Presentation and Status in Health Basket
10 X 600 mg
The recommended durations of treatment are 5-14 days for cSSTI and 5-7 days for CAP.
For dosage in adults with normal renal function, creatinine clearance (CrCL) > 50 mL/min – please refer to Table 1 at the attached doctor’s leaflet.
For dosage in paediatric patients with normal renal function, creatinine clearance (CrCL) > 50 mL/min – please refer to Table 1 at the attached doctor’s leaflet.
Elderly patients (> 65 years): No dosage adjustment is required for the elderly with creatinine clearance values > 50 mL/min.
Renal impairment: The dose should be adjusted when creatinine clearance (CrCL) is ≤ 50 mL/min, as shown in Tables 3 and 4 at the attached doctor’s leaflet. The recommended durations of treatment are 5-14 days for cSSTI and 5-7 days for CAP.
Dose recommendations for children and adolescents are based on pharmacokinetic (PK) modelling.
There is insufficient information to recommend dosage adjustments in adolescents aged from 12 to < 18 years with bodyweight < 33 kg and in children aged from 2 to 12 years with End-stage renal disease (ESRD).
There is insufficient information to recommend dosage adjustments in children aged from 2 months to < 2 years with moderate or severe renal impairment or ESRD.
Hepatic impairment: No dosage adjustment is considered necessary in patients with hepatic impairment.
Paediatric population: The safety and efficacy of Zinforo in children below the age of 2 months have not yet been established. No data are available
Method of administration: Zinforo is administered by intravenous infusion over 60 minutes for all infusion volumes (50 ml, 100 ml or 250 ml).
Infusion volumes for paediatric patients will vary according to the weight of the child. The infusion solution concentration during preparation and administration should not exceed 12 mg/ml ceftaroline fosamil.
Zinforo is indicated in adults and children from age of 2 months for the treatment of the following infections:
• Complicated skin and soft tissue infections (cSSTI)
• Community-acquired pneumonia (CAP)
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Hypersensitivity to the active substance or to any of the excipients.
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).
Hypersensitivity reactions: Serious and occasionally fatal hypersensitivity reactions and serious skin reactions are possible.
Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in association with beta-lactam antibiotics (including cephalosporins) treatment.
Patients who have a history of hypersensitivity to cephalosporins, penicillins or other beta-lactam antibacterials may also be hypersensitive to ceftaroline fosamil. Ceftaroline should be used with caution in patients with a history of non-severe hypersensitivity reactions to any other beta-lactam antibiotics (e.g. penicillins or carbapenems). If a severe allergic reaction or SCAR occurs during treatment with Zinforo, the medicinal product should be discontinued and appropriate measures taken.
Clostridium difficile-associated diarrhoea: Antibacterial-associated colitis and pseudomembranous colitis have been reported with ceftaroline fosamil and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of ceftaroline fosamil. In such circumstance, the discontinuation of therapy with ceftaroline fosamil and the use of supportive measures together with the administration of specific treatment for Clostridium difficile should be considered.
Non-susceptible organisms: Superinfections may occur during or following treatment with Zinforo.
Patients with pre-existing seizure disorder: Seizures have occurred in toxicology studies at 7-25 times human ceftaroline Cmax levels. Clinical study experience with ceftaroline fosamil in patients with pre-existing seizure disorders is very limited. Therefore, Zinforo should be used with caution in this patient population.
Renal impairment: There is insufficient data to make specific dosage adjustment recommendations for patients with severe renal impairment (CrCL ≤ 30 ml/min) and end-stage renal disease (ESRD), including patients undergoing haemodialysis. Therefore, use of Zinforo is not recommended in these patient populations.
Direct antiglobulin test (Coombs test) seroconversion and potential risk of haemolytic anaemia: The development of a positive direct antiglobulin test (DAGT) may occur during treatment with cephalosporins. The incidence of DAGT seroconversion in patients receiving ceftaroline fosamil was 11.2% in the five pooled pivotal studies with administration every 12 hours (600 mg administered over 60 minutes every 12 hours) and 32.3% in a study in patients receiving ceftaroline fosamil every 8 hours (600 mg administered over 120 minutes every 8 hours), (see section 4.8). In clinical studies there was no evidence of haemolysis in patients who developed a positive DAGT on treatment. However, the possibility that haemolytic anaemia may occur in association with cephalosporins including Zinforo treatment cannot be ruled out. Patients experiencing anaemia during or after treatment with Zinforo should be investigated for this possibility.
