Zinforo Safety, Tolerability and Dosing

Prescribing information is available at the bottom of this page.

Zinforo®: A reassuring safety profile

A safety and tolerability profile consistent with comparator therapies in clinical studies *†2–7 

Low potential for drug–drug interactions1,4

No routine monitoring of renal function required§1

Suitable for use in elderly patients and those with comorbidities§1–3,5,6,8,9

Similar safety profile in paediatric patients to that observed in adults||1

 

Footnotes:
*Zinforo® is contraindicated in patients with hypersensitivity to any active substance or excipient and should not be used in patients with a history of hypersensitivity to other cephalosporin-class antibiotics or who have had an immediate and severe hypersensitivity reaction (e.g., anaphylaxis to other β-lactam antibacterial agents). Fatal hypersensitivity reactions are possible.1
Antibacterial-associated colitis and pseudomembranous colitis (Clostridium difficile) have been reported including cases that were life-threatening.1
Patients with a pre-existing seizure disorder should use Zinforo® with caution as seizures occurred in toxicology studies at doses higher than typical human exposures.
DAGT (Coombs test) became positive in 11.2% of patients from five pooled pivotal studies in patients who received Zinforo® every 12 hours and in 32.3% of patients who received Zinforo® every 8 hours. Although no patients developed haemolytic anaemia, there remains a potential risk.
The most common adverse reactions occurring in ≥3% of patients treated with Zinforo® were diarrhoea, headache, nausea, and pruritus and were generally mild or moderate in severity.
Comparator therapies: cSSTI, ceftriaxone; CAP, vancomycin or cefazolin, plus optional aztreonam.
‡No clinical drug–drug interaction studies have been conducted with Zinforo®.1
§The dose should be adjusted when CrCL is ≤50 mL/min.1
||Based on two clinical trials in 227 paediatric patients aged from 2 months to 17 years. In addition, the safety assessment in neonates is based on the safety data from 2 trials in which 34 patients (age range from birth to less than 60 days) received Zinforo; 23 of these patients received only a single dose of Zinforo. Overall, the adverse events reported in these studies were consistent with the known safety profile for Zinforo.1

Abbreviations: CrCL, creatinine clearance; DAGT, direct antiglobulin test.
References: 1. . Zinforo® Summary of Product Characteristics; 2. Ramani A, et al. J Chemother 2014;26:229–34; 3. File TM, et al. Clin Infect Dis 2010;51:1395–405; 4. Lodise TP, Low DE. Drugs 2012;72:1473–93; 5. Corey G, et al. Clin Infect Dis 2010;51:641–50; 6. Santos PD, et al. J Chemother 2013;25:341–6; 7. Corrado ML. J Antimicrob Chemother 2010;65(Suppl 4):iv67–iv71; 8. Evans JD, et al. Postgrad Med 2014;126:128–34; 9. Dryden M, et al. J Antimicrob Chemother 2016;71:3575–84.

 

Prescribing Information

Zinforo® 600 mg powder for concentrate for solution for infusion: SPC
Legal category: POM
Basic NHS cost: 10 vial pack £375.00

PP-ZFO-GBR-0110. March 2020

Zinforo® Treat the majority of patients with simple dosing and a flexible infusion time

Dose in adult and adolescents ages 12 to <18 years with a bodyweight of ≥33 kg and CrCL >50 mL/min1

 
  • Based on PK/PD analyses, the recommended dose regimen for treatment of cSSTI due to Staphylococcus aureus for which the Zinforo® MIC is 2 or 4 mg/L is 600 mg every 8 hours using 2-hour infusions1
  • No dosage adjustment required for those with hepatic or mild renal impairment*1
  • For paediatric dosing and dosing for patients with renal impairment please refer to the SPC1

 

Zinforo® PK/PD 

Zinforo® has relatively low protein binding (<20%)2

Zinforo® penetrates the bronchial ELF of healthy subjects, with a penetration relative to plasma of 23%.3

At a dose of 600 mg every 12 hours and an MIC of 1 mg/L: 

  • 98.1% of patients would be expected to achieve a target free drug concentration above the MIC in plasma; for 600 mg every 8 hours, the proportion would be 100%3
  • 81.7% would be expected to achieve a target MIC in ELF3

 

Footnotes:
*Applies only for standard dose regimens in adults and paediatrics, including patients with renal impairment. For patients with supranormal renal clearance receiving the standard dose, an infusion time of 60 minutes may be preferable. Prolonging the infusion duration may also help to manage infusion-related reactions (e.g. phlebitis).1
†Infusion times of <60 minutes and neonatal recommendations are based on PK/PD analyses only.1
‡Dosage adjustment required for patients with moderate or severe renal impairment (CrCl ≤50 mL/min).

Abbreviations: CAP, community-acquired pneumonia; cSSTI, complicated skin and soft tissue infections; ELF, epithelial lining fluid; IV, intravenous; MIC, minimum inhibitory concentration; PD, pharmacodynamic; PK, pharmacokinetic.
References:1. .ZINFORO®. Summary of Product Characteristics; 2. Drusano GL. J Antimicrob Chemother 2011;66(Suppl3):iii61–7; 3. Riccobene TA, et al. Antimicrob Agents Chemother 2016;60:5849–57.

 

Prescribing Information

Zinforo® 600 mg powder for concentrate for solution for infusion: SPC
Legal category: POM
Basic NHS cost: 10 vial pack £375.00

PP-ZFO-GBR-0110. March 2020