ZINFORO Powder for concentrate for solution Ref.[6598] Active ingredients: Ceftaroline fosamil

Posology

The recommended durations of treatment are 5-14 days for cSSTI and 5-7 days for CAP.

Table 1. Dosage in adults with normal renal function, creatinine clearance (CrCL) >50 mL/min:

^a For patients with supranormal renal clearance receiving the standard dose, an infusion time of 60 minutes may be preferable.
^b Infusion times of less than 60 minutes and high dose recommendations are based on pharmacokinetic and pharmacodynamic analyses only. See sections 4.4 and 5.1.
^c For treatment of S. aureus for which the ceftaroline MIC is ≤1 mg/L, the standard dose is recommended.

Table 2. Dosage in paediatric patients with normal renal function, creatinine clearance (CrCL) >50 mL/min*:

^a For patients with supranormal renal clearance receiving the standard dose, an infusion time of 60 minutes may be preferable.
^b Infusion times of less than 60 minutes, neonatal and high dose recommendations are based on pharmacokinetic and pharmacodynamic analyses only. See sections 4.4 and 5.1.
^c For treatment of S. aureus for which the ceftaroline MIC is ≤1 mg/L, the standard dose is recommended.
^* Calculated using the Schwartz formula (in mL/min/1.73 m²) for paediatric patients.

Special populations

Elderly

No dosage adjustment is required for the elderly with creatinine clearance values >50 mL/min (see section 5.2).

Renal impairment

The dose should be adjusted when creatinine clearance (CrCL) is ≤50 mL/min, as shown in Tables 3 and 4 (see sections 4.9 and 5.2). The recommended durations of treatment are 5-14 days for cSSTI and 5-7 days for CAP.

Table 3. Dosage in adults with impaired renal function, creatinine clearance (CrCL) ≤50 mL/min:

^a Calculated using the Cockcroft-Gault formula for adults. Dose is based on CrCL. CrCL should be closely monitored and the dose adjusted according to changing renal function.
^b Ceftaroline is haemodialyzable; thus Zinforo should be administered after haemodialysis on haemodialysis days.
^c Infusion times of less than 60 minutes and high dose recommendations are based on pharmacokinetic and pharmacodynamic analyses only. See sections 4.4 and 5.1.
^d For treatment of S. aureus for which the ceftaroline MIC is ≤1 mg/L, the standard dose is recommended.

Dose recommendations for neonates, infants and 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 paediatric patients <2 years with moderate or severe renal impairment or ESRD.

Table 4. Dosage in paediatric patients with impaired renal function, creatinine clearance (CrCL) ≤50 mL/min:

^a Calculated using the Schwartz formula for paediatric patients (in mL/min/1.73 m²). Dose is based on CrCL. CrCL should be closely monitored and the dose adjusted according to changing renal function.
^b Ceftaroline is haemodialyzable; thus Zinforo should be administered after haemodialysis on haemodialysis days.
^c Infusion times of less than 60 minutes and high dose recommendations are based on pharmacokinetic and pharmacodynamic analyses only. See sections 4.4 and 5.1.
^d For treatment of S. aureus for which the ceftaroline MIC is ≤1 mg/L, the standard dose is recommended.

Hepatic impairment

No dosage adjustment is considered necessary in patients with hepatic impairment (see section 5.2).

Method of administration

Intravenous use. Zinforo is administered by intravenous infusion over 5 to 60 minutes for standard dose or 120 minutes for high dose (for cSSTI caused by S. aureus with MIC of 2 or 4 mg/L to ceftaroline) in infusion volumes of 50 mL, 100 mL or 250 mL (see section 6.6). Infusion related reactions (such as phlebitis) can be managed by prolonging the infusion duration.

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.

For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.

Limited data in patients receiving higher than recommended Zinforo dosages show similar adverse reactions as observed in the patients receiving recommended dosages. Treatment of overdose should follow standard medical practice.

Patients with renal impairment

Relative overdosing could occur in patients with moderate renal impairment. Neurological sequelae, including encephalopathy, have been noted in cases where beta-lactam antibiotics (including cephalosporins) have been given to patients with impaired renal function without reducing the dose (see section 4.2).

Ceftaroline can be removed by haemodialysis; over a 4 hour dialysis period, approximately 74% of a given dose was recovered in the dialysate.

Dry powder:

3 years.

After reconstitution:

The reconstituted vial should be diluted immediately.

After dilution:

The chemical and physical in-use stability has been demonstrated for up to 12 hours at 2-8°C and 6 hours at 25°C.

From a microbiological point of view, unless the method of opening/reconstitution/dilution precludes the risk of microbial contamination 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.

Store below 30°C.

Store in the original package in order to protect from light.

For storage conditions after reconstitution of the medicinal product, see section 6.3.

20 ml glass vial (Type 1) closed with a rubber (halobutyl) stopper and aluminium seal with flip-off cap.

The medicinal product is supplied in packs of 10 vials.

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, based on the patient’s volume requirements. The total time interval between starting reconstitution and completing preparation of the intravenous infusion should not exceed 30 minutes.

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.

Each vial is for single use only.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.