticus)
Respiratory, thoracic and mediastinal disorders
Uncommon: Dyspnoea, pharyngolaryngeal pain, asthma
Gastrointestinal disorders
Common: Nausea, vomiting , diarrhoea, abdominal pain, dyspepsia
Hepatobiliary disorders
Common: Hepatic enzymes increased (including AST, ALT, LDH and alkaline phosphatase)
Skin and subcutaneous tissue disorders
Common: Rash (including macular, papular, maculo-papular and generalised rash), pruritus
Musculoskeletal and connective tissue disorders
Uncommon: Muscle spasms
Renal and urinary disorders
Uncommon: Renal failure (including potential interactions with nephrotoxic drugs)
General disorders and administration site conditions
Common: Infusion site reactions
Uncommon: Peripheral oedema
Investigations
Uncommon: Blood triglycerides increased, blood creatinine increased, blood glucose increased
Not known: Coombs Direct Test Positive
Paediatric population
In one therapeutic clinical study in paediatric patients with community-acquired or nosocomial pneumonia, 94 subjects aged 3 months to 17 years received ceftobiprole. In two other clinical studies, 64 subjects aged 3 months to 17 years and 15 subjects aged 0 (birth) to < 3 months received a single dose of ceftobiprole. Overall, the safety profile in paediatric patients was similar to that observed in the adult population.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
4.9. Overdose
Information on overdosage with ceftobiprole in humans is not available. The highest total daily dose administered in Phase 1 trials was 3 g (1 g every 8 hours). If overdosage should occur, it should be treated symptomatically. Ceftobiprole plasma concentrations can be reduced by haemodialysis.
🇵🇱 Known in Poland as
Medicines sold in Poland with the same active substance: W Polsce znany jako
⚠ Not the same combination. This medicine contains Ceftobiprole medocaril sodium. The products below do not contain exactly the same set of active substances — they are not direct substitutes.
- Zevtera partial — not the same combinationCeftobiprolum · injection / infusion
Some of these do not contain exactly the same active substances — check each one. The strength, the form and whether you need a prescription can differ. Always ask a pharmacist before you switch. Polish medicines in the UK →
💬 Ask about this leaflet
Ask anything about Zevtera 500 mg powder for concentrate for solution for infusion. The assistant answers only from this leaflet — if the leaflet does not cover it, it will say so. It does not give medical advice.
Answers come from the patient leaflet published on the electronic medicines compendium (emc). They are not medical advice. Ask a pharmacist or your GP if you are unsure. For urgent help call NHS 111, or 999 in an emergency.