Limitations of the clinical data: There is no experience with ceftaroline in the treatment of CAP in the following patient groups: the immunocompromised, patients with severe sepsis/septic shock, severe underlying lung disease, those with PORT Risk Class V, and/or CAP requiring ventilation at presentation, CAP due to methicillin-resistant S.aureus or patients requiring intensive care. Caution is advised when treating such patients.
There is no experience with ceftaroline in the treatment of cSSTI in the following
patient groups: the immunocompromised, patients with severe sepsis/septic shock, necrotizing fasciitis, perirectal abscess and patients with third degree and extensive burns. There is limited experience in treating patients with diabetic foot infections. Caution is advised when treating such patients.
The most common adverse reactions occurring in ≥ 3% of approximately 3,242 patients treated with Zinforo in clinical studies were diarrhoea, headache, nausea, and pruritus, and were generally mild or moderate in severity. Clostridium difficile-associated disease (CDAD)and severe hypersensitivity reactions may also occur.
See prescribing information for full details.
No clinical drug-drug interaction studies have been conducted with ceftaroline fosamil. The interaction potential of ceftaroline or ceftaroline fosamil on medicinal products metabolised by P450 enzymes is expected to be low since they are not inhibitors nor inducers of P450 enzymes in vitro. Ceftaroline or ceftaroline fosamil are not metabolised by P450 enzymes in vitro, therefore co-administered P450 inducers or inhibitors are unlikely to influence the pharmacokinetics of ceftaroline.
Ceftaroline is neither a substrate, nor an inhibitor of renal uptake transporters (OCT2, OAT1, and OAT3) in vitro. Therefore, interactions of ceftaroline with medicinal products that are substrates or inhibitors (e.g. probenecid) of these transporters would not be expected.
Pregnancy and Lactation
Pregnancy: There are no or limited data from the use of ceftaroline fosamil in pregnant women. As a precautionary measure, it is preferable to avoid the use of this drug during pregnancy unless the clinical condition of the woman requires treatment with ceftaroline fosamil.
Lactation: It is unknown whether ceftaroline fosamil or ceftaroline is excreted in human milk. A risk to the newborns/ infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Zinforo therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
See prescribing information for full details.
Limited data in patients receiving higher than recommended Zinforo dosages show similar adverse reactions as observed in the patients receiving recommended dosages. Relative overdosing could occur in patients with moderate renal impairment. Treatment of overdose should follow standard medical practice.
Ceftaroline can be removed by haemodialysis; 21.6% of the dose was removed
over a 4 hour dialysis period.
Compatibility: The powder must be reconstituted with water for injections and the resulting concentrate must then be immediately diluted prior to use. The reconstituted solution is a pale yellow solution that is free of any particles.
Standard aseptic techniques should be used for solution preparation and administration.
Zinforo powder should be reconstituted with 20 ml of sterile water for injections. The resulting solution should be shaken prior to being transferred to an infusion bag or bottle containing either sodium chloride 9 mg/ml (0.9%) solution for injection, dextrose 50 mg/ml (5%) solution for injection, sodium chloride 4.5 mg/ml and dextrose 25 mg/ml solution for injection (0.45% sodium chloride and 2.5% dextrose) or Lactated Ringer’s solution.
A 250 ml 100 ml or 50 ml infusion bag can be used to prepare the infusion. The total time interval between starting reconstitution and completing preparation of the intravenous infusion should not exceed 30 minutes. Each vial is for single use only. Any unused product or waste material should be disposed of in accordance with local requirements.
Storage: Store below 25°C. In the original package in order to protect from light.
After dilution: Once the intravenous solution is prepared with diluents listed in section 6.6 it should be administered within 6 hours of preparation. The chemical and physical in-use stability has been demonstrated for up to 24 hours at 2-8°C. Once removed from refrigeration to room temperature, the diluted product must be used within 6 hours.
From a microbiological point of view, the medicinal product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.
See prescribing information for full details.