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

Posology

Adults and adolescents (aged from 12 to < 18 years with bodyweight ≥33 kg) with creatinine clearance (CrCL) > 50 mL/min: see Table 1.

Table 1. Dosage in adults and adolescents (aged from 12 to <18 years with bodyweight ≥33 kg) with CrCL >50 mL/min:

^a Based on pharmacokinetic and pharmacodynamic analyses the recommended dose regimen for treatment of cSSTI due to S. aureus for which the ceftaroline MIC is 2 or 4 mg/L is 600 mg every 8 hours using 2 hour infusions. See sections 4.4 and 5.1.

Children aged from 2 months to <12 years with CrCL >50 mL/min and adolescents aged from 12 to <18 years with bodyweight < 33 kg and with CrCL >50 mL/min: see Table 2.

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

Table 2. Dosage in children aged from 2 months to <12 years with CrCL >50 mL/min and adolescents aged from 12 to <18 years with bodyweight <33 kg and CrCL >50 mL/min^a:

^a The dose recommendations are applicable to treatment of S.aureus for which the ceftaroline MIC is ≤1 mg/L
^b The dose administered every 8 hours should not exceed 400 mg

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 section 5.2). The recommended durations of treatment are the same as for patients with CrCL >50 mL/min.

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.

Table 3. Dosage in adults and adolescents (aged from 12 to <18 years with bodyweight ≥33 kg) with CrCL ≤50 mL/min:

^a Calculated using the Cockcroft-Gault formula
^b Zinforo should be administered after haemodialysis on haemodialysis days
^c Based on pharmacokinetic and pharmacodynamic analyses the recommended dose regimen for treatment of cSSTI due to S. aureus for which the ceftaroline MIC is 2 or 4 mg/L is the dose recommended in the table by renal function category administered every 8 hours using 2 hour infusions. See sections 4.4 and 5.1.

Table 4. Dosage in children aged from 2 to <12 years with CrCL ≤50 mL/min and adolescents aged from 12 to <18 years with bodyweight <33 kg and CrCL ≤50 mL/min:

^a Calculated using the Schwartz formula
^b The dose recommendations are applicable to treatment of S. aureus for which the ceftaroline MIC is ≤1 mg/L
^c Dose is based on CrCL. CrCL should be closely monitored and the dose adjusted according to changing renal function
^d The dose administered every 8 hours should not exceed 300 mg
^e The dose administered every 8 hours should not exceed 200 mg

Hepatic impairment

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

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

Intravenous use. Zinforo is administered by intravenous infusion over 60 minutes or 120 minutes for all infusion volumes (50 ml, 100 ml or 250 ml) (see section 6.6).

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. Relative overdosing could occur in patients with moderate renal impairment. Treatment of overdose should follow standard medical practice.

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

Shelf life

Dry powder: 3 years.

After reconstitution:

The reconstituted vial should be diluted immediately.

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.

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.